Impact of HIV and antiretroviral initiation on skeletal biology

摘要 骨质疏松症和骨折是艾滋病毒和抗逆转录病毒治疗（ART）的已知并发症，但其机制 由于缺乏组织水平的数据，艾滋病毒和ART相关的骨质流失仍不确定。在父母补助金中 （R21 TW 012367），我们正在进行一项全面的纵向研究，以比较 两种ART方案（TDF/拉米夫定/依法韦仑和拉米夫定/度鲁特韦）。我们将评估骨密度， 使用双能X线吸收测定法（DXA）和高分辨率外周定量CT进行强度检查 （HRpQCT）与有限元分析（目的1），获得配对髂嵴骨活检，以评估 使用纳米压痕/拉曼光谱法进行组织形态测量和组织水平机械性能（目标2）， 并进行骨细胞转录组学以探索基础分子途径。随着威尔斯亲王年龄的增长， 损伤可能增加，骨折频率也可能增加。蛋白尿与 骨质疏松症/骨折已被确认在有和没有艾滋病毒的人，虽然机制， 尿蛋白流失和骨脆性的基础尚未建立。特异性抗逆转录病毒药物，如 由于TDF引起近端肾小管功能障碍，导致蛋白尿，但其他合并症的影响， 传统因素也有影响。这一行政补充提供了一个独特的机会，研究的作用， 蛋白尿在巴西PWH骨质流失中的作用。基于HIV和骨的多学科合作 来自美国的研究人员.和圣保罗大学建立在家长补助金，这种补充将 提供更多的机会，进行与老龄化有关的研究和能力建设，重点是 肾骨轴

ABSTRACT Osteoporosis and fractures are known complications of HIV and antiretroviral therapy (ART) but the mechanisms of HIV and ART associated bone loss are still uncertain because tissue-level data are lacking. In the parent grant (R21TW012367), we are performing a comprehensive longitudinal study to compare the skeletal effects of the two ART regimens (TDF/lamivudine/efavirenz and lamivudine/dolutegravir). We will evaluate bone density and strength using dual energy Xray absorptiometry (DXA) and High Resolution peripheral Quantitative CT (HRpQCT) with finite element analysis (Aim 1), obtain paired iliac-crest bone biopsies to evaluate histomorphometry and tissue-level mechanical properties using nanoindentation/ramen spectroscopy (Aim 2), and perform bone cell transcriptomics to explore underpinning molecular pathways. As PWH age, renal impairment is likely to increase as well as frequency of fracture. An association between proteinuria and osteoporosis/fracture has been recognized in people with and without HIV, although the mechanistic underpinnings of urinary loss of protein and bone fragility has not been established. Specific antiretrovirals, such as TDF cause proximal tubular dysfunction resulting in proteinuria but the effect of other co-morbidities and traditional factors also contribute. This administrative supplement offers a unique opportunity to study the role of proteinuria in bone loss among PWH in Brazil. Building upon the multidisciplinary collaboration of HIV and bone researchers from the U.S. and the University of São Paulo established in the parent grant, this supplement will provide additional opportunities for research and capacity building for aging-related research focusing on the kidney-bone axis