SECTION B: Mobility

LEARNING OBJECTIVES

INTRODUCTION

Age-related losses of muscle mass and strength are common and can lead to sarcopenia, a condition typically consisting of a combination of loss of strength, physical function, and muscle mass. This chapter will cover concepts related to the process of muscle aging as well as the current status of sarcopenia detection, evaluation, and management.

The human body is made up of more than 600 skeletal muscles, accounting for around 40% of the total body mass. Excluding water, muscles are composed of about 80% protein, or about 50% of total body protein. The main functions of skeletal muscle are mobility and regulation of proteins. Adults tend to lose muscle mass at a rate of about 8% per decade after age 40. At age 70, an adult will have lost a mean of 24% of the muscle mass present at age 30. The rate of muscle mass loss accelerates and almost doubles after age 70. It is essential to note that adults lose muscle strength much faster; about 3% to 4% per year after age 50. Strength loss renders older persons vulnerable to physical disability.

MOTOR UNITS AND THEIR REGULATION

The basic functional unit of skeletal muscles is the motor unit. Each motor unit consists of a neuron, its axon, and the muscle fibers innervated by that neuron. The neuron terminal is connected to the muscle fiber through the neuromuscular junction, where neurons release neurotransmitters that bind to muscle cells receptors. A single motor neuron may innervate from a few to thousands of muscle fibers, depending on the muscle, with neurons responsible for higher force production innervating a higher number of fibers. Human muscles harbor three types of muscle fibers: type I, type IIa, and type IIx (formerly named IIb). Type I fibers (slow-twitch) are well adapted to perform aerobic exercise and are highly resistant to fatigue, having high oxidative capacity and a low capacity to generate adenosine triphosphate (ATP). Type IIx fibers (fast-twitch) contract several times faster but fatigue rapidly, adapted to brief, intense contractions (as in weight lifting) and have a high ATP-generating capacity and low glycolytic capacity. Type IIa fibers (also fast-twitch) are also fast but are fatigue-resistant (Table 49-1). Muscle myofibrils are made of two main contractile proteins actin and myosin, with a double helix structure, regulated by troponin and tropomyosin.

The nervous system regulates recruitment of motor units to carry out movements by generating action potentials in the motor cortex of the brain, that propagate down to the neuromuscular junction, triggering contraction of muscle fibers in a highly energy dependent process. The motor cortex is regulated by many other brain regions.

MUSCLE AGING

Age-related changes have been described at all levels of the motor unit. With increasing age the number of muscle fibers is reduced, reflected in a loss of almost one-third of muscle mass in late life. This loss seems to be faster in type II than in type I muscle fibers. Compared to younger adults, more than one-third of motor neurons are typically lost in older adults. By age 70, the number of motor units is reduced about 40% compared with the number found in 25-year-olds. Continued loss with age after age 70 can lead to nonagenarians having only one-third of the number of motor units of young persons, even in apparently healthy aging. Apoptosis of motor neurons with denervation of the innervated muscle fibers leads to muscle weakness. This process has been associated with sarcopenia. An adaptive response to motor neuron loss is motor unit remodeling in a denervation-innervation cycle, where the same nerve fiber reinnervates larger bundles of muscle fibers to counteract neuron loss (Figure 49-1). This process preferentially involves fast fibers, which may gradually become slower and thus reduce muscle force and muscle power (the ability to use full force in a given period of time).

The firing capacity of motor units is also reduced with age during submaximal and maximal intensity contractions, a phenomenon that has been linked to motor unit remodeling, by shifting the fastest firing fibers to a slower phenotype. The consequence is that older persons need to increase the number of activated fibers and come closer to maximal effort to perform usual tasks such as climbing stairs or rising from a chair. The control of muscle contraction and movement also depends on other integrative neural mechanisms that show age-related changes, including neural excitability and brain connectivity.

The magnitude of change in muscle size and function is strongly associated with long-term lifestyle, especially with the degree of physical activity and the amount of endurance exercise. This was first demonstrated in animal models, where long-term exercise is associated with reduced loss of motor neurons and muscle fibers compared to sedentary animals. Studies in runners have shown that at least part of the age-related motor unit loss may be prevented or retarded by usual physical exercise, perhaps via an increase of the reinnervation capacity of denervated units. A low protein intake over long periods of time is also associated with reduced muscle mass loss and may help upregulate the balance between muscle protein anabolism and catabolism. Other genetic and molecular changes involved in age-related changes of the skeletal muscle and the motor unit are still largely the focus of research.

SARCOPENIA: CHANGING DEFINITIONS ALONG TIME

Sarcopenia is the most frequent age-associated disease of the skeletal muscle. It is defined as a progressive and generalized disease involving the accelerated loss of muscle mass and function that is associated with increased likelihood of adverse outcomes including falls, frailty, physical disability, and mortality. It may be considered “skeletal muscle insufficiency,” similar to cardiac or renal insufficiency as a useful clinical construct.

The term “sarcopenia” is derived from the Greek words for “poverty of flesh.” It was first described in the 1980s as an age-related decline in lean body mass affecting mobility, nutritional status, and independence. Initial studies of sarcopenia focused mostly on body composition (for some, sarcopenia is still a synonym of low skeletal muscle mass). However, over the years it has become clear that muscle mass measures or estimations with any available method are poor predictors of clinical outcomes, including physical disability. On the other hand, functional measures (muscle strength and some measures of physical performance, especially gait speed) were confirmed to be good predictors of disability and other relevant outcomes. Such evidence radically changed the concept of sarcopenia in recent years. This is not surprising; cardiac muscle function is also more relevant than mass, except for diseases linked to reduced distensibility, a property that is not relevant for most skeletal muscles.

Building on this evidence, six expert consensus definitions were published from 2010 to 2014 by different groups and organizations: some working groups of the European Society for Clinical Nutrition (ESPEN), the European Working Group on Sarcopenia in Older People (EWGSOP, nurtured by the European Geriatric Medicine Society and ESPEN), an International Working Group on Sarcopenia (IWGS), a group around the Society on Sarcopenia, Cachexia and Wasting Disorders (SSCWD), the Asian Working Group for Sarcopenia (AWGS), and the US Foundation of the National Institutes of Health (FNIH) (Table 49-2). Although not equivalent, all definitions added functional measures to muscle mass estimates, were widely accepted by the scientific community, and triggered an increase in research that confirmed that defining sarcopenia as low muscle mass plus low muscle function was a relevant clinical construct that predicted outcomes and was potentially amenable to improve with interventions. These advances led to the recognition of sarcopenia as a disease with an ICD-10-CM code in 2016.

In recent years, measures and estimations of muscle mass have gradually lost credibility. Methods are unreliable, clear cutoff points could never be agreed upon, and the lack of correlation of muscle mass measures with relevant outcomes was confirmed. This reduced credibility, among other factors, led to a low uptake of the diagnosis of sarcopenia in clinical practice, missing the opportunity to prevent or reverse some outcomes. Therefore, some working groups decided to update their definitions, highlighting the importance of low muscle function and reducing the role of muscle mass in the diagnosis of sarcopenia, with the declared aim to make the diagnosis more friendly to practitioners.

The first update came from the EWGSOP (EWGSOP2) in 2019. This advanced definition opted to move muscle strength to the first parameter to be measured when sarcopenia is suspected, with muscle mass used as confirmation of the involvement of muscle in strength loss. In fact, the EWGSOP2 proposes the use of the term “suspected sarcopenia” for patients with low muscle strength when muscle mass has not been measured. It also suggests alternative use of measures of muscle quality (both in terms of muscle composition and in the ability of muscle mass volume to deliver strength) to replace muscle mass. For the EWGSOP2, low physical performance (defined as the full body ability to move or endure, as measured with walking or chair standing tests) is a marker of severity of sarcopenia that increases the risk of adverse outcomes. There is some evidence than mild or moderate sarcopenia may respond to some treatments that could be insufficient to tackle severe sarcopenia. This group also includes the concept of case finding (already suggested by the SSCWD group) by clinical symptoms or questionnaires with the aim to improve the detection of sarcopenia in clinical settings.

The AWGS (whose first definition was identical to the EWGSOP with distinct cutoff points for Asian populations) also published an updated version in 2020, where case-finding is also the first diagnostic step, albeit the algorithm, instruments or suspicion depend on the clinical setting (community vs other care settings). In specialized settings, muscle strength would be the first measure, followed by physical performance and muscle mass. However, this definition still requires impairments in either muscle mass and function to define sarcopenia, and in both to consider it severe.

Finally, the FNIH group, now named Sarcopenia Definition and Outcomes Consortium (SDOC), recently published an international expert panel position on 13 statements on the putative components of a sarcopenia definition. They confirmed by new analyses of available epidemiologic databases that low muscle strength is associated with physical performance (slowness) and that both low grip strength and low gait speed independently predict falls, self-reported mobility limitation, hip fractures, and mortality in community-dwelling older adults. On the other hand, they found again that lean mass measured by DXA was not associated with incident adverse health-related outcomes in community-dwelling older adults with or without adjustment for body size. This group recommends that low grip strength and usual gait speed should be included in the definition of sarcopenia, while low muscle mass (measured by DXA) should not be included. The evolution of definitions of sarcopenia is depicted in Figure 49-2.

EPIDEMIOLOGY

Sarcopenia is a relatively common condition in old age with adverse effects on current as well as future health. Estimates of disease prevalence and incidence are changing with the availability of more accurate definitions. The prevalence of sarcopenia using definitions that only consider low muscle mass can be as high as 40% in community dwelling older persons. However, when muscle function is also included, estimates of the prevalence of sarcopenia in the community are around 10% to 15%. The incidence of new cases of sarcopenia in older adults may be higher than 3% per year, although this has been less studied. There are no clear differences in the prevalence of sarcopenia in males and females. However, the prevalence may be higher in acutely ill hospitalized patients (especially those with severe chronic diseases, present in > 20% of hospitalized older patients), in post-acute and rehabilitation settings (where prevalence may be > 50%), and in nursing homes (> 40% of residents will be sarcopenic).

Many risk factors for sarcopenia have been described. The association with age is probably related to long-term lifestyle. Protein intake has been shown to be related to muscle mass and function in epidemiological studies. People in the lowest quartile of protein intake show a higher age-related loss of muscle mass that those in the upper quartile. A slight deficit in protein intake, when sustained for many years, may have a strong impact on muscle mass and function in old age. Low levels of vitamin D, omega 3 fatty acids, and some micronutrients (magnesium, selenium) may also be associated with impaired muscle function, although evidence is still weak. Dietary patterns are also important to muscle health. Good adherence to a Mediterranean diet or having high scores in other measures of healthy eating (usually involving higher intake of fruits, vegetables, fatty fish, or whole grains) are also related to better muscle function and reduced disability than less healthy diets.

Low physical activity and sedentariness are usually considered risk factors for sarcopenia, but evidence is weak, as no robust long-term studies have shown an association between lifetime physical activity and exercise and muscle health. Chronic diseases may also be a risk factor for sarcopenia, especially when they limit mobility or appropriate nutrition in old age. Low-grade inflammation has been shown to be associated with sarcopenia. When inflammation is severe, sarcopenia blends into cachexia. Diabetes mellitus is also an established risk factor of sarcopenia; sarcopenia is more common in persons with diabetes compared to those without. On the other hand, sarcopenia may contribute to the development and progression of diabetes through altered glucose disposal due to low muscle mass and intramuscular adipose tissue accumulation.

Obesity and sarcopenia are also related, in a construct named sarcopenic obesity. Patients with sarcopenic obesity have high adiposity and low lean mass. However, this condition is still ill defined, as some patients may have adequate muscle mass (compared with standard population measures) but have muscle strength that is unable to move an increased total body mass. There is an initiative under the auspice of ESPEN to propose a definition of sarcopenic obesity that may advance the field, expected to be released in 2022.

Sarcopenia is associated with many adverse health consequences. Many studies have confirmed that mortality is 3 to 4 times higher in sarcopenic compared with non-sarcopenic persons with otherwise similar health conditions, and the impact of sarcopenia on mortality may be even higher in persons older than 80 years. Sarcopenia is also associated with a much higher risk of physical and cognitive frailty, functional decline, and disability. The risk of falls and fractures is also slightly increased in sarcopenia, although evidence about this association is not yet unequivocal. Sarcopenia also seems to increase the risk of hospitalization, readmission, and impaired health-related quality of life, whether assessed by general instruments or disease-specific instruments. Whether sarcopenia increases the risk of nursing home admission or global health care costs remains to be elucidated.

PATHOPHYSIOLOGY

Processes leading to sarcopenia are complex and interacting. They include anatomical and functional changes imposed on an aging skeletal muscle and nervous system, and also changes in hormonal regulatory mechanisms. Research is continuing, but it may well be that the phenotype of sarcopenia is produced through different mechanisms in different individuals, which could be relevant when tailoring interventions to individual patients.

Aging disturbs skeletal muscle homeostasis, which requires balance between hypertrophy and regeneration through complex and not yet fully understood mechanisms and pathways. Aging modifies the balance between muscle protein anabolic and catabolic pathways, with reduced protein uptake and probably increased catabolism, leading to an overall loss of skeletal muscle mass. As mentioned above, cellular changes include a reduction in the size and number of myofibers, particularly affecting type II fibers, with a partial transition of muscle fibers from type II to type I. Satellite cells (muscle progenitor cells) decrease, especially those associated with type II fibers. Extracellular fat increases with aging, as do intra- and intermuscular fat, infiltrating muscles in a process named myosteatosis. The metabolic and hormonal interrelations between adipose and muscle tissue seem to be important in the pathogenesis of sarcopenia. This may help to explain the still confusing relation between sarcopenia and obesity. Mitochondrial integrity in myocytes is altered, with an impairment in intracellular energy processes. Other intracellular signaling pathways, including insulin-like growth factor 1 (IGF-1), mTOR, and FoxO transcription factors, have also been shown to be altered in sarcopenic muscles. Changes in muscle gene expression, probably mediated through epigenetic changes, have also been described.

Age-related changes in neurologic signaling and central nervous system control mechanisms, as described above, also have a role in the pathogenesis of sarcopenia. However, it is unknown to what degree, as research in this area is still limited. Untangling the role of muscle and nervous changes is urgent, as it has a direct impact on therapeutic approaches. For example, the fact that nutritional interventions to promote increasing muscle show mixed results may be due to the fact that such interventions would not improve neural mechanisms. Also, innovative treatments aiming to improve cortical and associative brain areas may well be useful, at least in some instances. Physical exercise, the best-established treatment for sarcopenia, has been shown to act through both muscular and neural pathways.

Finally, the relation between bones and muscles is currently being explored. Both are key to mobility and they are anatomically and physically related. Osteoporosis and sarcopenia frequently coexist and, when present together, exponentially increase the risk of some adverse outcomes, so the term “osteosarcopenia” is gaining momentum. Research has found evidence of cross-talk between muscle and bone through endocrine factors such as myostatin, irisin, osteocalcin, and many other substances, although the relevance of this communication in the pathogenesis of sarcopenia has not been established.

DIAGNOSIS OF SARCOPENIA IN CLINICAL PRACTICE

Awaiting a global consensus on the definition of sarcopenia, clinicians will probably opt to choose one of the most recent definitions and use it in their practice. The diagnosis of sarcopenia using any modern definition is relatively straightforward and requires measurement of a combination of muscle mass, muscle strength, and physical performance. All definitions use at least two of these three, suggesting different cutoff points depending on the measure used and the population.

Screening

At this time, screening for sarcopenia has not been proved to be cost-effective, either universally or in defined care settings or populations. A screening instrument, the SARC-F questionnaire, which explores five items and can be self-administered, has the strongest evidence, with high sensitivity with low cutoffs (> 1 point) and a good specificity when using high cutoffs (> 4) (Table 49-3). This instrument can be used in clinical scenarios with a high expected prevalence of sarcopenia, including geriatric outpatient clinics, hospitalized older patients, rehabilitation settings, or nursing homes. Some modified versions have been proposed, including other elements such as muscle calf circumference.

Also, the diagnosis of sarcopenia may be triggered by the presence of signs and symptoms associated with this condition, including complaints of weakness, slowness, muscle wasting, falls, difficulties carrying out activities of daily living, or problems in rising from a chair or bed.

Muscle Strength

Because it is the most widely used definition worldwide, here we follow the suggestions of the updated EWGSOP2 that proposes a stepwise approach to the diagnosis of sarcopenia. The AWGS suggests a similar—but not identical—approach that differs in primary care or specialized settings. The SDOC has not provided recommendations for clinical practice.

The recommended first parameter to be measured when sarcopenia is suspected clinically or by a positive SARC-F is muscle strength, usually through handgrip strength. Although measuring leg strength would seem to be more intuitive, it requires expensive equipment, cutoffs have not been defined for populations, and the link between leg strength and grip strength is consistent enough to use the latter as a proxy. Most evidence from grip strength comes from studies that use a hydraulic (Jamar) dynamometer, but other models are being progressively incorporated into clinical practice. Grip strength measures need to be standardized by using a validated protocol (as is true for blood pressure or other physical measures). If grip strength is below the reference values for gender and population (Table 49-4), sarcopenia should be suspected, as it is the most frequent reason of muscle weakness. However, the differential diagnosis is wide and other potential causes for low muscle strength should be considered—for example hand osteoarthritis, low motivation, or neurological disorders. Low grip strength is highly predictive of a range of adverse outcomes, disregarding its cause, and merits the launch of therapeutic interventions even when no further diagnostic tests are available.

Muscle Mass and Quality

The second step may be measuring muscle mass, although all experts do not agree on the need of having a muscle mass measure to diagnose sarcopenia. As mentioned, this is because all available measures are in fact estimations of muscle mass based on a number of presumptions that depend on the technique, results have a high inter- and intra-rater variability, cutoff points are inconsistent and a low muscle mass has not been consistently shown to be linked to adverse outcomes. Also, a low muscle mass may be due to malnutrition or cachexia and thus not directly caused by sarcopenia. Being said, an estimation of muscle mass would help linking low muscle strength to a muscle problem. More accurate techniques, such as the creatine dilution test are in development to measure active muscle mass. If more consistent links with outcomes are shown, they may help solve the limitations of available methods in the near future.

The most widely used methods to estimate muscle mass in practice at present are dual energy X-ray absorptiometry (DXA) and bioimpedance absorptiometry (BIA). The first has the widest evidence and definitions usually refer to it when defining cutoff points. It has the advantage that bone mineral density can be measured simultaneously. Usually, appendicular lean mass (skeletal muscle in the extremities) is measured, and in most cases adjustment for height is added to define cutoff values. BIA is useful as a bedside test; but as BIA equations and cut points are population- and device-specific, there is a lack of standardization that limits its accuracy. CT and MRI can also estimate muscle mass, usually by a cross-sectional image of the psoas muscle or the thigh. As such images are obtained routinely in some conditions and disciplines (surgery, oncology), they may be helpful in these settings, although the link to outcomes is still to be defined in larger populations. Ultrasound has also been proposed as a simple alternative to measure muscle mass in clinical practice, and a standardization of measures (the SARCUS project) has been proposed by a European Geriatric Medicine Society working group, but it still lacks validated cutoff points for major muscles. Finding a very low muscle mass with any of these techniques, together with a low grip strength, would make sarcopenia very likely, while measures closer to the cutoff points used (that depend on gender, population, and method) may be more equivocal.

Muscle quality is a widely used term for an ill-defined concept. It may refer at least to two different concepts: (1) the relation between muscle strength and muscle mass (ie, the amount of strength delivered by each muscle mass unit) or (2) some observable characteristics of the muscle, either macroscopically or microscopically (such as inter- or intramuscular adiposity, or the rates between different muscle fiber types). Quality may prove to be a relevant concept, but as yet is not sufficiently defined for use in clinical practice. An estimation of fat infiltration or muscle heterogeneity in imaging (CT, MRI, or ultrasounds), if shown to be relevant to outcomes, would be a simple and useful approach to define a muscle problem as the cause of low muscle strength.

Physical Performance

Physical performance has been defined as the ability to carry out physical tasks in order to function independently in daily life. It measures composite functions of the whole body as opposed to the function of a single organ and depends on an intact musculoskeletal system integrated with the central and peripheral nervous systems, with significant involvement of a range of other body systems (cardiovascular, vision, balance, and other). Measures of physical performance usually involve standing or walking, and may include measures of mobility, strength, power, balance, and endurance. The most commonly used test in geriatric practice is gait speed in a 4- to 6-m track, again using standardized protocols. Gait speed has been shown to be related to functional outcomes and mortality along the whole spectrum of results, and even small losses (0.1 m/s) are predictive of impaired outcomes. Cutoffs have been proposed (Table 49-4). There is no agreement yet on the exact position of gait speed in the definition of sarcopenia: as an outcome (FNIH), as part of the core definition (EWGSOP, AWGS) or as a measure of severity of sarcopenia that shows the impact of a reduced muscle function in body function (EWGSOP2, AWGS). Nevertheless, gait speed is probably a basic vital sign in geriatric practice.

Other measures of physical performance that are not unusual in geriatric practice are used as well to define sarcopenia or its severity. The Short Physical Performance Battery (SPPB) adds a measure of balance and of muscle strength/power/endurance (sit to stand test) to gait speed. It has been validated in many clinical settings and is associated with frailty. The sit-to-stand test has also been proposed as a proxy for muscle strength when a dynamometer is not available (EWGSOP2 and AWGS). The Timed Up and Go (TUG) test is a widely used and useful measure of physical performance. Other walking tests (6 minutes, 400 m) may be chosen in some clinical and research settings.

Biomarkers

Most of the proposed diagnostic measures are (physical) biomarkers of sarcopenia. However, clinicians are used to including blood biomarkers in the diagnostic scheme of most diseases, so a search for such blood (or other tissues) biomarkers of sarcopenia is underway. Many of the elements that are known to be altered in sarcopenia, including the neuromuscular junction, inflammation, micro-RNAs, hormones, metabolic by-products, and others, have been proposed as potential biomarkers. Research in this area is complex and to date results are inconclusive. It may well be that composite panels including several biomarkers, rather than individual biomarkers, are needed.

Underlying Causes

Once sarcopenia has been confirmed, a systematic approach that includes a comprehensive geriatric assessment is recommended to search for potential underlying causes. Frequent causes of sarcopenia are described in Table 49-5. Most older patients will have more than one associated condition, and not all may be treatable. However, understanding the full picture of the individual patient will be helpful when deciding a therapeutic approach. When no evident cause of a gradual-onset chronic sarcopenia is present in an older person, age-associated (primary) sarcopenia is diagnosed, and further exploration of long-term habits that may have led to sarcopenia is appropriate.

DIFFERENTIAL DIAGNOSIS WITH CACHEXIA, MALNUTRITION, AND FRAILTY

The recent global definition of malnutrition, the Global Leadership Initiative on Malnutrition (GLIM), includes low muscle mass as one of the three phenotypic criteria that are part of the five criteria that define malnutrition (the three phenotypic criteria are nonvolitional weight loss, low body mass index, and reduced muscle mass, and the two etiologic criteria are reduced food intake or assimilation and inflammation or disease burden). Thus, when low muscle mass is found in a given patient, checking if any of the other four proposed GLIM criteria are present can help determine if malnutrition is present, since the coexistence of sarcopenia and malnutrition is not infrequent. When low muscle mass is not associated with low muscle function, malnutrition will probably be present and will be the main diagnosis of that patient. When both low muscle mass and low muscle function are present in a malnourished patient, the most usual scenario will be that malnutrition has caused sarcopenia.

“Cachexia” is a term used to describe severe weight loss and muscle wasting associated with cancer, HIV infection, or end-stage organ failure. The most common definitions of cachexia include the presence of a low muscle mass as well. In fact, cachexia and sarcopenia may coexist. Cachexia has a complex pathophysiology including excess catabolism and inflammation, and endocrine and neurological changes that are different from those described in sarcopenia. Conceptually, cachexia may be the end result of some disease-related cases of sarcopenia. International consensus definitions of cachexia may guide clinical judgment to decide if sarcopenia or cachexia predominate; this is relevant for the choice of treatment, as cachexia would not respond to sarcopenia treatment.

Frailty, addressed in Chapter 42, has a physical aspect that is closely related to sarcopenia. In fact, the three elements that define sarcopenia are embedded in the Fried physical frailty phenotype: unintentional weight loss—that usually involves muscle mass loss, weakness (low grip strength), and slow walking speed. Sarcopenia is a major determinant of physical frailty, as it impairs the main mobility-related organ. Of course, physical frailty can be caused by nonmuscular diseases, and mild sarcopenia may not lead to frailty. Thus, they are distinct but overlapping constructs.

TREATMENT

Because sarcopenia is a complex condition—and a quite recently defined one—evidence about treatment is still limited. Understanding the pathophysiology of sarcopenia is key to developing effective new interventions and translational research in this area is needed. Of course, addressing the causes and risk factors that are found in the comprehensive geriatric assessment may be useful in treating sarcopenia and preventing relapses, but to date no trials have been carried out with a multimodal approach. The first available evidence-based clinical practice guideline only places a strong recommendation on physical activity as the cornerstone for treatment of sarcopenia.

Physical Exercise

There is compelling evidence that supports the benefits of resistance exercise in improving skeletal muscle function and mass both in younger and older persons, and this evidence extends to patients with sarcopenia. However, the optimal mode, duration, and intensity of exercise are still ill-defined. Resistance exercise uses weights or elastic bands in repetitive movements to improve strength and power of groups of muscles. To treat sarcopenia, both lower and upper extremities should be exercised, at least twice a week. The minimum expected time to obtain an objective improvement seems to be close to 3 months. Ideally, exercises should be started under the advice and vigilance of an expert exercise or physical therapist, in order to teach the correct way to perform each exercise and avoid injuries. Gradually the patient will be able to start unsupervised exercise. Compliance is key to obtain results; it may be improved with supervision or peer support in an exercise group.

Many trials have shown that resistance exercise can be embedded in a multifaceted exercise program that includes aerobic (cardiovascular) and balance training, and possibly stretching and joint range-of-motion movements. However, patients should be aware that the usual cardiovascular exercise that physicians recommend widely to improve aging and well-being (walking, swimming, dancing, bicycling) will not have an impact on sarcopenia. Including resistance exercise is key to improve muscle function.

A recommendation to increase physical activity and reduce sedentariness in usual life is common sense; it is perceived to help in the prevention and treatment of sarcopenia and other conditions. However, this has not been tested as a treatment for sarcopenia and should not replace a formal exercise program as the cornerstone of treatment.

Nutrition

The evidence about nutrition interventions in treating sarcopenia is less consistent, with only conditional or weak recommendations in the clinical practice guideline. However, some recommendations can be made. Protein intake is key to muscle health, and the recommendations for protein intake in older people have recently been raised from the former 0.8 g per kg of body weight per day to 1–1.2 g in healthy older adults, and up to 1.5 g in disease. Most older persons do not reach these targets, so a careful review of patient food intake by an expert nutritionist is needed to consistently increase protein intake. This approach has been shown to be feasible and effective in a large multicenter randomized controlled trial. When the required levels of protein intake cannot be reached with usual food, the use of high protein nutritional supplements may be considered (usually in the form of oral nutritional supplements rather than protein-only supplements).

Some individual nutrients may also be useful to improve muscle mass and function. The essential amino acid leucine and its metabolite beta-hydroxy beta-methylbutyric acid (HMB) have shown some effects in improving muscle mass and function in randomized controlled trials, although it is not yet clear which individuals benefit most. Mild sarcopenia seems to respond better. Trials have usually included leucine and HMB in full oral supplements, so the effect of leucine and HMB in isolated forms in older people is unknown. There is also some evidence supporting the use of fish oil–derived n-3 (omega-3) polyunsaturated fatty acids (PUFA) and creatine. Vitamin D has not been shown to improve muscle function in sarcopenic patients. It may be useful in improving muscle function in persons with severe vitamin D deficiency.

Some trials have explored nutrition interventions in combination with physical exercise in the treatment of sarcopenia, with mixed results; only a few trials show some synergistic effects. Since physical exercise increases energy needs, energy intake (carbohydrates and fat) should be adjusted to the new requirements to increase the caloric content of the diet. Supplements may be occasionally needed. Also, incorporation of proteins into muscles seems to be limited in terms of time in older people and has a higher threshold in older compared to younger adults. Therefore, a timed boost of proteins seems to be better than increasing protein content over the day. Basic research has shown that aged muscle will most avidly take up proteins immediately after exercise.

Pharmacologic Treatments

At this time, there are no drugs approved for sarcopenia, nor are any expected in the short term. There are many reasons for this situation, including the lack of guidance from drug approval agencies on what would be acceptable clinical trial outcome measures for drug approval, uncertainty about which particular groups of patients with sarcopenia would benefit more, issues about the optimal trial design and timing, lack of strong basic science research to support most drugs, and the multifaceted pathophysiology of the condition.

Trials to date have been performed mostly with hormones. Combined estrogen–progesterone, dehydroepiandrosterone (DHEA), growth hormone, growth hormone-releasing hormone, combined testosterone-growth hormone, and insulin-like growth factor-1 have all shown negative results, but many studies have not included well-defined sarcopenic patients. Testosterone may increase muscle mass in men with low serum testosterone levels (< 200–300 ng/dL), but physical function does not seem to improve, and this drug is not devoid of side effects. In more recent trials, the initial interest in selective androgen receptor modulators (SARMs, which may be used in women as well as men) from small phase I and II trials has not been followed by convincing results from larger studies. Pioglitazone and angiotensin-converting enzyme inhibitors have also been explored with negative results.

Myostatin is a myokine, a growth factor that inhibits muscle cell growth. There is evidence that myostatin inhibition may be able to increase muscle mass, consistent with the recognition that myostatin acts as a brake on muscle differentiation, hypertrophy, and protein synthesis. A phase II proof of concept trial reported that a myostatin antibody was associated with increased muscle mass and improvement in some measures of physical performance in older, weak patients with a history of falling (but not diagnosed sarcopenia). Bimagrumab has been shown to increase muscle mass and reduce adiposity in diabetic patients, but again the effects on muscle function and physical performance seem to be limited. Myostatin inhibitor research seems to be evolving to explore changes in body composition and moving away from muscle function.

ASSESSING THE EFFECT OF TREATMENTS

There is still no agreement on what intermediate and final outcomes should be expected to improve with an intervention for sarcopenia. In clinical practice, the simplest approach is to assess changes in the parameters used for the diagnosis. Gains in muscle mass are usually difficult to assess (due to the mentioned technical issues of available instruments) and do not seem to be relevant for most older patients. Gains in muscle strength may be easier to assess but more difficult to obtain with available treatments. The minimum clinically significant difference for muscle strength is not yet defined in older patients with sarcopenia. At present, there is a case for using physical performance measures to assess improvement in clinical practice. Improvements gait speed over 0.1 m/s or over 1 point in the SPPB are accepted as being clinically relevant. Improvement in final outcomes including activities of daily living, the number of falls, or quality of life are even more relevant but not as straightforward to determine. Patients rate improved mobility as the most desired outcome of treatment, followed by the ability to manage domestic activities, a lower risk of falls, reduced fatigue, and a better quality of life.

FURTHER READING

LEARNING OBJECTIVES

INTRODUCTION

Mobility problems are pervasive in older adults. Mobility limitations affect personal independence, need for human help, and quality of life. Limited mobility predicts future health, function, and survival. Like other geriatric syndromes, mobility disorders are often caused by diseases and impairments across many organ systems; so evaluation and management require multiple perspectives and disciplines. Health care providers should be able to assess and treat mobility problems. They should be able to measure and interpret clinical indicators of mobility such as gait speed and the short physical performance battery. They should know the physiologic and biomechanical mechanisms underlying normal and abnormal mobility, the differential diagnosis of the causes of mobility disorders, and the approaches to management of mobility problems. With rapid technological advancements in the measurements of mobility, geriatricians should be aware of novel assessments that could be used in the clinic.

DEFINITIONS AND METHODS OF CLASSIFICATION

Defining Mobility

Mobility is the ability to move one’s own body through space. Mobility requires force production and feedback control systems to navigate the mass of the body through a three-dimensional environment. Walking is the fundamental mobility task for human life. Mobility also includes a wide range of other important activities that require moving one’s body, from turning over in bed to climbing stairs. Mobility tasks have an inherent hierarchical order based on the biomechanical and physiologic demands made on the body. This orderedness is apparent in the developmental tasks of infancy and childhood when mobility independence is first achieved. The simplest and first mobility task is turning over in bed, followed by sitting upright, transferring from lying to sitting and from sitting to standing. From there, individuals progress to locomotion with an increased base of support (like crawling or using a walker), independent two-legged walking, and finally to more challenging tasks like ascending and descending stairs, running, climbing ladders, and playing sports.

Mobility disability is best defined within a conceptual framework such as that of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) (Table 50-1). The concept of disability in general has transitioned from being considered a biological consequence of pathologic processes to a social construct influenced by personal and environmental factors. For example, the inability to climb 12 stairs may be considered a disability in a region with primarily two-story homes but not in an area largely made of ranch-style homes. Mobility disability occurs at the level of the whole person and can be manifested by difficulty in carrying out basic hygiene activities such as bathing or by limitations in participating in life roles, such as shopping for family members. Mobility disability is often defined by functional limitations in walking, transferring, or climbing stairs, which are caused by problems with strength, endurance, coordination, balance, and range of motion. Impaired dual-task capacity, such as attending to cognitive tasks while walking, is another clinical manifestation of mobility disability. These functional limitations can be caused by numerous pathologic processes at the body structure level. Mobility disability can precipitate a cycle of negative consequences because it often leads to decreased activity, which in turn worsens functional limitations and causes organ system deconditioning, including muscle weakness, loss of joint range of motion, and poor cardiovascular endurance. Whether or not an individual is classified as having mobility disability can be modified by psychological, social, and environmental factors.

Classification Methods for Mobility

Mobility classification is often driven by a tacit assumption of orderedness. Few single current instruments assess the full range of mobility from the lowest levels of rolling over in bed to the highest levels of endurance and coordination required for athletics or dance. The Patient-Reported Outcomes Measurement Information System (PROMIS®) measures, an NIH-funded initiative, include both computer-adaptive tests and fixed short forms that are highly comprehensive assessments of domains, such as mobility. These batteries are used in both research and clinical practice. Mobility assessment tools for older adults generally address one or more of the following three mobility levels: nonambulatory, ambulatory, and vigorous, corresponding broadly to Tinetti’s levels of frail, transitional, and vigorous mobility status. Mobility levels are surprisingly stable. While day-to-day variability does occur, people in general tend to remain in one level or decline very gradually unless a major event has occurred. Within the nonambulatory level, there are important mobility skills that affect independence in personal care activities, care needs, and demand for human help; these activities include bed mobility, self-transfer skills, and wheelchair mobility. Within the vigorous mobility level, the degree of fitness, as represented by the ability to perform demanding or challenging mobility activities, may be a useful indicator of the extent of physiologic reserve. As an indicator of the extent of physiologic reserve, vigorous mobility status may be a marker of ability to tolerate physiologic stressors such as acute illness, surgery, or periods of reduced activity.

Mobility can be assessed by self-report, professional observation, or performance-based measures. Instruments to assess mobility from all three perspectives have been developed. We selected instruments with established reliability and validity for use with older adults (Table 50-2). Each has advantages and disadvantages, including floor or ceiling effects. These tools have been used to estimate the population incidence and prevalence of mobility disorders, predict the consequences of mobility problems, screen patient populations, determine care needs, and determine reimbursement of services in rehabilitation settings. More detailed instruments have been developed specifically for sorting out causes and mechanisms. Detailed instruments for diagnosing the etiology of mobility limitations will be discussed separately in the section on causes of mobility limitations. Mobility measures have varying strengths and limitations, depending on characteristics such as reliability and validity, respondent burden, feasibility and convenience of use, and assessor skill required.

Self-report measures are the easiest type of measure to obtain when gathering data from large populations. Self-report measures have high face validity in that they reflect the opinion of the person themselves. Various self-reported walking measures predict performance of functional mobility in older adults. Since self-report measures usually ask about a period of time, such as recent weeks or months, they can identify fluctuating ability over time. Self-report measures can be limited by problems with reliability, accuracy, and nonresponse. Because these are usually ordinal scales, they lack ability to discriminate small but important differences.

Professional observation measures reflect the opinion of an experienced assessor and may be more feasible when an individual is considered an unreliable informant or is unable to cooperate with testing (eg, individuals with severe cognitive decline). Professional report is limited by the need for assessor experience and training and can be vulnerable to problems with inter-assessor reliability unless extensive efforts to standardize assessment are made. Since professional reports are usually based on ordinal scales, ability to discriminate small but important differences might be limited.

Performance-based measures are independent of assessor opinion. Most performance measures produce continuous quantitative results, which allow for discrimination of small but important or subclinical differences. Performance-based measures are limited in that they require direct observation, subject understanding and cooperation, and standardization of instructions and procedures. These tools measure capability rather than actual daily mobility activities (ie, the assessment of gait speed in a clinician’s office is not a valid assessment of a person’s gait speed at home). The need for subject cooperation can lead to problems with nonresponse. Performance-based measures do not account well for short-term fluctuations over hours to weeks. Despite these limitations, performance-based testing may have direct application in clinical settings because it is brief and can provide useful information.

Psychological aspects of fear, attention, mobility confidence, and activity avoidance can have great effect on mobility disability, separately or in combination with observable mobility limitations. Several instruments to assess psychological factors related to mobility disability have been developed (Table 50-3). Items from these scales might have use in the clinical setting.

EPIDEMIOLOGY

Prevalence

The epidemiology of mobility disability can be considered from the perspective of basic or higher-level mobility. Basic mobility problems map to the nonambulatory to ambulatory range; higher-level mobility problems map to the ambulatory to vigorous range.

Mobility disability increases dramatically with age; dependence in getting around inside increases from 5% of persons aged 65 to 74 years to 30% of persons aged 85 or older. Women tend to have higher rates of mobility disability than men, 30% compared to 23% of those 65 years and older. Racial differences exist in older adults as well; 34% of Blacks/African Americans, 23% of Asian Americans, 35% of other/multiracial background, and 25% of White people self-report experiencing mobility disability. Those with higher levels of depression report greater prevalence of mobility limitations.

Basic mobility problems include tasks such as getting around inside the house and transferring from bed or chair. Examples of higher-level mobility problems are getting around outside the house, ability to walk one-quarter or one-half mile, and ability to climb stairs. Basic mobility problems are uncommon in community-dwelling older persons but are very frequent in institutionalized older people. Among community-dwelling persons aged 65 and older, approximately 5% are dependent in getting in and out of a chair or bed and 7.5% are dependent in getting around inside. Among institutionalized persons older than 65 years, approximately 80% are dependent in getting in and out of a chair or bed and getting around inside.

In the past decade, basic mobility problems have decreased in prevalence for those older than 85 years, while remaining stable for those aged 65 to 84 years old. The decline in prevalence observed in the oldest old may be due to decreasing rates of disability in some chronic diseases in late life; for example, arthritis and heart disease, the two diseases that have been most associated with increased disability, have become less disabling. With advances in the management of these conditions, progression is delayed; consequently, the disabling effect on mobility is reduced. At the same time, there has been an increase in the incidence of obesity and sedentary lifestyle in middle age and among young old: these are also major contributing factors to disability, and these trends may explain why there is not a reduction in disability among the younger old.

Higher-level mobility problems, defined as difficulty walking a quarter mile or climbing stairs, increase with age, are more common in women than in men, and appear to be decreasing. Approximately 13% of Americans older than 60 years report higher-level mobility problems in that they have difficulty going outside the home alone. There is a marked increase with age. There is also geographic variation; self-reported difficulty going outside the home alone is more common among older adults in the southern United States.

Risk of Adverse Consequences Associated with Mobility Status

Mobility problems have serious consequences. Mobility status predicts mortality. Older people with difficulty walking 2 km or climbing one flight of stairs are twice as likely to die during the next 8 years compared to those with no difficulty. Mortality risk is even higher among those who have mobility difficulty and are also physically inactive. Poor mobility performance, even in the absence of self-reported mobility limitations, is an independent predictor of death. Among persons who report no mobility problems, gait speed less than 1.0 m/s is associated with an increased risk of death. Older persons who have a 0.1 m/s decline in gait speed over 1 year have a double risk of dying during the subsequent 5 years, whereas older persons who have a 0.1 m/s improvement in gait speed over 1 year have a 40% decreased risk of dying in the following 8 years. Improving mobility through exercise is associated with reduced risk of future falls. In a pooled analysis of over 30,000 community-dwelling older adults, each 0.1 m/s faster gait speed was associated with a 13% reduction in risk of mortality.

Poor mobility performance is an independent predictor of future self-care difficulty and mobility disability. Among community-dwelling persons older than 70 years without disability, baseline physical performance score was a powerful predictor of incident disability in both activities of daily living and in higher-level mobility disability. Mobility self-report and performance have been shown to predict disability in older populations from numerous countries and cultures, including Mexican American, British, Italian, French, Dutch, Spanish, Scandinavian, Australian, Japanese, and Chinese.

Poor mobility performance is also an independent predictor of hospitalization and nursing home placement. In a population-based study of nondisabled older adults, poor baseline physical performance score was associated with a twofold increased risk of hospitalization and more days in the hospital over the following 4 years, independent of baseline health status. The risk was mostly associated with hospitalization for dementia, pressure ulcer, hip fractures, other fracture, pneumonia, and dehydration.

Mobility may be part of an underlying constellation of core factors that link multiple outcomes associated with aging. Poor mobility, as measured by timed chair stands, is one of four factors proposed to be common risk factors for geriatric syndromes (the others are incontinence, falls, and functional decline). Conversely, good mobility, along with good cognition and nutritional status, is an independent predictor of recovery of functional independence after a period of disability. Abnormalities of gait and slow gait speed have been found to precede the onset of cognitive decline and dementia, especially vascular dementia. Among older adults, simultaneous abnormalities of mobility, cognition, and mood are more common than would be expected by chance, perhaps implying potential common underlying causes.

Severe mobility disability, sometimes called immobility, has widespread and devastating consequences. It accelerates impairments in multiple organ systems, including bone, muscle, heart, circulation, lung, skin, blood, bowel, kidney, nutrition, and metabolism. Loss of organ system function can be rapid and severe; muscle strength can decline by 1% to 5% per day of enforced bed rest. Skin breakdown and pressure ulcers start to occur after only hours of persistent and unrelieved pressure. Major consequences of clinical significance include decreased plasma volume, orthostatic hypotension, accelerated loss of bone density, muscle weakness, decreased pulmonary ventilation, and constipation leading to fecal impaction. When even temporary bed rest is combined with the increased vulnerability of aging and acute illness, there is a marked increased risk of death, disability, and institutionalization.

PATHOPHYSIOLOGY

The causes of mobility problems are complex. Unique and complementary etiologic perspectives can all contribute to a better understanding of mobility. Three perspectives are described here: biomechanical, biomedical, and biopsychosocial. Each has advantages and disadvantages when used as frameworks to understand mobility problems.

Biomechanical Perspective: Direct Assessment of the Body in Motion

Age affects the biomechanics of walking. Normal gait can be defined in terms of the gait cycle with two main phases: stance and swing (Figure 50-1). A normal cycle begins with a push off from the forefoot, then a swing through and heel strike, timed tightly to be followed by the push off of the other leg; normal gait initiates at the ankle, not the hip. Normal gait has highly characteristic patterns of foot, ankle, knee, hip, pelvis, trunk, and arm motion. Gait biomechanics can also be viewed from the perspective of the pattern of steps (footprints) (Figure 50-2). Step length is the forward distance between two foot falls. Stride length is the distance covered by one foot until it falls again. Stride length is, therefore, twice the step length, assuming the step lengths are the same on both sides. Step width is the lateral distance between two foot falls. With age, gait speed slows, step length decreases, and the proportion of the gait cycle when both feet are in contact with the ground (double support time) increases. During gait, older people compared to young adults tend to have more thoracic kyphosis, more posterior pelvic tilt, decreased hip extension, and greater external rotation of the foot. Older people tend to generate less power from the ankle and use hip flexion to compensate more than young adults. Normal gait has a very regular spatial and temporal pattern. An irregular gait can be either regularly irregular, like a limp, or irregularly irregular, with no pattern at all (Figure 50-3). Irregularly irregular gait, often called gait variability, predicts falls and mobility disability.

Normal walking maximizes energy efficiency. When walking changes owing to biomechanical alterations caused by disease or aging, walking becomes more energy demanding. Normal walking also requires excellent control of balance and timing. When problems develop with balance and timing, the priority for safe walking may be to increase stability and support at the expense of losses of energy efficiency. Thus, many changes with aging increase the energy cost of walking and decrease gait efficiency.

A biomechanical perspective can be applied broadly to mobility and balance, based on the increasing biomechanical demand placed on the body in motion. Typically, tasks are considered more challenging as the base of support narrows and transfers of mass over the base become more demanding. Thus, difficulty increases from sitting to standing to walking, to climbing stairs, walking a line, or running. A biomechanical approach to postural alterations and body-segment movement abnormalities can be useful for identifying causes of, and solutions to, mobility problems. Specific abnormalities can be addressed by targeting rehabilitative programs or the type of assistive devices. Limitations to the biomechanical framework include lack of consideration of how various physiologic or external factors impact mobility problems.

Biomedical Perspective: Using Organ System Impairment to Link Function and Disease

The causes of mobility limitation can be assessed from a physiologic standpoint. There are three main physiologic components of mobility: balance control (neurologic system), force production (cardiopulmonary and muscular systems), and structural support (skeletal system—bone and joints). Ferrucci created a framework that identifies six main physiologic subsystems that influence walking ability: central nervous system, perceptual system, peripheral nervous system, muscles, bones and joints, and energy production. Another way of organizing the systems that affect walking is to consider inputs and outputs. In this approach, the physiologic elements of mobility can be assigned to three main components based on a sequence of information from (1) sensory inputs to (2) central processing to (3) effector factors that carry out instructions from the brain. Sensory inputs include vision, vestibular function, and peripheral sensation. Central processing includes level of attention, rapid integration of sensory inputs, coordinated timing of multiple segmental body motions, and postural reflexes. Effector-related factors include generation of muscle strength and power, endurance, pain, speed of reaction, and flexibility. There are several important emerging areas of knowledge related to our understanding of the physiologic contributors to walking. Brain abnormalities found on magnetic resonance imaging (MRI) are associated with alterations in attention, rapid processing and integration of multiple sensorimotor inputs, and abnormal gait. Small vessel cerebrovascular disease in the absence of stroke and MRI findings of “white matter disease” or focal grey matter atrophy are associated with slower gait speed, even among high-functioning older adults. These MRI findings predict the onset of mobility disability. Such brain abnormalities appear to be most pronounced in the frontal areas and basal ganglia, regions that are most vulnerable to changes in cerebral perfusion with older age. These areas have been found to concurrently affect mobility, cognition, and mood and may suggest a shared underlying cerebrovascular process. Another emerging area of knowledge is related to subclinical losses of dopaminergic transmission in the brain in the aged. These losses of dopaminergic function also contribute to altered mobility and may present clinically in patterns that differ from traditional Parkinson disease. Dopamine deficiency in the aged may be related to cerebrovascular disease. Loss of oxygen-carrying capacity because of anemia has been recognized as a potential contributor to mobility limitations, especially in Caucasians, perhaps owing to decreased endurance but also possibly because of chronic subclinical ischemic effects on the brain. Disorders of glucose regulation, including poorly controlled diabetes, may also affect the integrity of brain motor areas and compromise mobility control. Research on the links among cardiovascular risk factors, brain structural abnormalities, mobility, cognition, and mood is developing rapidly. In the future, it may be possible to refine these observations into diagnosable and possibly treatable disorders. It is possible that attention to cardiovascular and metabolic risk factors might reduce the risk of developing some of these brain abnormalities and thus potentially reduce the incidence of mobility problems.

A physiologic perspective on mobility helps define organ system impairments, which can be linked to treatable diseases, conditions, and pathologic processes, as described by the disablement process in Table 50-1. A physiologic perspective is also helpful when accounting for the multiple interacting health problems of many older adults. When more than one organ system that is important for mobility is impaired, the risk of mobility problems increases. Thus, mobility can be affected when one system is severely disrupted, when several are modestly disrupted or when many are mildly disrupted. A physiologic perspective also helps account for the phenomenon of stress-induced disability. Organ systems have excess capacity, called physiologic reserve. Losses of organ system function can be clinically unapparent because these are losses of unused reserve or because one system is compensating for another. Many subclinical physiologic losses may not be recognized until stress is placed on the system by further physiologic decline or by an unexpected high demand on the system. When sufficient reserve is lost or a compensating organ system fails, mobility disability becomes overt. For example, when persons with many subclinical physiologic losses face an unexpected mobility demand, such as walking on ice at night, they may face a demand that is greater than their mobility capacity. Mobility reserve can now be assessed. One way to challenge reserve is to perform simultaneous physical and cognitive tasks. Described as “dual tasks,” older individuals may deteriorate significantly when asked to walk and talk or walk and perform a mental calculation. Mobility tests that incorporate obstacles also assess reserve. Tests of gait variability may be another way to detect subclinical change in mobility.

A physiologic perspective can help define interventions, based on the disablement structure described in Table 50-1. Treatments could be aimed at managing the underlying pathologic conditions that are causing the impairment (eg, improving cardiac ejection fraction through treatment of congestive heart failure), treating the impairments themselves (eg, strength training), or creating compensations and adaptations at the level of functional limitations (such as using a cane). A physiologic approach offers a constructive way to connect biomechanical and clinical mobility assessment to a biomedical model of diagnosis and treatment. The individual is the focus of the biomedical model, however, and addressing biomechanical and clinical factors may improve the physiologic impairments of mobility problems but not address mobility disability.

Biopsychosocial Perspective: Addressing Personal, Social, and Environmental Contributions

The experience of mobility disability can be viewed as mismatched personal capacities (physiologic and psychologic) and social and environmental demands. Psychological factors that influence mobility include negative attitudes toward aging, fear of falling, and poor attention and emotional vitality. Self-reported conditions associated with increased risk of new higher-level mobility disability include baseline and incident heart attack and stroke, baseline hypertension, diabetes, angina, dyspnea, exertional leg pain and incident cancer, and hip fracture. Epidemiologic risk factors for the onset of higher-level mobility disability include demographics, diseases, and health behaviors. Among the demographic factors associated with increased risk, advancing age has the strongest effect, with lower income, and lower educational level also playing a role. Behavior-related risk factors include current smoking, alcohol abstention, low physical activity, high body mass index, and high waist circumference. Exposure to some of these factors as early as in mid-life can influence development of disability later in life. Physical activity, a health behavior that is a key to mobility, is influenced by multiple psychological, social, and environmental factors. Common reasons given by older adults for limiting or avoiding physical activity include lack of an exercise companion, lack of interest, fatigue, fear of falling, weather, and safety. Self-reported conditions identified as major barriers to physical activity by older adults include arthritis and past injury.

Environmental demands can exacerbate mobility limitations or reinforce positive behaviors. The experience of disability is lessened when older adults’ physical capacities match the challenges present. An overly challenging environment reduces access, for example, an ambulatory older adult who struggles with stairs cannot enter a restaurant which lacks a ramp. Alternatively, inappropriate simplification of environments reinforces maladaptive behaviors with negative health consequences, for example, use of a power lift chair by an individual with intact lower extremity strength reduces use of leg muscles, potentially initiating muscle mass loss and resulting in difficulty standing from chairs without assistance. Social support follows a similar pattern. Too little social support increases mobility disability, whereas inappropriately high support diminishes opportunities to reduce development of mobility limitations.

Advantages of the biopsychosocial model include a holistic view of all influencing factors related to mobility disability. Disadvantages are the complexity in identifying, evaluating, and intervening on disposing factors.

Gait Speed as an Integrator of Multiple Approaches

Walking is the foundation of mobility, is influenced by biomechanical and physiologic processes and environmental factors and is a major driver of disability. Walking speed is considered a “vital sign” in older adults. While there are several influences on measures of gait speed such as leg length, gender, or periods of acceleration and deceleration, in general, gait speed can be interpreted clinically. Normal usual walking speed in the older adult should be at least 1 m/s. When measuring a fixed walk distance, this means that the time should be less than the distance in meters. For example, a 4-m walk time should be less than 4 seconds. When measuring a fixed time, this means that the distance should be more than the time in seconds. For example, the distance walked in a 6-minute walk (360 seconds) should be more than 360 m. The normal step frequency of walking (called the cadence) is a little more than two steps per second or somewhat more than 120 steps per minute. With approximately two steps per second at a normal pace of 1 m/s, there is approximately 0.5 m or 20 in. in a step. Clinically, this translates into approximately two shoe-lengths per step, or an imaginary “shoe” in between each step (see Figure 50-2).

As a general rule, there are links among walking speed, energy expenditure, and disability. Energy expenditure can be measured in metabolic equivalents (METs). One MET is the energy requirement for lying in bed. Two METs is twice the energy requirement for lying in bed and is approximately the energy requirement for self-care activities. The usual energy cost in METs of walking at various speeds has been reported in relationship to miles per hour, and walking speed can be translated directly between meters per second and miles per hour. Therefore, the energy requirements in METs and the expected activity level can be associated with gait speed, as described in Table 50-4. This conversion table allows clinicians and researchers to approximate the functional status of individuals or populations based on any measure of gait speed. Using METs as a basis for function, a sequence of mobility capacities is described in Table 50-5.

EVALUATION

Strategy for the Clinical Encounter

There are no established standards for the overall evaluation and treatment of mobility problems in older adults. Currently, the most common approach is similar to the ones used for other geriatric syndromes. These approaches are all based on a biopsychosocial model that incorporates biomedical, rehabilitative, and psychosocial elements and a multidisciplinary team. The initial goal of assessment is to classify the mobility problem into one of three large groups: nonambulatory, ambulatory, or vigorous. For the person who presents in a wheelchair or bed, one can screen for ability to stand or walk with assistance. For ambulatory individuals, a quick sorting strategy is to observe gait. Since most gait parameters are highly interrelated, abnormal gait can be grossly distinguished from normal by a few simple characteristics like use of a gait aid, gait speed less than 1 m/s (or step length less than twice foot length), or step asymmetry. Persons with normal gait can be assessed for higher level fitness by use of one or more screening tests for higher level abilities such as single foot stand for 30 seconds, ability to tandem walk or ability to walk more than 450 to 500 m in 6 minutes. Persons with normal walking but inability to perform higher level tasks might be good candidates for exercise programs for well elders or for further evaluation if the mobility change is recent or causing problems.

Further assessment of the nonambulatory or for those with abnormal gait depends in part on the treatment goals. The team can select a basic strategy; either to try to improve mobility or to compensate for irreversible mobility loss (Figure 50-4). This decision is based on patient preferences, the time course of the mobility loss, the potential to reverse impairments, and the ability of the patient to participate in treatment. For example, a person with severe cognitive deficits or severe irreversible motor paralysis might be considered more appropriate for compensation than for interventions to improve mobility. Planning for compensation might target mobility care needs and resources. For the person considered to have potential for improving mobility, the major decisions are the timing and value of interventions directly on mobility (usually through exercise and rehabilitation) and on underlying physiologic impairments (usually through medical team care). In primary care, the provider can screen and triage function by recognizing mobility disorders, assessing potential for intervention, and referring to other providers as appropriate. Table 50-6 gives examples of a quick system of assessment for symptoms and clinical findings based on the three main involved organ systems. The primary provider can identify and treat overt clinical impairments that can be detected quickly in the clinic, like weight-bearing pain caused by osteoarthritis, or dyspnea caused by congestive heart failure. When the cause of the mobility problem is less obvious, a referral to multidisciplinary team for comprehensive mobility assessment should be considered. Since the potential causes range across many organ systems, this strategy might be more efficient than referral to several organ system–based specialists. Research into mobility problems is an active and high-priority area in aging; in the future, efficient clinical practice and referral may be better informed by evidence.

The comprehensive approach to the clinical assessment of treatable causes of mobility is currently a specialized referral function that is resource intensive. Evaluation starts with the clinical assessment of the severity, course and consequences of mobility limitation, and the determination of potential to improve mobility. Mobility performance is assessed in more detail, including biomechanical aspects of functional limitations during movement. Potential contributing factors are identified based on physiologic impairments, and evidence is sought for psychosocial and environmental influences.

Clinical Assessment of Mobility Performance

In ambulatory patients, simple assessment of gait speed is a useful place to start. The gait speed can be used to estimate function as described above. Gait can be assessed in more detail from a biomechanical perspective (Table 50-7). Gait can be examined for general characteristics like path deviations, irregular or variable stepping, or a widened base of support and for altered motion of the component parts: trunk, arms, hip, knee, ankle, and foot. Mobility tasks can be examined for performance difficulty or altered movement patterns as task demands increase. Sometimes, the finding of an abnormal body-segment movement or gait characteristic suggests a specific impairment or disease. More often, the abnormality is nonspecific but is amenable to direct intervention in rehabilitation. Clinical gait assessments that capture many of these biomechanical elements (eg, variable stepping, path deviation, hip range of motion, arm swing) are the modified Gait Abnormality Rating Scale and the Tinetti Performance Oriented Mobility Assessment.

Mobility assessment scales usually have a functional rather than a biomedical perspective and are not designed to detect specific impairments. These scales can be used to identify areas for task practice or adaptation in rehabilitation and to assess the effects of treatment. When selecting an assessment tool, level of mobility of the patient should be considered. For nonambulatory patients, assessments should focus on bed mobility and transfers. The Hierarchical Assessment of Balance and Mobility assesses mobility, transfers, and balance and detects multiple levels within the bed and chair. For ambulatory patients, assessments should focus on walking including unchallenged (straight path walking) and some challenged walking. For patients with vigorous mobility, assessments should focus on more challenging walking tasks such as uneven surfaces, obstacles, curved paths, dual task, and walking for longer distances. Some clinical measures focus on one mobility group (ie, nonambulatory) but many clinical assessments of mobility are based on a hierarchy of task difficulty and will span the various mobility groups. One such measure, the Berg Balance Scale, assesses 14 tasks of progressive difficulty from sitting balance to one leg standing and rising onto a step. The Physical Disability Index has eight mobility tasks including six items for nonambulatory persons. The Activity Measure for Post-Acute Care (AM-PAC) was developed specifically for use across post-acute care settings (from inpatient to outpatient settings) and can also capture a range of mobility. The AM-PAC is based on patient responses and clinician observation, and captures three domains: basic mobility, daily activities, and applied cognitive. The Dynamic Gait Index, which includes eight challenging gait items such as changing gait speed, walking with head turns, and stepping over an obstacle, may be appropriate for patients with higher level (ie, vigorous) mobility.

Differential Diagnosis Based on a Physiologic Perspective

A clinical schema for the comprehensive evaluation of mobility that is derived from Ferrucci, Tinetti, and the authors’ own work is proposed in Table 50-8. Many impairments are detectable through the usual geriatric clinical history and physical examination. Some sensory systems are amenable to clinical evaluation. Some impairments are hard to detect in the clinic and require further testing. Vestibular testing may be helpful when there is unsteadiness that is not well explained by other impairments or when specific vestibular symptoms are present. Electrodiagnostic testing of nerve conduction velocity or abnormal muscle activity may be indicated when neurologic findings are suspicious. Exertional chest pain or dyspnea requires appropriate cardiac and pulmonary testing and a screen for anemia. Leg pain on exertion suggests testing for peripheral vascular disease or lumbar stenosis.

Psychosocial and Environmental Assessment

Mobility limitations are influenced by psychological, social, and environmental factors (Table 50-9). Depression can have a powerful effect on the desire to be mobile. Fear of falling, lack of confidence, lower attention, and low self-efficacy can also adversely influence a person’s mobility. Screens for these conditions can include a single question or multiple questions (see Table 50-3) and should be part of a comprehensive mobility assessment. Apathy and lack of motivation are a common concern in geriatric rehabilitation. Formal and informal social support resources can be critical for the person with mobility limitations. Cultural and financial factors can influence attitudes toward disability and resources for addressing the problem. The safety and accessibility of the living environment can be a barrier or facilitator for persons with mobility problems. Self-report measures, such as the life-space mobility questionnaire, quantify how often and with what level of difficulty older adults engage with progressively wider environments (eg, leaving bedroom, going outside, traveling beyond neighborhood, etc.). A home visit for assessment can offer many opportunities for creative problem solving.

In recent years, mobile health technologies, such as wearable devices and smartphones, have become widely used to monitor physical activity in the person’s own environment. These devices could also be used to gain insights into spatiotemporal parameters of gait.

MANAGEMENT

Intervening Directly on Mobility

Interventions directed at functional limitations are often rehabilitative in nature and involve exercise, adaptive equipment, and environmental modifications. Mobility limitations can be addressed through mobility task practice and exercise to improve specific impairments in strength, balance, endurance, and/or flexibility. Deconditioning is almost always present as a direct consequence of reduced mobility and inactivity, and deconditioning has been found to be treatable in many older adults who are sick or frail. General conditioning programs of exercise are frequently indicated. Task-specific exercises and assistive and orthotic devices can improve stability and reduce weight-bearing pain. The evidence for the effectiveness of rehabilitation and exercise interventions is growing and has been examined in older adults with varying levels of mobility limitations. In general, increasing the amount of time spent walking, even at moderate pace and in the absence of direct cardiovascular beneficial effects, can improve mobility and reduce disability. Recent studies suggest that a focus on neural control of walking through the development of progressively more complex motor skills may be especially effective in improving walking speed and the energy efficiency of walking. Chapter 55 on rehabilitation and Chapter 54 on exercise present these interventions in more detail.

Treating Impairments

Some impairments can be linked to diseases and pathologic processes that are amenable to medical treatment, and some impairments can be improved directly regardless of pathologic cause (see Table 50-8). Peripheral sensory disorders are often not correctable, but compensation can be achieved with lighting to improve visual information and increasing haptic feedback (for example, through use of a cane). Haptic perception is demonstrated by the remarkable decrease in sway with eyes closed, seen in persons with peripheral sensory or vestibular disorders, when they are allowed even minimal, nonsupporting contact with a stable surface such as a table, wall, or assistive device. Shoe inserts that increase sensory feedback are in development.

Progress in rehabilitation technology demonstrates some beneficial effects on recovery of mobility after a stroke or other injuries. For example, individuals with unilateral cerebral lesions after stroke may improve symmetric stepping in walking following split-belt treadmill training, in which the legs move at different speeds to encourage post-training even stepping. Other technologies include body weight–supported treadmill training, although evidence indicates that robust physical therapy leads to similar benefits. These technological advancements can potentially revolutionize the approach to physical therapy for older adults.

The slowed gait of Parkinson disease can be responsive to medication although the balance disorder is not. Parkinson patients may move faster when medications are initiated and thus increase their risk of fall injury unless appropriate rehabilitative measures are coordinated. Likewise, current evidence indicates individuals with BPV benefit from a combination of the canalith repositioning maneuver and balance rehabilitation more than from the repositioning maneuver alone. From the lens of improving mobility limitations, most pharmacologic interventions work best in concert with rehabilitation.

Attention to Factors That Modify Behavior and Environment

The modifiable psychosocial factors that influence physical activity may offer opportunities to intervene (see Table 50-9). Depression can be managed medically or with psychotherapy. Social support and encouragement can be promoted through group activities. Exercise (ie, balance, strength training, Tai chi/dance) may reduce fear of falling without increasing the risk or frequency of falls. The beneficial effects of physical activity on mobility could also be indirect, for example because it promotes attention, alertness, mood, as well as increasing one’s motivation to move better and more. Physical environmental adaptations in the home include ramps and railings, bathroom modifications, proper lighting, and strategic placement of stable furniture items. Further modifications are often indicated in institutional settings.

Care for the Immobile Person

Interventions to reduce the consequences of immobility include determining the level of care need and living setting, training others to properly position and move the patient, implementing a mobilization plan, use of pressure-reducing devices to prevent pressure ulcer, and, sometimes, using equipment to aid in transfers (see Chapter 46). Persons who are responsible for carrying out transfers of immobile patients, including health aides and family caregivers, need training in proper techniques that reduce injury to the patient and the assistant. Appropriate assistive devices, such as wheelchairs or powerchairs should be considered to increase environmental accessibility.

Absolute bed rest is almost never indicated and should be discouraged in all settings. Mobility-related activities such as scooting in bed, sitting up, and standing can promote improved physiologic function when walking is not feasible. Mobilization, including walking, has been shown to be feasible even in the intensive care setting and is associated with reduced intensive care unit delirium. An exception to routine mobilization might be for humanitarian reasons when an individual is actively dying, where routine mobilization might cause suffering without associated benefit. Mobilization, rather than bed rest, during hospitalization for acute illness has been one of the most consistently efficacious interventions in geriatric care units.

SUMMARY

Mobility disorders are widespread in older adults. Mobility limitations constrain many functions required for independent living and are powerful indicators of future problems. Mobility can be classified using simple screening. Evaluation starts with a triage function or simple measures like gait speed. Many common contributors to mobility limitations can be managed in the primary care setting. A comprehensive mobility evaluation is resource intensive and requires a multidisciplinary team. Evaluation and management include a biomechanical approach to function, a biomedical approach to the physiologic components of mobility, and a biopsychosocial and environmental approach to modifying factors.

FURTHER READING

LEARNING OBJECTIVES

DEFINITION OF OSTEOPOROSIS

The term osteoporosis was first introduced in the nineteenth century based on histologic diagnosis (“porous bone”). Osteoporosis is a “disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture incidence.” Osteoporosis may also be defined either by the presence of a fragility fracture (a fracture resulting from a fall from standing height or less) or by bone mineral density (BMD) measurement. In defining BMD criteria for osteoporosis, the World Health Organization (WHO) used as the standard the BMD of young adult women who were at the age of peak bone mass. For each standard deviation below peak bone mass (or 1 unit decrease in T-score), a woman’s fracture risk approximately doubles. As seen in Table 51-1, a T-score less than −2.5 defines osteoporosis; osteopenia (low bone mass) and normal bone mass are also defined.

A BMD measurement may confirm the diagnosis of osteoporosis and indicates that interventions are needed prior to fracture in older adults. In addition, individuals with osteopenia could be still at risk of fractures. They, therefore, should be followed carefully for further bone loss while also promoting nonpharmacologic interventions that maintain bone health. Although the original standards for definitions of osteoporosis were determined in White women, the standards for men and Hispanic women are similar to those of White and African-American women. However, defining osteoporosis solely by T-score does not effectively capture all patients at risk of a fracture. Greater than 50% of all hip fractures occur in those with T-scores that are better than −2.5. Failure to evaluate and treat such patients adds to the individual and societal cost and consequences of osteoporosis. Therefore, we are still faced with the challenge of improving the identification of the individual patient at risk of fracture and subsequently optimizing both prevention and treatment for older adults.

Primary or idiopathic osteoporosis has been historically classified as postmenopausal or senile osteoporosis. Postmenopausal osteoporosis occurs in women between 51 and 75 years. It is related to estrogen deficiency seen with the menopausal transition, which associates with very high levels of bone resorption. In contrast, senile osteoporosis typically occurs in persons older than 60 years. It affects both men and women and has different pathophysiology, which involves reduced levels of bone turnover due to a reduction in the numbers of bone-forming cells (osteoblasts). Increasing evidence points to a progressive age-related alteration in stem cell physiology that favors adipogenesis and thereby reduces osteoblastogenesis and bone formation. Nevertheless, estrogen probably plays a role in the pathophysiology of senile osteoporosis as well. Secondary osteoporosis is the result of underlying conditions or medications that adversely affect bone. This chapter will focus on the typical characteristics of senile osteoporosis from its pathophysiology to therapeutic approaches.

EPIDEMIOLOGY

Due to the increasing osteoporosis prevalence with age, the worldwide aging of the population and the changing lifestyle habits, the prevalence of osteoporosis has risen significantly and will continue to in the future. In 2018, the National Osteoporosis Foundation (NOF) announced that 54 million Americans, half of all adults age 50 and older, are at risk of breaking a bone and should be concerned about bone health; this means that approximately 10 million adults in the United States have osteoporosis, with an additional 43 million having low bone mass. In addition, women have more than 250,000 and 500,000 hip and spine fractures per year, respectively. Men account for an additional 250,000 fractures per year, of which 75,000 are hip fractures.

On reaching the age of 90, one-third of women and one-sixth of men will suffer a hip fracture. Both women and men have a similar lifetime vertebral fracture risk of 12%. The consequences of osteoporotic fracture include diminished quality of life (QoL), decreased functional independence, and increased morbidity and mortality. Pain and kyphosis, height loss, and other changes in body habitus resulting from vertebral compression fractures diminish the QoL in women and men. These changes lead to declines in functional status, such as the inability to bathe, dress, or ambulate independently and decrease pulmonary and gastrointestinal function. Approximately 50% of women do not fully recover prior function after hip fracture; older adults have 20% to 25% mortality in the year following hip fracture. Indeed, men are at a higher risk of dying after a hip fracture than women. Osteoporosis-related bone breaks cost patients, their families, and the health care system. The estimated annual cost of osteoporotic fractures in the United States is more than $22 billion, and by 2025 the NOF predicts that osteoporosis will be responsible for 3 million fractures costing $25 billion annually, which is higher than the money spent treating cardiovascular disease. Therefore, prevention and early diagnosis and treatment of osteoporosis are vital to improving the health of older adults.

PATHOPHYSIOLOGY

New advances in understanding bone physiology have elucidated an active interaction among bone and bone marrow cells, growth factors, and hormones responsible for maintaining calcium levels, skeletal structure, and resistance to trauma. Bone is not simply a mineralized structure but a complex system of cell–cell, cell–matrix, and cell–hormone interactions influenced by genetic background, lifestyle, and diet.

Bone is composed of inorganic (calcium phosphate crystals) and organic compounds (90% collagen and 10% noncollagenous proteins). Noncollagenous proteins include albumin, osteopontin, osteocalcin, α2-HS-glycoprotein, and growth factors, constituting the so-called bone matrix. The bone matrix is produced by osteoblasts and is the environment in which bone and external factors interact in a well-coordinated manner. There are two types of bone: cortical and trabecular. Cortical bone predominates in the long bones of the extremities, while trabecular bone predominates in the vertebrae and pelvis and makes up 80% of skeletal mass. While both types of bone have an active remodeling process, trabecular bone is metabolically more active than cortical bone and more acutely responsive to alterations in sex steroid hormone status. The bone marrow is also a complex environment in which bone cells interact with hematopoietic and marrow adipose tissues (Figure 51-1), playing an essential role in regulating bone turnover.

During childhood and adolescence, skeletal growth occurs at growth plates, areas in which cartilage proliferates and gradually undergoes calcification, resulting in new bone formation. However, bone remodeling is a lifelong process that maintains bone to harbor bone marrow, support the body, protect vital organs, and provide a source of minerals. Remodeling replaces older, frailer bone with newer, more resilient bone in an organized manner. The end product of remodeling is the maintenance of skeletal homeostasis and the preservation of anatomical integrity. With aging or with menopausal transition, the once-coordinated mechanism of bone remodeling with balanced formation and resorption becomes uncoupled, leading to bone loss and increased risk of fracture.

BONE CELLS

The cells involved in bone turnover are osteoclasts, osteoblasts, and osteocytes (Figure 51-2). Osteoclasts are macrophage-like cells that secrete proteolytic enzymes and hydrogen ions required to remove the deposited bone matrix. The remodeling cycle begins when osteoclast precursors interact with other marrow cells and are activated, becoming multinucleated osteoclasts, which initiates resorption. Bone resorption occurs within the resorption lacuna, a tightly sealed zone beneath the ruffled border of the osteoclast where it has attached to the bone surface. Resorption depends on acidification of this extracellular compartment leading to demineralization. Subsequently, the organic matrix is degraded by cysteine proteases, chief of which is cathepsin K. Osteoclasts consequently create a functional extracellular lysosome, containing both an acidic environment and specific lysosomal enzymes.

In cortical bone, the resorption period lasts approximately 30 days; the final result is a resorption tunnel that osteoblasts will later fill in in a haversian manner, in which plates of bone are laid down in layers of concentric rings around a central channel. The apposition of these haversian canals takes the shape of a “cut onion,” which gives the cortical bone its typical morphology. In trabecular bone, the erosion period lasts approximately 43 days, resulting in a trench between the trabeculae. The life span of osteoclasts is around 2 weeks; once these cells complete their role as bone-resorbing cells, they undergo apoptosis or programmed cell death.

Osteoblasts are fibroblast-like cells derived from pluripotent mesenchymal cells that localize on periosteal surfaces (Figure 51-2). Such pluripotent stromal cells can be induced to differentiate along the osteoblastic, adipocytic, fibroblastic, or chondrocytic lineages when required. When bone integrity has to be conserved, mesenchymal stromal cells are committed toward the osteoblastic lineage. Many factors are involved in the process of osteoblastogenesis (Figure 51-3), including the bone morphogenic protein family; bone morphogenic proteins 2, 4, and 7 are potent inducers of osteoblast differentiation. A transcription factor called Runx2/Cbfa1 plays a crucial role in osteoblast differentiation; mice lacking Runx2/Cbfa1 do not form bone. A mature osteoblast is a cuboidal cell with a large nucleus and enlarged Golgi highly enriched in alkaline phosphatase. It produces type I collagen and specialized bone-matrix proteins such as osteoid, the primary protein for further bone formation and mineralization. Osteoblasts produce alkaline phosphatase, the specific function of which has yet to be determined. Nevertheless, it is used as a marker of osteoblast differentiation and activity and indirectly as a marker of subsequent osteoclast resorption. Mice lacking functional alkaline phosphatase suffer from hypophosphatasia characterized by impaired mineralization of cartilage and bone matrix. After osteoblasts complete their bone-forming function, they face one of three fates: (1) they become embedded in the newly formed matrix, becoming osteocytes; (2) they remain on the surface of the newly formed bone and become lining cells; or (3) they undergo apoptosis. Hormonal changes, the presence or absence of growth factors, inflammatory conditions, and the aging process in bone determine the ultimate fate of the osteoblast.

In contrast, osteoclasts belong to the macrophage lineage and express multiple very potent degradative enzymes. Osteoclast differentiation, formation, and, to a lesser degree, activation depend upon the proximity and products of the osteoblast (Figure 51-3). Without exception, the fate of the osteoclasts is to die by apoptosis.

Osteocytes constitute the third group of bone cells that are involved in bone metabolism. These cells are the most abundant cell type in bone and are the focus of intense research. Osteocytes are postmitotic terminally differentiated osteoblasts that are entrapped within the new bone matrix. Once considered inert, these cells are now recognized as key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. Osteocytes are the critical responders to mechanical forces and orchestrators of bone remodeling and mineral homeostasis (Figure 51-3). Although osteocytes are entombed within their hosting lacunae, they are not isolated and instead maintain close communication with other cells and micro environments through a complex network of channels (canaliculi) in which osteocyte projections (cilia) are in close contact with blood vessels. Several functions attributed to osteocytes include the synthesis of matrix molecules such as osteocalcin and an essential role in direct communication with surface osteoblasts through molecules known as connexins. Two of those connexins, sclerostin and DKK1, are potent inhibitors of osteoblast differentiation and function and play an important role in the activation and regulation of bone metabolism in response to physiologic and mechanical stimuli. These modulate the response of bone during functional adaptation of the skeleton to mechanical forces and the need for repair of microdamage. Any mechanical force applied on the bone (ie, exercise) will have an inhibitory effect on sclerostin and DKK1, thus facilitating osteoblast differentiation and function. Osteocytes are very long-lived cells with a half-life of 25 years, after which most undergo apoptosis.

BONE TURNOVER

Bone homeostasis depends on the intimate coupling of bone formation and bone resorption. After osteoclasts resorb bone, preosteoblasts differentiate into osteoblasts and migrate to the area of excavated bone and begin to deposit osteoid, which is eventually mineralized into new bone. Osteoclasts and osteoblasts belong to a temporary structure known as a basic multicellular unit (see Figure 51-2). The coordinated process of bone resorption and formation by the basic multicellular unit lasts 6 to 9 months and results in newly mineralized bone. Osteoblasts are not only active as bone-forming cells, but these also play an important role in the regulation of osteoclast activity. The interaction between osteoblasts and osteoclasts requires a complex system of factors facilitated by integrins and cadherins (see Figure 51-4). Briefly, the primary osteoclast/osteoblast interaction depends on the expression by osteoclast precursors and mature osteoclasts of a membrane receptor known as receptor activator of nuclear factor-κ B (RANK), which belongs to the family of tumor necrosis factor (TNF) receptors. Osteoclast differentiation, maturation, and survival depend on RANK activation by its cognate ligand (RANK ligand—RANKL), which is produced by osteocytes, osteoblasts, and osteoblast precursors after exposure to different stimuli such as hormones and cytokines (Figure 51-4). Multiple other factors also act to either enhance or suppress osteoclast formation and activation and subsequent bone resorption (see Table 51-2).

RANKL is mainly a cytoplasmic membrane-bound molecule; to a lesser extent, it is secreted. Mature osteoblasts and osteocytes also produce a decoy receptor for RANKL called osteoprotegerin (OPG). OPG competitively binds to RANKL and prevents the interaction between RANK and RANKL, thus decreasing osteoclastogenesis and osteoclastic bone resorption and increasing osteoclast apoptosis. More recently, a group of molecules known as ephrins has been identified as key players in regulating osteoblast/osteoclast interaction. This cellular communication is bidirectional and involves a trans-membrane ligand known as ephrinB2, expressed by osteoclasts, and its receptor EphB4 expressed by osteoblasts (see Figure 51-4). This signaling seems to limit osteoclast activity while enhancing osteoblast differentiation. Consequently, osteoblastogenesis and osteoclastogenesis, along with corresponding bone formation and resorption, are tightly and ineluctably coupled. The differentiation and activation of both osteoblasts and osteoclasts depend critically on each other; however, recent evidence indicates that osteocytes also play an essential role in bone turnover by regulating osteoblast function and survival as well as osteoclast function; all modulated by hormones, growth factors, and mechanical forces.

GENETICS

Genetics plays a role in the determination of peak bone mass. Racial differences in the incidence of osteoporosis have been reported, including a lower relative risk of fractures and higher peak bone mass in African-American women compared with White women. No single gene, gene product, or polymorphism has yet been credibly identified to account for the variance seen in BMD in specific geographic areas. Several environmental factors, such as diet, topography, and yearly sunlight exposure, almost certainly interact with a genetic predisposition to explain the variance seen in periosteal expansion before puberty and trabecular number and thickness and periosteal-endosteal remodeling during aging. Candidate genes for determining peak bone mass are the vitamin D receptor, vitamin D binding protein, the peroxisome proliferator activator gamma, the Jagged 1 gene, and the low-density lipoprotein receptor-related protein 5. All these polymorphisms have been associated with different levels of peak of bone mass and predisposition to fractures in adulthood. However, multiple studies have shown that BMD and fracture predisposition are complex traits controlled by multiple genetic loci. More generally, there does appear to be a familial predisposition to osteoporotic fracture. Therefore, the fracture risk increases if an immediate family member (most typically a mother or sister) has experienced an osteoporotic fracture.

MECHANICAL FACTORS

Approximately 95% of peak adult bone mass is gained by the end of puberty. The level of peak bone mass attained and the subsequent rate of bone loss are the primary factors that determine an individual’s bone mass in early and late adulthood. Initial bone formation does not require a mechanical stimulus, but further appositional and endochondral growth is dependent on the mechanical forces generated by the muscles. The magnitude of this loading is directly related to body mass and physical activity. There is some evidence that after mechanical load, microfractures may occur in bone, with subsequent activation of interleukins (ILs) and growth factors, thereby regulating bone turnover and formation. In addition, osteocytes play an important role in the response to mechanical stress by stimulating bone turnover and facilitating bone formation through the release of RANKL and the inhibition of sclerostin and DKK1.

LOCAL FACTORS

Local factors are important in regulating bone turnover and in the interaction between bone matrix and systemic factors and hormones (see Table 51-2 and Figures 51-2 to 51-4). The skeleton responds to mechanical forces by several regulatory mechanisms, including the release of cytokines, such as macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor regulating cell differentiation. Mediators and regulators of cell–cell interaction include insulin-like growth factor (IGF)-1 and IGF-2, parathyroid hormone (PTH)-related peptide, IL-1, IL-6, and TNF-α. In addition, TNF-α, IL-6, IL-1, and prostaglandins largely mediate the response to sex-steroid hormones. Although high levels of these factors are necessary for osteoblast–osteoclast regulation and pathogenesis of osteoporosis, their usually stable systemic levels suggest that alterations in local secretion and concentration are critical to bone physiology. These local factors largely determine the activation or inhibition of bone cells, cell recruitment, cell differentiation, and life span.

SYSTEMIC HORMONES

A number of systemic hormones affect bone metabolism, including vitamin D, PTH, calcitonin, and sex-steroid hormones (estrogens and androgens) (see Table 51-2). The major effect of vitamin D is to maintain calcium homeostasis by increasing the efficiency of the small intestine in absorbing dietary calcium. Vitamin D also plays a role in bone resorption by inducing RANKL expression by osteoblasts, thereby inducing osteoclast differentiation and activation and subsequent bone formation by stimulating osteoblastogenesis and inhibiting apoptosis of mature osteoblasts. Hypovitaminosis D, widespread in older adults, is associated with lower BMD, frequent falls, and more osteoporotic fractures.

The parathyroid glands secrete PTH through a calcium sensor mechanism. When calcium levels decrease, PTH is released and exerts its function on two primary target tissues: kidney and bone. In the kidney, PTH acts on the proximal tubule to reduce PO₄ resorption and to increase the activity of 1-α-hydroxylase, the enzyme that converts 25(OH)-vitamin D to 1,25(OH)2-vitamin D₃, the active form of vitamin D. In bone, PTH increases osteoclast-induced bone resorption by inducing RANKL expression and subsequent signaling via RANK. Hypovitaminosis D is often, but not always, accompanied by elevated PTH—secondary hyperparathyroidism. Acute and cyclical exposure to PTH in bone has an antiapoptotic as well as an anabolic effect on osteoblasts. This is the basis for using PTH to treat severe osteoporosis (see further discussion below). Calcitonin is a hormone secreted by thyroidal C cells in mammals. Its main biologic effect is the inhibition of osteoclastic bone resorption. In vitro and in vivo studies in animals demonstrate that calcitonin causes the osteoclast to shrink and retract from the bone surface, decreasing its bone-resorbing activity and enhancing bone-forming osteoblasts.

Sex-steroid hormones play a variety of roles in bone turnover. Although some aspects of its effects remain unclear, estrogen increases the level of OPG, inhibiting osteoclastogenesis. Estrogen also induces osteoclast apoptosis and regulates the action of IL-1, IL-1 receptor antagonist (IL-1Ra), IL-6, and TNF-α, and their binding proteins and receptors. Declining estrogen levels lead to increased expression of IL-1, IL-6, and TNF-α, all of which enhance bone resorption. In response to diminished estrogen, osteoblasts produce more RANKL and less OPG, which induces RANKL–RANK interaction and signaling, further stimulating osteoclast differentiation and activation. Since estrogen increases osteoblast differentiation and decreases osteoblast apoptosis, bone formation declines at the time of menopause. Overall, there is a high turnover state with predominant bone resorption, which results in bone loss and susceptibility to fractures.

Androgens play an important role in the formation of adolescent bone by regulating cytokines in the bone matrix. The effect of progesterone on bone seems to be indirect and limited through its regulation of calcitonin secretion and thus bone resorption.

Women are at higher risk of osteoporosis because they have lower peak bone mass than men and experience accelerated bone loss during menopause, as described above. Histomorphometric data on the skeletal changes associated with postmenopausal bone loss show increased bone turnover in both cancellous and cortical bones. Biochemical markers also reflect high bone resorption after menopause. These markers return to normal with estrogen replacement. Trabecular bone is affected earlier in menopause than cortical bone because it is more metabolically active. Thus, rapid bone loss is seen primarily in the spine (3% per year) for approximately 5 years after menopause. Subsequently, there is a slower rate of bone loss that is more generalized (> 0.5% per year at many sites). A consistent finding in untreated postmenopausal women is a reduction in wall width of bone, indicating decreased osteoblast activity. Although this could be related to the loss of the antiapoptotic effect of estrogen on osteoblasts, studies are inconclusive.

AGE-RELATED MECHANISMS OF OSTEOPOROSIS

Age-related bone loss is a complex phenomenon, with many factors involved in its pathogenesis (see Figures 51-4 and 51-5). As individuals age, distinct changes occur in trabecular bone, cortical bone, and bone marrow. The onset and triggers of age-related bone loss are still not fully defined. However, densitometric studies show a slow and progressive decline in BMD after the third decade of approximately 0.5% per year, even though serum levels of estrogens are still within the normal range. With aging, osteoblastogenesis decreases, resulting in lower numbers of osteoblast precursors and increasing bone marrow adiposity (see Figures 51-1 and 51-4). The bone marrow of a young individual is virtually devoid of adipocytes. However, in older adults, adipose deposits may occupy up to 90% of the bone marrow cavity.

Pluripotent mesenchymal cells within the bone marrow stroma are, by default, programmed to differentiate into adipocytes, but the presence of specific osteogenic factors in the bone marrow induces osteoblastic differentiation. With aging, those osteogenic factors are decreased, generating a predominant adipocyte differentiation of those precursors. In addition, osteoblast and osteocyte apoptosis increase with aging. Histomorphometric data demonstrate that 50% to 70% of the osteoblasts present at the remodeling site cannot be accounted for after the enumeration of lining cells and osteocytes. The discrepancy in osteoblast numbers is believed to be a consequence of osteoblast apoptosis. This phenomenon may account for the significant reduction in bone formation associated with aging, which is added to high levels of marrow adipogenesis.

In addition, increasing marrow fat levels directly negatively affects bone metabolism by regulating the function and survival of bone cells. By secreting fatty acids and adipokines, marrow adipocytes inhibit osteoblast differentiation, function, and survival and osteocyte survival. This effect has been described as lipotoxicity, defined as the ectopic accumulation of lipid and lipid products in nonadipose tissues leading to cellular dysfunction, cell death (lipoapoptosis) and disease. Additionally, adipocyte-secreted factors (primarily fatty acids) affect autophagy, defined as the conserved process whereby aggregated proteins, intracellular pathogens, and damaged organelles are degraded and recycled. Autophagy appears to play a significant role in skeletal maintenance after recent reports reveal that suppression of autophagy in osteocytes mimics skeletal aging. Furthermore, marrow adipocytes induce osteoclastic activity by facilitating the release of RANKL into the bone marrow milieu, thus stimulating bone resorption in addition to decreasing bone formation (Figure 51-5).

The early changes associated with age-related bone loss are similar in men and women, as described above. However, women also experience accelerated bone loss of approximately 3% to 5% per year during menopause. In men, the decline in bone mass is gradual until very late in life, when the risk for fractures increases rapidly. Concurrent with osteoblast and adipocyte formation changes, multiple factors enhance osteoclastogenesis and bone resorption (see Figure 51-4). In particular, the interactions between osteoblasts, osteocytes, and osteoclasts, crucial to the dynamic equilibrium that maintains healthy bone, are altered. Consequently, the combination of decreased bone formation and increased bone resorption leads to diminished BMD, more flawed bone structure and quality, and, ultimately, enhanced fragility and fractures.

Muscle-secreted factors could also explain the cellular changes observed in aging bone. There is growing evidence that a complex bone/muscle cross-talk system exerted via osteokines and adipokines plays a critical regulatory role in bone metabolism (Figure 51-6). This cross-talk is affected by aging and other factors such as hormones and inactivity, associated with reduced osteogenic myokines levels. In addition, adipokines and fatty acids are also involved in this cross-talk by affecting bone and muscle structure and function. Overall, this growing evidence on the communication and close interaction between muscle and bone allowed us to propose the term osteosarcopenia as a new geriatric condition in which both osteopenia/osteoporosis and sarcopenia (loss of muscle mass, function, and strength) simultaneously occur in the same subject, increasing their risk of falls and fractures.

In addition to cellular changes, there are two major changes in calciotropic hormones that impact aging bone. Vitamin D levels decrease with age and reduce calcium absorption. Changes in the aging skin lessen the amount of 7-dehydrocholesterol, the precursor of cholecalciferol (vitamin D₃), and its conversion rate. Furthermore, declining renal function leads to a reduction in the production and activity of 1-α-hydroxylase, the enzyme responsible for the activation of vitamin D₃. Consequently, a negative calcium balance ensues, which activates the calcium sensor receptor in parathyroid glands. PTH is secreted as a physiologic response, stimulating osteoclast activity, maintaining normal serum calcium levels at the expense of bone mineralization. This theory of secondary hyperparathyroidism was once the definitive explanation for age-related bone loss. However, not all individuals with hypovitaminosis D exhibit secondary hyperparathyroidism. Therefore, it is just one of the elements of a syndrome that results in osteoporosis in older adults. However, this mechanism has been recently associated with additional important risk factors for fractures: sarcopenia and falls. Vitamin D and PTH appear to modulate neuromuscular function, particularly in frail older adults. Serum levels of 25(OH)-vitamin D lower than 35 nmol/L increase the risk of falls by 30%, which highly predisposes to fractures. Patients with serum levels between 35 and 80 nmol/L, which were considered normal in the past, are still at risk of falls, suggesting that the therapeutic goal should be to obtain serum levels greater than 80 nmol/L.

In summary, age-related bone loss results from changes at the cellular level, including decreased osteoblastogenesis, shortened osteoblast and osteocyte life span, increased adipogenesis and lipotoxicity, simultaneous occurrence of sarcopenia, and hormonal changes, including decreased levels and activity of sex-steroid hormones and vitamin D, and increased levels and activity of PTH.

OSTEOPOROSIS IN MEN

Although the pathophysiology of osteoporosis in men has been a subject of active research in recent years, the relative contribution of hormones and aging, per se, remains to be elucidated. It is well established that androgen levels decrease with aging. Testosterone levels decrease by approximately 1.2% per year, and the binding protein levels increase with aging, resulting in lower bioavailable testosterone. There is evidence that androgens exert their effect on bone through the action of IGF-1. IGF-1 levels are increased during puberty and are closely related to sex-steroid levels.

With aging, lower levels of sex-steroid hormones result in decreased levels of IGF-1, with a reduction in bone formation and bone mass. Dehydroepiandrosterone, another androgen, declines slightly in the sixth decade without significant changes after that. Contradictory evidence is available about the importance of this decline in dehydroepiandrosterone and its administration in treating male osteoporosis. Thus, osteoporosis in men appears to result from cellular and hormonal changes, including lower levels of testosterone, dehydroepiandrosterone, and IGF-1 with subsequent lower osteoblast activity and higher osteoblast apoptosis. However, further study is necessary to delineate the specific roles of these factors in the decline of BMD and the high rate of fractures in men after the seventh decade of life.

Case reports of low bone mass and increased bone turnover in men with estrogen deficiency—either from an estrogen receptor abnormality or an absence of aromatase, the enzyme responsible for converting testosterone to estrogen—suggest that estrogen is required for normal bone homeostasis in men. Serum estrogen levels better predict BMD in men than do serum testosterone levels. In older men in whom both gonadotropin secretion and aromatase conversion are suppressed, estrogen acts as the principal sex-steroid-regulating bone resorption. Blocking the conversion of testosterone to estrogen using an aromatase inhibitor has been shown to increase bone resorption in a short-term study conducted in healthy older men, further supporting a role for estrogen in bone metabolism. Some of the effects of testosterone on bone may be mediated through aromatization of testosterone to estrogen, a possibility that warrants further study.

PRESENTATION

Osteoporosis is frequently underdiagnosed and undertreated by medical professionals. Osteoporosis is a silent disease, and symptoms may not appear until an incident fracture. Both men and women can have osteoporosis (as characterized by low BMD according to the WHO criteria) prior to a fracture, which is why it is so important to consider clinical risk factors, use risk identification tools (see further), and perform BMD measurement in those at risk of osteoporosis. Osteoporosis may be detected on plain x-rays (usually a chest x-ray) either by the presence of vertebral fractures or by “osteopenia” in the x-ray report. As many as a third or more of those with “osteopenia” on an x-ray may have T-scores worse than −2.5, and as many as half will have T-scores in the −2.5 to −1.0 range. Therefore, persons who are diagnosed with “osteopenia” by plain x-ray are candidates for BMD measurement. Osteoporosis may also present as an acute fracture. Most fractures that occur in old age are caused, at least in part, by osteoporosis, and it is crucial to initiate a therapeutic regimen in these adults.

Even after a minimal trauma fracture, the diagnosis is often not considered. Three-quarters of postmenopausal women with a distal radius fracture were either undiagnosed or not treated in one study. As many as 50% of women with a hip fracture leave the hospital without treatment. The overall risk of repeat fracture within the first year is 20%. Fractures that are likely related to osteoporosis and thus should trigger therapy with an approved agent include wrist, vertebral, and hip fractures. Frequently, these fractures are classified as fragility fractures because there is often little or no trauma associated with the event. Those with such fractures do not require BMD testing, although a baseline BMD is usually helpful to assure treatment adherence and response.

In older persons, several clinical findings could indicate the presence of vertebral fractures. This includes height loss and progressive kyphosis. It is recommended that older persons be assessed routinely and that simple measurements such as occiput/wall distance be performed to identify those patients with asymptomatic vertebral fractures.

SECONDARY CAUSES OF OSTEOPOROSIS

The diagnosis of primary osteoporosis is made by BMD measurement before fracture or by incident fracture. Secondary osteoporosis is the consequence of diseases or drugs affecting bone directly (involving changes in bone cells or bone matrix composition) or indirectly (by increasing endogenous or ectopic hormonal production). It is important to exclude diseases that may present as a fracture or low BMD in evaluating women and men with osteoporosis. Table 51-3 lists the major secondary causes of osteoporosis along with laboratory tests used to exclude each disease. These laboratory tests should be considered in persons who present with acute compression fracture or who present with a diagnosis of osteoporosis by BMD measurement, particularly in those with Z scores below 2 SD. Men are more likely to have a secondary cause of osteoporosis than are women. The most commonly reported secondary causes of osteoporosis in men include hypogonadism and malabsorption syndromes. An additional secondary cause of osteoporosis in men relates to using luteinizing hormone-releasing hormone agonists in prostate cancer. Luteinizing hormone-releasing hormone agonists suppress the pituitary gland, decrease testosterone and estrogen to castrate levels, and render men at increased risk of osteoporosis. Several retrospective studies have found increased fracture rates in this population of men. Many studies demonstrate rates of bone loss that are up to three- to fourfold higher in men treated with luteinizing hormone releasing hormone agonists, compared with annual rates of bone loss in normal aging men.

Medications also may have a detrimental effect on bone. Consideration should be given to dose adjustment, discontinuation of the drugs, or preventive treatment. Medications that adversely affect BMD include glucocorticoids, proton pump inhibitors (PPIs), excess thyroid supplementation, anticonvulsants, methotrexate, cyclosporine, and heparin. In older adults, glucocorticoids, PPIs, and thyroid hormone are used quite commonly; accordingly, clinicians should consider the effects of these medications on the already increased fracture risk when prescribing these to older adults.

The prevalence of osteoporosis in adults taking glucocorticoids is approximately 30%. Bone loss typically occurs in the first 6 months of therapy, usually associated with doses of ≥7.5 mg/d administered for longer than 3 months. The risk also increases with increasing glucocorticoid dose. Glucocorticoids both suppress bone formation through direct effects on osteoblasts and increase resorption through indirect effects on osteoclasts. Glucocorticoid-induced osteoporosis is preventable if treatment is considered when therapy with corticosteroids is initiated. Replacement of gonadal hormones and treatment with anti-resorptives (bisphosphonates and denosumab) or intermittent PTH has been shown to prevent bone loss in patients taking glucocorticoids. Other measures for preventing bone loss are calcium and vitamin D supplementation and reduction of glucocorticoid dose to the lowest effective dose for the underlying disease.

In most cases, secondary osteoporosis can be either prevented or treated if suspected by the clinician. Immobilization predisposes to bone mineral loss and osteosarcopenia; thus, a program of early mobilization of hospitalized older patients is essential. Mild-to-moderate vitamin D deficiency may give rise to osteoporosis rather than osteomalacia; oral replacement may prevent its occurrence. Finally, a comprehensive medication review could also identify those medications placing the patient at risk of osteoporosis; thus, adjusting their doses or reevaluating their indications constitutes the most appropriate approach.

EVALUATION

Risk Identification

While approaches to the patient with osteoporosis have often based treatment on T-scores, assessing clinical risk factors can facilitate early identification of individual patients who are more likely to suffer from vertebral and nonvertebral fractures. This is particularly important, since most fractures occur in postmenopausal women with T-scores that are better than −2.5. The age of the patient is the most critical contributor to fracture risk. Additional important factors include a previous fracture history as an adult, history of fracture risk in a first-degree relative, body weight less than 127 lb, current history of smoking, and corticosteroid use for more than 3 months (Table 51-4). Impaired vision, early estrogen deficiency, dementia, frailty, recent falls, low calcium and vitamin D intake, low physical activity, and alcohol consumption of more than two drinks per day are additional clinical risk factors. Prior recent fracture is a robust predictor of future fracture. The increased risk is similar in both men and women and is the same as the risk of the first fracture in a woman who is 10 years older. Half of the patients will refracture within 10 years, and half of those will occur within 2 years of the first fracture. Therefore, most older patients with a prior fracture are candidates for treatment.

Identifying patients at risk of osteoporosis and osteoporotic fractures should be routine practice in geriatric medicine. The presence of risk factors (see Table 51-4) has a very high predictive value for osteoporotic fractures, especially in older persons. However, except for age, which has the highest predictive value, these risk factors have a different weight in predicting the absolute risk of future fractures. Therefore, to help the clinician accurately calculate a patient’s risk of suffering a fracture within 5 or 10 years, two online assessment tools have been widely validated.

The FRAX index (http://www.shef.ac.uk/FRAX) estimates the absolute risk of suffering a fracture in 10 years. This calculator has been demonstrated to be extremely useful since it includes specific data obtained from large cohorts worldwide. However, a major limitation of this tool is that falls are not included in the algorithm. Considering that falls are an important risk factor for fractures, the FRAX tool could be underestimating the level of risk in frequent fallers, particularly in frail older adults. In contrast to the FRAX tool, the Garvan tool (http://www.garvan.org.au/bone-fracture-risk) includes a history of previous falls in its algorithm. Although it has been recently tested in non-Australian populations, this tool was initially developed and validated using the Dubbo Osteoporosis Study database. Another major advantage of this tool is that it calculates fracture risk at 5 and 10 years, providing valuable information that could be easily shared with the patient.

Since many osteoporotic fractures result from falls (Chapter 43) or the simultaneous presence of sarcopenia (Chapter 49), it is essential to assess patients for fall risk and sarcopenia and institute preventive measures where appropriate. Figure 51-7 proposes a practical diagnostic algorithm to identify osteoporosis and sarcopenia in clinical practice. The risk factors for osteoporosis and sarcopenia are almost identical; thus, identification of secondary causes of osteoporosis should trigger the assessment for the presence of sarcopenia. The causes of falls are often multifactorial and include medications, poor vision, impaired cognition, maladaptive devices, alcohol, orthostatic hypotension, impaired balance and gait, environmental hazards, and lower extremity weakness. Recent studies suggest that specific performance measures can help to identify those at greater risk of falling. Individuals who cannot maintain a semi tandem stand for 10 seconds with their eyes open are at increased risk. A gait velocity of less than 0.8 m/s also predicts a greater propensity to fall. Additional office-based screening tests that identify potential fallers include the inability to complete the timed up and go test in 14 seconds, the inability to maintain a one-leg stand for at least 5 seconds, and a score of less than 19 in the performance-oriented mobility assessment. Finally, the SARC-F questionnaire (Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls) has a high specificity (~95%) to detect sarcopenia. The criteria are: (1) difficulty lifting and carrying 10 pounds, (2) difficulty walking across a room, (3) difficulty transferring from a chair or bed, (4) difficulty climbing a flight of 10 steps, and (5) falls in the past year. The first four criteria are scored as none = 0, some = 1, and a lot = 2. The last criterion is none = 0, 1 to 3 falls = 1, and ≥ 3 falls = 2. A score of 4 or greater is predictive of clinically important sarcopenia and is associated with adverse outcomes.

Bone Mineral Density (BMD) Assessment

BMD measurement has historically been considered the gold standard for the diagnosis of osteoporosis in the clinical setting. Various techniques could be used to measure BMD of the hip, spine, wrist, or calcaneus. The preferred method of BMD measurement is dual-energy x-ray absorptiometry (DXA). BMD of the hip, anteroposterior spine, lateral spine, and wrist can be measured using this technology. Quantitative computerized tomography is also used to measure BMD of the spine. Specific software can adapt computerized tomography scanners for BMD measurement. The advantages of DXA over quantitative computerized tomography include lower cost, lower radiation exposure, and better reproducibility over time. Peripheral DXA (measures wrist BMD) or ultrasonography of the calcaneus may be helpful for general osteoporosis screening, and these have the advantage of reduced cost and portability. Peripheral bone densitometry (performed at the heel, finger, or forearm) is highly predictive of hip, spine, wrist, rib, and forearm fractures for the subsequent 12 months.

Assessment of BMD should be considered for (1) postmenopausal women younger than 65 years with one or more additional risk factors (other than menopause); (2) all women older than 65 years, regardless of additional risk factors; and (3) patients with a history of minimal trauma fracture in which osteoporosis treatment is being started (as a baseline BMD assessment and to evaluate future therapeutic response). A study of more than 200,000 postmenopausal women from more than 4000 primary care practices in 34 states reported that approximately 50% of this population had low BMD previously undetected, including 7% of women with osteoporosis. An additional study found that screening postmenopausal women with BMD reduced the incidence of hip fracture by 36%. These studies suggest that efforts should be made to increase BMD measurements in postmenopausal women.

Postmenopausal women with significant kyphosis and clinical risk factors also do not require BMD testing to confirm the diagnosis of osteoporosis. Instead, both of these subsets of patients deserve treatment. In a cohort of over 8000 women participating in the Study of Osteoporotic Fractures, of the 243 that suffered a hip fracture, 54% had a total hip BMD T-score better than −2.5 at the start of the study. Similarly, in a study of 257 men aged 70 and older, although those with lower T-scores had a higher fracture rate, the majority of fractures occurred in men with T-scores better than −2.5. These studies emphasize that BMD is not the fundamental determinant of fracture risk; the microarchitecture and quality of bone are also important, which is not directly assessed with densitometry, as is the propensity to fall.

As noted above, clinical risk factors need to be assessed. Furthermore, it is imperative to recognize that age is a much more significant factor than BMD in determining fracture risk. The 10-year probability of a fracture in an 80-year-old is more than twice as great as the probability of fracture in a 50-year-old with the same BMD T-score. BMD may also be used to establish the diagnosis and severity of osteoporosis in men and should be considered in men with low-trauma fracture, radiographic changes consistent with low bone mass, or diseases known to place an individual at risk of osteoporosis. Data relating BMD to fracture risk were initially derived from studies completed in women, but recent data suggest that similar associations may be valid in men as well. Assessment of BMD should also be strongly considered in both perimenopausal women and older men who are about to undergo long-term treatment with corticosteroids. Bone densitometry can be used to assess response to therapy. However, usually 2 years between tests are necessary to obtain accurate and valuable information. Biochemical markers of bone turnover yield much quicker details about compliance and success of therapy.

Biochemical Markers of Bone Turnover

Serum and urine biochemical markers that reflect collagen breakdown (or bone resorption) and bone formation help monitor osteoporosis treatment. Higher levels of resorption markers have been associated with increased hip fracture risk, decreased BMD, and increased bone loss in older adults in some studies. However, biochemical markers in many patients with osteoporosis will lie within the normal range. In addition, there is often a substantial overlap of marker values in women with high and low bone density or rate of bone loss. Therefore, at this time, markers are not recommended for screening or diagnosis of osteoporosis. In addition, few studies have compared the response of a particular marker (or combination of markers) and BMD to therapy in order to determine the magnitude of decrease of a biochemical marker necessary to prevent bone loss or, more importantly, fracture. Markers are most useful in assessing the response of an individual patient to treatment. Markers of bone resorption and formation decrease in response to antiresorptive therapy and increase in response to PTH, treatment with anabolic properties. The advantage of the serum versus urinary markers is that the intra-patient variability tends to be lower with serum markers, thus reducing error. Many of the osteoclast-specific markers can then be rechecked as early as 6 weeks after beginning therapy. Successful antiresorptive therapy, which also means compliance, will reduce serum levels of markers of both resorption and formation, since these processes are tightly coupled. However, changes in bone formation markers will lag several months behind changes in bone resorption markers.

MANAGEMENT

Osteoporosis develops in older adults when the normal processes of bone formation and resorption become uncoupled or unbalanced, resulting in bone loss. Osteoporosis prevention and treatment programs, then, should focus on strategies that minimize bone resorption and maximize bone formation, as well as strategies that reduce falls. Several nonpharmacologic and pharmacologic options are available to health care providers. Importantly, modifying risk factors (see Table 51-4) should be the first step in preventing osteoporotic fractures in older adults.

Nonpharmacologic Interventions

Exercise

Exercise is an essential component of osteoporosis treatment and prevention programs. Data in older men and women suggest a positive association between current exercise and hip BMD. Among regular exercisers, those who reported strenuous or moderate exercise had higher BMD at the hip than those who reported mild or less-than-mild exercise. Similar associations were seen for lifelong regular exercisers and hip BMD. In a randomized study of women at least 10 years past menopause, the group receiving calcium supplementation plus exercise had less bone loss at the hip than those assigned to calcium alone. Furthermore, high-intensity strength training effectively maintains femoral neck BMD and improves muscle mass, strength, and balance in postmenopausal women compared to nonexercising controls, suggesting that resistance training would be helpful to maintain BMD and to reduce the risk of falls in older adults.

A marked decrease in physical activity or immobilization results in a decline in bone mass; accordingly, it is essential to encourage older adults to be as active as possible. However, not all types of exercises have proved to be beneficial. Progressive resistance strength training of the lower limb improved BMD at the neck of the femur in postmenopausal women. In contrast, aerobic exercises and low impact activities like brisk walking and cycling have failed to increase BMD at any site. Whole-body vibration (WBV) has been shown to increase BMD in some studies; however, some trials have also reported no effect. Evidence regarding the role of exercise in preventing fracture is limited as no randomized controlled trial (RCT) has so far evaluated the role of exercise as a single intervention to prevent fractures. However, exercise and focused physical therapy can prevent falls, which are significant contributors to increased fracture risk. Concerning exercise, an important consideration in older people is configuring a program according to comorbidities and functional status, as adherence may vary depending upon underlying conditions, particularly osteoarthritis and/or cardiopulmonary disease.

Physical therapy is an integral part of osteoporosis treatment programs, especially after an acute vertebral compression or hip fracture. The physical therapist can provide postural exercises, alternative modalities for pain reduction, and suggest changes in body mechanics that may help prevent future falls and fractures. Gait training or balance training and muscle strengthening can help prevent falls, even for relatively frail older persons. A meta-analysis of randomized clinical trial interventions to reduce falls concluded that all types of exercises achieved similar benefits in balance, endurance, flexibility, and strength. The key message is to prescribe a program for those patients who are mobile and functional enough, in addition to cognitively capable, to participate.

Nutrition (calcium and vitamin D)

Calcium and vitamin D are required for bone health at all ages. Elemental calcium, 1200 to 1500 mg/day, for postmenopausal women and men older than 65 is needed to maintain a positive calcium balance. The amount of vitamin D required is at least 800 IU/day, although evidence suggests that as much as 2000 IU of cholecalciferol per day and more are necessary to achieve serum levels (25[OH] vitamin D ≥ 75 nmol/L) that are optimally effective for fall and fracture prevention.

Overall, adequate calcium and vitamin D should be recommended for all older adults, regardless of BMD, to maximize bone health. In osteoporotic patients who require pharmacologic treatment, administration of calcium and vitamin D alone is not recommended. Indeed, supplementation with vitamin D enhances the BMD response to osteoporosis treatment. It is also worth noting that all pivotal trials of anti-osteoporotic agents (antiresorptive, anabolic, or dual-action agents) have included supplementation with calcium and vitamin D.

Despite our understanding of the role of calcium and vitamin D in bone physiology, recent analyses have raised some controversies about their role in increasing BMD and fracture prevention. Several recent meta-analyses showed that calcium intake from diet or supplements produced only a small increase in BMD. Notably, the increase was considered unlikely to decrease fracture risk. There is also controversy regarding supplementation with a high dose of calcium, as some reports have suggested an increased risk of cardiovascular disease. However, a recent systematic review and dose-response meta-analysis of prospective cohort studies found that total calcium intake was associated with lower cardiovascular mortality in postmenopausal women. Dietary calcium was associated with all-cause mortality, and supplemental intake was not associated with the risk of all-cause, cancer, or cardiovascular mortality.

Like calcium, the role of vitamin D supplements in improving BMD and decreasing fracture risk is debated as the latest meta-analyses have failed to show any benefit in improving BMD or reducing fracture risk. This is despite earlier analyses conclusively stating the positive role of vitamin D supplements in osteoporosis management by decreasing the risk of nonvertebral fractures. This lack of apparent benefit could be due to the inclusion of a significant number of healthy people with no risk factors for osteoporosis, with normal serum levels of vitamin D, or with different doses of vitamin D supplements in RCTs. To add to the controversy surrounding its use, high doses of vitamin D by bolus administration (500,000 IU/year or 60,000 IU/monthly) have consistently been shown to increase the risk of falls and trends to increased fractures. Despite these controversies, it is accepted that vitamin D has a role in osteoporosis (and sarcopenia) management, particularly in those with vitamin D deficiency. While frank vitamin D deficiency (≤ 30 nmol/L) should be treated with a loading dose of 50,000 IU cholecalciferol or ergocalciferol, it is recommended that all others be treated with an appropriate daily dose of 1000 to 4000 IU cholecalciferol.

Nutrition (additional factors)

Two prospective studies examined the effect of additional nutritional factors on bone loss and fracture risk in older adults. The Framingham Osteoporosis Study found that higher baseline magnesium, potassium, and fruit and vegetable intakes were associated with higher baseline BMD. In men, increased potassium and magnesium intakes were associated with lower bone loss at the femoral neck. Additionally, this study showed a correlation of hip fractures with higher serum levels of homocysteine. Although homocysteine levels are associated with vitamin B₁₂, serum levels of this vitamin have not been associated with lower BMD, suggesting that the role homocysteine plays in bone biology remains to be elucidated. However, other studies have not found a clear association between homocysteine levels and fracture. In addition, lower baseline protein intake or percent of total energy from animal protein has been associated with more significant bone loss at the femoral neck and lumbar spine. In another prospective cohort study, the Study of Osteoporotic Fractures, BMD was not related to the ratio of animal to vegetable protein intake. Still, a higher proportion of animal to vegetable protein intake was associated with more significant femoral neck bone loss and an increased risk of hip fracture. These studies suggest that nutritional factors other than calcium and vitamin D are essential for bone health in older adults. Prospective randomized studies are indicated to elucidate further the role of nutrition in preventing and treating osteoporosis in older adults.

PHARMACOLOGIC TREATMENT

Estrogen Replacement Therapy

Multiple studies demonstrate that postmenopausal estrogen use will prevent bone loss at the hip and spine when initiated within 10 years of menopause (Table 51-5). However, there have been few prospective studies of estrogen replacement therapy and fracture prevention. One small study demonstrated a reduction in vertebral fractures in postmenopausal women with transdermal estradiol compared to placebo. The Women’s Health Initiative study showed a 24% reduction in all fractures and a 33% reduction in hip fractures in women taking estrogen plus progestin. However, the Women’s Health Initiative study also concluded that the overall risks of estrogen plus progestin outweighed the benefits, including those associated with reducing fractures. Few studies have evaluated the use of estrogen in women older than 70 years. Observational data, however, from the Study of Osteoporotic Fractures support a protective effect of current estrogen use against hip fracture, even in the oldest women.

Lower doses of estrogen also effectively reduce bone resorption and bone loss in older women; the lower doses also result in fewer side effects than the usual replacement doses typically used by clinicians. 17β-estradiol 0.25 mg/day was as effective as 0.5 and 1.0 mg/day in reducing biochemical markers of bone turnover in 75-year-old women compared to placebo. The side-effect profile of 0.25 mg/day was similar to placebo and significantly different from the two higher doses. In a longer-term study, 0.3 mg/day of conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone acetate increased bone density of the hip and spine in older women who were vitamin D replete. While a recent report from the Women’s Health Initiative study demonstrates cardiovascular benefit in women aged 50 to 59 who took estrogen, at this time, better alternatives to the treatment of osteoporosis in older patients exist. Therefore, in older patients, particularly those at least 5 to 10 years postmenopausal, estrogen is not recommended.

Bisphosphonates

Bisphosphonates decrease bone resorption by inhibiting osteoclast action and survival while promoting secondary mineralization. They are structurally similar to pyrophosphates, which bind to hydroxyapatite on the bone surface and inhibit osteoclast activity.

Alendronate

The efficacy of alendronate has been well established in increasing BMD at all sites and reducing the risk of vertebral fracture in older persons. However, evidence regarding its effectiveness for nonvertebral or hip fracture is less robust. Alendronate treatment for 3 years in postmenopausal women (mean age 71) with existing vertebral fracture and low femoral neck BMD decreased the risk of new morphological and clinical vertebral fractures. For postmenopausal women (mean age 68) with no preexisting fracture, alendronate was only effective in reducing the risk of clinical fracture in those with femoral neck BMD ≤ −2.5. Additionally, a subanalysis showed a decrease in the risk of nonvertebral fractures in those with femoral neck BMD ≤ −2.5. Alendronate treatment was equally effective in those ≤ 75 and those > 75 and reduced the risk of vertebral fracture by 51% and 38%, respectively after 12 months. There was not enough power to conduct subgroup analyses to determine if alendronate prevented hip fracture in older people (aged ≥ 75). The time to therapeutic benefit for alendronate in individuals ≥ 70 was calculated to be 8 months. Therefore, limited life expectancy in older and frail people should not delay the clinical decision to commence treatment. Furthermore, in a study of older women with osteoporosis living in residential aged care, alendronate treatment for 2 years was well tolerated and increased BMD at all sites.

Risedronate

Risedronate has reduced the cumulative incidence of new vertebral fracture over 3 years by 41% in postmenopausal women (mean age 69) with established osteoporosis. Risedronate also has reduced the incidence of hip fracture in postmenopausal women (mean age 74) and an older group with osteoporosis (aged ≥ 80, mean age 83). However, the risk of hip fracture in the older cohort with nonskeletal risk factors (such as propensity for falls) remained unaffected. The lack of efficacy may be explained by the fact that bone density was not measured in those > 80, so that group would have likely included women who did not have osteoporosis as measured by BMD. A pooled analysis of multiple trials found that risedronate treatment for 3 years in women > 80 reduced the risk of vertebral fracture by 44%. As the risk and prevalence of vertebral fractures increase with age, older people are more likely to benefit from risedronate, evidenced by a higher absolute risk reduction—similar to that seen with alendronate. For nonvertebral fractures, the reduction in the cumulative incidence over 3 years was not statistically different between the risedronate group and placebo in the same cohort. The lack of apparent benefit for nonvertebral fracture in older adults could be due to nonskeletal risk factors for fragility fracture in this age group (age ≥ 80); however, further analysis is required to confirm this.

Zoledronic acid

In postmenopausal women (mean age 73) with osteoporosis (BMD ≤ −2.5 or radiological evidence of at least one vertebral fracture), intravenous infusion of zoledronic acid yearly for 3 years reduced the risk of vertebral fracture by 70%, nonvertebral fracture by 25%, and hip fracture by 41%. In postmenopausal women with a previous hip fracture (mean age 74), zoledronic acid reduced the risk of any new clinical fracture by 35%. Moreover, zoledronic acid treatment had an additional benefit for all-cause mortality, with fewer deaths in the subjects receiving zoledronic acid (9.6%) than the placebo (13%). Zoledronic acid also significantly reduced the incidence of clinical vertebral, nonvertebral, or any clinical fracture in adults aged 75 or older.

Zoledronic acid was shown to be safe and well-tolerated by older adults in the trial at the once-a-year dose (5 mg IV). The most common adverse effects were postinfusion influenza-like symptoms that include fever, arthralgia, myalgia, and headache; however, these symptoms decreased with subsequent infusions. Although bisphosphonate therapy in frequent and high doses in cancer patients is associated with osteonecrosis of the jaw (ONJ), when used to treat osteoporosis in the recommended dose, ONJ is very rare (estimated incidence 0.001%–0.01%). The antifracture effectiveness of bisphosphonates persists even after discontinuation. This, together with recommended yearly infusion doses, improves compliance and efficacy in older adults who often struggle with compliance due to pill burden. Intravenous zoledronic acid also avoids gastrointestinal side effects commonly encountered with oral preparations of bisphosphonates, particularly frequent in older adults. Prolonged use of bisphosphonates is associated with an increased risk of atypical femoral fracture (AFF). However, absolute numbers are small, and the relative risk is much smaller than the risk of osteoporotic hip fracture and its significant adverse consequences and the significant reductions in the risk of hip and other fractures. The risk of AFF increases with more prolonged treatment of any bisphosphonate and should be investigated with x-ray in patients complaining of groin or thigh pain, as fracture precedes pain in most cases. Further investigations with a bone scan or MRI may be required. The risk of AFF rapidly diminishes after the termination of bisphosphonate treatment.

Denosumab

Denosumab is a humanized monoclonal antibody that binds to RANKL and inhibits osteoclast activation and activity. Denosumab (60 μg) given subcutaneously every 6 months to postmenopausal women (age 60–90; mean 72) over 3 years reduced hip fracture by 40%. Denosumab also decreased the risk of new radiological vertebral fracture by 68% and nonvertebral fracture by 20%. Denosumab was very effective in individuals aged 75 or older and significantly decreased the risk of hip fractures. Very interestingly, the denosumab group experienced fewer falls compared to the placebo group. However, preliminary analyses conducted by comparing a strength-related questionnaire did not reveal any difference between the treatment and placebo groups. Prospective clinical studies are needed to investigate the effects of denosumab on muscle function. However, decreasing the risk of falls by improving muscle function would reduce the risk of fragility fracture in older adults. Denosumab was well-tolerated, and the ease of administration by subcutaneous route every 6 months makes it a preferred choice in many older adults. However, unlike bisphosphonates, denosumab is not incorporated into bones. Therefore, its effect diminishes when treatment is ceased. The antifracture effect declines to pretreatment levels 12 months after discontinuing therapy, and the risk of fracture increases markedly in those with prior vertebral fracture. The risk of atypical fractures increases with prolonged treatment; however, the risk to benefit ratio is small and should not preclude denosumab use. Indeed, denosumab treatment in long-term care residents may be preferred over other osteoporosis treatment modalities given the route of administration, the paucity of side effects, and the certainty of compliance.

Teriparatide

Teriparatide is a synthetic analogue of PTH and promotes both bone resorption and synthesis. Intermittent doses of teriparatide (20 mcg/d subcutaneously) exert an anabolic effect on bone, whereas continuous infusion promotes catabolic action. Treatment with teriparatide in postmenopausal women (mean age 71) over 18 months increased BMD at all sites. It also decreased the risk of vertebral fracture by 65% and nonvertebral fracture by 53%. Teriparatide was as effective in individuals 75 years or older as in a younger cohort younger than 75 years. In adults 75 years or older, after a median treatment period of 19 months, teriparatide reduced new vertebral fractures by 65%; the number needed to treat was 11. The risk of hip fracture was not investigated as a primary endpoint in this trial. In a head-to-head comparison of teriparatide with risedronate in postmenopausal women (mean age 72), the teriparatide treatment group had a 56% less cumulative incidence of new vertebral fracture over 24 months.

Indications for teriparatide include a T-score worse than −3.5 or prevalent fractures in the setting of a T-score worse than −2.5. In addition, patients who continue to fracture or lose BMD after 2 years of bisphosphonate treatment are also candidates for teriparatide. The major limitations to the use of teriparatide in older adults are its significant cost and the mode of administration, since subcutaneous dosages require an appropriate cognitive status, a high degree of motivation, and a considerable level of functional independence. At present, studies suggest that teriparatide should not be combined with bisphosphonate therapy since concurrent bisphosphonate treatment appears to blunt the BMD response to teriparatide. Due to concerns regarding osteosarcoma in animal studies, teriparatide therapy should continue no longer than 2 years. It is also contraindicated in Paget disease and those at risk of osteosarcoma or unexplained alkaline phosphatase elevation. However, it is imperative to treat with an antiresorptive after discontinuation of teriparatide to maintain gains in BMD.

Abaloparatide

Abaloparatide is a synthetic analogue of PTH-related peptide (PTHrP) and, due to preferential binding with PTH receptor, differs from teriparatide with predominantly anabolic action on bones. In a phase 3 trial, abaloparatide (80 mcg/d subcutaneously) given for 18 months to postmenopausal women (mean age 69) improved total hip BMD and reduced the risk of new vertebral fractures by 86% and nonvertebral fracture by 43%. A subgroup analysis in participants 80 years or older demonstrated that abaloparatide effectively increased BMD in both the hip and the spine. However, while there were numerical reductions in vertebral and nonvertebral fracture risk, they were not significantly different from placebo. Like teriparatide, the use of abaloparatide is restricted to a maximum of 2 years, based on the results of nonclinical studies on teriparatide, where it was associated with an increased risk of cancer. In general, as anabolic agents, both abaloparatide and teriparatide should be considered as starting therapy for patients with very high fracture risk and/or history of multiple fractures.

Romosozumab

Romosozumab is a humanized monoclonal antibody to sclerostin and thereby antagonizes its inhibitory impacts on osteoblasts. Romosozumab differs from other antiosteoporosis agents as it has dual effects on bone by decreasing bone resorption and increasing bone formation. Romosozumab administered for 12 months, followed by 12 months of denosumab treatment. lowers the risk of vertebral fracture by 75%. Romosozumab was compared with alendronate in postmenopausal women (mean age 74) and, after 2 years, was associated with 48% lower risk of vertebral fracture, 19% lower risk of nonvertebral fracture, and 38% lower risk of hip fracture versus alendronate. When compared with the anabolic agent teriparatide, romosozumab treatment significantly increased spine BMD and trabecular hip BMD. Romosozumab treatment was also very effective in men with osteoporosis (mean age 72) and after 1 year markedly increased BMD at the lumbar spine and the hip.

Romosozumab, due to its anabolic effect on bone and ease of administration (210 mg monthly SC), when compared to teriparatide (20 mcg daily SC), has the potential to be the preferred agent to treat osteoporosis and therefore decrease the risk of fractures. Its use is currently restricted to a maximum of 12 months due to concerns regarding increased risk of cardiovascular events as observed in one phase 3 clinical trial and the potential for oncogenesis due to previous known association of teriparatide with cancer in rodents. The subanalysis of the antifracture efficacy of romosozumab in old and very old adults is still awaited.

OSTEONECROSIS OF THE JAW AND ATYPICAL FEMORAL FRACTURES

Longer-term administration of antiresorptives has been associated with two major complications: ONJ and AFFs. ONJ is defined as the presence of exposed and necrotic bone in the maxillofacial region that does not heal within 8 weeks. The risk of ONJ may be increased in those undergoing invasive dental procedures, such as tooth extractions. The risk of ONJ in patients with postmenopausal osteoporosis taking oral bisphosphonates is proportional to the duration and cumulative dose of antiresorptive agents and is exceedingly low with an estimated incidence of 0.02% to 0.06%. Therefore, in general, the minimal risk of ONJ associated with bisphosphonate use appears to be significantly outweighed by the potential benefit of fracture risk reduction and the reduction in subsequent morbidity due to fractures. Overall, a professional dental checkup should not delay osteoporosis treatment initiation in older persons, particularly those at a very high fracture risk.

AFFs are stress or insufficiency fractures located in the subtrochanteric region and diaphysis of the femur. Radiographically, AFFs are located in the lateral cortex and with a transverse short oblique configuration, and are associated with cortical thickening (periosteal stress reaction). They have been reported in patients taking bisphosphonates and patients treated with denosumab, but they also occur in patients with no exposure to these drugs. The absolute risk of AFFs in patients on bisphosphonates is very low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with a higher risk (> 100 per 100,000 person-years). More importantly, however, the number of fragility fractures prevented by bisphosphonate therapy far outweighs the number of AFFs that occur. To enable early detection, intervention, and prevention of AFF, clinicians should be vigilant and obtain imaging studies when patients on an antiresorptive present with thigh pain, as this may be an early sign of an AFF.

DRUG HOLIDAYS IN OSTEOPOROSIS TREATMENT

All long-term trials with bisphosphonates and denosumab have demonstrated sustained therapeutic efficacy and a very low incidence of side effects. Findings from pooled analyses of three long-term extension trials involving bisphosphonates reveal that patients who received 6 years or more of bisphosphonates had fracture rates of 9.3% to 11%, whereas the fracture rate for patients switched to placebo was 8.0% to 8.8%. Consequently, it is reasonable to evaluate whether continued therapy imparts additional benefit. However, it is still crucial to evaluate future fracture risk when considering patients who may benefit from a drug holiday. A drug holiday may be considered after 3 to 5 years of antiresorptive therapy in patients with moderate or low risk of fracture because stopping these medications for a short period of time poses minimal risk to the patient. In high-risk patients, careful consideration for a drug holiday’s timing and/or duration is needed, as these patients may derive benefit from treatment beyond 5 years.

OSTEOPOROSIS IN NURSING HOMES

There is increasing concern about the underdiagnosis and undertreatment of patients with osteoporosis in particular settings, such as long-term care institutions. Institutionalized patients, whether mobile or immobile, are at high risk of osteoporosis. Residents should be assessed upon admission and multifactorial prevention measures implemented. All should be treated with a combination of vitamin D (minimal dose of 800 IU/day) plus calcium (1200 mg/day). Because frail older adults may be markedly hypovitaminotic D or exhibit an unpredictable response to supplementation, the serum level of 25(OH) vitamin D should be obtained before beginning supplementation. Between 1500 and as much as 4000 IU/day may be needed. If the 25(OH) vitamin D level is less than or equal to 50 nmol/L, patients should be started on 2000 IU/day of cholecalciferol. Individuals with levels ≤ 30 nmol/L should be started on a loading dose of 50,000 IU and then continued with a dose of 3000 to 4000 IU/day. Additionally, the presence of risk factors and/or previous fractures strongly supports the use of pharmacologic treatment with either antiresorptives or anabolic agents. Since osteosarcopenia is highly prevalent in this population, a combined diagnostic and therapeutic approach for osteoporosis and sarcopenia should be implemented. The clinician should consider the patient’s level of functionality, QoL, and life expectancy before starting pharmacologic treatment for osteoporosis in a long-term care setting. However, since hip fractures lead to a decline in QoL and life expectancy, and fracture risk reduction can be achieved as quickly as 6 months of treatment, pharmacologic approaches are justified in institutionalized patients who are at risk. Bisphosphonates are the first-line choice, and intravenous administration is likely to achieve better adherence. Denosumab appears to offer equal protection and may enhance adherence because of its subcutaneous administration. Anabolic agents such as teriparatide, abaloparatide, and romosozumab are not first-line agents and should only be used in those with severe osteoporosis and repeated fractures in the setting of antiresorptive treatment.

FURTHER READING

LEARNING OBJECTIVES

INTRODUCTION

Osteoarthritis (OA) is a highly prevalent and disabling disease and has been designated as a serious disease by the US Food and Drug Administration (FDA). Approximately 240 million people worldwide are affected by symptomatic OA, including at least 32 million in the United States. This number is expected to rise with longer life expectancies and the worsening obesity epidemic. OA is the third leading cause of years lived with a disability in the United States and is the most common cause of mobility limitation among older adults. Overall, there is a 1 in 2 lifetime risk of developing symptomatic knee OA. In addition, OA is associated with an increased risk of dying prematurely and with increased prevalence of comorbid conditions such as cardiovascular disease, diabetes mellitus, and depression. Those with hip or knee OA have a 20% excess mortality compared to those without it, partly due to limitation in their physical activity levels. Finally, OA-associated economic burden is highly significant due to direct medical costs and indirect costs (eg, lost wages, home care, hospital expenditures). It is estimated that wages lost due to OA approximate $65 billion, and medical costs can exceed $100 billion annually in the United States.

EPIDEMIOLOGY, CAUSES, AND PREDISPOSING FACTORS

Age, Sex, and Race

Age is the strongest risk factor for developing OA. The prevalence of the disease increases with increasing age. Among adults older than age 60 in North America, approximately 20% to 40% have radiographic evidence of hand OA while 30% to 40% have radiographic evidence of knee OA. Symptomatic OA is less prevalent, with 13% to 26% of all adults having symptomatic hand OA and 10% to 14% having symptomatic knee OA. At age 50, the pooled radiographic prevalence of thumb base OA is 5.8% for men and 7.3% for women; whereas at age 80, the pooled radiographic prevalence of thumb base OA for men and women are 33% and 39%, respectively. Among adults 45 years or older, the prevalence of symptomatic hip OA is about 10%. In one study, symptomatic foot OA was present in 17% of adults older than 50 years, with disabling symptoms presenting in 9.5%.

Women are more likely than men to be affected by hand OA, hip OA, and knee OA, especially after menopause. The prevalence of OA may also vary by race and ethnicity. OA of the knee is more common in African Americans than in non-Hispanic Whites or Mexican Americans. OA of the hip is more common in people of European descent compared to those of Asian or African descent. Compared to older Whites in the United States, older Chinese subjects in China have higher prevalence of knee OA but lower prevalence of hip and hand OA. Increasing evidence shows that the prevalence of arthritis-attributable activity and work limitation and severe joint pain is significantly higher among Hispanics compared to non-Hispanic Whites.

Obesity

Obesity is the strongest modifiable risk factor for the development of OA. It is estimated that the reduction of body weight from obese to normal weight would reduce knee OA incidence by 21% in men and 33% in women. Obesity is also associated with having an increased risk of developing hand and foot OA. However, there is less consistent data supporting the relationship between hip OA and obesity.

Occupation, Sports, and Joint Trauma

OA has also been linked to certain occupations. Working as a farmer or a construction worker/laborer increases the risk of developing knee and hip OA, especially among those who are overweight. Specific occupational activities such as more than 30 minutes of squatting, more than 30 minutes of kneeling, and climbing more than 10 flights of stairs per day increase the risk of developing radiographic knee OA. Among older adults, recreational walking, jogging, and other recreational activities do not seem to increase the risk of developing knee OA. However, high-impact sports are associated with increased risk of OA in certain joints: American football (knees, feet, ankles); baseball (shoulders, elbows); soccer (knees, hips, ankles); ice hockey (knee); and boxing (carpometacarpal). These often account for the development of OA at joints that are not usually affected by OA.

The increased risk of OA from occupational and sports activities is likely due to injury rather than participation in these activities. Hip dislocation and femoral acetabular impingement are associated with the development of hip OA. Ligamentous or meniscal damage in the knee and/or surgical meniscectomy increases the risk of knee OA. In parallel, quadriceps muscle weakness is linked to tibiofemoral and patellofemoral knee OA. Prior foot or ankle injuries have also been linked to the development of foot OA.

Malalignment and Physical Abnormalities

Joint malalignment may also increase the risk of developing OA. Varus alignment or knee extensor muscle weakness increases the risk of knee OA development and progression. This increased risk is most prominent in overweight and obese persons. Similarly, congenital hip dysplasia or cam deformity increases the risk of hip OA, especially in middle-aged (55–65 years) and younger (< 50 years) individuals. Specific physical attributes, such as leg length inequality, having a higher knee height and having an index finger shorter than the ring finger have all been associated with an increased risk of developing radiographic knee OA.

Genetics

The number of OA genetic risk loci has recently increased significantly through genome-wide association studies and now includes 90 genome-wide significant loci for OA. The effect size associated with these genes is small, however. Genes that code for structural proteins of the cartilage’s extracellular matrix seem to have a role, especially those that code for collagen type II (COL2A1). Genes that code for different interleukins (eg, IL-1A, IL-1B, IL-1RN, IL-4R, IL-17A, IL-17F, and IL-6) may also affect genetic susceptibility to OA. Other genes that have been implicated in the development of OA include the estrogen receptor α gene, vitamin D receptor gene, frizzled related protein gene, asporin, and proteins related to cartilage and bone development and bone homeostasis. In addition, genes related to height, hip shape, bone area, and developmental hip dysplasia may also play a role.

CLASSIFICATION AND PATHOPHYSIOLOGY

Classification

OA has traditionally been classified as either primary (idiopathic) or secondary to known causes (Table 52-1). Primary OA most commonly affects the joints of the hands, knees, hips, spine, and feet. Nodal generalized OA is characterized by polyarticular finger involvement (distal interphalangeal [DIP], proximal interphalangeal [PIP], first carpometacarpal [CMC] joints) and a predisposition to OA of the knee, hip, and spine. It commonly affects middle-aged women with a strong family history of OA. Inflammation is being increasingly recognized as having a role in the pathophysiology of OA. Only a minority of OA patients have inflammatory symptoms, such as swelling and redness of the joints, however, and often these symptoms are mild and intermittent. Erosive OA is a variant that occurs when there is an additional erosive/inflammatory component, often involving the DIP and PIP joints of the hands. Other individuals may have a phenotype that indicates a larger role for mechanical factors in the pathophysiology. Secondary OA occurs when another disease or condition causes OA. Conditions that can lead to secondary OA include trauma; inflammatory arthritis (eg, septic arthritis, rheumatoid arthritis, seronegative spondyloarthropathy, gout); metabolic/endocrine disorders (eg, hemochromatosis, hyperparathyroidism); neuropathic disorders; and anatomical abnormalities.

The American College of Rheumatology (ACR) has proposed specific criteria to standardize the classification of OA of the knee, hip, and hands for clinical and epidemiologic studies. These criteria are based on a combination of features such as patient age (> 50 years), clinical symptoms (ie, pain, < 30 minutes of morning stiffness), physical examination (ie, presence of crepitus, bony enlargement/tenderness), laboratory findings (ie, normal inflammatory parameters, synovial fluid consistent with OA and negative rheumatoid factor), and radiographic findings (ie, presence of osteophytes). These criteria only apply to patients with symptomatic disease, exclude patients with secondary OA, and are intended to classify and not diagnose OA.

Pathophysiology

OA can be thought of as a failed repair of joint damage due to abnormal intra- and extra-articular processes involving a combination of biomechanical, biochemical, and genetic factors. A single or a combination of insults to the joints, including biomechanical trauma, chronic inflammation, genetic and metabolic factors, oxidative damage, and chondrocyte senescence, can trigger or contribute to the cascade of events that leads to OA. In the earliest stage of OA, fibrillation of the superficial layer of the articular cartilage may be observed with loss of glycosaminoglycan content in those areas. Eventually, the fibrillation extends to the subchondral bone, the cartilage fragments into the joint, the matrix degrades, and the cartilage is completely lost, leaving a denuded bone.

Chondrocytes in the articular cartilage react to insults in the joint, leading to changes in cellular function and matrix elements. Chondrocytes and synovial cells release matrix metalloproteinase (MMP) enzymes, such as collagenases, stromelysins, and gelatinases responsible for cartilage degradation. While these MMPs may be susceptible to MMP inhibitors, synthesis of MMPs is enhanced and the inhibitors are overwhelmed in OA. Cytokines have been implicated in the regulation of this process. Interleukin-1 (IL-1), a catabolic cytokine, is known to suppress type 2 cartilage synthesis and to induce proteases. IL-1 level and cell sensitivity are increased in OA. Anabolic cytokines, such as insulin-like growth factor-1 and transforming growth factor β, on the other hand, are found in decreased levels in the serum and synovial fluid of OA patients. Besides cartilage degradation, subchondral bone may also increase in density, potentially reflective of healing response to microfractures that have occurred. Cyst-like bone cavities may form, in addition to synovial inflammation and hypertrophy, which is not seen in normal aging joints. Osteophytes, or bony projections that form along joint margins, are often considered a hallmark of OA.

Several other factors have also been implicated in the development of OA. Crystals, including calcium pyrophosphate dihydrate and basic calcium phosphate crystals, have been identified in the synovial fluid of OA joints. Other than their ability to induce inflammation, their role in the pathogenesis of OA remains unclear. Protein levels of nuclear receptor erythroid 2-related factors 1 and 2 (NRF1 and NRF2), which regulate antioxidant gene expression for cellular protection, are present in lower levels in chondrocytes of persons with OA. An imbalance in antioxidant production by the chondrocyte compared to reactive oxygen species production has been found to damage lipids, protein, DNA, and normal cell signaling, contributing to the development of OA. In addition, the complement system may stimulate inflammatory mediators and enzymes that can contribute to the pathogenesis of inflammatory OA, while nitric oxide, known to activate MMPs in articular cartilage, may also mediate the osteoarthritic development process. Supported by epidemiologic studies, sex-related hormones have also been considered to play a role in the development of OA, especially in women.

PRESENTATION

Symptoms

Patients with symptomatic OA most commonly present with pain in the joint. Pain tends to worsen with increased activity or weight-bearing and to improve with rest. Early in the disease, patients may complain of pain that is sharp, intermittent, and unpredictable. These features may often lead patients to limit their activity to avoid pain. As the disease progresses, the pain becomes more constant and aching in nature. Late in the disease, pain may be noted with progressively less activity, possibly occurring even at rest and at night. Patients may also complain of morning stiffness that typically resolves within 30 minutes or less. Joint stiffness may also occur after periods of prolonged inactivity, also known as the “gelling” phenomenon. Other patients may report joint locking or joint instability. In contrast, joint stiffness lasting more than an hour, joint pain and stiffness that improve with activity, and persistent joint swelling all suggest an inflammatory type of arthritis, such as rheumatoid arthritis, instead of OA.

Knee OA patients may complain of localized pain, often in the medial and lateral joint lines, or diffuse knee pain. They may have difficulty climbing the stairs or walking for even short periods of time. With laxity in the knee joint, patients may have feelings of knee instability, which may lead to falls. Hip OA patients may complain of pain in the anterior hip or inguinal area. Less commonly, their pain may also be felt laterally (ie, in the trochanter) or referred to the knee. They may have difficulty crossing their legs or putting on a pair of shoes.

Hand OA patients may report pain involving the DIP, PIP, and first CMC joints. Gripping, pinching, holding, or lifting objects may be particularly challenging in patients with symptomatic hand OA. Foot OA can cause such disabling foot pain with ambulation that can lead to significant functional limitations and increased risk of falls.

OA most commonly affects the cervical and lumbar spine areas. Cervical spine OA typically causes neck pain but can also cause occipital headaches, upper extremity radicular pain, shoulder pain, and loss of dexterity of the hands. Rarely, large osteophytes may compromise the spinal canal, causing lower-extremity spasticity and gait disturbance. Lumbar spine OA can often cause lower back pain that may radiate into the lower extremities and worsen with bending ipsilateral to the involved joint. Lumbar facet joint osteophytes can lead to lumbar canal stenosis with symptoms of claudication and/or pain at night; symptoms of spinal stenosis are often relieved by bending slightly forward (eg, walking uphill, upstairs or leaning forward on a shopping cart) and worsened by bending backward (eg, walking downhill or downstairs). Other symptoms of spinal stenosis include pain, tingling, numbness, and weakness,

Physical Examination

OA patients may have a completely normal physical examination. Typically, they have joint-line tenderness, crepitus (ie, a peculiar crackling, crinkly, or grating feeling on palpation, which may also be audible) and bony enlargement. There may be joint swelling that tends to be intermittent and without palpable warmth. Synovitis can also be noted in OA, and some patients may have prominent joint effusions. With disease progression, the joint’s range of motion may decrease. Joint deformity, contractures, and/or laxity may also develop later in the disease.

In hand OA, there may be tenderness of the affected finger joints and/or tenderness of the first CMC joint. Enlargement of the first CMC joint can result in a squared appearance of the hand. Prominent bony enlargements of the DIP and PIP joints are known as Heberden and Bouchard nodes, respectively.

In knee OA, there is often crepitus on active knee motion and bony tenderness. There may also be effusion (without warmth) and a limited range of motion. The joint fluid may migrate into the semimembranosus bursa posteriorly, causing swelling along the posterior knee known as a popliteal or “Baker’s” cyst. Knee varus (“bow-legged”) or valgus (“knock-kneed”) deformities may be observed later in the disease. Medial/lateral knee joint laxity may be evident on examination and lead to joint instability.

In hip OA there may be reproducible pain along the anterior hip or the inguinal area with passive or active range of motion, particularly with extension and internal rotation. The range of motion in the hip joint may also be affected; limited internal rotation and/or extension may be an early indication of hip OA. Hip OA patients may also develop an antalgic gait in which the stance phase of the gait is abnormally shortened on the affected hip joint.

In foot OA, the first metatarsophalangeal (MTP) joint is most commonly affected, followed by the second cuneometatarsal (CMT) and talonavicular (TN) joints. There are limited agreed upon guidelines for the clinical assessment of foot OA. For first MTP joint OA specifically, the patient may exhibit pain in that joint upon walking, limited dorsiflexion in the first MTP joint and pain on direct palpation of the joint. Other exam findings that may be present include hallux valgus, first interphalangeal joint hyperextension, and decrease in ankle joint dorsiflexion range of motion.

EVALUATION

Diagnostic Imaging

OA can usually be diagnosed clinically based on history and physical examination alone. Although conventional radiography can demonstrate the severity of damage and may be used to confirm the diagnosis with an atypical presentation, radiographs are not necessary to make a diagnosis. Before making a clinical diagnosis of OA, however, other diseases should be excluded. At the very least, OA should be distinguished from referred pain, inflammatory arthritis conditions (eg, rheumatoid arthritis, gout, pseudogout) and periarticular bursitis (eg, trochanteric bursitis of the hip, pes anserine bursitis of the knee). Radiographic findings suggestive of OA are very common in older adults, yet many of these patients have minimal to no OA-related symptoms. Radiographic features of OA include joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts, and/or altered bone contours. X-rays may also show calcification of cartilage or other structures and soft-tissue swelling.

Radiographic findings specific to knee OA patients include medial tibiofemoral and/or patellofemoral joint space narrowing, along with osteophyte formation. Lateral joint space narrowing may also be seen but is less common (Figure 52-1). Osteophytes may be seen anteriorly and medially at the distal femur and proximal tibia and posteriorly at the patella and tibia. Radiographic changes seen in hip OA include joint space narrowing (superior, axial, or medial), osteophyte (femoral or acetabular) formation, and subchondral sclerosis.

With hand OA, the first CMC, the DIP, and the PIP joints are most commonly involved. Joint space loss is typically nonuniform and asymmetric. Involvement of more than two metacarpophalangeal joints suggests different type of arthritis other than OA. Hand x-rays of those with erosive OA will reveal erosions and the “gull-wing” deformity (Figure 52-2). X-rays of patients with lumbar or cervical OA will reveal intervertebral disc narrowing and osteophytes arising from the vertebral body margins (Figure 52-3). Sclerosis and cyst formation may also be seen. Neural foraminal narrowing may result from osteophyte formation, but this is best seen using a computed tomographic (CT) scan.

With foot OA, a foot-specific atlas that grades osteophytes and joint space narrowing can be used to classify radiographic OA in the commonly affected areas, although this requires both dorsoplantar and lateral views to be taken while standing.

It is important to remember that conventional radiographs have limited resolution and cannot detect early OA. They also only provide images of bony structure and are two-dimensional projections of three-dimensional joints, meaning multiple views are necessary to visualize the joint and detect possible OA involvement properly.

As a research tool, MRI has allowed the detection of preradiographic OA. It offers greater resolution than an x-ray, provides depiction in three dimensions, and allows visualization of bone and soft tissue structures. MRI allows visualization of subchondral cyst-like lesions, subchondral bone attrition, joint effusion, synovitis and meniscal damage. The integrity of ligaments, periarticular cysts and bursae, and osteophytes may also be assessed through MRI. It is important to remember that although research with MRI has contributed to understanding the relevance of these structures in explaining pain and structural progression in OA, MRI is not necessary to diagnose OA.

Laboratory Studies

Laboratory tests are unhelpful in diagnosing OA but are helpful in excluding other causes of arthritis such as rheumatoid arthritis, gout, or infectious arthritis. Inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein level, and immunologic tests, such as antinuclear antibodies and rheumatoid factor, should not be routinely ordered unless there are signs or symptoms suggestive of inflammatory arthritis or autoimmune disease. Uric acid level may be ordered if gout is suspected.

Performing an arthrocentesis may be valuable in evaluating patients with presumptive OA. Synovial fluid findings in OA often show a white blood cell count of less than 2000 cells/mm³. Counts that are greater than 2000 cells/mm³ suggest an inflammatory or infectious arthritis etiology. Under polarized microscopy, there should be no visible crystals. The presence of gout or pseudogout crystals suggests crystalline arthritis as the underlying cause of joint pain.

A variety of OA-related biomarkers have been identified and validated for several OA outcomes. They are products of cartilage and bone turnover (eg, urine/serum carboxy-telopeptide of type II collagen, serum hyaluronan). However, their utility in diagnosing OA, determining the risk of disease progression, and assessing the response to OA therapies is unclear and currently under investigation.

MANAGEMENT

The ACR/Arthritis Foundation (AF) and the Osteoarthritis Research Society International (OARSI) have published updated recommendations for management of OA. The main goals of management are to minimize OA-related pain, improve physical functioning and optimize the quality of life of patients with OA. There are nonpharmacologic, pharmacologic, and surgical treatment options for the management of OA (Figures 52-4 and 52-5). OA management should be tailored to the individual patient, and optimal management likely includes a combination of these treatment modalities. For example, evidence suggests that patient education, exercise programs, weight reduction, and wedge insoles all offer additional benefit in combination with an analgesic or nonsteroidal anti-inflammatory drug (NSAID).

Physical, Psychosocial, and Mind-Body Approaches

Self-efficacy and self-management

OA patients should be taught the goals of OA treatment, the importance of changes in lifestyle, exercise, pacing of activities and weight loss, and various ways to minimize joint loading. The educational focus should be on initiating self-help and patient-driven treatments that reflect the nature and course of the disease rather than simply accepting therapies delivered by providers. Thereafter, the emphasis should be on maintaining adherence to nonpharmacologic and pharmacologic therapies. Such information may be taught through group courses, individual consultations, and regular telephone calls. Participants in these programs report reduction in pain, improvement in function, and weight loss. These programs may also increase patient self-efficacy and physical activity, and decrease the number of OA-related physician visits.

Exercise

Aerobic exercise and muscle strengthening can significantly improve the physical health and symptoms of patients with OA. Regular aerobic activities that older adults can engage in include walking, bicycling, swimming, and tai chi. Quadriceps muscle strengthening can be particularly helpful for a patient with knee OA. In general, there is no significant difference in reducing arthritis-related symptoms and disability in knee and hip OA patients between aerobic and resistance training. In addition, balance exercises may be beneficial by improving a person’s ability to control and stabilize their body position.

For patients with advanced OA, mobilization exercises (ie, stretching and flexibility training) and isometric strengthening exercises can initially be prescribed. Mobilization exercises increase length and elasticity in muscles and periarticular tissues. Mobilization of the sesamoid apparatus and strengthening of hallux plantar flexors is beneficial for first MTP joint OA. During isometric exercises, muscle length does not noticeably change and the affected joint does not move. Isometric exercises for older adults include chair leg extensions, wall sits, and hip extensions. The exercise regimen may then progress toward isotonic strengthening and aerobic exercises. During isotonic exercise, muscle tension remains unchanged but muscle length changes. Beneficial isotonic exercises include squats, wall slides, and leg presses. Finally, water-based exercise is a low-impact activity that takes the pressure off joints, muscles, and bones. It is particularly beneficial for those with severe OA and marked deconditioning.

Physical therapists are valuable for providing instructions and appropriate exercises. They are essential for outlining individualized treatment and a progressive home exercise program. Indeed, a physical therapy regimen that includes strengthening and neuromuscular training can improve symptoms in two-thirds of patients with advanced knee OA. Physical therapy evaluation may also result in provision of assistive devices, such as canes and walkers, as necessary.

In summary, exercise can be a joint-specific range of motion and/or strengthening program or a general aerobic conditioning regimen. Exercise may be supervised on land, in water or in a self-directed home-based program. Regardless of the type of exercise regimen, extra attention is needed for the older patient to enhance safety and compliance with the program, taking into account potential comorbidities. Those with knee or hip OA should also cautiously engage in moderately or severely strenuous exercises (eg, stair climbing, heavy weightlifting and running).

Weight loss

All existing guidelines highly recommend weight loss in overweight and obese individuals with OA of the hip or knee for OA management. In many patients, a structured weight management program may be necessary. An effective program focuses on developing healthy eating and physical activity habits. It should include a plan for the individual to lose weight slowly and steadily to maintain weight loss over the long run. Patients should avoid fad diets, which often result in rapid weight loss in the short term, but weight gain over the longer term. A realistic goal is weight loss of more than 5% to be achieved within a 20-week period. The program may include ongoing feedback, monitoring, and support. Weight reduction has been shown to improve knee and hip OA-related pain, stiffness and disability.

Tai chi and acupuncture

Tai chi, a practice that originated in China, is referred to as “moving meditation.” Practitioners move their bodies slowly, gently, and with awareness while incorporating deep breathing, meditation, and relaxation. It may be beneficial in improving strength, balance, and self-efficacy while decreasing the risk of falls in patients with lower extremity OA.

In contrast, the efficacy of acupuncture in patients with knee, hip, or hand OA remains controversial. Clinical trials have demonstrated that it may provide a short-lived duration of analgesia, mostly for those with knee OA.

Braces and taping

A tibiofemoral knee brace, and at times patellofemoral knee braces, can reduce pain and improve stability and ambulation, leading to lower risk of falling for knee OA patients with varus or valgus instability. Separately, a brace and a neoprene sleeve offer additional beneficial effects for knee OA compared with medical treatment alone. A brace tends to be more effective than a neoprene sleeve, however. Medially directed patellar taping may also benefit patients with knee OA.

Orthoses

All patients with knee, hip, or foot OA should receive advice regarding appropriate footwear. However, laterally and medially wedged insoles have not demonstrated clear efficacy or benefit. Hand orthoses may benefit patients with first digit CMC joint OA of the hand, although evidence supporting hand orthoses for OA in other joints of the hand has not yet been established. With foot OA, footwear known as a “rockersole,” where the sole of the shoe is curved, reduces the need for first MTP joint dorsiflexion and has been shown to reduce the pressure under the first MTP joint. Foot orthoses include shoe-stiffening inserts and contoured orthoses that may reduce foot pain.

Assistive devices

Walking aids can reduce OA-related pain in patients with knee and hip OA. A cane can significantly reduce joint loading and pain. In addition, it can provide additional stability in a patient where joint disease affects ambulation. It should be properly fitted to approximately the level of the greater trochanter of the hip. Patients should be instructed to use the cane with the hand opposite the affected knee or hip. The final bend to the elbow when walking with the cane should be approximately 15 to 20 degrees. When disability is more severe or when OA is bilateral, a walker may be a better option. Assistive devices, such as zipper pulls, built-up handles on pencils/pens, cushioned carrying tools, and meal preparation devices, can be very beneficial for patients with hand OA. Occupational therapists are likely to be helpful in recommending lifestyle modifications and assistive devices to patients with arthritis symptoms.

Heat and cold therapy

Thermal modalities may be effective for relieving OA symptoms, but the benefits may be temporary. All patients with hand, knee, and hip OA should be instructed in the use of thermal agents. Heat can be administered by various techniques, including the application of heat packs, ultrasound, electrically delivered heat, immersion in warm water, and paraffin baths. There are also store-bought heat patches, belts, packs, and wraps. Patients should be instructed that heat therapies should be limited to 20-minute intervals to reduce the risk of burns. Cold (or cryotherapy) can be administered by application of ice packs or massage with ice. It can decrease inflammation, minimize muscle spasms, and reduce pain. Patients should also be instructed to limit the use of ice or cold packs to 20 minutes. The choice of heat or cold is often based on patient preference.

Topical Agents

Capsaicin and rubefacients

Topical capsaicin creams contain a lipophilic alkaloid extracted from chili peppers, which activates and sensitizes peripheral c-nociceptors. Both 0.03% and 0.08% topical capsaicin have been shown to reduce pain in knee OA, although a dose of 0.03% topical Capsaicin is better tolerated than a dose of 0.08%. At this time, efficacy in treating hand OA has not been well demonstrated, and the risk of contaminating the eyes is high. Capsaicin has also not demonstrated any benefit in treating hip OA, likely due to the depth of the joint under the skin. Topical capsaicin can be considered as an adjunct therapy or used instead of topical NSAIDs for foot OA as studies have shown similar improvement in pain. Rubefacients containing salicylates (eg, trolamine salicylate, hydroxyethyl salicylate, diethylamine salicylate) may also be used as adjunctive agents, albeit supportive data is scant. Skin burning, stinging and erythema are potential side effects.

Topical NSAIDs

Topical NSAIDs, such as diclofenac sodium gel, are recommended as first-line pharmacological therapy to treat hand and knee OA prior to starting oral NSAIDs, given their favorable side effect profile and efficacy of pain relief. They are also recommended as first-line pharmacologic therapy for the treatment of symptomatic foot OA. In February 2020, the FDA approved Voltaren gel (diclofenac sodium topical gel 1%) for sale over the counter. Topical NSAIDs have a high safety margin and are not associated with acute renal failure or gastrointestinal adverse events when used as instructed. Thus, they may be particularly useful in patients with cardiac, renal, or gastrointestinal comorbidities. They may be less ideal for those with a large number of affected joints, in which case systemic therapy would be preferred. Similar to capsaicin, topical NSAIDs are not recommended for treating hip OA due to the depth of the joint under the skin precluding their efficacy.

Oral Pharmacologic Therapies

Acetaminophen

Acetaminophen has traditionally been used as a first-line agent in treating mild-moderate OA. However, some meta-analyses have shown that acetaminophen was no better than placebo for symptom control. Other studies showed its use was associated with minimal improvement in pain control, which may be outweighed by the side effect profile of the medication. Acetaminophen use may still play a role in the treatment of knee, hip, hand, or foot OA for short treatment durations, or in patients who have contraindications precluding the use of oral or topical NSAIDs. The FDA has reduced the maximum daily dose of acetaminophen to 3 g/day. Regular monitoring for hepatotoxicity is recommended in those with prolonged use, especially for those taking the maximum recommended daily dose.

Oral NSAIDs

NSAIDs inhibit the activity of cyclooxygenase (COX)-1 and -2 enzymes, providing analgesic and anti-inflammatory effects. They are recommended as first-line oral pharmacotherapy over all other oral medications and can be very helpful for OA patients who do not respond to topical NSAIDs, have multiple joint involvement, or suffer from moderate-to-severe levels of pain. There is no strong evidence that a particular NSAID is more effective than other NSAIDs, but the side effect profiles make some safer than others for specific patients. Some patients may prefer specific NSAIDs (eg, meloxicam, naproxen) based on the frequency of dosing for convenience.

Patients may be started on a low-cost NSAID with a short half-life, such as ibuprofen. Initially, the medication should be started on the lowest possible dose, and if the response is not satisfactory after a few weeks, then the medication dosage may be slowly increased up to the maximum recommended dose. Switching to a different NSAID is another OA treatment management option.

While efficacious, NSAIDs should be prescribed with caution, particularly in patients with comorbidities that may increase NSAID toxicity. Gastrointestinal complications such as peptic ulcers and bleeding are potential side effects. This risk increases with older age, concurrent use of other medications (eg, glucocorticoids, anticoagulants), and longer therapy duration. Using either a COX-2 selective inhibitor or a nonselective NSAID in combination with a proton-pump inhibitor reduces this risk. Nephrotoxicity is another potential toxicity. Patients with chronic kidney disease (CKD) stage IV or V (estimated glomerular filtration rate < 30 cc/min) should avoid NSAIDs. Nonacetylated salicylates, sulindac, and nabumetone may be less nephrotoxic than other NSAIDs.

Patients with cardiovascular disease are also at increased risk for cardiovascular adverse events (eg, myocardial infarct or stroke) associated with NSAIDs, particularly with the use of diclofenac. Patients should be made aware of such risks and monitored closely during treatment. Finally, concomitant use of low-dose aspirin and nonselective NSAIDs (eg, ibuprofen) may also render aspirin less effective when used for cardioprotection and stroke prevention.

COX-2 selective inhibitors

A COX-2 inhibitor (ie, celecoxib) or a COX-2 selective NSAID (eg, meloxicam) can be a better treatment option for a subset of OA patients. They can effectively relieve painful OA symptoms with significantly less risk of GI side effects as compared to nonselective NSAIDs. Prescribing these medications to patients with cardiovascular risk factors should be done with caution however, as they may increase the risk of myocardial infarct, stroke, and other related conditions.

Narcotic analgesics

Tramadol is a weak μ-opioid receptor inhibitor that inhibits the reuptake of serotonin and norepinephrine. It can relieve pain in patients with hand, knee, or hip OA, but should only be used when they have contraindications to NSAIDs, inadequate response to other pharmacologic and nonpharmacologic treatment modalities, or are not a good surgical candidate. Tramadol should be trialed prior to any nontramadol opioids. Like other narcotic agents, it can also cause nausea, dizziness, somnolence, vomiting, and increased mortality risk. Long-term use may also lead to physical dependence. However, respiratory depression and constipation are considered less of a problem with tramadol.

More potent narcotic medicines, such as oxycodone, hydrocodone, or morphine sulfate, may be considered in some OA patients only after failure of all other treatments. Patients who continue to have severe OA-related pain and disability despite trying other pharmacologic and nonpharmacologic OA treatments may be good candidates. Those who are unwilling or unable to undergo joint replacement surgery due to comorbid conditions (eg, significant cardiac or pulmonary disease) may also be reasonable candidates.

Narcotic agents are poorly tolerated in older people due to increased sensitivity to certain side effects, including constipation, urinary retention, confusion, and sedation. The risk of falls may also be increased in a population already vulnerable to falls due to joint disease and other risk factors. If narcotic medicines are to be started in older people, then the lowest dose should be prescribed for the shortest possible length of time. Adjuvant therapies with nonnarcotic pain relievers should also be considered.

Nutraceuticals

Glucosamine and chondroitin sulfate are naturally occurring constituents of cartilage proteoglycans. They are popular “nutritional supplements” used by many OA patients, but their use is highly controversial. Although several clinical trials showed their efficacy in improving pain and function, these trials were primarily industry-sponsored and utilized a pharmaceutical grade of glucosamine sulfate, which is not available in the United States. The best available data with the lowest risk of bias indicate that these supplements were no more effective than placebo. The ACR/AF and OARSI recommend against the use of either glucosamine or chondroitin sulfate to treat knee or hip OA.

Other nutraceuticals have been investigated for their potential benefits in the treatment of OA. A number of nutraceuticals have reported a short-term reduction of pain, but most of the current studies on nutraceuticals are small, exhibit various forms of bias, and have short follow-up times.

Other options

The use of serotonin and norepinephrine reuptake inhibitors, such as duloxetine, seems promising in the treatment of OA. It has shown moderate efficacy in treating symptoms for knee OA when used alone or when combined with NSAIDs, and its effects are likely to be similar in the treatment of hip and hand OA. The tolerability of the medication may be a limiting factor, however.

Disease-modifying osteoarthritis drugs (DMOADs) can potentially inhibit the structural disease progression of OA and improve OA-related symptoms. At present, there are no DMOAD therapies available on the market. However, several research studies are being conducted to determine DMOAD efficacy and safety. Many studies have focused primarily on preventing hyaline cartilage loss. Because the pathogenesis of OA involves multiple tissues, more recent studies are also targeting other tissues, including the subchondral bone. Most DMOADs under investigation have an anti-catabolic effect on cartilage and may also structurally modify subchondral bone. Studies of bisphosphonates showed no efficacy in the control of OA pain or improvement in function. Similarly, tumor necrosis factor inhibitors and IL-1 receptor antagonists administered subcutaneously or intra-articularly did not prove to be efficacious for treating erosive OA and are not recommended for use. Other options under investigation include inducible nitric oxide synthase inhibitors, MMP inhibitors, aggrecanase inhibitors, doxycycline, Wnt inhibition, intra-articular injection of an anabolic growth factor, fibroblast growth factor 18, and a cathepsin K inhibitor.

Intra-Articular Therapies

Glucocorticoid agents

Intra-articular glucocorticoid (eg, methylprednisolone, triamcinolone) injections can significantly relieve pain due to OA. They can be most beneficial to OA patients with one or a few joints that continue to be bothersome despite oral pharmacologic therapies. They are particularly efficacious in patients with knee or hip OA. Knee joint injection can be administered in an ambulatory care setting. Hip joint injection, though, is often done with ultrasonographic or fluoroscopic guidance. When proper technique is used, complications from intra-articular injections such as bleeding and infection are rare. Benefits may be short-lived, however, and pain relief typically lasts for up to 2 months. More than three injections within a 6-month period are not recommended, and the long-term effects these steroids have on the cartilage are still controversial.

Viscosupplementation

Viscosupplementation, the intra-articular injection of hyaluronic acid, has been used for symptomatic knee OA. Hyaluronic acid is a large molecular weight glycosaminoglycan, which is a constituent of synovial fluid. Hyaluronic acid in OA joints is often of low molecular weight, losing its biomechanical and anti-inflammatory properties. Recent meta-analyses demonstrated no clear benefit of intra-articular hyaluronic acid injection for the treatment of OA symptoms after addressing the component of bias from studies, especially in hip OA. Although the ACR/AF and OARSI OA management guidelines do not recommend using viscosupplementation based on the lack of evidence for treatment benefit, there may be individual patients who would benefit from a trial after the failure of all other treatment options.

Platelet-rich plasma and mesenchymal stem cell therapy

Platelet-rich plasma (PRP) and mesenchymal stem cell (MSC) therapy are heavily marketed for many conditions including OA. These therapies are still experimental, have not been approved by the FDA, and should not be administered or obtained except in the case of an FDA-approved clinical trial. They may be marketed as “FDA-approved,” but only the equipment used to obtain and administer the PRP or MSC therapy has been FDA-approved.

Surgical Interventions

Surgical intervention should be considered in OA patients who continue to have significant pain and disability despite maximal use of nonpharmacologic and pharmacologic therapies. Patients must also be healthy enough to withstand surgery. Shared decision making has been shown to be beneficial for patients and surgeons with regards to expectations, satisfaction, and outcomes.

Arthroscopic debridement and joint lavage

Arthroscopic debridement is the removal of loose bodies, debris, mobile fragments of articular cartilage, unstable torn menisci, and impinging osteophytes. The procedure invariably also includes joint lavage. While it is a relatively common procedure, its practice is highly controversial. While a few uncontrolled studies have demonstrated short-term efficacy, most studies have shown that this procedure is no better than placebo in providing symptomatic relief for knee OA. Arthroscopic debridement or joint lavage alone is not recommended as treatment options in the OARSI OA management guidelines.

Osteotomy

Osteotomy is a surgical procedure in which the bone is cut to shorten, lengthen, or change bone alignment. High tibial osteotomy is a potential surgical treatment for knee OA. It is appropriate for unilateral knee OA with varus malalignment. Realignment of the varus deformity would reduce stress on the medial compartment of the knee by redistributing the weight of the body from the arthritic medial compartment to the healthier lateral compartment. Although the overall failure rate at 10 years is approximately 25%, the procedure can reduce pain, improve function, and delay the need for joint replacement.

Intertrochanteric varus or valgus osteotomy has been used for hip OA treatment for nearly a century. Pelvic or femoral osteotomies have also been used to correct the biomechanics and joint congruency in young patients with hip dysplasia to prevent the development of hip OA. Evidence in the efficacy of these procedures, however, is limited.

Joint replacement

Joint replacement surgery is an irreversible procedure used in those with severe OA who have failed conservative treatment modalities, have persistent pain, and have had associated loss of function secondary to their symptoms. The average age at the time of knee replacement is the mid-sixties, although this procedure is being done more and more often in younger patients. Patients who undergo surgery often attain substantial improvements in pain, quality of life, and physical functioning; however, between 20% and 30% of patients have reported not being satisfied with surgery outcomes after total joint replacement. Maximal improvements are usually observed in the first 3 to 6 months with long-term benefit plateauing after 9 to 12 months. Quality of life indicators following joint replacement also improve approximately a year after surgery and only decline gradually over time. Certain patient characteristics such as advanced age, obesity, and comorbidities may limit improvement in patient-reported outcomes after surgery and increase rates of complications, but the presence of these characteristics should not prevent patients from being offered surgery; rather, these factors should inform the shared decision-making process. With current advances, implants typically last 15 years or more. The risk of revision is higher in patients with diabetes, obesity, and those who received surgery before 65 years compared to those aged 65 or older.

Unicompartmental knee arthroplasty involves replacement of a part or section of the knee that is arthritic. It may be considered in patients with discrete knee pain and disease localized to the medial compartment. Compared to total knee arthroplasty, it may also improve knee pain and function and requires a smaller surgical incision. Consequently, there is less postoperative pain, and hospital stays are shorter. The rehabilitation process also tends to be more rapid. Postsurgical complications, such as deep vein thrombosis and infection, are also fewer with unicompartmental than total knee replacement surgery. However, unicompartmental knee arthroplasty may make subsequent total knee replacement surgery more complex and has a shorter lifespan than a total knee arthroplasty joint, making rates of revision higher.

Joint fusion

Joint fusion surgery, also known as arthrodesis, may be selected in patients with severe OA of the wrist, ankle, or first MTP joint. It may also be used as a salvage procedure when knee joint replacement has failed. During the procedure, two bones on each end of a joint are fused, eliminating the joint itself. While a fused joint loses flexibility, it can bear weight better and may leave the patient completely pain-free.

Hand surgeries

Surgery is considered when nonsurgical treatment options have not significantly helped patients with OA of the thumb base or OA of the interphalangeal joints. In the case of the first CMC joint OA, trapeziectomy is the procedure of choice. More complicated surgical techniques have not proven to be more effective and are linked to increased rates of adverse events such as pain, instability, nerve dysfunction, chronic regional pain syndrome, and infections. The procedure of choice for OA in the PIP joint is arthroplasty with a silicone implant, except for the second PIP joint, for which arthrodesis is the preferred surgical method. Similarly, arthrodesis is the best approach for the DIP joints.

PREVENTION

There are currently no therapies known to prevent the progression of joint damage due to OA. However, current research efforts are trying to identify preclinical biochemical and imaging biomarkers that will provide opportunities to diagnose and treat OA earlier in the disease course. Hence, we may eventually be able to prevent the development and further progression of the disease.

There are also known potential theoretical targets for primary and secondary prevention of OA. A person’s weight is the largest identified modifiable risk factor for the development and progression of OA. The risk of knee OA has been shown to increase along with an increase in BMI. Therefore, weight loss for those who fall into the obese and overweight categories is important in primary prevention. Patients need to be educated on the benefits of weight loss and the need to achieve a normal body weight.

The Physical Activity Guidelines for Americans recommend at least 150 minutes of moderate-intensity aerobic physical activity or 75 minutes of vigorous-intensity physical activity per week; walking is a great way to accomplish this. Repetitive use due to a job, hobby, or sport and joint-related injuries have also been linked to OA. Therefore, avoidance of repetitive movements and education on joint protection techniques (eg, using good body mechanics) to reduce joint injury while working or playing sports are important. Finally, joint malalignment is one of the strongest predictors for progressive OA. Nonsurgical and surgical strategies may be considered to correct anatomical abnormalities.

CONCLUSIONS

OA is a highly prevalent disease among older adults worldwide. Older age, obesity, structural abnormalities, and previous injury are among the known risk factors for disease development. Patients often present with chronic pain, stiffness, and functional disabilities. Diagnosis is based on history and physical examination, and can be supported by characteristic radiographic findings. Management of OA should be tailored to the individual patient. Treatment may include a combination of nonpharmacologic, pharmacologic, and surgical approaches, with different approaches being used at appropriate timepoints throughout the natural history of the disease.

FURTHER READING

LEARNING OBJECTIVES

INTRODUCTION

Hip fracture is a major public health problem with significant consequences for older patients, their families, and the health care system. In 2010, there were approximately 260,000 adults aged 65 and older hospitalized for a hip fracture in the United States and this number is expected to increase to 289,000 by 2030 due to the aging of the population and people living longer. Recent worldwide estimates are in the order of 1.7 million hip fractures annually, and are expected to surpass 6 million by the middle of this century. As seen in Figure 53-1, hip fracture incidence increases exponentially in both men and women with advancing age. The average age of a patient with hip fracture is 82 years. Among those who reach age 85, approximately 19% of women and 12% of men will experience a hip fracture and, of those who reach 90 years, 30% of women and 20% of men will sustain a hip fracture. Although the majority of hip fractures occur in older White women, 25% to 30% of hip fractures occur in men and, in the United States, 8% occur in non-Whites. Prominent risk factors for hip fracture are osteoporosis and propensity to fall. Underlying these essential conditions for having a hip fracture are the reduced bone strength and quality that are characteristic of osteoporosis and the multiplicity of medical, psychosocial, and environmental factors that lead to falls.

The direct medical and indirect nonreimbursed costs (eg, unpaid caregiving services and lost wages of patients and caregivers) of hip fracture have been estimated to be as high as $20 billion annually in the United States. Over the past few years, measures have been taken in an attempt to reduce costs of care for hip fractures. This approach, called bundling, gives a single standardized payment that includes the total cost for all care for the patient for 90 days after surgery. Hospitals with high costs are at risk to lose money with bundled care. The largest costs are typically postacute care and readmissions. The switch to bundled care forces hospitals to work to reduce readmissions and complications when possible, and attempt to send patients home rather than to subacute care. Bundling also promotes interaction between surgeons, geriatricians, and postacute care centers to try to focus rehabilitation goals and reduce length of stay in the postacute center.

Among those who have experienced a hip fracture, approximately 18% of women and 36% of men are expected to die within the first year of their fracture. The highest mortality rates occur within the first few months after a fracture among those who are in the poorest health. In addition, comparison of survival rates of female hip fracture patients to similarly impaired women without fractures indicates that the fracture itself is responsible for nine extra deaths per 100 patients during the first 4 years following the fracture. Epidemiological data from studies of women indicate that even in those with the lowest number of medical comorbidities and best functioning at the time of fracture, the mortality attributable to hip fracture continues to increase well beyond the first year post fracture. Causes of death in women and men are similar and approximately four times greater than their nonfracture counterparts for heart disease, three times greater for cerebrovascular disease, and three times greater for chronic obstructive pulmonary disease. Interestingly, one study showed that men are far more likely than their nonfracture counterparts to die from infectious causes such as septicemia and pneumonia, in the first 2 years following hip fracture.

The intent of this chapter is to provide information about the medical and psychosocial status of the older patient who presents with a hip fracture and to discuss strategies for care and the role of the geriatrician in providing care during the acute hospital stay and the subsequent year or more of follow-up care.

WHAT TO EXPECT WHEN SEEING PATIENTS IN HOSPITAL

Medical Presentation and Fracture Characteristics

Classically, a patient with a hip fracture presents with a painful, shortened, and externally rotated lower extremity after a fall and landing on the affected hip. Most patients are unable to weight bear on the extremity. A small percentage of fractures are nondisplaced or “hairline” fractures and the patient may be able to bear weight and ambulate with pain. Nondisplaced fracture may progress to displaced fractures if not recognized. Patients having pain with gentle rolling of the lower extremity and a history of trauma should be evaluated for fracture. If plain radiographs are negative, magnetic resonance imaging (MRI) should be performed to look for bone marrow edema and fracture. MRI is more sensitive than computed tomography. If a nondisplaced fracture is found, treatment is either with non–weight bearing or in situ fixation to prevent propagation.

Approximately half of all hip fractures occur in the area of the femoral neck (or “intracapsular fractures”), and the other half occur in the area between the greater and lesser trochanters (“intertrochanteric fractures” or “extracapsular fractures”). Less common are fractures that occur within 5 cm below the lesser trochanter; these are called “subtrochanteric fractures.” Patients with intertrochanteric fractures tend to be older than those with femoral neck fractures and are more likely to have multiple medical comorbidities. A schematic of the hip anatomy is shown in Figure 53-2, which indicates the anatomy of the vascular supply to the hip region. This schematic is useful to understand the various surgical approaches to hip fracture care and the potential for blood loss at each site. As demonstrated in the schematic, the regions of the femoral neck and the femoral head derive their main blood supply from fine retinacular arteries that stem from the medial circumflex femoral artery. These delicate vessels are closely apposed to the femoral neck in this region. A fracture in the femoral neck is more likely to disrupt the vascular supply to the femoral neck and head, which can result in longer-term nonunion and osteonecrosis. Thus, fractures in the femoral neck region, particularly displaced fractures, are usually managed with joint replacement or arthroplasty rather than internal fixation. Arthroplasty may be partial or total replacement. Total hip replacement is thought to give better long-term results and less pain for patients who are active. In contrast, the blood supply to the intertrochanteric area is plentiful and redundant, such that nonunion and osteonecrosis are less common in this region, and fractures can heal well after internal fixation procedures. Internal fixation is most commonly performed with a hip plate and screw or with an intramedullary hip screw. All of these procedures allow the patient to bear weight as tolerated after hip fracture repair.

Impact of Age-Associated Physiological Changes and Comorbidities

The cumulative effect of environmental exposures, lifestyle, and genetic factors results in a remarkably heterogeneous geriatric population. Aging impacts most organ systems, although the degree to which organs are impaired from aging varies from individual to individual. In addition, several chronic medical conditions may also exist in a given individual. Medical care of the patient with hip fracture must, therefore, be adapted to the individual patient’s needs. This requirement for a tailored approach to care provides opportunities for challenges and satisfaction from the practice of geriatric medicine.

The changes that occur with aging physiology result in decreased resilience to stress, or the so-called “homeostenosis” in most organs. For example, older individuals may have lung volumes and decreased mucociliary clearance of their lungs, resulting in an increased propensity for postoperative atelectasis and pneumonia. Because of decreased physiological reserve, older individuals are at particular risk for a wider range of iatrogenic complications and do not recover as well when complications and adverse events occur. Older individuals are more susceptible to delirium during the pre- and postoperative period. This complication not only increases the patient’s risk of dying in the subsequent year, but also can impair an individual’s ability to participate in rehabilitation. Many of these complications are predictable and the geriatrician plays a critical role in team coordination and preventing complications. Hip fracture brings all of these known and unknown challenges together with the psychological insult of an acute fracture and need for surgical repair. The geriatrician must work with the surgical team to rapidly get the patient to surgery and progress the patient thought rehabilitation to hopefully bring them back to their baseline function.

Cognitive Status

Dementia is a prominent risk factor for falls and fractures and, not surprisingly, a significant number of patients with hip fracture have underlying cognitive impairment. Delirium is a common occurrence both at time of presentation to the emergency department and postoperatively, occurring in up to 60% of patients after hip fracture repair. Underlying dementia is a major risk factor for the development of delirium. The presence of delirium and cognitive impairment portend a worse functional recovery for patients with hip fracture. Identification of underlying dementia and risk factors for delirium is important for both prognostication, and so that modifiable risk factors can be avoided or minimized. Given the high risk of delirium in this patient population, it is particularly important to prepare the patient and family emotionally for this potential complication as it can be quite frightening to unprepared family members.

Risk factors for delirium in hospitalized patients have been well described. Some of the most consistently reported risk factors include advanced age, chronic cognitive impairment or dementia, sensory impairment, male sex, presence of comorbid psychiatric disease, polypharmacy and use of psychoactive and narcotic medications, infection, use of restraints, sleep deprivation, and undertreatment of pain. Among hip fracture patients, admission from an institutional setting and congestive heart failure (CHF) are important risk factors for delirium. Multi-component and nonpharmacologic interventions, preferably implemented by an interdisciplinary team, can prevent delirium and are cost-effective. Studies of proactive geriatric consultation with targeted recommendations, such as oxygen delivery, fluid balance, analgesia, elimination of unnecessary medications, regulation of bowel and bladder function, nutritional intake, mobilization, prevention of postoperative complications, assessment of environmental stimuli, and treatment of agitated delirium, have shown reductions in the incidence of delirium overall by a third, and in one study, a reduction in the incidence of severe delirium by half.

Nutritional Status and Physiologic Changes after Hip Fracture

Due to a number of factors, including pain and medications, reduced appetite is common during the acute hospital and rehabilitation period, and a significant number of patients will have difficulty meeting their caloric needs. Many hip fracture patients are undernourished prior to the fracture and therefore at high risk for malnutrition during their recovery.

Changes in body composition also are notable after a hip fracture. The average woman who fractures a hip can expect to lose 3% to 6% of her muscle mass within 2 months of the hip fracture and to have an increase in fat mass of 3% to 4% during the post fracture year. Losses of bone mineral density also are profound in this already osteoporotic group of older women. Older women lose nearly 3% of their total hip bone mineral density and more than 4.5% of their bone mineral density in the contralateral femoral neck during the year following a hip fracture. This is 12.5 times more than the loss of 0.5% that would have been expected in a group of women of the same age, comorbid disease status, and starting level of bone mineral density (Figure 53-3). Older men with hip fracture also show accelerated loss of bone mineral density in the contralateral hip that are greater than that expected from aging. Pharmacologic interventions to prevent secondary fractures should be considered for both women and men after hip fracture.

In addition, the prevalence of vitamin D deficiency among hip fracture patients is very high, and contributes to the observed losses in bone density and muscle strength, and fall and fracture risk.

The Geriatrician’s Role in Preoperative Care

The geriatrician can serve a central role in caring for patients upon admission to the acute care hospital by evaluating the medical and perioperative issues, ensuring maximal medical stabilization prior to surgery, and providing early detection and ongoing vigilance regarding risks for and development of, postoperative medical complications. The geriatrician is well positioned to discuss with the patient and family the anticipated hospital and postacute care procedures and transitions, thereby reducing uncertainty and alleviating anxiety at this unanticipated and challenging time.

Studies indicate that a multidisciplinary approach to acute care for hip fracture can improve clinical outcomes. Several models of orthogeriatrics comanagement have been developed. Models vary from geriatric consultation or liaison services, management on a geriatric ward with orthopedic consultation, and integrated inpatient orthogeriatric units. A systematic review and meta-analysis of 18 studies found that orthogeriatric collaboration was associated with reduced in-hospital mortality, reduced long-term mortality, and reduced length of stay. A randomized trial of orthogeriatric care provided on a geriatrics ward (vs an orthopedic ward without geriatrics consultation) did not reduce the rate of in-hospital delirium, but did improve mobility at 4 months after surgery.

The majority of patients with a hip fracture will undergo surgical repair. The types of surgical approach and anesthesia employed are largely the purview of the surgeon and the anesthesiologist and often depend on local practice patterns and physician training. No differences have been found in mortality between general and spinal anesthetic. Preoperative regional anesthetic with a nerve block has been shown to decrease pain in hip fracture patients. The nerve block can be done by an anesthesiologist or a trained emergency room physician. The pain relief from the nerve block may make the use of a Foley catheter unnecessary. The geriatrician should help to limit the use of catheters to those who can’t roll or get on a bed pan because of pain.

To prepare the patient for hip fracture surgery, the attending physician should determine the risks of cardiovascular, pulmonary, and other complications and strive to reduce those risks. (Refer to Chapter 27, Perioperative Care: Evaluation and Management, for more details on the use of preoperative testing for risk stratification, preoperative pulmonary treatments, and the use of β-blockers and other medications to reduce the risk of perioperative adverse cardiac events in high-risk patients.) Medication reconciliation is particularly important. The patient may not have an accurate medicine list upon presentation to the emergency department, and calls to the pharmacy and/or primary care physician may be necessary to obtain correct information or clarify questions.

While surgical approaches usually offer more benefits than nonsurgical approaches, nonsurgical approaches should be considered for some selected patients. The clearest benefit of surgery over the nonsurgical approach is that surgery results in better anatomic alignment and better likelihood of ambulation. Nonsurgical approaches may be considered in patients who are unable to ambulate prior to the fracture, those with advanced dementia and contractures, those with little pain from the fracture, and those in whom surgical risks are very high or life expectancy is very short. The geriatrician can help by providing a “big picture” view of whether or not the patient will benefit from surgical repair of the hip or whether palliative care should be considered. The determination of what may be most appropriate for a patient requires a thorough understanding of the patient’s pre-fracture functional and cognitive status, comorbidities, psychosocial factors, and the patient’s prior goals, values, and priorities. If it is determined that the patient is not a good surgical candidate, the geriatrician should be prepared to discuss the patient’s care goals and priorities and the palliative care management strategies and resources and to refer to palliative care and hospice colleagues and providers, as appropriate. Discussion of options for those not considered good candidates for surgery, including palliative and hospice care, also can be initiated and led by the geriatrician.

The Geriatrician’s Role in Postoperative Care

In the United States, a patient will usually remain in the acute hospital setting for 1 to 5 days after surgery for hip fracture. Patients should be mobilized the day of surgery if possible and certainly by postoperative day number 1. Early mobilization has been shown to be safe and effective for minimizing deconditioning and reducing the risk of complications such as delirium, constipation, pneumonia, thromboembolism, and pressure ulcer formation. If a catheter was placed, this should be removed the morning after surgery. Adequate treatment of postoperative pain is important for maximizing participation in physical therapy and increasing mobility. The optimal pain medication regimen has not been determined. The preoperative nerve block often helps postoperative pain considerably and intravenous pain medicine is not required after surgery. Care should be taken to prescribe a customized regimen that provides sustained pain relief early in the postoperative period, minimizes sedation, and also anticipates episodic increases in pain associated with activities such as therapy sessions.

The geriatrician must monitor the patient closely for the development of postoperative complications and is in a key position to detect subtle delirium that could be a harbinger of an ominous underlying complication, such as pulmonary embolus, urinary tract infection, and pneumonia. Postoperative pulmonary complications are among the most lethal complications in this population. Deep breathing exercises with or without an incentive spirometer, early mobility, and use of physical and/or pharmacologic approaches to reduce the risk of deep venous thrombosis should all be instituted. Other important postoperative medical considerations the geriatrician may be particularly adept at managing are reducing polypharmacy, pressure ulcer detection and management, maximizing sensory input, explaining the treatments and progression of care to patients and family, and communicating across the transitions of care to reduce errors during this vulnerable time. Atrial fibrillation and CHF are other typical postoperative complications. Worsening of CHF often happens after hospital discharge and this should be taken in account if the patient is transferred to a subacute nursing facility.

The geriatrician should also determine the patient’s risk for subsequent falls and fractures. A falls history should be obtained, including a complete description of the fall that led to the fracture as well as any previous falls, with particular attention to remediable risk factors to be addressed prior to discharge back to home (see Chapter 43, Falls). The geriatrician should discuss with the patient, family, and other providers the issue of osteoporosis treatment (see Chapter 51, Osteoporosis). To facilitate optimal secondary fracture prevention measures, many hospitals have enrolled in the International Osteoporosis Foundation “Capture the Fracture” program (www.capturethefracture.org) to implement a postfracture care coordination program. Such programs bring together and coordinate a multidisciplinary team of providers who can assess and manage osteoporosis and fall prevention.

If antiresorptive therapy is being considered for treatment of osteoporosis, the vitamin D level should be repleted prior to starting a bisphosphonate. Therefore, if not performed recently, a serum vitamin D level should be checked during the acute hospital admission.

Discharge Planning

Prior to discharge from the in-patient setting, a multidisciplinary assessment involving the geriatrician, the orthopedic surgeon, nursing, social work, physical therapy, and occupational therapy should be performed. The goal of this assessment is to decide on discharge plans and rehabilitation needs and goals. The following considerations should be taken into account: the patient’s current level of mobility, the patient’s postoperative medical and skilled nursing needs, the home environment, social support and economic resources available, self-care skills, and requirements for activities of daily living (ADL). The geriatrician plays a key role in coordinating the patient’s care and communicating with patients and families as they transition through the health care system. A critical role for the geriatrician is to ensure continuity of care. Recent studies have shown that, with each transition to a different site of care, there is the potential for an adverse effect on the care of patients with hip fracture, and physicians must, therefore, be vigilant to ensure adequate communication and good continuity of care to minimize this risk.

While a patient’s medical diagnoses and baseline functional status are important considerations for maximal functional recovery, his or her social support network and home environment are equally important. Social support will often dictate how long a patient needs to stay in in-patient rehabilitation before safe to discharge to home or the appropriate level of care. For example, if a patient had been previously living independently in a multistory home where the bathroom and bedroom are on the second floor and the kitchen on the first floor, one of three things would need to occur prior to discharge home: (1) the patient would need to be able to negotiate a full flight of stairs independently and safely; (2) the patient would need to rearrange the home to live on the ground floor and be able to transfer and ambulate short distances on a level surface independently and safely; (3) the patient would need a responsible caregiver to assist with daily tasks; or (4) the patient would need to stay with a family member on one floor. Not all patients have access to, or resources for, assistance in their homes, but some have families or friends who are able to provide this support, which is usually unreimbursed. This can also be a major stressor when the caregiver has to take time off from work and/or travel long distances to provide assistance. In collaboration with the interdisciplinary team, the geriatrician can assist family members and caregivers to anticipate and prepare for the patient’s upcoming needs. An assessment of the home environment by an occupational and/or physical therapist provides essential information for home discharge planning.

Transitions of Care

After the acute hospital stay, the hip fracture patient may be discharged home or to a postacute setting. This is typically an acute rehabilitation center or a subacute nursing facility. Very functional patients with capable families and good social support should be discharged home if possible. Those who cannot return home upon hospital discharge will require a short-term stay in an acute inpatient rehabilitation facility or a subacute skilled nursing facility (SNF). Transitions of care to these facilities are difficult and fraught with potential for medical errors. The accepting physician may rarely see the patient in the facility and the amount of rehabilitation services provided can vary. In the best situation, a trained geriatrician will continue care for the patient at the site of rehabilitation, and a handoff can be performed prior to transfer. A detailed consultation note immediately prior to the date of transfer, which details the comorbidities that are being managed by the geriatrician and the plan of care, can be extremely helpful to the accepting physician and rehabilitation team.

Changes in Hip Fracture Care: Bundled Care for Hip Fracture and COVID-19

Bundled care means that one payment is given to the hospital for the entirety of care of a patient for 90 days after surgery. This rate is set by Medicare. Hip fractures are part of several voluntary bundles which are radically changing the way care is delivered. If a hip fracture is treated with arthroplasty, the patient may be part of the arthroplasty bundle. This includes mostly elective patients with osteoarthritis. Another bundle includes care of other procedures of the entire femur bone which include hip fractures. This bundle also includes periprosthetic fracture treated with plates and patients with fixation of the mid or lower portion of the femur. Bundled care is different, because any complication requiring hospital readmissions is included within the single payment given for the bundle. The payment also includes the cost of any postdischarge care, including inpatient or outpatient services. The most expensive portion of care for the hip fracture patient is generally the postacute care and readmission and not the initial hospital stay. Participation in a bundle requires active involvement of the entire care team to minimize postsurgical complications, facilitate communication and continuity across transitions of care, shorten postacute stays without reducing quality of care, and avoid readmissions. This can involve follow-up via telemedicine, and close monitoring of patients while in a subacute facility. Utilizing rehabilitation facilities or programs with a relationship to the acute care hospital or medical center can be helpful to try to ensure that clearly articulated rehabilitation goals are set and achieved to get the patient home earlier.

The COVID-19 virus changed hip fracture care. The treatment of patients with active COVID-19 and hip fracture depends upon the severity of the COVID-19 infection. Those who have respiratory symptoms and fracture seem to have poor outcomes. Those who are asymptomatic should probably have early surgery as is usually performed. Postoperative visits are often curtailed if patients are COVID-19-positive and telemedicine visits must be used. The COVID-19 epidemic also made patients fearful of being in the hospital or of being in a nursing home, and this further stressed the importance of home discharge when possible.

POSTFRACTURE CHANGES IN PHYSICAL AND PSYCHOSOCIAL FUNCTION AND IMPLICATIONS FOR CARE

Physical Function

Hip fractures have significant effects on functioning and body composition. Figure 53-4 shows the proportion of patients with hip fracture who, prior to their fracture, were able to perform routine tasks involving lower extremities but were not able to perform them a year later. Twenty percent of those who could put on their own pants without assistance prior to their fracture required assistance to do so 1 year later. More striking is the proportion of patients who needed assistance from another person or required the use of equipment to walk across a small room (40%), use the toilet (66%), or climb five stairs (90%). Instrumental tasks also are affected, with 62%, 53%, and 42% who could do their own housecleaning, get to places out of walking distance independently, and shop without assistance, respectively, prior to their fracture, requiring assistance to perform these tasks a year later. Other functional consequences of hip fracture include increases in cognitive impairment and depressive symptoms, as well as increases in problems with gait and balance. Despite advances in surgical procedures, postoperative care, and long-term rehabilitation, hip fractures rank in the top 10 of all impairments worldwide in terms of causing disability and functional decline.

Psychological Status

The diagnosis of hip fracture conveys to patients and families a significant degree of psychological stress. Most lay persons are quite aware of the risk of mortality and poor recovery of function after a hip fracture, the high rate of nursing home use and long-term placement and, for those who do return home, the high rates of dependency on others for care. Although not the case for most patients, many patients and families believe that having a hip fracture signifies the “beginning of the end.” These psychological stressors may contribute to the high rates of postoperative depression that have been described. Patients may endorse depressive symptoms during their hospital stay and for up to 6 months after fracture; those who report symptoms of depression even transiently tend to recover less well than those who do not endorse depressive symptoms at all.

FUNCTIONAL RECOVERY POSTHIP FRACTURE

Recovery in function following a hip fracture can be anticipated in most patients, although many will fail to reach their prefracture functional levels. This recovery appears to follow a sequence that may be instructive for management during the initial year after the fracture. Depression, upper extremity ADL, and cognitive function reach their peak level of recovery by approximately 4 months postfracture, while tasks associated with mobility, such as balance and gait, reach a plateau at approximately 9 months postfracture. Interestingly, the more complex tasks that are indicative of disability, such as performing lower extremity activities and instrumental tasks, recover by approximately a year (Figure 53-5).

Patients who recover more slowly than anticipated should have an assessment of factors that may be contributing, such as persistent delirium, depression, polypharmacy, vitamin D and other nutritional deficiencies, and social isolation, so that a targeted multidisciplinary plan can be developed to address the issues of concern.

POSTFRACTURE REHABILITATION

Rehabilitation Services

The majority of patients with hip fracture will undergo a period of rehabilitation therapy after the fracture repair (see Chapter 55, Rehabilitation). Rehabilitation services are provided only if both of the following requirements are fulfilled: (1) the patient has a functional loss and (2) is able to participate in rehabilitation efforts. Individuals with severe cognitive impairment or those with unresolved delirium that interferes with participation in standard rehabilitation, those with severe prefracture disability (eg, bed-bound), and those with terminal illness, may not qualify for standard rehabilitation services. Alternative approaches may be required. The geriatrician can judge potential benefits and work with the multidisciplinary rehabilitation team to recommend the most appropriate rehabilitative care.

Rehabilitation services can be provided in one or more of the following settings: an inpatient acute rehabilitation unit, a subacute rehabilitation unit in a SNF, or on an outpatient basis, either at home or in a clinic. The location of postdischarge rehabilitation is determined by a number of factors, including the patient’s functional impairments, comorbidities, ability to participate in skilled therapy sessions, social support, and personal preferences. In the United States, rehabilitation is typically limited by Medicare reimbursement and rarely goes beyond 30 days. In one study, approximately 50% of hip fracture patients were discharged to a SNF subacute unit, 20% were discharged to an acute inpatient rehabilitation unit, 15% were discharged to home, and 14% were discharged directly to a long-term care facility. The COVID-19 pandemic shifted services more toward home care, when feasible.

Inpatient acute rehabilitation units are usually located in specialized units of an acute care hospital, or in a dedicated rehabilitation hospital. Patients with complex medical or rehabilitation needs and with good endurance may receive their rehabilitation in the acute setting. The requirements for acute rehabilitation are that the individual must be able to participate in therapy for at least 3 hours/day, and at least two rehabilitation therapeutic disciplines be involved (eg, physical therapy and occupational therapy).

Patients with less complex medical or rehabilitation needs, who are not able to participate in 3 hours/day of rehabilitation but who otherwise have a functional decline that would benefit from rehabilitation and are unable to be discharged to home, can receive rehabilitation in the subacute SNF setting. These patients typically receive interventions from a licensed professional 5 days a week, however, on a less intense basis than in the acute rehabilitation setting.

Patients with more mild functional and mobility impairments or with good support at home may receive their rehabilitation on an outpatient basis, either at home or at an outpatient facility. In order to qualify for home rehabilitation, patients must have a functional decline that would benefit from rehabilitation, have sufficient caregiver support to enable them to be cared for at home, and be homebound and therefore unable to attend rehabilitation at an outpatient clinic. Since rehabilitation will be delivered by homecare professionals in the patient’s home, heavy equipment must not be required.

For individuals with less complex rehabilitation needs, services may be delivered in an outpatient clinic. Outpatient rehabilitation may also continue after acute, subacute, and homecare services, to facilitate attainment of rehabilitation goals.

The Role of the Geriatrician in the Rehabilitation Setting

The geriatrician can also play a key role in medical management at rehabilitation settings, especially at SNFs. Regardless of the rehabilitation setting, medical care should focus on the following principles: treatment of chronic medical conditions, continued postoperative hip fracture care, prevention of complications from the associated functional decline and immobility, and prevention of future falls and fractures.

Despite ongoing therapy by rehabilitation professionals, increased risk for complications related to immobility, such as DVT, pressure ulcers, and constipation, persist at the rehabilitation setting. Thus, continued vigilance to their prevention and detection must be exercised. Based on current recommendations, DVT prophylaxis should be continued for 21 to 31 days after hip fracture surgery. Pressure ulcers are common after hip fracture surgery, with reports of an incidence rate of stage II or greater ulcers within 21 days of fracture of approximately 5%. Given the decreased mobility and frequency of use of narcotic analgesics for postoperative pain, constipation is a common occurrence and efforts should be made to prevent this with an adequate bowel regimen. Continued monitoring by the geriatrician of the patient’s weight, nutritional status, symptoms of depression and cognitive impairment, and the success of related interventions is very important for ensuring optimal recovery.

Many patients with hip fracture in the acute and subacute rehabilitation settings receive their medical care from a physician who was not their primary care provider prefracture and may not be familiar with their history or support system. Care for these patients represents a challenge for the attending physician, as these patients are typically older and with significant and complicated comorbid disease. More than 75% of patients with hip fracture have at least four comorbid medical conditions prior to their fracture. In addition to supervising the care of the hip fracture and any sequelae, the attending physician must ensure that these chronic medical conditions continue to be addressed.

What to Tell the Patient and Family to Expect With Regard to Function

Because hip fracture may result in persistent functional limitations and disability, patients with hip fracture may anticipate significant changes in their lifestyle. The geriatrician needs to provide support and encouragement during the initial recovery period following hip fracture surgery when pain and disability are greatest. Patients and their families can be reassured that significant improvements in lower extremity function during the first few months postfracture are likely to occur, while at the same time cautioned that lower extremity limitations can be prolonged. Up to 50% of older adults who had previously been independent may be dependent on mobility aids, such as a cane or a walker, for ambulation at 1 year postfracture. These limitations and fear of recurrent falls may result in self-limitation of daily activities.

These declines in function may result in loss of independence in the older patient, and, as a result, the older patient with hip fracture may be facing the prospect of moving from their independent residence to a higher level of care for the first time. Individuals who have an injury as a result of a fall, such as a hip fracture, are 10 times more likely to be admitted to a SNF. This may be one of the most frightening aspects of the postfracture recovery period, and helping patients to understand that this is an expected reaction to having a hip fracture may enable them to overcome this fear and resume their activities more quickly.

Older patients and those with multiple health conditions may need to be told that their recovery may be slower than for others. Compared to younger patients, those who are older than 85 years have been found to require longer rehabilitation stays, have worse recovery of lower extremity function, are more likely to be discharged to long-term care, and are more likely to have persistent pain, which may be accompanied by ADL limitations and reduced quality of life. Depression and cognitive limitations should also be discussed with patients and families. It is important for them to understand that depressive symptoms and cognitive limitations are common after a hip fracture. They should also be informed that these changes are not always persistent, as depressive symptoms and cognitive limitations will frequently resolve with limited intervention within 2 months, and that treatment for mild depression is often useful to avoid any lingering anxiety or depression that accompanies the hip fracture.

The Geriatrician’s Role after Formal Rehabilitation for the Hip Fracture

After the patient has returned home, the focus of follow-up care should be to monitor whether the patient is making expected gains in recovery, evaluate barriers if expected gains are not achieved, and prevent subsequent falls and injury. Most hip fracture patients plateau in their functional level by 6 months after fracture event. The occurrence of complications may alter that course and many will continue to realize gains with longer amounts of time. Geriatricians are well trained to identify barriers to recovery after a hip fracture and initiate interventions that can further enhance recovery and reduce fall risk. Optimally, the patient should be reevaluated at the time of discharge from the acute rehabilitation setting, and again upon discharge from home physical therapy, to assess the patient’s recovery level, physical impairments, and need for outpatient services. Multidisciplinary fall risk assessment (eg, home environment assessment, medication review, vision testing, postural blood pressure measurement, gait and balance testing, and targeted neurological, musculoskeletal, and cardiac examinations) followed by interventions directed at these risks can reduce fall risk and are cost-effective in older adults at risk of recurrent falls.

Continuation of an exercise program after formal rehabilitation services have ended has been shown to improve physical function during the year following surgical repair of the fracture. Exercise programs that include progressive-resistance training appear to be most effective at improving measures of physical function and quality of life. However, home-based exercise programs for hip fracture patients have also shown modest improvement in physical function. The physician should discuss with patients their options for continued outpatient therapy and/or exercise, determine their preferences, and provide appropriate referrals and prescriptions.

Although hip protectors have received attention for their potential to reduce hip fractures, meta-analyses suggest that these offer little or no benefit for patients in randomized studies. As a result, these devices should not be considered as alternatives to the other fall reduction and bone-strengthening interventions discussed above.

CONCLUSION

Care for older patients with hip fracture represents one of the greatest challenges for the geriatrician because of the multiplicity of medical and psychosocial factors involved in postfracture care. A summary of some of the key issues a geriatrician should focus on at various stages of hip fracture care appears in Table 53-1. Answering these questions requires vigilant attention preoperatively, postoperatively, in the rehabilitation setting, and after rehabilitation efforts have terminated. Although a hip fracture event has significant consequences for patients and their families, through this attention and communication with patients, families, and the other clinicians involved in the care of patients as they transition through the various sites of care, it is the goal of the geriatrician to minimize long-term adverse effects and to ensure that the overall well-being of the patient is maximized.

FURTHER READING

LEARNING OBJECTIVES

AGING AND BENEFITS OF EXERCISE

A common belief among the lay public, as well as among many health care professionals, is that much of the disease and functional decline that accompanies aging is inevitable, a result of the “aging process” itself. However, much of the physical decline and reduced physiologic reserve attributed to aging is, in fact, caused by complex interactions of disuse, environmental and lifestyle factors, disease, and genetics.

Physical activity level and fitness are associated with a greater average lifespan and inversely related to the risk of mortality. Among adults older than 60 years, engaging in at least 150 minutes per week of moderate to vigorous physical activity is associated with a 28% reduction in all-cause mortality. Even a modest dose of moderate to vigorous physical activity confers a mortality benefit compared to no activity. Higher cardiorespiratory fitness is associated with lower mortality, with a striking 80% reduction in mortality risk between elite performers (those > 2 standard deviations above the mean for age and sex) and the lowest performers.

With respect to resistance exercise, older adults performing guideline-concordant strength training had 46% lower odds of all-cause mortality than those who did not. A recent meta-analysis of more than 1400 studies reported that compared to no exercise, any resistance training was associated with 21% reduction in all-cause mortality. Combining resistance and aerobic exercise appears to confer even greater benefit than either alone. In the above meta-analysis, resistance exercise plus aerobic exercise was associated with a 40% reduction in all-cause mortality. Among older women, those who participated in both strength training and greater than or equal to 150 minutes per week of aerobic activity had a 46% lower risk of all-cause mortality.

An inverse dose–response relationship has also been noted between physical activity and the risk of developing many chronic diseases, as discussed later in this chapter. Despite the overwhelming benefits of physical activity, only 35% of persons older than 60 years meet current recommendations for physical activity (these recommendations are included in Table 54-3, discussed later in this chapter); this percentage drops significantly in older age groups.

It is increasingly clear that many of the health benefits of exercise can be accrued simply through a more active (nonsedentary) lifestyle. This concept may be especially helpful in trying to encourage older individuals who feel they are unable or unwilling to engage in formal exercise training.

Sedentary behavior includes activities that require an energy expenditure of more than or equal to 1.5 times resting energy expenditure, and encompasses activities such as sitting, watching TV, using a computer, reclining, or lying down during waking hours. Objective measurements of sedentary time in the National Health and Nutrition Examination Survey (NHANES) indicate that adults aged 60 or older spend more time engaged in sedentary behaviors (8–9 hours per day, or 60% of their waking time) than any other segment of the population. In older adults, sedentary behavior is associated with an increased risk of sarcopenia and functional limitations, and inversely associated with physical function. Prolonged periods of sedentary behavior appear particularly deleterious, particularly for metabolic health. In older adults, the number of breaks in sedentary time is associated with higher levels of physical function, independent of moderate to vigorous physical activity. Changing sedentary behavior may have an immediate impact on the health of older adults. In one study, older adults who reduced their sedentary time over a 2-year period had a lower risk of all-cause mortality compared to those who either increased or did not change their sedentary time.

AGING AND EXERCISE

Aerobic Exercise Capacity

One of the key physiologic changes that occurs with aging and contributes to the decline in physical function is a decline in aerobic exercise capacity, best measured by the amount of oxygen consumed at maximal or peak exercise (maximal or peak aerobic power; VO_2max or VO_2peak). Longitudinal data indicate that the rate of decline in VO_2peak accelerates markedly with each successive decade, reaching more than 20% per decade from the 1970s onward (Figure 54-1).

Age-associated declines in VO_2max can be attributed to alterations in both central and peripheral determinants of exercise capacity. Reductions in maximal heart rate and in the maximal ability of muscle to extract oxygen from the blood, driven in large part by the age-associated loss of muscle mass, appear to contribute to declines in VO₂ max in older adults (also see Chapter 73, The Aging Cardiovascular System). In all age groups, endurance-trained adults have a higher VO₂ max than their age-matched sedentary peers, suggesting that participation in habitual aerobic exercise may attenuate the age-related decline in VO₂ max.

Despite declines in VO_2max with aging, the response to an aerobic exercise training program in previously sedentary, healthy older adults is comparable to that observed in younger subjects, with improvements mediated by both central and peripheral adaptations (also see Chapter 73). Improvement in VO_2max has been reported to be between 6% and 30%, with significant improvements observed in as little as 3 weeks.

Skeletal Muscle Strength and Power

Aging is associated with a significant loss in skeletal muscle mass, and consequently in muscle strength (maximum force exerted) and power (rate of force development) in men and women, independent of physical activity status. The loss in muscle strength also accelerates with advancing age; by age 80, strength is approximately 30% to 40% of peak. The rate of decline in muscle power, which is a stronger determinant of physical function in older age than muscle strength, appears to be even greater than the decline in strength. The loss of muscle strength and power is associated with both mortality and physical disability in older adults; however, both can be increased by improving muscular function (eg, muscle cell hypertrophy) or by improving neurological function (eg, learning).

To a large extent, the age-associated loss of muscle strength and power reflects loss of muscle mass. However, other factors are clearly involved. In the Health, Aging and Body Composition (Health ABC) Study, for example, the decline in muscle strength over 3 years was three times greater than the parallel rate of decline in muscle mass. Regular physical activity may prevent or attenuate some of the age-related loss in strength. Importantly, vigorous strengthening exercise can produce substantial gains in strength in older adults.

A primary mechanism for the effects of resistance exercise is muscle hypertrophy, and older adults appear to achieve increases in muscle fiber size and cross-sectional area comparable to those in younger adults. However, even modest increases in muscle fiber size or cross-sectional area are accompanied by proportionally greater increases in strength, again suggesting involvement of other mechanisms. Proposed mechanisms include learning effects from improvements in motor skill coordination, and neural adaptations such as increased voluntary muscle activation, reflecting recruitment, firing and synchronization of motor units, and better coordination of synergistic and antagonist muscle cocontraction.

Nonlinear Relationship Between Physiologic Impairment and Functional Limitation

Healthy humans have excess physiologic capacity not tapped during most daily activities and can thus lose a fair amount of physiologic reserve before functional limitations occur. Indeed, the relationship between leg strength and walking speed is nonlinear. This nonlinear relationship is intuitive: if strength was linearly related to walking speed, highly trained weightlifters would walk ridiculously fast (16–30 km/h) because they are several times as strong as normal adults, who walk at around 5–8 km/h. That is, above a certain threshold level of adequate physiologic reserve, function is normal; below the threshold, function is impaired (Figure 54-2). The exact shape of the curve depends on the task and the physiologic capacity of interest. Figure 54-2 may oversimplify the situation because most tasks have multiple physiologic determinants that may interact to affect behavioral ability.

To illustrate the concept of thresholds, consider that in steady-state measures of oxygen consumption, walking on a level grade at 5 km/h requires 3.2 METs (1 MET = 3.5 mL O₂/kg/min). With illness or inactivity, aerobic capacity may fall below the 3.2 METs required for walking. Because exercise can increase aerobic capacity, it should improve walking in this situation. However, aerobic exercise would not affect ability to walk at 5 km/h in adults whose aerobic capacity already exceeds 3.2 METs.

Thus, exercise may produce a large improvement in function in frail adults with little or no physiologic reserve. Indeed, well-designed studies of exercise in frail adults report improvements in functional limitations with exercise. For example, the Lifestyle Interventions and Independence for Elders (LIFE) study of frail older adults (70–89 years) demonstrated that a structured, moderate-intensity physical activity intervention reduced the risk of mobility disability compared to a control health education program. The greatest risk reduction (HR = 0.75) was observed in older adults with lower physical function at baseline, compared to those with moderate functional impairments at baseline (HR = 0.95). In contrast, exercise would be expected to have much smaller effects on functional limitations in healthy older adults, at least in basic activities of daily life.

EXERCISE AND COMMON GERIATRIC DISORDERS

A number of common geriatric disorders can be improved with exercise, although many questions remain about the type and intensity of exercise, sex differences in response to exercise, and mechanisms underlying the benefits. Table 54-1 summarizes the current knowledge of the effects of different exercise modalities on several common geriatric disorders.

Cardiovascular Diseases

Although the mortality rates attributable to cardiovascular diseases (CVD) have declined, CVD burden in older adults remains high. There is a consistent, independent inverse relationship between aerobic fitness and physical activity levels and CVD mortality. Both short bouts and longer continuous sessions of physical activity are equally effective for reducing coronary heart disease (CHD) risk, provided the total energy expended is similar. Although a dose response has been demonstrated in some studies, even low to moderate physical activity can reduce risk for CVD mortality, with no additional protection from participating in more vigorous activities.

In contrast to the overwhelming evidence of the benefit of aerobic exercise to reduce CVD risk, few data exist on the association between strength training and CVD risk. Strength training is generally associated with reduced CVD mortality; however, the relationship may be J-shaped, with low to moderate levels (1–50 minutes per week) associated with the lowest risk of CVD mortality.

Similar to physical activity, fitness has been reported as being at least as good a predictor of both overall and CVD-related death as blood pressure, obesity, smoking, or diabetes. Because of the reported benefit of increasing physical activity and fitness levels on CVD risk, aerobic exercise and strength training are typically prescribed for older adults with CVD as part of a comprehensive cardiac rehabilitation program to increase aerobic capacity, improve CVD risk factors, prevent disease progression, and reduce the risk for future cardiovascular events and death. In fact, individuals with stable coronary artery disease randomized to exercise training improved their aerobic capacity and had a higher event-free survival (reduced repeat revascularization and hospitalizations) than those receiving percutaneous coronary intervention.

Both aerobic exercise and strength training improve aerobic exercise capacity to a similar degree in patients with CHD, and the improvements are enhanced when the two exercise modalities are combined. Aerobic exercise and strength training are also beneficial in improving exercise tolerance and quality of life in other CVD patient populations including heart failure (see Chapter 76) and peripheral arterial disease (PAD, see Chapter 78). Supervised aerobic exercise training is associated with reduced mortality (35%) and hospital readmission (28%) in patients with chronic heart failure. In patients with PAD, any physical activity greater than light intensity is associated with reduced mortality compared to no physical activity or only light-intensity activities. Because walking is effective in improving absolute claudication distance (ACD), guidelines recommend that individuals with PAD participate in a supervised walking program that gradually increases speed and distance as an initial noninvasive approach, using walking claudication pain—either onset of pain, or mild to moderate or maximal level tolerable—for prescribing exercise intensity. Other modes of exercise also improve ACD. However, the data are insufficient, particularly with regard to resistance training, to make any clinical recommendations. Thus, there is a need for further definitive, large clinical trials of alternative or complementary exercise interventions for PAD in older adults.

Exercise training programs in CVD patients have numerous physiologic effects on the cardiovascular system and CVD risk factors (Table 54-2). Improvements in VO_2max of 15% to 25% are driven by either central (ie, improved myocardial oxygenation, enhanced left ventricular function) and/or peripheral adaptations, depending on the population. For example, in coronary artery disease (CAD) and heart failure patients, those with depressed left ventricular function may not show cardiac adaptations, but rather, the improvements in VO_2max are largely attributed to improvements in maximal arteriovenous oxygen difference due to improved mitochondrial oxidative enzymatic capacity.

In addition to improving multiple CVD risk factors, exercise training programs reduce arterial stiffness and improve vascular endothelial function in patients with CVD, measures that are important for overall vascular homeostasis. In general, aerobic exercise training programs improve vascular function in older adults independent of disease state. However, there are noted sex differences between the magnitude of improvement with exercise training, with near restoration of endothelial function to youthful levels in healthy older men, but attenuated or minimal improvements in postmenopausal women not on estrogen-based hormone therapy. Exercise training may also increase circulating bone marrow derived endothelial progenitor cells (EPCs) and improve EPC function. EPCs facilitate vascular repair and vasculogenesis, and are reduced in CVD patients. Other potential mechanisms of exercise training on CVD could be related to regression of coronary artery stenosis and formation of collateral vessels, resulting in enhanced myocardial perfusion.

The benefits of exercise on CVD risk are thought to be due at least in part to improvements in lipid profiles. Higher levels of physical activity are associated with less atherogenic lipoprotein profiles in young and middle-aged individuals, although data in older adults are lacking. There is no consistent effect of resistance training on lipoproteins.

Although exercise training is beneficial overall for CVD patients, there are a few conditions in which exercise may not be as beneficial and actually contraindicated. These conditions include unstable angina, uncontrolled hypertension, uncontrolled cardiac arrhythmias, recent myocardial infarction, severe aortic stenosis and other valvular diseases, acute pericarditis, and decompensated heart failure.

Hypertension

Hypertension is covered in Chapter 79. Over 80% of adults age 60 or older with hypertension are treated with antihypertensive therapies, and more than 30% of hypertensive adults age 80 or older are taking three or more classes of antihypertensive medications. Although antihypertensive medications produce long-term benefit, these medications can have numerous side effects, especially in older patients. Thus, using nonpharmacologic treatments (eg, weight loss, low-sodium diet, and exercise) is appealing, especially in older adults with mild to moderate hypertension.

Both leisure-time activity and aerobic exercise capacity (ie, VO_2max) are inversely related to risk for hypertension, with the lowest risk for hypertension in the most active and fit people. Hypertensive older Swedish men (born in 1914) who regularly exercised vigorously had an adjusted relative risk of 0.43 for total mortality and 0.33 for cardiovascular mortality. Given the apparent benefits of increased physical activity on aerobic exercise capacity and reduced hypertension risk, the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) recommends increased physical activity designed to enhance aerobic exercise capacity as initial therapy to prevent, treat, and control hypertension.

Aerobic exercise training programs effectively lower blood pressure in older adults with mild to moderate hypertension. Overall, aerobic exercise training programs or increasing physical activity of moderate intensity and of adequate volume result in a 4 to 10 mm Hg decline in systolic blood pressure and a 3 to 8 mm Hg decline in diastolic blood pressure in individuals with stage 1 hypertension, regardless of age or sex. The effects of aerobic exercise training in older adults with stage 2 hypertension, or those with resistant hypertension are less clear. In resistant hypertension, moderate-intensity exercise training reduced 24-hour ambulatory blood pressure similarly to that reported for mild to moderate hypertensives. Although there are limited data comparing different exercise intensities, low- to moderate-intensity exercise may be more effective at lowering blood pressure than more vigorous exercise. Indeed, even light Tai chi exercise or increasing daily walking can reduce and even normalize blood pressure in sedentary older hypertensive patients.

There is limited and inconsistent data on the effect of strength training on blood pressure in older hypertensive adults. Excessive blood pressure elevations can occur during high-intensity resistance training, especially if associated with Valsalva. However, with low- to moderate-intensity strength training and proper breathing techniques, this is not a concern. Overall, progressive resistance training results in a 3 mm Hg decrease in both systolic and diastolic blood pressure. However, the effect of resistance training on systolic blood pressure in adults older than 50 years and on systolic and diastolic blood pressures in hypertensives is less and not significant. Given the small number of studies available in hypertensive older adults, additional research is warranted to provide recommendations on the effect of resistance training for blood pressure reduction in hypertensive older adults.

The mechanisms underlying the blood pressure lowering effects of exercise in hypertensive adults are not completely understood, although changes in body composition, sympathetic nervous system activity, peripheral vascular resistance, and insulin levels have all been postulated. For example, weight loss alone or combined with exercise provides a greater blood pressure lowering effect than exercise alone. Aerobic exercise training decreases arterial stiffness and improves endothelial function in hypertensive adults. However, whether the decreases in blood pressure with exercise are due to improvements in arterial stiffness and endothelial function, or vice versa, are unclear.

Obesity

As described in Chapter 30, obesity is associated with increased morbidity and mortality from multiple medical complications, and has been consistently correlated with mobility impairment and poor physical function, especially in older adults. While weight loss alone can improve cardiometabolic risk factors, fitness, function, and quality of life in obese older adults, it is also associated with loss of fat-free mass (FFM) and decreases in bone mineral density (BMD). Given these potential harms, there is general agreement that exercise should be a component of any weight loss intervention, in order to minimize loss of muscle and bone with weight loss in older obese adults.

Diet plus exercise interventions improve multiple cardiometabolic and functional outcomes in older adults, although effects on cardiovascular events or mortality have not been demonstrated yet. For example, the Diabetes Prevention Program (DPP) lifestyle intervention of moderate-intensity exercise and modest weight loss (7%) was very effective in preventing progression to diabetes in older (60–85 years) participants. Compared to younger people in the DPP, older participants had greater reductions in waist circumference, lost more weight, and were more likely to achieve the goal of at least 150 minutes of exercise per week.

A randomized, controlled trial by Villareal et al. provides the most compelling evidence for including exercise in any weight loss intervention in older obese adults. They compared 52 weeks of weight loss diet, exercise (aerobic and strength training), or both in more than 100 older obese adults with mild to moderate functional impairment. Participants receiving the diet intervention lost weight, whereas weight remained stable in the exercise only group. Physical and metabolic function improved in all groups, but was greatest in the diet plus exercise group. The expected decreases in FFM and BMD with weight loss were attenuated in the diet plus exercise group, but not completely reversed. Because the negative effects of weight loss on body composition and BMD in older obese adults are not fully offset by exercise, an important question is whether weight loss per se is necessary, or whether exercise alone can confer most of the benefits without the associated risks of weight loss in this population.

Osteoporosis

The decline in BMD with age is well recognized (see Chapter 51), and there is an epidemic of osteoporotic fractures that affects women more than men and that primarily involves hip, vertebral, and wrist fractures. Mechanical loads are critical to skeletal integrity. Animal studies confirm the importance of mechanical strain to bone modeling and remodeling. They have also identified that (1) the osteogenic response to mechanical loading is optimized with relatively few repetitions of high-magnitude forces; (2) the application of force must be in a dynamic, rather than static, fashion; and (3) fast strain rates are more osteogenic than slow strain rates. Furthermore, the osteogenic response to mechanical loading is mediated locally in skeletal regions subjected to the strain, highlighting the need for exercises to specifically target regions of the skeleton at risk of fracture. It appears that bone cells lose sensitivity to mechanical loading after relatively few loading cycles. For example, four sets of 90 load applications per day were more osteogenic than one set of 360 loading cycles, and interposing an 8-hour recovery period between loading sessions resulted in a greater osteogenic response than when the recovery period was 0.5 hour. These concepts have not been rigorously evaluated in humans, but they suggest that multiple short bouts of exercise per day may be more effective in preserving bone health than a single, longer daily session. The concept of allowing bone to “rest” between loading cycles may also have implications for resistance training. For example, if the intent is to perform three sets of eight repetitions of several exercises, it might be of greater benefit to bone to perform one set of each exercise and then cycle back through for the second and third sets, rather than doing three consecutive sets of each exercise.

The effects of exercise on bone mass have been estimated by comparing athletes who participate in different sports or physically active versus sedentary people. For example, the humerus in the dominant arm of tennis players had approximately 30% greater cortical bone thickness when compared to the nondominant arm. Athletes who participate in muscle-building activities (eg, weight lifting and body building) and in activities that involve jumping or vaulting (eg, volleyball and gymnastics) also tend to have elevated BMD. These data suggest that exercise in younger individuals may increase peak bone mass—an important protective factor for reducing osteopenia later in life. In contrast, the primary benefit of physical activity in older adults may be to preserve, rather than increase, bone mass.

Although both weight-bearing aerobic exercise and resistance exercise can increase bone mass in older women and men, increases in BMD appear to require a vigorous level of exercise, which supports the contention that the osteogenic response to exercise is attenuated with aging. In postmenopausal women, exercise may increase BMD by up to 5%, as compared to no-exercise controls, but average increases generally are only 1% to 3%. These modest increases may reflect difficulty reaching the strain threshold needed for bone remodeling to occur due to decreased muscle mass and strength, declines in hormones and growth factors that affect the sensitivity of bone to strain, and/or insufficient calcium and vitamin D.

There is also evidence that exercise can prevent fractures. Results from prospective cohort studies, such as the Nurses’ Health Study and the Study of Osteoporotic Fractures, suggest that the risk for hip fracture is reduced by approximately 50% in the most physically active quintile of the population. In evaluating the potential benefit of simple walking activity, the Nurses’ Health Study found a dose-response benefit for both duration and speed of walking, such that more hours per week spent walking and fast walking speed conferred reduced fracture risk. Even hours per week spent standing was inversely related to hip fracture incidence. Perhaps most importantly, changes in physical activity for several years were related to hip fracture incidence in the expected manner: decreases in physical activity were associated increased risk and vice versa. Such findings suggest that any type of ambulatory physical activity may confer skeletal benefits and that increased physical activity should be advocated at any age as a strategy to reduce fracture risk.

The low frequency of fractures makes well-designed, adequately powered randomized controlled trials extremely expensive. Very few exercise trials have included fractures as an outcome, or reported fractures as an observation. Analysis of 11 exercise intervention studies that reported fractures found that exercise reduced the risk of overall fracture by approximately 50% and vertebral fracture by approximately 40% compared to controls, although the authors urged caution due to the strong likelihood of publication bias. The Erlangen Fitness and Osteoporosis Prevention Study compared fracture incidence among 137 postmenopausal osteopenic women either participating in a supervised exercise intervention (two group and two home sessions per week), or a sedentary control group for 12 years. Although fewer fractures occurred in the exercise group, the difference between groups did not reach statistical significance.

Important areas for future research include determining the effects of age and sex in the response of bone to exercise. In addition, new methods such as peripheral quantitative computed tomography may provide important information on bone quality (eg, strength and geometry) in response to exercise.

Cancer

Cohort and case control studies consistently support an inverse relation between physical activity and overall cancer incidence and mortality. The effects appear to be stronger in men than in women, but many studies excluded women. Overall, occupational and leisure physical activities were associated with a 30% independent protective effect on overall cancer risk in men, and men who engaged in regular vigorous activities had a 20% reduction in cancer risk compared to sedentary men. Analysis of more than 15,000 cancer deaths over 12 years in the NIH-AARP Diet and Health Study found that compared to those who reported rarely or never engaging in moderate to vigorous physical activity, those who reported more than 7 hours/week had a lower risk of cancer mortality (HR = 0.89).

In persons diagnosed with cancer, exercise is associated with improved surgical outcomes, decreased symptoms and side effects of treatment, and improved physical function and psychological health. Participation in exercise post cancer diagnosis has been estimated to increase cancer survivorship by 50% to 60%.

To date, the most compelling data involve the relationship between activity and risk of colon or breast cancer. A reduced risk of colon cancer (relative risk, 0.4–0.9) has been found in groups with high physical activity levels compared to those with low levels. In general, controlling for other cancer risks including tobacco, alcohol, age, obesity, and diet does not diminish the relationships, and this finding has been demonstrated in men and women of different racial and ethnic groups. Among patients with colon cancer, any prediagnosis physical activity was associated with a 25% reduction in colon-cancer mortality, and a 26% reduction in all-cause mortality compared to patients who reported no physical activity prior to diagnosis. Moderate to high levels of postdiagnosis physical activity were also associated with reductions in all-cause mortality ranging from 24% to 39%.

Physical activity reduces the risk of breast cancer overall by 15% to 20%. The strongest effect appears to be in postmenopausal breast cancer, where the risk reduction ranges from 20% to 80% when comparing the most active to the least active groups. These associations remain even after adjusting for potential confounding factors such as age, body mass index (BMI), reproductive history, tobacco use, and diet. There appears to be a dose response, with higher levels of activity associated with greater risk reduction. As with colon cancer, exercise in breast cancer patients is associated with better physical function and fewer treatment-related side effects.

Depressed Mood

Subjects who exercise regularly consistently report an improved sense of well-being and reduced tension and anxiety. Large epidemiological studies have demonstrated an association between low levels of physical activity and depressive symptoms. These studies have also shown physical activity to be an independent predictor of the development of depressive symptoms. In the National Health and Nutrition Education Survey I Epidemiologic Follow-Up Study, low levels of physical activity predicted depressive symptoms 8 years later in White women, with those reporting little to no physical activity twice as likely to develop depressive symptoms as those reporting moderate to high levels.

As for treatment for clinical depression, structured, mixed exercise programs result in a modest reduction in symptom severity. The effects of exercise appear to be comparable to those of behavioral or pharmacologic therapy. Proposed mechanisms for the effects of exercise on mood include increases in endorphin and monoamine levels, as well as social engagement and improvements in self-efficacy and self-esteem.

Impaired Cognition

There may be a positive effect of exercise on cognition. Numerous cross-sectional and longitudinal studies including the Nurse’s Health Study and the Mayo Clinic Study on Aging have found an association between higher levels of physical activity and both better cognitive test scores and reduced risk of cognitive impairment and dementia. Among 1200 older adults in the Framingham Study, a hazard ratio of 0.55 was found for incident all-cause dementia after 10 years of follow-up in participants reporting moderate to heavy physical activity compared to less active participants. Among those in the lowest quintile of physical activity, the hazard ratio for incident dementia was 1.45.

Results from exercise intervention studies have been mixed, although the balance of evidence supports moderate positive effects of exercise training on cognition in both cognitively normal and cognitively impaired individuals. In older adults without known cognitive impairment, 8 of 11 studies using aerobic exercise interventions found positive effects on cognitive function that coincided with improvements in maximal oxygen uptake (VO_2max). A meta-analysis of 16 trials in older patients with dementia found a significant positive effect on cognitive function with exercise training, although the authors emphasized caution given the substantial heterogeneity between trials.

Some studies have also reported cognitive benefits with resistance training alone, but the greatest cognitive effects were observed with mixed training paradigms. Exercise appears to improve function in multiple cognitive domains, with the strongest effects in executive control functions. Important areas for further study include determining the duration and intensity of exercise needed to realize cognitive benefits, and potential sex differences in the cognitive responses to exercise.

The bases for the exercise-associated improvements in cognition are presently an active area of investigation. Animal studies support a neuroprotective effect of exercise through promotion of neuroplasticity, increases in brain-derived neurotrophic factor and enhanced neurogenesis.

Sleep Disorders

Age effects on sleep and sleep disorders are covered in Chapter 44.

Physical activity and regular exercise are beneficial for sleep in older adults. Higher levels of cardiorespiratory fitness and physical activity in older adults are associated with better self-reported sleep quality. For instance, objectively measured indices of sleep quality (eg, sleep onset latency, wake time after sleep onset, sleep efficiency) are better in physically fit older men compared to sedentary controls, and higher levels of physical activity are protective against insomnia in older adults. Although few longitudinal exercise studies have specifically focused on older adults, a systematic review and meta-analysis of six studies in adults older than 40 years demonstrated that 10 to 16 weeks of aerobic exercise has positive effects on self-reported sleep quality measured using the Pittsburgh Sleep Quality Index.

It appears that slow wave sleep (SWS), which plays a role in the restorative functions of sleep, is particularly sensitive to exercise training. Older physically fit men have more SWS than sedentary older men, and exercise training increases SWS in older men and women. One longer-term study (12 months) demonstrated that in older adults with mild to moderate sleep problems, exercise was associated with decreases in stage 1 sleep, increases in stage 2 sleep, and fewer awakenings.

There remain many questions regarding the effects of exercise on sleep in older adults. For example, most studies in older adults have examined the effects of aerobic training, but at least one study has shown that progressive resistance training can improve subjective measures of sleep quality. It is not known if aerobic, resistance, or a combination is most effective for improving sleep. The effects of exercise intensity have not been established, but lower intensity activities such as yoga and Tai chi also improve self-reported measures of sleep quality. Similarly, lower-intensity exercise (eg, stretching and flexibility) was associated with greater improvements in self-reported sleep quality than higher-intensity exercise performed at 60% to 75% of maximal heart rate. The effects of frequency of exercise have also not been defined, but a study in older men (~64 years) showed that after a 16-week exercise training period, SWS increased on a day when exercise was performed, but not on a sedentary day. These findings suggest that physical activity should be done on most days of the week to maximize the benefits on sleep. Whether exercise has different effects in men and women is not known.

It should also be recognized that there may be a reciprocal relationship: poor sleep is associated with lower levels of physical activity. For example, in sample of subjects from the Healthy Women Study (~73 years), greater self-reported sleep efficiency and less sleep fragmentation were associated with higher physical activity levels the following day. Thus, there appears to be a circular association whereby increased physical activity improves sleep, and improved sleep facilitates greater physical activity levels.

Parkinson Disease

Exercise is associated with reduced mortality rate and with improvements in functional mobility and activities of daily living in individuals with Parkinson disease (see Chapter 61). Though data are limited, controlled trials of both resistance and aerobic training in individuals with Parkinson disease have demonstrated improvements in mobility, gait, and quality of life. The intensity of exercise required to realize benefits in Parkinson disease is an area of active investigation, as some studies have found greater improvements with a higher dose of exercise, while others have not.

Despite impaired force production and increased fatigability, individuals with Parkinson disease are able to participate safely and effectively in high-intensity resistance exercise, and appear to derive benefits similar to those in neurologically healthy adults. In one study, 12 weeks of high-force eccentric resistance training in adults with Parkinson disease was associated with a 6% increase in muscle hypertrophy, a 24% increase in torque, and an 18% improvement in 6-minute walk time compared to a standard exercise program. Aerobic exercise interventions—mainly treadmill exercise—consistently improve gait, mobility, and quality of life.

Stroke

Stroke is a leading cause of disability in older adults, with 20% to 25% of stroke survivors requiring at least some assistance with activities of daily living (see Chapter 62). These functional deficits predispose patients to a sedentary lifestyle, further increasing the risk of stroke and CVD, the leading causes of death among stroke survivors. Physical rehabilitation in stroke patients has traditionally focused on the first few months after the event, as prevailing wisdom held that further functional improvements were unlikely after this time. However, improvements in aerobic capacity and sensorimotor function can be achieved with continued rehabilitation. Physical activity and exercise recommendations for stroke survivors from the American Heart Association identify three primary goals: (1) preventing complications from prolonged inactivity; (2) decreasing the risk of recurrent stroke and cardiovascular events; and (3) increasing aerobic fitness. Specific recommendations for aerobic exercise and strength training are similar to those recommended for all adults. In addition, incorporation of stretching and balance/coordination activities is recommended to prevent muscle contractures, and to improve the ability to safely perform activities of daily living.

RISKS ASSOCIATED WITH EXERCISE

Despite the overwhelming evidence that exercise confers multiple benefits and can be performed safely even in frail older adults, concerns about potential injury and other adverse events are common among patients and health care providers. These fears may prevent patients from engaging in the amount and intensity of exercise needed to realize health benefits, thus presenting a potential barrier to increasing physical activity levels.

“Overuse” injuries involving soft tissues are by far the most common and are likely to increase with advancing age. Eccentric exercise (eg, lowering a weight that has been lifted) may predispose to excess muscle injury. Appropriate warm-up and cool-down periods, as well as emphasis on stretching and flexibility, are likely to be especially important in reducing soft-tissue injury in an older population.

The prevalence of asymptomatic coronary artery disease is higher in older compared to younger adults, and there is a transient increase in the risk of sudden death occurring during a bout of vigorous exercise, especially in previously sedentary individuals. However, the small increased risk of a cardiovascular event with exercise is clearly outweighed by the reduction in risk during the nonexercising period of the day. Thus, the overall risk of sudden death in active men is only 30% of that in sedentary men. Furthermore, there is lower cardiovascular-related and overall mortality in active individuals.

In older patients with diabetes mellitus, careful attention to the possibility of exercise-induced hypoglycemia is critical because of the sustained improvement in insulin sensitivity for 24 to 48 hours following vigorous exercise. Meticulous foot care and supportive, well-fitted shoes are also important for the exercising diabetic patient. Patients with proliferative retinopathy should avoid anaerobic (specifically isometric) exercise, such as power lifting, because of the increased ocular and systemic pressure occurring with the Valsalva maneuver.

In the past, a pre-exercise assessment, including a complete history and physical examination, and an exercise stress test were recommended for adults older than 60 before vigorous exercise. Such an evaluation is expensive and could present a significant barrier to exercise. Furthermore, there are little data to substantiate this recommendation. Current recommendations suggest that asymptomatic individuals who plan to exercise at moderate intensity do not need screening before initiating an activity program. The geriatric medicine axiom of “start low and go slow” should be applied to beginning a safe physical activity program. It is appropriate for patients to notify their health care providers of their intent to begin an exercise program, because adjustments in medications or dosages may be necessary. The health care provider can also work with the individual to tailor the exercise program to the individual’s abilities and be a source of ongoing support and encouragement.

RECOMMENDATIONS

There is now ample evidence that older adults can safely engage in both aerobic and resistance exercise training, and that exercise has beneficial effects on numerous important health-related end points in this population. Despite these acknowledged benefits, older adults are the least physically active age group. Potential barriers to exercise in older adults include perceptions of safety, chronic conditions and physical limitations, and access to exercise programs or facilities.

Consensus recommendations for physical activity in older adults are summarized in Table 54-3 and were updated in 2018 by the Department of Health and Human Services (DHHS) in the Physical Activity Guidelines for Americans, 2nd edition. The DHHS guidelines stress the importance of avoiding sedentary behavior, and that any amount of physical activity provides some health benefits. The specific modifications for older adults include: (1) being as physically active as their conditions allow if the target of 150 min/week is not possible because of chronic conditions; (2) engaging in balance exercises for individuals at risk of falling; (3) determining the level of effort for physical activity relative to level of fitness; and (4) understanding how chronic conditions may affect the ability to safely engage in regular physical activity. Key to recommendations for exercise in older adults is the need to individualize the program of physical activity. While there is a dose-response relationship between the intensity of exercise and the improvement in most outcome measures, significant cardiovascular and metabolic improvements can be obtained when less intense exercise is maintained over sufficiently long periods of time. Less intense exercise regimens may be more acceptable to some older individuals and appear to make long-term compliance more likely. Low-intensity programs may be necessary in frail populations, such as those with stroke, heart failure, and chronic lung disease, in which more intensive exercise is not tolerated. While multiple short bouts of exercise (at least 10 minutes each) may be effective in improving certain outcome measures, longer sessions remain preferable if these can be tolerated.

Because the physical activity goals may seem daunting, especially for inactive older adults, specific instructions are more helpful than general advice to “increase physical activity.” Provision of written exercise prescriptions from health care providers increases activity levels among previously sedentary adults. In addition, an increasing array of technologies allows individuals to set activity goals and to monitor and track activity in real time.

Changes in lifestyle are difficult to maintain at any age, and recidivism rates for exercise programs are high. This problem may be reduced by: (1) careful attention to warm-up periods and slow progression in an effort to reduce early injuries; (2) enthusiastic leadership; (3) regular assessment of improvement with personalized feedback and praise; (4) spousal and family support for participation; (5) flexible goals (time rather than distance) set by the participant; and (6) use of distraction techniques such as music.