Department of Nephrology, Laboratório de Investigação Médica 16, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, SP, Brazil.
Post-Graduation in Medicine Department, Universidade Nove de Julho, Sao Paulo, SP, Brazil.
J Bone Miner Res. 2019 Sep;34(9):1574-1584. doi: 10.1002/jbmr.3751. Epub 2019 Jul 3.
Bone mineral density (BMD) loss is a known complication of human immunodeficiency virus (HIV) infection and its treatment, particularly with tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens. Although renal proximal tubular dysfunction and phosphaturia is common with TDF, it is unknown whether BMD loss results from inadequate mineralization. We evaluated change in BMD by dual-energy X-ray absorptiometry (DXA) and bone histomorphometry by tetracycline double-labeled transiliac crest biopsies in young men living with HIV before (n = 20) and 12 months after (n = 16) initiating TDF/lamivudine/efavirenz. We examined relationships between calciotropic hormones, urinary phosphate excretion, pro-inflammatory and pro-resorptive cytokines, and bone remodeling-related proteins with changes in BMD and histomorphometry. Mean age was 29.6 ± 5.5 years, with mean CD4 + T cell count of 473 ± 196 cells/mm . At baseline, decreased bone formation rate and increased mineralization lag time were identified in 16 (80%) and 12 (60%) patients, respectively. After 12 months, we detected a 2% to 3% decrease in lumbar spine and hip BMD by DXA. By histomorphometry, we observed no change in bone volume/total volume (BV/TV) and trabecular parameters, but rather, increases in cortical thickness, osteoid volume, and osteoblast and osteoclast surfaces. We did not observe significant worsening of renal phosphate excretion or mineralization parameters. Increases in PTH correlated with decreased BMD but not histomorphometric parameters. Overall, these data suggest abnormalities in bone formation and mineralization occur with HIV infection and are evident at early stages. With TDF-containing antiretroviral therapy (ART), there is an increase in bone remodeling, reflected by increased osteoblast and osteoclast surfaces, but a persistence in mineralization defect, resulting in increased osteoid volume. © 2019 American Society for Bone and Mineral Research.
骨密度（BMD）丢失是人类免疫缺陷病毒（HIV）感染及其治疗的已知并发症，特别是使用包含替诺福韦二吡呋酯（TDF）的抗逆转录病毒方案。尽管 TDF 常引起肾近端小管功能障碍和磷酸盐尿，但尚不清楚 BMD 丢失是否是由于矿化不足引起的。我们通过双能 X 射线吸收法（DXA）评估了年轻 HIV 感染者在开始 TDF/拉米夫定/依非韦伦治疗前（n=20）和 12 个月后（n=16）的 BMD 变化，并通过四环素双标记髂嵴活检评估了骨组织形态计量学变化。我们研究了钙调节激素、尿磷酸盐排泄、促炎和促吸收细胞因子以及与骨重建相关的蛋白与 BMD 和骨组织形态计量学变化之间的关系。平均年龄为 29.6±5.5 岁，平均 CD4+T 细胞计数为 473±196 个/毫米。在基线时，分别有 16（80%）和 12（60%）名患者存在骨形成率降低和矿化延迟时间延长。12 个月后，我们通过 DXA 检测到腰椎和髋部 BMD 降低 2%至 3%。通过骨组织形态计量学，我们观察到骨体积/总体积（BV/TV）和小梁参数没有变化，而是皮质厚度、类骨质体积、成骨细胞和破骨细胞表面增加。我们没有观察到肾磷酸盐排泄或矿化参数的显著恶化。PTH 的增加与 BMD 降低相关，但与骨组织形态计量学参数无关。总的来说，这些数据表明 HIV 感染时存在骨形成和矿化异常，且在早期阶段就已经存在。在使用包含 TDF 的抗逆转录病毒治疗（ART）时，骨重建增加，表现为成骨细胞和破骨细胞表面增加，但矿化缺陷持续存在，导致类骨质体积增加。© 2019 美国骨矿研究协会。
