As the life expectancy of women has reached the mid-80s, osteoporosis has taken on epidemic proportions, especially among white women in industrialized societies. In the United States, the prevalence of low bone density in older adults approaches 50%; a woman’s risk for an osteoporotic fracture by age 80 years is approximately 40% (several times greater than the risk for breast cancer). The risk for death after a hip fracture is nearly 25%. The disability and expense attributable to the consequences of osteoporosis are enormous and growing.

More fractures occur in individuals in the low bone mass or osteopenic category (T-score between -1.0 and -2.5 on bone density measurement) than the osteoporosis category because there are many more individuals in that category. Thus, it is important to assess all risk factors and not rely just on bone mineral density (BMD) measurements.

The National Osteoporosis Risk Assessment Study examined risk factors of low BMD and the relationship of low BMD to fracture risk in a large population-based cohort of postmenopausal women (mean age 64 years). Age was the greatest risk factor. Women of ages 70 to 74 years, 75 to 79 years, and older than 80 years had a 9.5-fold, 14.3-fold, and 22.6-fold risk of osteoporosis, respectively. Other risk factors for osteoporosis included body mass index below the 25th percentile (<23 kg/m²), maternal history of fracture, and personal history of fracture during adulthood. Osteoporosis was associated with a fourfold increase in fracture rate (any site) at 1 year. After controlling for BMD, all of these risk factors were independently associated with fracture risk (Table 144-1).

In addition, a number of contributing risk factors have emerged. These include lifelong inadequate intake of calcium, white race, inadequate physical activity, early menopause (onset before the age of 45 years), cigarette smoking, and excessive intake of alcohol. All may predispose a woman to a lower bone mass and osteoporotic fractures with aging. Women in whom osteoporosis does not develop may have a larger skeletal mass, which can be increased through physical activity and calcium supplementation. Estrogen use and African American race are protective factors.

Medical conditions that are secondary causes of osteoporosis include Cushing syndrome, exogenous glucocorticoid administration, rheumatoid arthritis, prolonged heparin therapy, thyrotoxicosis (including excessive thyroid replacement therapy), hypogonadism, hyperprolactinemia, anorexia nervosa, and hyperparathyroidism. However, these diseases account for only a small percentage of cases of osteoporosis.

The resorption and formation of bone is a continuous process throughout life. Under physiologic circumstances, the rates of these processes are equal and coupled. Skeletal mass is usually maximal by age 35 years and declines in women after age 40 years and in men after age 50 years, when the rate of new bone formation no longer equals the rate of bone resorption. The rate of decline in skeletal mass is most rapid in women within 2 years of menopause and can average 2% to 4% a year during the first several years after menopause. Bone mineral content may decline by as much as 25% to 33% during this
period. Afterward, loss continues, but at a slower rate (1% or less a year). The areas of greatest loss include the femoral neck and lumbar vertebrae, sites rich in trabecular bone and subject to future fracture. Cortical bone, comprising 80% of skeletal bone, is lost less rapidly.

The progressive decline in skeletal mass becomes clinically manifest when fractures are sustained spontaneously or after minimal trauma. Loss of height and developing kyphosis may indicate vertebral compression fractures have occurred. Fractures most commonly occur in the thoracic and lumbar vertebrae, hip, humerus, and wrist. The clinical course and frequency of fractures in individual patients are hard to predict.

There are now many therapies that have been shown to reduce bone loss, increase bone density, and reduce the risk of fracture. Estrogen replacement can prevent bone loss and even lead to skeletal accretion (see Chapter 164). Observational studies and the prospective Women’s Health Initiative have noted a 35% to 50% reduction in hip, wrist, and vertebral fractures in women who have used estrogen for at least 5 years after menopause. However, if estrogen is discontinued, bone loss rapidly ensues, and it is difficult to reverse the significant bone loss that occurs in the first few years of menopause. Bisphosphonates (e.g., alendronate, risedronate, ibandronate, and zoledronic acid) prevent bone loss, increase bone density, and reduce fracture risk in osteoporotic patients by up to 70%. Selective estrogen receptor modulators (e.g., raloxifene) also halt bone resorption, modestly increase BMD, and reduce spine fracture risk. Teriparatide, an anabolic agent, and denosumab, an antiresorptive agent and a human monoclonal antibody to RANKL, can prevent bone loss, increase bone density, and reduce fracture risk. Calcium supplementation with vitamin D helps to preserve cortical bone mass but does not prevent bone loss to the degree that estrogen or other therapies do.