EFFECT OF AROMATASE INHIBITION ON BONE TURNOVER IN OLDER MEN

基于雌激素受体遗传缺陷或芳香酶缺乏患者的发现，有强有力的证据表明雌激素在调节男性骨转换中起作用。所有患者均表现为身材高大，骨骺闭合延迟，骨密度降低，骨转换增加。几项观察性研究表明，血清雌激素水平比血清睾酮水平更能预测骨密度。因此，雌激素可能会影响男性一生的骨转换。我们之前的研究表明，14名65岁以上的男性中有9名接受了1毫克/天的17-b微细雌二醇9周的治疗，骨吸收减少了15-50%。因此，我们假设老年男性对芳香酶抑制的反应会增加骨吸收。为了验证这一假设，15名65岁以上的健康男性接受了2.0 mg/d的阿那曲唑治疗9周，阿那曲唑是一种芳香化酶抑制剂，已被证明可以阻止乳腺癌女性的雄激素向雌激素的转化。每个人都是自己控制自己。在基线和治疗期间每3周测量骨吸收标志物，包括N端和c端胶原交联（NTX， CTX）和骨形成标志物骨特异性碱性磷酸酶（BSAP）。激素水平包括雌二醇（E2）、雌酮（E1）、睾酮(T)、性激素结合球蛋白（SHBG）和甲状旁腺激素（PTH）在基线和第9周。

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.