Bone Marrow Fat and Osteopenia in HIV Lipodystrophy

描述(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 通过脂肪再分配。先前的研究表明，感染艾滋病毒的男性与 脂肪营养不良有骨量减少的风险。另外，我们有初步的 有证据表明，这些人的骨髓脂肪比 年龄和BMI与对照组相匹配。这一新的发现可能反映了共同的 这组人中既存在脂肪生成减少，也存在成骨减少 个人。需要进一步的研究来证实这一观察结果，并 描述骨髓内脂肪与骨密度之间的关系 人口。这一决心对于建立 HIV感染者脂肪萎缩和骨量减少的合理治疗 患有脂肪营养不良的个体。为了研究这一假说， 骨髓光谱学与骨髓内脂肪的直接测量 骨活检的含量将在HIV感染的患者和 无脂营养不良者和健康对照组。这些决定将是 与直接(骨活检)和间接(QCT和DXA)测量相关 以确定骨髓内脂肪与骨的关系 质量。此外，还将通过比较来评估可能的性别差异 在男性和女性中，这些指标，身体成分和性类固醇水平 患有HIV脂肪营养不良综合症。 我们假设脂肪细胞在骨骼的协调中是不可或缺的。 并因此可能成为治疗的一个有前途的治疗靶点 HIV脂肪营养不良患者的骨量减少。在这项建议的第二个目标中，我们 将调查PPARγ激动剂罗格列酮的使用是否会 有效增加骨髓脂肪和骨密度的研究对象 艾滋病病毒脂营养不良。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的体脂分布变化。 总而言之，这项提案将调查 HIV脂营养不良综合征患者的骨髓内脂肪和骨量减少 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.