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Key Clinical Updates in Osteoporosis

Doses of vitamin D3 above 4000 international units daily in adults are generally not advised (except in patients with intestinal malabsorption), since gastrointestinal side effects or hypercalcemia may occur.

Vitamin D should not be taken with topical calcipotriene to avoid hypercalcemia.

The effects of denosumab on bone wane quickly after 6 months and patients can experience a dramatic increased risk of multiple vertebral fractures within 1–2 years following discontinuation of denosumab.

Therefore, denosumab must be given on-schedule without drug holidays.

Denosumab should not be discontinued without substituting another anti-resorptive agent (bisphosphonate, estradiol, or SERM) or other therapy.

ESSENTIALS OF DIAGNOSIS

  • Fracture propensity of spine, hip, pelvis, and wrist.

  • Asymptomatic until a fracture has occurred.

  • Serum PTH, calcium, phosphorus, and alkaline phosphatase usually normal.

  • Serum 25-hydroxyvitamin D levels often low as a comorbid condition.

GENERAL CONSIDERATIONS

Osteoporosis is a skeletal disorder characterized by a loss of bone matrix (osteoid) that reduces bone integrity and bone strength, predisposing to an increased risk of fragility and fracture. In the United States, osteoporosis causes over 1.5 million fractures annually. White women age 50 years and older (who do not receive estrogen replacement) have a 46% risk of sustaining an osteoporotic fracture during the remainder of their lives. Vertebral fractures are the most common fracture; they are usually diagnosed incidentally on radiographs or CT scanning.

Largely due to a reduction in smoking, the age-adjusted risk for hip fracture has declined in the United States in recent years. However, the risk for fragility fractures remains high and varies with ethnicity, sex, and age. The lifetime risk of hip fracture is 12.1% in White women and 4.6% in White men. The risks are lower in Hispanic women and men and lower yet in Chinese women and men (with similar gender differences). Blacks also have a lower risk for fracture due to higher BMD and hip morphology that is less fracture-prone. There is much less ethnic variability for vertebral fractures. The prevalence of vertebral fractures in women older than 65 years is 70% for White women, 68% for Japanese women, 55% for Mexican women, and 50% in Black women.

Osteoporosis is caused by a reduction and disarray of bone's microarchitectural organic collagenous matrix, which normally accounts for about 40% of bone mass and provides bone's tensile strength. Inorganic calcium and phosphate compounds, largely calcium hydroxyapatite, mineralize the available collagenous bone matrix and normally provide about 60% of bone mass and most of bone's compressive strength.

Osteoporosis can be caused by a variety of factors (Table 26–10). The most common causes include aging, sex hormone deficiency, alcohol use disorder, cigarette smoking, long-term proton pump inhibitor therapy, and high-dose corticosteroid administration. Women who chronically consume cola beverages are at increased risk for osteoporosis of the hip. Hypogonadal men frequently develop osteoporosis. Anti-androgen therapy for prostate cancer can cause osteoporosis, ...

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