EFFECT OF ANDROGEN REPLACEMENT ON BONE METABOLISM

雄激素替代对骨代谢的影响

• 批准号: 6098732
• 负责人: Sundeep Khosla
• 金额: $ 22.86万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6098732
• 关键词: age difference; aging; androgens; atomic absorption spectrometry; biomarker; bone density; bone metabolism; calcium metabolism; clinical research; dehydroepiandrosterone; gastrointestinal nutrient absorption; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; kidney metabolism; longitudinal human study; photon absorptiometry; testosterone

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.

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 随着年龄增长会导致大量骨丢失， 髋部骨折率和椎骨骨折的患病率， 至少有一半是女性。雌激素缺乏症已被明确确定 作为妇女骨质疏松症的主要危险因素， 雌激素对骨骼的影响一直是深入研究的主题 近年来相反，雄激素对骨骼影响的数据 目前相对稀疏。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， 有越来越多的媒体报道和流行的信念，睾丸激素或 脱氢表雄酮（DHEA）治疗可以预防或逆转一些 与年龄有关的变化，包括肌肉和骨质的退化， 以及一些与年龄相关的葡萄糖和脂肪代谢变化。 在这个项目中，我们的总体目标是确定对骨骼的影响 和钙代谢的雄激素治疗老年男女和 更好地理解这些影响的机制。我们会追查下去 在三个具体目标的框架内。具体目标1是 确定两年睾酮对骨密度的影响 治疗老年男性和DHEA治疗老年男性和女性。 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标志物的影响 周转具体目标3是确定雄激素治疗的效果 骨骼外钙代谢，即肠道钙吸收 和肾钙处理。因此，本项目的研究应 有助于更好地确定雄激素在预防 以及可能治疗与年龄相关的骨质流失。这些研究，结合 随着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），脂肪代谢和身体成分 （项目4），也应该提供一个更好地了解 老年人雄激素治疗的总体获益和风险。