EFFECT OF ANDROGEN REPLACEMENT ON BONE METABOLISM

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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.