Osteoporosis in HIV Infected Postmenopausal Women

描述(由申请人提供)：绝经后HIV+女性骨折的风险增加，容易受到D缺乏、HIV感染和与ART相关的骨丢失对骨骼强度的不利影响。老年少数族裔妇女感染艾滋病毒的比例越来越高，感染艾滋病毒的人口老龄化，因此必须阐明艾滋病毒及其治疗对骨骼健康的影响。 公共卫生相关性：老年少数族裔妇女在美国感染艾滋病毒的成年人中所占比例越来越大。该提案寻求继续支持研究“感染艾滋病毒的绝经后妇女中的骨质疏松症”(R01AI065200)。在目前的资助期间，我们记录了HIV+妇女比HIV妇女更低的骨密度(BMD)、更高的某些非脊椎骨折的患病率、更高的骨转换、更高的骨丢失率，以及间接证据表明破骨细胞数量增加，特别是在服用利托那韦促进的蛋白酶抑制剂(RTV-PI)方案的HIV+妇女中。此外，维生素D缺乏和缺乏是非常普遍的，影响到76%的受试者，并与目前较低的CD4计数有关。在更新中，我们将招募更多的HIV+受试者，以便有更大的权力调查不同抗逆转录病毒治疗(ART)亚组之间的骨密度、生化和骨细胞差异。具体地说，我们将测试这些假设，即某些ART方案与更高的骨周转率、循环中的破骨细胞和成骨细胞前体以及骨丢失率有关；D缺乏和缺乏HIV+绝经后妇女的维生素D补充将与骨周转和骨丢失率下降相关，并可能影响免疫功能的指标；启动ART可将未经治疗的HIV感染的低骨转换状态转变为与可检测到的骨丢失相关的高周转状态；以替诺福韦为基础的疗法，包括RTV-PI或细胞色素P450诱导剂efavirenz，将对BMD、矿物质代谢、骨细胞和周转产生不同的影响。我们将利用已建立的最先进的生化分析和新技术来验证这些假设，例如高分辨率外周定量CT(HR-pQCT)和循环成骨细胞和破骨细胞前体的定量和表征，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动。

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.