EFFECT OF ANDROGEN REPLACEMENT ON BONE METABOLISM

骨质疏松症是人类面临的最重要的公共卫生问题之一 老龄化的美国人。虽然骨质疏松症在女性中更常见，但男性也 随着年龄的增长导致大量的骨质流失，老年男性有特定的年龄特征 髋部骨折的发生率和脊柱骨折的患病率 至少是女性的一半。雌激素缺乏症已被明确识别 作为女性骨质疏松症的主要危险因素，以及 骨骼上的雌激素一直是深入调查的对象 在最近几年。相比之下，关于雄激素对骨骼影响的数据是 目前相对稀少。尽管如此，由于衰老也与 随着性腺和肾上腺雄激素水平的显著下降， 越来越多的媒体报道和普遍认为睾丸激素或 脱氢表雄酮(DHEA)疗法可以预防或逆转一些 与年龄相关的变化，包括肌肉和骨量的恶化， 以及一些与年龄相关的葡萄糖和脂肪代谢的变化。 在这个项目中，我们的总体目标是确定对骨骼的影响 和钙代谢的老年男性和女性雄激素治疗和 以更好地了解这些影响的机制。我们将继续追查此事 目的在三个具体目标的框架内。具体目标1是 测定两年睾酮对骨密度的影响 老年男性的治疗和老年男性和女性的脱氢表雄酮治疗。 具体目标2是评估短期(6个月)和长期(24 雄激素治疗对骨生化指标的影响 营业额。具体目标3是确定雄激素治疗的效果。 关于骨外钙代谢，即肠道钙吸收 和肾脏钙离子的处理。因此，这个项目中的研究应该， 帮助更好地确定雄激素在预防中的潜在效用 以及可能治疗与年龄相关的骨丢失。这些研究加在一起 随着关于雄激素对肌肉影响的拟议研究(项目1)， 胰岛素敏感性(项目3)、脂肪代谢和身体组成 (项目4)，还应更好地了解 老年个体雄激素治疗的总体益处和风险。

Osteoporosis is one of the most important public health problems facing aging Americans. Although osteoporosis is more common in women, men also incur substantial bone loss with aging and elderly men have age-specific hip fracture rates and a prevalence of vertebral fractures that are at least half those in women. Estrogen deficiency has clearly been identified as a major risk factor for osteoporosis in women, and the effects of estrogen on the skeleton have been the subject of intensive investigation in recent years. In contrast, data on androgen effects on the skeleton are relatively sparse at present. Nonetheless, since aging is also associated with significant declines in both gonadal and adrenal androgen levels, there is increasing media coverage and popular belief that testosterone or dehydroepiandrosterone (DHEA) therapy can prevent or reverse a number of age-relate changes, including the deterioration in muscle and bone mass, as well as some of the age-related changes in glucose and fat metabolism. In this project, our overall objective is to determine the effects on bone and calcium metabolism of androgen treatment of elderly men and women and to understand better the mechanisms of these effects. We will pursue this objective within the framework of 3 specific aims. Specific Aim 1 is to determine the effects on bone mineral density of two years of testosterone treatment in elderly men and DHEA treatment in elderly men and women. Specific Aim 2 is to assess the short term (6 months) and long term (24 months) effects of androgen therapy on biochemical markers of bone turnover. Specific Aim 3 is to determine the effects of androgen therapy on extra-skeletal calcium metabolism, namely intestinal calcium absorption and renal calcium handling. The studies in this project should,therefore, help define better the potential utility of androgens in the prevention and possible treatment of age-related bone loss. These studies, combined with the proposed studies on androgen effects on muscle (Project 1), insulin sensitivity (Project 3), and fat metabolism and body composition (Project 4), should also provide a much better understanding of the overall benefits and risks of androgen treatment in elderly individuals.