EFFECT OF ANDROGEN REPLACEMENT ON BONE METABOLISM

雄激素替代对骨代谢的影响

• 批准号: 6340635
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340635
• 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