FIGURE 6-2 Conceptual model of the pathogenesis of fractures related to osteoporosis. Source: Modified from B. L. Riggs, "Osteoporosis" in Cecil Textbook of Medicine, J. B. Wyngaarden and L. H. Smith, eds., 18th ed., W. B. Saunders, Philadelphia, Pa., 1988, pp. 1510-1515. Reprinted with permission.

the two processes are closely coupled so that bone mass remains stable until the early to middle thirties. With aging, however, bone formation does not keep pace with resorption, and bone mass gradually diminishes. Over the course of their life, women may lose a third of their original cortical (or compact) bone, which forms the shafts of limb bones and constitutes up to 80 percent of the skeleton.43 They may lose half of their trabecular (or cancellous) bone, which accounts for the remaining 20 percent and makes up the ends of the limb bones and most of the spine, pelvis, and other flat bones of the skeleton. Men lose about two-thirds of these amounts. This bone loss is the result of (1) age-related endogenous factors that occur universally in the population and account for the slow bone loss that occurs over life in both sexes; (2) an accelerated phase of bone loss associated with menopause in women and hypogonadism in a small number of men; and (3) factors that occur sporadically in the population and, when present, increase the rate of bone loss (e.g., certain medical and surgical diseases that produce "secondary" osteoporosis).43

This decline in bone mineral density (a pathogenic trait) leads to a disproportionately greater decrease in bone strength (asymptomatic disease) and to an increase in symptomatic disease (i.e., fractures). Because there are no symptoms until fractures occur, relatively few people are diagnosed in time for effective therapy to be administered, even though bone mineral density can be accurately assessed in vivo as a measure of fracture risk (see the appendix to this chapter). Population-based studies demonstrate a gradient of continuously increasing hip fracture incidence associated with declining bone

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