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Osteoporosis is characterized by abnormally low bone mass, micro-architectural deterioration of bone tissue leading to increased bone fragility, and a consequent increase in fracture risk.(1) The term osteoporosis is widely used clinically to mean generalized loss of bone, or osteopenia, accompanied by relatively atraumatic fractures of the spine, wrist, hips, or ribs. It is manifested clinically as fractures, and, on noninvasive quantitative imaging tests, as low bone density.
Osteoporotic fractures, particularly in aging women, represent a major health problem in industrialized nations. In the United States, approximately 150,000 hip fractures occur annually in women over age 65, with 15 percent to 25 percent of these women experiencing excess mortality or needing long-term nursing home care.(2) Osteoporotic vertebral crush fractures, manifested by back pain, loss of height, and decreased ambulation are present in 5 percent to 10 percent of women by age 60 and 40 percent by age 80.(3)
It is convenient to consider type I and type II osteoporosis: type I is associated with estrogen loss in women and androgen loss in men;(4) type II is the gradual age-related loss of bone mass that occurs in both sexes.(5) Type I osteoporosis is associated with increased bone turnover; resorption exceeds formation, with disproportionate loss of trabecular compared to cortical bone. These individuals are likely to experience fractures of the distal radius, vertebrae, ribs, and pelvic bones, and are usually women between 55 and 70 years of age. Type II osteoporosis is associated with loss of differentiated bone cells from stem cell precursors, resulting in predominant cortical bone loss and predisposition to hip fracture; most of these individuals are over 70 years old, and female predominance is less striking.(6)
Although bone turnover rates decrease progressively with age, bone formation is decreased to a slightly greater degree than is resorption, probably because resorption rates increase, resulting in a gradual net loss of bone. A variety of hypotheses regarding the nature of this pattern have been suggested, including relative osteoblast failure, calcium and vitamin D deficiencies related to dietary change, decreased efficiency of intestinal calcium absorption and renal calcium retention, and falling levels of calcitonin and estrogen in the face of rising levels of PTH.(7, 8) Thus, physiologic involutional osteopenia has multiple etiologic factors.(9) Pathologic osteopenia has additional etiologies and different phenotypic expressions in different individuals. For example, biopsies from men or women with mid-life symptomatic osteoporosis can contain a spectrum of changes, with some individuals showing inactive bone remodeling and others showing very high turnover rates.(10)
Diminished absorption of calcium by the intestine is a physiologic consequence of aging, although the reasons are unknown.(11, 12) In some women, this malabsorption becomes severe enough to add a component of hyperparathyroidism to their osteoporosis. Estrogen loss after menopause probably enhances bone resorption; androgenic hormones and some progestins, levels of which also decline with time, may have positive effects on bone mass. Premature menopause, occurring before the age of 45, is associated with rapid bone loss in some women.(11) Early menopause may be caused by the use of cytotoxic drugs in young women. Diminution in physical activity, in sunlight exposure, and dietary intake of calcium and vitamin D probably play important roles in the osteopenia of aging.
Several features of osteoporosis suggest a role for local factors in pathogenesis: (1) no systemic hormone plays an essential role; (2) differential bone loss occurs in different pa
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