The HIV lipodystrophy syndrome is a recognized complication of potent antiretroviral therapy that is characterized by fat redistribution. Prior research has shown that HIV-infected men with lipodystrophy are at risk for osteopenia. In addition, we have preliminary evidence that these individuals have reduced bone marrow fat as compared to age and BMI matched control subjects. This novel finding may reflect the co- existence of both reduced adipogenesis and osteogenesis in this group of individuals. Further studies are needed to verify this observation and to characterize the relationship between intramarrow fat and bone density in this population. This determination is critical for the establishment of appropriate therapy for both lipoatrophy and osteopenia in HIV-infected individuals with lipodystrophy. To investigate this hypothesis, MR spectroscopy of the bone marrow and direct measurement of intramarrow fat content by bone biopsy will be compared in both HIV-infected patients with and without lipodystrophy and in healthy controls. These determinations will be correlated with direct (bone biopsy) and indirect (QCT and DXA) measurements of bone density to determine the relationship between intramarrow fat and bone mass. Furthermore, possible gender differences will be evaluated by comparing these same indices, body composition, and sex steroid levels, in men and women with the HIV lipodystrophy syndrome. We hypothesize that the adipocyte is integral in the coordination of bone turnover and may thus serve as a promising therapeutic target in the treatment of osteopenia in HIV lipodystrophy. In the second aim of this proposal, we will investigate whether the use of a PPARgamma agonist, rosiglitazone, will effectively increase both bone marrow fat and bone density in subjects with HIV lipodystrophy. The potential benefits of rosiglitazone therapy include restoration of bone density, improvement of insulin resistance, and reversal of the changes in body fat distribution in the HIV lipodystrophy syndrome. In summary, this proposal will investigate the relationship between intramarrow fat and osteopenia in the HIV lipodystrophy syndrome and will evaluate a novel therapeutic strategy to treat and prevent the potential long- term morbidity associated with reduced bone density in this expanding population.
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