Moran Caitlin A, Weitzmann M Neale, Ofotokun Ighovwerha
aDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine bGrady Healthcare System, Atlanta cDepartment of Medicine, Division of Endocrinology, Metabolism & Lipids, Emory University School of Medicine, Atlanta dAtlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA.
Curr Opin HIV AIDS. 2016 May;11(3):333-42. doi: 10.1097/COH.0000000000000260.
HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2-6% bone mineral density (BMD) loss within the first 1-2 years of therapy. Although tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PIs), have adverse bone effects. In the current review, we examine bone loss associated with protease inhibitor use, describing the relative magnitude of bone loss reported for individual protease inhibitors. We also review the potential mechanisms associated with protease inhibitor-induced bone loss.
As a class, protease inhibitors contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in protease inhibitor-mediated bone loss in addition to plausible direct effects of protease inhibitors on bone cells.
Protease inhibitors remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population.
HIV感染是骨质疏松和骨折的既定危险因素。联合抗逆转录病毒疗法（cART）会增加骨吸收，导致在治疗的最初1 - 2年内骨矿物质密度（BMD）额外损失2 - 6%。尽管替诺福韦酯常被归咎于抗逆转录病毒药物相关的骨质流失，但有大量证据表明其他药物，包括蛋白酶抑制剂（PIs），也会对骨骼产生不良影响。在本综述中，我们研究与蛋白酶抑制剂使用相关的骨质流失，描述个别蛋白酶抑制剂报告的骨质流失相对程度。我们还回顾与蛋白酶抑制剂诱导骨质流失相关的潜在机制。
作为一类药物，蛋白酶抑制剂比其他主要药物导致的骨质流失程度更大。cART启动后HIV疾病的逆转及相关的免疫重建，除了蛋白酶抑制剂对骨细胞可能的直接作用外，在蛋白酶抑制剂介导的骨质流失中也起重要作用。
尽管蛋白酶抑制剂对骨骼有不良影响，但它们仍是cART的重要组成部分。需要更好地理解驱动HIV/cART诱导骨质流失的因素，以阻止HIV感染人群中不断上升的骨折发生率。
