Hirakawa Hiroyuki, Gatanaga Hiroyuki, Ochi Hiroki, Fukuda Toru, Sunamura Satoko, Oka Shinichi, Takeda Shu, Sato Shingo
Departments of 1Physiology and Cell Biology.
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
J Infect Dis. 2017 Jun 15;215(12):1893-1897. doi: 10.1093/infdis/jix246.
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.
长期抗逆转录病毒疗法与骨折风险增加相关，但其机制仍不清楚。我们检测了接受蛋白酶抑制剂（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血清中未羧化骨钙素和戊糖苷（骨质量差的标志物）。结果显示，接受PI治疗的患者中未羧化骨钙素和戊糖苷显著更高。改用整合酶链转移抑制剂可显著降低这些标志物。我们还发现，接受PI治疗的小鼠骨力学性能受损，未羧化骨钙素水平较高，且接受PI治疗的成骨细胞中骨细胞分化受到抑制。结果证实了PI对骨质量和成骨细胞分化的不良影响。
