Antiretroviral Therapy Containing HIV Protease Inhibitors Enhances Fracture Risk by Impairing Osteoblast Differentiation and Bone Quality
Antiretroviral Therapy Containing HIV Protease Inhibitors Enhances Fracture Risk by Impairing Osteoblast Differentiation and Bone Quality
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DOI：
10.1093/infdis/jix246
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发表时间：
2017-06-15
影响因子：
6.4
通讯作者：
Sato, Shingo
中科院分区：
文献类型：
--
作者：
Hirakawa, Hiroyuki;Gatanaga, Hiroyuki;Sato, Shingo
长期抗逆转录病毒治疗与骨折风险增加有关，但其机制尚不明确。我们测量了在接受蛋白酶抑制剂（pi）或含整合酶链转移抑制剂方案治疗的人类免疫缺陷病毒感染患者的血清羧化骨钙素和戊苷（骨质量差的标志物）。结果显示，在pi治疗的患者中，低羧化骨钙素和戊苷明显升高。切换到整合酶链转移抑制剂显著降低这些标记。我们还发现，在pi处理的小鼠中，骨力学性能受损，低羧化骨钙素水平较高，并且pi处理的成骨细胞分化受到抑制。结果证实了PIs对骨质量和成骨细胞分化的不利影响。
Long-term antiretroviral therapy is associated with increased fracture risk, but the mechanism remains elusive. We measured serum undercarboxylated osteocalcin and pentosidine (markers of poor bone quality) in human immunodeficiency virus-infected patients treated with protease inhibitors (PIs) or an integrase strand transfer inhibitor-containing regimen. The results demonstrated significantly higher undercarboxylated osteocalcin and pentosidine in PI-treated patients. Switching to integrase strand transfer inhibitor significant decreased these markers. We also showed impaired bone mechanical properties with higher undercarboxylated osteocalcin level in PI-treated mice and inhibited osteoblast differentiation in PI-treated osteogenic cells. The results confirmed the adverse effects of PIs on bone quality and osteoblast differentiation.