Bone Marrow Fat and Osteopenia in HIV Lipodystrophy

描述（由申请人提供）：HIV脂肪营养不良综合征是一种 公认的有效抗逆转录病毒治疗的并发症，其特征在于 脂肪再分配。 先前的研究表明， 脂肪营养不良有骨质减少的风险。此外，我们有初步的 有证据表明，这些人的骨髓脂肪减少， 年龄和BMI匹配的对照组。这一新的发现可能反映了共同的- 在这一组中存在脂肪生成和骨生成减少， 个体 需要进一步的研究来验证这一观察结果， 描述骨髓内脂肪和骨密度之间的关系， 人口 这 确定 的关键 建立 HIV感染者脂肪萎缩和骨质减少的适当治疗 个人 与 脂肪营养不良。 到 探讨 这 假设，MR 骨髓的光谱学和骨髓内脂肪的直接测量 通过骨活检的含量将在HIV感染患者和 没有脂肪代谢障碍和健康对照。 这些决定将是 与直接（骨活检）和间接（QCT和DXA）测量相关 以确定骨髓内脂肪和骨密度之间的关系 马萨诸塞州此外，将通过比较来评估可能的性别差异 这些相同的指数，身体成分，和性类固醇水平，在男性和女性， 艾滋病脂肪营养不良综合症 我们假设脂肪细胞在骨的协调中是不可或缺的 因此可以作为治疗中有希望的治疗靶点 艾滋病脂肪营养不良引起的骨质减少在本建议的第二个目标中，我们 将研究使用PPARgamma激动剂罗格列酮是否会 有效增加受试者的骨髓脂肪和骨密度 HIV脂肪营养不良罗格列酮治疗的潜在益处包括 恢复骨密度，改善胰岛素抵抗，逆转 HIV脂肪营养不良综合征中身体脂肪分布的变化。 总的来说， 这项建议 将调查 关系 HIV脂肪营养不良综合征中的骨髓内脂肪和骨质减少， 评估一种新的治疗策略，以治疗和预防潜在的长期- 长期发病率与骨密度降低有关， 人口

DESCRIPTION (provided by applicant): 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.