Ross Ryan D, Sharma Anjali, Shi Qiuhu, Hoover Donald R, Weber Kathleen M, Tien Phyllis C, French Audrey L, Al-Harthi Lena, Yin Michael T
Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America.
State University of New York, Downstate, Brooklyn, NY, United States of America.
Bone Rep. 2020 May 11;12:100279. doi: 10.1016/j.bonr.2020.100279. eCollection 2020 Jun.
Low bone mineral density (BMD) is commonly observed in people living with HIV (PLWH), however the cause for this BMD loss remains unclear. Sclerostin, a bone-derived antagonist to the Wnt/β-catenin-pathway, suppresses bone remodeling and is positively associated with BMD. The goal of the current study was to investigate associations between sclerostin and BMD in a cohort of HIV-seropositive and demographically-matched seronegative women.
This cross-sectional analysis used a subset of early postmenopausal women enrolled in the Women's Interagency HIV Study (WIHS). BMD was assessed at the lumbar spine, total hip, femoral neck, and distal and ultradistal radius via dual energy x-ray absorptiometry (DXA). Circulating sclerostin was assessed via commercial ELISAs. Univariate and multivariate linear regression modeling tested associations between sclerostin and BMD after adjusting for a variety of BMD-modifying variables.
HIV-seropositive women had significantly reduced BMD at all skeletal sites compared to HIV-seronegative women. There was no difference in sclerostin levels according to HIV-serostatus (0.25 vs 0.27 ng/mL in HIV-seronegative and HIV-seropositive, respectively, p = 0.71). Circulating sclerostin was positively associated with BMD at all sites in both univariate and multivariate models adjusting for HIV status, age, BMI, and race, although the coefficients of association were attenuated in HIV-seropositive women. The positive association between sclerostin and BMD among seropositive women remained statistically significant after adjusting for ART or tenofovir disoproxil fumarate (TDF) use.
The current study suggests that circulating sclerostin is a biomarker for bone mass for both HIV seronegative and seropositive women using and not using ART. The lower coefficients of association between sclerostin and BMD by HIV status may suggest HIV-induced alternation in osteocyte function.
低骨矿物质密度（BMD）在HIV感染者（PLWH）中普遍存在，然而这种骨矿物质密度降低的原因尚不清楚。硬化素是一种源自骨骼的Wnt/β-连环蛋白通路拮抗剂，可抑制骨重塑，与骨矿物质密度呈正相关。本研究的目的是调查一组HIV血清阳性和人口统计学匹配的血清阴性女性中硬化素与骨矿物质密度之间的关联。
本横断面分析使用了参与女性机构间HIV研究（WIHS）的绝经后早期女性的一个子集。通过双能X线吸收法（DXA）评估腰椎、全髋、股骨颈以及桡骨远端和超远端的骨矿物质密度。通过商业酶联免疫吸附测定（ELISA）评估循环硬化素。在调整了各种影响骨矿物质密度的变量后，使用单变量和多变量线性回归模型测试硬化素与骨矿物质密度之间的关联。
与HIV血清阴性女性相比，HIV血清阳性女性在所有骨骼部位的骨矿物质密度均显著降低。根据HIV血清状态，硬化素水平无差异（HIV血清阴性和HIV血清阳性分别为0.25 vs 0.27 ng/mL，p = 0.71）。在调整了HIV状态、年龄、体重指数和种族的单变量和多变量模型中，循环硬化素与所有部位的骨矿物质密度均呈正相关，尽管在HIV血清阳性女性中关联系数有所减弱。在调整了抗逆转录病毒治疗（ART）或替诺福韦酯（TDF）使用情况后，血清阳性女性中硬化素与骨矿物质密度之间的正相关在统计学上仍然显著。
本研究表明，对于使用和未使用ART的HIV血清阴性和血清阳性女性，循环硬化素都是骨量的生物标志物。硬化素与骨矿物质密度之间的关联系数因HIV状态而降低，这可能表明HIV诱导了骨细胞功能的改变。
