Osteoporosis and fractures are being recognized with increasing frequency in patients who have undergone cardiac transplantation. The increased survival of such patients and the expansion of cardiac (and other types of organ) transplantation programs in the United States, make it likely that the incidence of osteoporosis in this population will grow substantially in the coming decade. The purpose of this research proposal is to investigate osteoporosis following cardiac transplantation with data to be obtained from two protocols: a cross-sectional study of a representative group of 140 patients who have already undergone cardiac transplantation; and a prospective longitudinal study of 100 patients who will receive cardiac transplantation in the future. The specific aims of the proposal are to determine the epidemiology and the natural history of osteopenia and fractures in this population, as well as to measure and monitor bone density at the lumbar spine, hip and proximal radius. Epidemiological and statistical analysis will be. used as appropriate to these specific aims. In addition, biochemical and histomorphometric characteristics of transplantation osteoporosis will be evaluated. These specific aims will be addressed using the technique of dual energy x-ray absorptiometry to measure bone density as well as radiological techniques to determine the incidence and prevalence of vertebral fractures. Both established and newer assays for calciotropic hormones and bone matrix components will be utilized to clarify the pathogenetic mechanisms that lead to bone loss and fractures in this syndrome. Greater understanding of the epidemiological, clinical, biochemical and histomorphometric features of cardiac transplantation-associated osteoporosis is expected to lead to the design of future rational programs for prevention and treatment of this new syndrome.