Osteoporosis in HIV Infected Postmenopausal Women

描述（由申请人提供）：绝经后HIV阳性女性骨折风险增加，易受D缺乏、HIV感染和ART相关骨丢失对骨强度的不良影响。老年少数民族妇女艾滋病毒感染率的增加和艾滋病毒感染人口的老龄化使得阐明艾滋病毒及其治疗对骨骼健康的影响至关重要。 公共卫生相关性：在美国，老年少数民族妇女在感染艾滋病毒的成年人中所占的比例越来越大。该提案寻求继续支持研究“HIV感染的绝经后妇女骨质疏松症”（R 01 AI 065200）。在当前的资助期间，我们记录了较低的骨密度（BMD），某些非椎骨骨折的患病率较高，较高的骨转换，HIV+女性的骨丢失率高于HIV-女性，以及破骨细胞数量增加的间接证据，特别是在接受利托那韦增强蛋白酶抑制剂（RTV-PI）方案的HIV+女性中。此外，维生素D不足和缺乏非常常见，影响76%的受试者，并与当前CD 4计数较低相关。在更新中，我们将招募更多的HIV+受试者，以更好地研究不同抗逆转录病毒治疗（ART）亚组之间的BMD、生化和骨细胞差异。具体而言，我们将检验以下假设：某些ART方案与较高的骨转换、循环破骨细胞和成骨细胞前体细胞以及骨丢失率相关;维生素D不足和缺乏HIV+绝经后妇女的维生素D补充与骨转换和骨丢失率下降相关，并可能影响免疫功能指标; ART的启动将未经治疗的HIV感染的低骨转换状态转化为与可检测的骨丢失相关的高转换状态;并且基于替诺福韦酯富马酸盐（TDF）的方案，包括RTV-PI或依法韦仑（细胞色素P450诱导剂），将不同地影响BMD，矿物质代谢，骨细胞和周转。我们将利用已建立的最先进的生化测定和新技术，如高分辨率外周定量CT（HR-pQCT）以及循环成骨细胞和破骨细胞前体的定量和表征，来测试这些假设，这将允许在不需要骨活检的情况下评估骨微结构和重塑活性。

DESCRIPTION (provided by applicant): Postmenopausal HIV+ women are at increased risk of fracture and vulnerable to adverse effects of D deficiency, HIV infection and ART-related bone loss on bone strength. The increasing prevalence of HIV-infection on older minority women and the aging of the HIV-infected population make it critical to elucidate the effects of HIV and its treatment on bone health. PUBLIC HEALTH RELEVANCE: Older minority women comprise a growing proportion of HIV-infected adults in the United States. This proposal seeks continued support to study "Osteoporosis in HIV-infected Postmenopausal Women" (R01 AI065200). During the current funding period, we documented lower bone density (BMD), higher prevalence of certain non-vertebral fractures, higher bone turnover, higher rates of bone loss in HIV+ women than HIV- women, and indirect evidence of increased osteoclast numbers particularly in HIV+ women on ritonavir-boosted protease inhibitor (RTV-PI) regimens. In addition, vitamin D insufficiency and deficiency were extremely common, affecting 76% of the subjects and were associated with lower current CD4 counts. In the renewal, we will recruit additional HIV+ subjects in order to have greater power to investigate BMD, biochemical and bone cell differences among different antiretroviral therapy (ART) subgroups. Specifically, we will test the hypotheses that certain ART regimens are associated with higher bone turnover, circulating osteoclast and osteoblast precursors, and rates of bone loss; that repletion of vitamin D in D insufficient and deficient HIV+ postmenopausal women will be associated with a decline in bone turnover and rates of bone loss and may influence indices of immune function; that initiation of ART converts the low bone turnover state of untreated HIV infection to a high turnover state associated with detectable bone loss; and that tenofovir disoproxil fumarate (TDF)-based regimens that include RTV-PIs or efavirenz, a cytochrome P450 inducer, will differentially affect BMD, mineral metabolism, bone cells and turnover. We will test these hypotheses utilizing established state-of-the-art biochemical assays and novel technologies, such as high-resolution peripheral quantitative CT (HR- pQCT) and quantification and characterization of circulating osteoblast and osteoclast precursors, which will permit assessment of bone microarchitecture and remodeling activity without the requirement for a bone biopsy.