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 two global aims. The first global aim is to investigate the anabolic actions of parathyroid hormone (PTH) on the skeleton, particularly as an agent to prevent estrogen deficiency bone loss. There are 2 major projects to address this aim: 1) an investigation of the effects of ability of short-term parathyroid hormone administration on bone loss in young women with GnRH analog-induced estrogen deficiency and 2) an investigation of the effects of ability of long-term parathyroid hormone administration to prevent bone loss in early postmenopausal women. The first of these projects was supported by an NIH FIRST Award that expires next year. This project demonstrated that daily PTH administration prevents bone loss from the spine, hip, and total body when a GnRH analog is administered to young women for 1 year. This study was too short, however, to determine whether PTH could prevent cortical bone loss in estrogen- deficient women but it did provide the basic premise for the second project which is funded as a portion of the MGH Specialized Center of Research (SCOR) grant on osteoporosis. The second global aim of my research program is to assess the roles of androgens and estrogens on the skeleton.
This aim encompasses 2 additional projects: 1) The Study of Women's Health Across the Nation (SWAN) and 2) a group of newly designed studies to investigate several key questions about the roles of androgens and estrogens in bone metabolism in men. SWAN is a multicenter, multi-ethnic study investigating a wide range of physiologic, endocrinologic, epidemiologic, and psychosocial issues as women transition through the menopause. One key aim of SWAN, which is the major reason for my participation, is to assess the relationship between estrogen deficiency and bone loss during the menopause transition. The newly designed studies on androgens and bone will examine the relative roles of androgens and estrogens in maintaining bone turnover in men, the dose-response relationship between gonadal steroids and bone turnover in men, and novel ways to prevent androgen-deficiency bone loss in men. If I am successful in obtaining this award, I will be able to reduce my current clinical activities by 50 percent and devote the additional time to my clinical research studies. Moreover, I am now training a clinical research fellow in endocrinology and a junior staff member of the Department of Medicine, both of whom are interested in the roles of androgens on the skeleton. It is clearly necessary for me to reduce my current clinical activities in order to devote sufficient time to the training of these young clinical investigators.
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