Effects of androgens, estrogens, and PTH on bone

描述（由申请人提供）： 该应用程序的目标是支持我作为临床研究者的个人发展，并帮助我培训未来的临床研究者。我的临床研究计划有4个主要研究领域：1）雄激素和雌激素在男性骨代谢中的作用，2）绝经过渡对骨代谢的影响（SWAN研究），3）PTH对男性和女性骨代谢的合成代谢作用，以及4）膳食磷酸盐对FGF23调节的影响。第一个领域包括许多已完成、正在进行和计划进行的研究。我们以前曾报道过性腺功能减退和性类固醇替代对GnRH缺乏男性、青春期延迟男性和成年期性腺功能减退男性的骨密度（BMD）的影响。我们还报道了预防前列腺癌患者性腺功能减退引起的骨丢失的新方法，并研究了雄激素和雌激素在男性骨代谢中的生理作用。在这个提议中，我们计划确定男性雄激素和雌激素与骨代谢之间的特定剂量反应关系。全国妇女健康研究（SWAN）是一项大型多中心、多种族研究，调查了妇女在更年期过渡期间的各种生理、内分泌、流行病学和心理社会问题。在SWAN中，我们最近描述了BMD和骨转换的新的种族模式，现在专注于BMD的纵向变化。我在SWAN的主要目标是评估绝经过渡期骨丢失的时间和卵巢老化的作用，并确定与不同骨丢失率相关的因素。我们小组对PTH的合成代谢作用有着长期的兴趣。我们发表了第一个使用PTH治疗人类的随机对照试验，最近报道阿仑膦酸钠降低PTH的合成代谢作用。在本提案中，我们将检查停止PTH后BMD的变化，PTH再治疗对骨代谢的影响，以及PTH剂量分级增加的影响。研究的第四个领域是探索FGF23的生理调节，一个假定的新描述的磷酸尿激素，膳食磷酸盐。如果我成功获得这个奖项，我将能够继续把我的大部分时间用于我的临床研究和指导。我目前指导3名学员（2名获得K23奖，1名获得NRSA），还有几名学员有兴趣加入我们的团队。目前的K24非常成功，使我能够追求自己的临床研究职业目标，并培养了一批有前途的年轻研究人员。如果没有K24的持续支持，我将需要增加我的临床活动，减少我的研究时间，并放弃对新临床研究者的培训。

DESCRIPTION (provided by applicant): The goal of this application is to support my personal development as a clinical investigator and to help me train future clinical investigators. My clinical research program has 4 major areas of investigation: 1) the roles of androgens and estrogens in bone metabolism in men, 2) effects of the menopause transition on bone metabolism (The SWAN Study), 3) anabolic effects of PTH on bone metabolism in men and women, and 4) effects of dietary phosphate on the regulation of FGF23. The first area encompasses many completed, ongoing, and planned studies. We have previously reported the effects of hypogonadism and sex steroid replacement on bone mineral density (BMD) in GnRH-deficient men, men with histories of delayed puberty, and men with adult-onset hypogonadism. We have also reported novel ways to prevent hypogonadism-induced bone loss in men with prostate cancer and have examined the physiological roles of androgens and estrogens in male bone metabolism. In this proposal we plan to determine the specific dose-response relationships between androgens and estrogens and bone metabolism in men. The Study of Women's Health Across the Nation (SWAN) is a large multicenter, multi-ethnic study investigating a wide range of physiologic, endocrinologic, epidemiologic, and psychosocial issues as women transition through the menopause. In SWAN we recently described novel ethnic patterns of BMD and bone turnover and are now focusing on longitudinal changes in BMD. My primary goals in SWAN are to assess the roles of chronological and ovarian aging in bone loss during the menopause transition and to identify factors associated with varying rates of bone loss. Our group has a long interest in anabolic effects of PTH. We published the first randomized, controlled trial using PTH therapy in humans and recently reported that alendronate reduces the anabolic actions of PTH. In this proposal we will examine the changes in BMD after stopping PTH, the effects of PTH re-treatment on bone metabolism, and effects of graded increases in PTH dosing. The fourth area of investigation is to explore the physiological regulation of FGF23, a putative newly described phosphaturic hormone, by dietary phosphate. If I am successful in obtaining this award, I will be able to continue t o devote the most of my time to my clinical research studies and mentoring. I currently mentor 3 trainees (2 with K23 Awards and 1 with an NRSA) and several additional trainees are interested in joining our group. The current K24 has been extremely successful in allowing me to pursue my own clinical research career goals and to train a group of promising young investigators. Without continued K24 support, I will need to increase my clinical activities, reduce my research time, and forego training of new clinical investigators.