Hypogonadal Bone Loss

Estrogen deficiency at menopause is an important cause of bone loss and subsequent fractures. Perimenopausal women experience an accelerated phase of bone loss lasting five years or more that accounts for a substantial proportion of their lifetime bone loss.43 This accelerated phase is associated with a high rate of bone turnover (there is an increase in bone formation but an even greater increase in bone resorption) that can be prevented by estrogen replacement therapy (ERT). Men do not undergo the equivalent of menopause, but gonadal function does decrease in some elderly men, and overt male hypogonadism often is associated with vertebral fractures.28

A large number of trials have compared estrogens with placebos and other treatments to determine their effect on bone mass, and nearly all indicate that estrogens are more effective in maintaining bone mass.17 For example, in one randomized controlled trial of three groups of women followed from six weeks, three years, or six years after oophorectomy, estrogen significantly retarded bone loss for as long as prescribed but at least ten years.22 Recent data suggest that ERT may be effective in slowing bone loss up to the age of 70.39 Because the effect of treatment is to reduce bone resorption, however, postmenopausal ERT can slow bone loss, but it cannot restore the biomechanical competence of the skeleton to normal once a substantial amount of bone has been lost.34 Because lost bone is essentially irreplaceable, emphasis in women 50 to 69 years of age must be on preserving existing bone mass. Greater benefits are achieved with earlier treatment because bone mass is maintained at a higher level.

Estrogens also appear to be effective in preventing fractures. One randomized controlled trial showed that only 4 percent of oophorectomized women on ERT lost height compared with 38 percent of women who were not being treated; almost 90 percent of the latter group with height loss had evidence of vertebral fractures.23 Although randomized trials of ERT for prevention of hip fracture are less feasible owing to the long delay between menopause and the typical age at which these fractures occur, case-control studies consistently show about a 50 percent reduction in hip and Colles' fractures with long-term ERT.17

To intervene by preserving bone density before irreversible bone loss has occurred, patients must be stratified on the basis of fracture risk so that high-risk individuals can be identified. The bone density of any specific individual cannot be determined without direct measurement.17 A variety of noninvasive bone mass measurement techniques can be used (Table 6-2), including single-photon absorptiometry



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