Joint pain from OA is activity-related. Pain comes on either during or just after joint use and then gradually resolves. Examples include knee or hip pain with going up or down stairs, pain in weight-bearing joints when walking, and, for hand OA, pain when cooking. Early in disease, pain is episodic, triggered often by a day or two of overactive use of a diseased joint, such as a person with knee OA taking a long run and noticing a few days of pain thereafter. As disease progresses, the pain becomes continuous and even begins to be bothersome at night. Stiffness of the affected joint may be prominent, but morning stiffness is usually brief (<30 min).
In knees, buckling may occur, in part, due to weakness of muscles crossing the joint. Mechanical symptoms, such as buckling, catching, or locking, could also signify internal derangement, such as meniscal tears, and need to be evaluated. In the knee, pain with activities requiring knee flexion, such as stair climbing and arising from a chair, often emanates from the patellofemoral compartment of the knee, which does not actively articulate until the knee is bent ∼35°.
The goals of the treatment of OA are to alleviate pain and minimize loss of physical function. To the extent that pain and loss of function are consequences of inflammation, of weakness across the joint, and of laxity and instability, the treatment of OA involves addressing each of these impairments. Comprehensive therapy consists of a multimodality approach including nonpharmacologic and pharmacologic elements.
Patients with mild and intermittent symptoms may need only reassurance or nonpharmacologic treatments. Patients with ongoing, disabling pain are likely to need both nonpharmaco- and pharmacotherapy.
Treatments for knee OA have been more completely evaluated than those for hip and hand OA or for disease in other joints. Thus, while the principles of treatment are identical for OA in all joints, we shall focus below on the treatment of knee OA, noting specific recommendations for disease in other joints, especially when they differ from those for disease in the knee.
Since OA is a mechanically driven disease, the mainstay of treatment involves altering loading across the painful joint and improving the function of joint protectors, so they can better distribute load across the joint. Ways of lessening focal load across the joint include
(1) avoiding activities that overload the joint, as evidenced by their causing pain;
(2) improving the strength and conditioning of muscles that bridge the joint, so as to optimize their function; and
(3) unloading the joint, either by redistributing load within the joint with a brace or a splint or by unloading the joint during weight bearing with a cane or a crutch.
The simplest effective treatment for many patients is to avoid activities that precipitate pain. For example, for the middle-aged patient whose long-distance running brings on symptoms of knee OA, a less demanding form of weight-bearing activity may alleviate all symptoms. For an older person whose daily constitutionals up and down hills bring on knee pain, routing the constitutional away from hills might eliminate symptoms.
Each pound of weight increases the loading across the knee three- to sixfold. Weight loss may have a commensurate multiplier effect, unloading both knees and hips. Thus, weight loss, especially if substantial, may lessen symptoms of knee and hip OA.
In hand joints affected by OA, splinting, by limiting motion, often minimizes pain for patients with involvement either in the base of the thumb or in the DIP or proximal IP joints. With an appropriate splint, function can often be preserved. Weight-bearing joints such as knees and hips can be unloaded by using a cane in the hand opposite to the affected joint for partial weight bearing. A physical therapist can help teach the patient how to use the cane optimally, including ensuring that its height is optimal for unloading. Crutches or walkers can serve a similar beneficial function.
Osteoarthritic pain in knees or hips during weight bearing results in lack of activity and poor mobility and, because OA is so common, the inactivity that results represents a public health concern, increasing the risk of cardiovascular disease and of obesity. Aerobic capacity is poor in most elders with symptomatic knee OA, worse than others of the same age.
The development of weakness in muscles that bridge osteoarthritic joints is multifactorial in etiology. First, there is a decline in strength with age. Second, with limited mobility comes disuse muscle atrophy. Third, patients with painful knee or hip OA alter their gait so as to lessen loading across the affected joint, and this further diminishes muscle use. Fourth, “arthrogenous inhibition” may occur, whereby contraction of muscles bridging the joint is inhibited by a nerve afferent feedback loop emanating in a swollen and stretched joint capsule; this prevents maximal attainment of voluntary maximal strength. Since adequate muscle strength and conditioning are critical to joint protection, weakness in a muscle that bridges a diseased joint makes the joint more susceptible to further damage and pain. The degree of weakness correlates strongly with the severity of joint pain and the degree of physical limitation. One of the cardinal elements of the treatment of OA is to improve the functioning of muscles surrounding the joint.
For knee and hip OA, trials have shown that exercise lessens pain and improves physical function. Most effective exercise regimens consist of aerobic and/or resistance training, the latter of which focuses on strengthening muscles across the joint. Exercises are likely to be effective, especially if they train muscles for the activities a person performs daily. Some exercises may actually increase pain in the joint; these should be avoided, and the regimen needs to be individualized to optimize effectiveness and minimize discomfort. Range-of-motion exercises, which do not strengthen muscles, and isometric exercises that strengthen muscles, but not through range of motion, are unlikely to be effective by themselves. Isokinetic and isotonic strengthening (strengthening that occurs when a person flexes or extends the knees against resistance) have been shown consistently to be efficacious. Low-impact exercises, including water aerobics and water resistance training, are often better tolerated by patients than exercises involving impact loading, such as running or treadmill exercises. A patient should be referred to an exercise class or to a therapist who can create an individualized regimen, and then an individualized home-based regimen can be crafted.
There is no strong evidence that patients with hand OA benefit from therapeutic exercise, although for any patient with OA, individualized exercise programs should be tried. Adherence to exercise over the long term is the major challenge to an exercise prescription. In trials involving patients with knee OA, who are interested in exercise treatment, a third to over a half of patients stopped exercising by 6 months. Less than 50% continued regular exercise at 1 year. The strongest predictor of continued exercise in a patient is a previous personal history of successful exercise. Physicians should reinforce the exercise prescription at each clinic visit, help the patient recognize barriers to ongoing exercise, and identify convenient times for exercise to be done routinely. The combination of exercise with calorie restriction is especially effective in lessening pain.
One clinical trial has suggested that, among those with very early OA, participating in a strengthening and multimodality exercise program led to improvement in cartilage biochemistry, as evidenced by MRI imaging. There is little other evidence, however, that strengthening or other exercise has an effect on joint structure.
Correction of Malalignment
Malalignment in the frontal plane (varus-valgus) markedly increases the stress across the joint, which can lead to progression of disease and to pain and disability (Fig. 332-5). Correcting malalignment, either surgically or with bracing, may relieve pain in persons whose knees are maligned. Malalignment develops over years as a consequence of gradual anatomic alterations of the joint and bone, and correcting it is often very challenging. One way is with a fitted brace, which takes an often varus osteoarthritic knee and straightens it by putting valgus stress across the knee. Unfortunately, many patients are unwilling to wear a realigning knee brace, plus in patients with obese legs, braces may slip with usage and lose their realigning effect. They are indicated for willing patients who can learn to put them on correctly and on whom they do not slip.
Other ways of correcting malalignment across the knee include the use of orthotics in footwear. Unfortunately, while they may have modest effects on knee alignment, trials have heretofore not demonstrated efficacy of a lateral wedge orthotic vs. placebo wedges.
Pain from the patellofemoral compartment of the knee can be caused by tilting of the patella or patellar malalignment with the patella riding laterally (or less often, medially) in the femoral trochlear groove. Using a brace to realign the patella, or tape to pull the patella back into the trochlear sulcus or reduce its tilt, has been shown, when compared to placebo taping in clinical trials, to lessen patellofemoral pain. However, patients may find it difficult to apply tape, and skin irritation from the tape is common. Commercial patellar braces may be a solution, but they have not been tested.
While their effect on malalignment is questionable, neoprene sleeves pulled to cover the knee lessen pain and are easy to use and popular among patients. The explanation for their therapeutic effect on pain is unclear.
In patients with knee OA, acupuncture produces modest pain relief compared to placebo needles and may be an adjunctive treatment.
While nonpharmacologic approaches to therapy constitute its mainstay, pharmacotherapy serves an important adjunctive role in OA treatment. Available drugs are administered using oral, topical, and intraarticular routes.
Acetaminophen, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), and COX-2 Inhibitors
Acetaminophen (paracetamol) is the initial analgesic of choice for patients with OA in knee, hip, or hands. For some patients, it is adequate to control symptoms, in which case more toxic drugs such as NSAIDs can be avoided. Doses up to 1 g 4 times daily can be used (Table 332-1).
Table 332-1 Pharmacologic Treatment for Osteoarthritis |Favorite Table|Download (.pdf)
Table 332-1 Pharmacologic Treatment for Osteoarthritis
|Acetaminophen||Up to 1 g qid||Prolongs half-life of warfarin|
|Oral NSAIDs and COX-2 inhibitorsa||Take with food. Increased risk of myocardial infarction and stroke for some NSAIDs and especially COX-2 inhibitors. High rates of gastrointestinal side effects, including ulcers and bleeding, occur. Patients at high risk for gastrointestinal side effects should also take either a proton pump inhibitor or misoprostol.b There is an increased gastrointestinal side effects or bleeding when taken with acetylsalicylic acid. Can also cause edema and renal insufficiency.|
|Naproxen||375–500 mg bid|
|Salsalate||1500 mg bid|
|Ibuprofen||600–800 mg 3–4 times a day|
|Topical NSAIDs||Rub onto joint. Few systemic side effects. Skin irritation common.|
|Diclofenac Na 1% gel||4gm qid (for knees)|
|Opiates||Various||Common side effects include dizziness, sedation, nausea or vomiting, dry mouth, constipation, urinary retention, and pruritis. Respiratory and central nervous system depression can occur.|
|Capsaicin||0.025–0.075% cream 3–4 times a day||Can irritate mucous membranes.|
|Hyaluronans||Varies from 3–5 weekly injections depending on preparation||Mild to moderate pain at injection site. Controversy exists re: efficacy.|
NSAIDs are the most popular drugs to treat osteoarthritic pain. They can be administered either topically or orally. In clinical trials, oral NSAIDs produce ∼30% greater improvement in pain than high-dose acetaminophen. Occasional patients treated with NSAIDs experience dramatic pain relief, whereas others experience little improvement. Initially, NSAIDs should be administered topically or taken orally on an “as needed” basis because side effects are less frequent with low intermittent doses, which may be highly efficacious. If occasional medication use is insufficiently effective, then daily treatment may be indicated, with an anti-inflammatory dose selected (Table 332-1). Patients should be reminded to take low-dose aspirin and ibuprofen at different times to eliminate a drug interaction.
NSAIDs taken orally have substantial and frequent side effects, the most common of which is upper gastrointestinal toxicity, including dyspepsia, nausea, bloating, gastrointestinal bleeding, and ulcer disease. Some 30–40% of patients experience upper gastrointestinal (GI) side effects so severe as to require discontinuation of medication. To minimize the risk of nonsteroidal-related GI side effects, patients should not take two NSAIDs, and should take medications after food; if risk is high, patients should take a gastroprotective agent, such as a proton pump inhibitor. Certain oral agents are safer to the stomach than others including nonacetylated salicylates and nabumetone. Major NSAID-related GI side effects can occur in patients who do not complain of upper GI symptoms. In one study of patients hospitalized for GI bleeding, 81% had no premonitory symptoms.
Because of the increased rates of cardiovascular events associated with cyclooxygenase 2 (COX-2) inhibitors and with some conventional NSAIDs such as diclofenac, many of these drugs are not appropriate long-term treatment choices for older persons with osteoarthritis, especially those at high risk of heart disease or stroke. The American Heart Association has identified rofecoxib and all other COX-2 inhibitors as putting patients at high risk, although low doses of celecoxib, such as 200 mg/d, may not be associated with an elevation of risk. The only conventional NSAID that appears safe from a cardiovascular perspective is naproxen, but it does have gastrointestinal toxicity.
There are other common side effects of NSAIDs, including the tendency to develop edema, because of prostaglandin inhibition of afferent blood supply to glomeruli in the kidneys and, for similar reasons, a predilection toward reversible renal insufficiency. Blood pressure may increase modestly in some NSAID-treated patients.
With the approval by the U.S. Food and Drug Administration of topical diclofenac and the availability of these agents in Europe, clinicians have a choice of administration modality for anti-inflammatory drugs. NSAIDs can be placed into a gel or topical solution with another chemical modality that enhances penetration of the skin barrier. When absorbed through the skin, plasma concentrations are an order of magnitude lower than with the same amount of drug administered orally or parenterally. However, when these drugs are administered topically in proximity to a superficial joint, (knees, hands, but not hips), the drug can be found in joint tissues such as the synovium and cartilage. Trial results have varied but generally have found that topical NSAIDs are slightly less efficacious than oral agents, but have far fewer gastrointestinal and systemic side effects. Unfortunately, topical NSAIDs often cause local skin irritation where the medication is applied, inducing redness, burning or itching in up to 40 percent of patients (see Table 332-1).
Intraarticular Injections: Glucocorticoids and Hyaluronic Acid
Since synovial inflammation is likely to be a major cause of pain in patients with OA, local anti-inflammatory treatments administered intraarticularly may be effective in ameliorating pain, at least temporarily. Glucocorticoid injections provide such efficacy, but work better than placebo injections for only 1 or 2 weeks. This may be because the disease remains mechanically driven and, when a person begins to use the joint, the loading factors that induce pain return. Glucocorticoid injections are useful to get patients over acute flares of pain and may be especially indicated if the patient has coexistent OA and crystal deposition disease, especially from calcium pyrophosphate dihydrate crystals (Chap. 333). There is no evidence that repeated glucocorticoid injections into the joint are dangerous.
Hyaluronic acid injections can be given for treatment of symptoms in knee and hip OA, but there is controversy as to whether they have efficacy vs. placebo (Table 332-1).
Optimal therapy for OA is often achieved by trial and error, with each patient having idiosyncratic responses to specific treatments. When medical therapies have failed and the patient has an unacceptable reduction in their quality of life and ongoing pain and disability, then at least for knee and hip OA, total joint arthroplasty is indicated.
For knee OA, several operations are available. Among the most popular surgeries, at least in the United States, is arthroscopic debridement and lavage. Randomized trials evaluating this operation have showed that its efficacy is no greater than that of sham surgery or no treatment for relief of pain or disability. Even mechanical symptoms such as buckling, which are extremely common in patients with knee OA, do not respond to arthroscopic debridement. Arthroscopic meniscectomy is indicated for acute meniscal tears in which symptoms such as locking and acute pain are clearly related temporally to a knee injury that produced the tear.
For patients with knee OA isolated to the medial compartment, operations to realign the knee to lessen medial loading can relieve pain. These include a high tibial osteotomy, in which the tibia is broken just below the tibial plateau and realigned so as to load the lateral, nondiseased compartment, or a unicompartmental replacement with realignment. Each surgery may provide the patient with years of pain relief before they require a total knee replacement.
Ultimately, when the patient with knee or hip OA has failed medical treatment modalities and remains in pain, with limitations of physical function that compromise the quality of life, the patient should be referred for total knee or hip arthroplasty. These are highly efficacious operations that relieve pain and improve function in the vast majority of patients. Currently failure rates are ∼1% per year, although these rates are higher in obese patients. The chance of surgical success is greater in centers where at least 25 such operations are performed yearly or with surgeons who perform multiple operations annually. The timing of knee or hip replacement is critical. If the patient suffers for many years until their functional status has declined substantially, with considerable muscle weakness, postoperative functional status may not improve to a level achieved by others who underwent operation earlier in their disease course.
Chondrocyte transplantation has not been found to be efficacious in OA, perhaps because OA includes pathology of joint mechanics, which is not corrected by chondrocyte transplants. Similarly, abrasion arthroplasty (chondroplasty) has not been well studied for efficacy in OA, but it produces fibrocartilage in place of damaged hyaline cartilage. Both of these surgical attempts to regenerate and reconstitute articular cartilage may be more likely to be efficacious early in disease when joint malalignment and many of the other noncartilage abnormalities that characterize OA have not yet developed.