EFFECT OF AROMATASE INHIBITION ON BONE TURNOVER IN OLDER MEN

根据对雌激素受体基因缺陷或芳香酶缺乏症患者的研究，有强有力的证据表明雌激素在调节男性骨转换方面起到了作用。所有患者均表现为身材高大，骨盆关闭延迟，骨密度降低，骨转换增加。一些观察性研究表明，血清雌激素水平比血清睾酮水平更能预测骨密度。因此，雌激素很可能会影响男性一生中的骨转换。我们之前已经表明，在14名65岁以上的男性中，有9人对每天1毫克的17-b微粒化雌二醇治疗9周有反应，骨吸收减少了15%-50%。因此，我们假设老年男性会表现出对芳香酶抑制反应的骨吸收增加。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酶抑制剂，已被证明可以阻止乳腺癌女性患者雄激素向雌激素的转化。每个人都充当自己的控制者。在治疗前和治疗期间每隔3周检测骨吸收指标，包括N端和C端胶原交联物(NTX、CTX)和骨形成标志物骨特异性碱性磷酸酶(BSAP)。分别于基线和9周抽血测定雌二醇(E_2)、雌酮(E_1)、睾酮(T)、性激素结合球蛋白(SHBG)和甲状旁腺激素(PTH)水平。

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.