EFFECT OF AROMATASE INHIBITION ON BONE TURNOVER IN OLDER MEN

芳香酶抑制对老年男性骨转换的影响

• 批准号: 6122683
• 负责人: PAMELA TAXEL
• 金额: $ 1.91万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122683
• 关键词: aromatase; bone density; bone fracture; bone metabolism; calcium metabolism; clinical research; drug screening /evaluation; enzyme inhibitors; hormone metabolism; hormone regulation /control mechanism; human old age (65+); human subject; human therapy evaluation; male; sex hormones; skeletal disorder chemotherapy; testosterone

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.

有强有力的证据表明雌激素在调节男性骨转换中的作用，这是基于对雌激素受体遗传缺陷或芳香化酶缺乏患者的发现。 所有患者均表现出身材高大、骨骺闭合延迟、骨密度降低和骨转换增加。 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。 我们以前已经证明，14名65岁以上的男性中有9名对17-B微粒化雌二醇1 mg/d治疗9周有反应，骨吸收减少15- 50%。 因此，我们假设老年男性对芳香化酶抑制剂的反应是骨吸收增加。为了验证这一假设，15名65岁以上的健康男性接受了9周的阿那曲唑治疗，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雄激素向雌激素的转化。 每个人都是自己的控制者。 在基线和治疗期间每3周测量一次骨吸收标志物，包括N-和C-末端胶原交联（NTX，CTX）和骨形成标志物骨特异性碱性磷酸酶（BSAP）。 在基线和第9周时测定激素水平，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）。