There is strong evidence for a role for estrogen in regulating bone turnover in men, based on findings in patients with genetic defects in the estrogen receptor or with aromatase deficiency. All exhibited tall stature, delayed epiphysial closure, decreased bone density and increased bone turnover. Several observational studies have demonstrated that serum estrogen levels are better predictors of Bone Mineral Density than serum testosterone levels. Thus, estrogen is likely to affect bone turnover in men throughout life. We have previously shown that 9 of 14 men over age 65 responded to 9 weeks of treatment with 1 mg/d of 17-b micronized estradiol, with a decrease of bone resorption of 15-50%. Therefore, we hypothesized that older men would show increased bone resorption in response to aromatase inhibition. To test this hypothesis, 15 healthy men over the age of 65 years were treated for 9 weeks with 2.0 mg/d of anastrozole, an aromatase inhibitor that has been shown to block the conversion of androgens to estrogens in women with breast cancer. Each man served as his own control. Markers of bone resorption including N- and C-terminal collagen crosslinks (NTX, CTX) and a marker of bone formation, bone specific alkaline phosphatase (BSAP), were measured at baseline and every 3 weeks during treatment. Hormone levels including estradiol (E2), estrone (E1), testosterone (T), sex-hormone binding globulin (SHBG), and parathyroid hormone (PTH) were drawn at baseline and 9 weeks.
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