The Journal of infectious diseases 2017 05 19() doi 10.1093/infdis/jix246
Long-term ART is associated with increased fracture risk, but the mechanism remains elusive. We measured serum undercarboxylated osteocalcin and pentosidine (markers of poor bone quality) in HIV-infected patients treated with protease inhibitors (PIs) or an integrase strand transfer inhibitor (INSTI)-containing regimens. The results demonstrated significantly higher undercarboxylated osteocalcin and pentosidine in PIs-treated patients. Switching to INSTI resulted in significant decrease in these markers. We also showed impaired bone mechanical properties with higher undercarboxylated osteocalcin level in PIs-treated mice and inhibited osteoblast differentiation in PIs-treated osteogenic cells. The results confirmed the adverse effects of PIs on bone quality and osteoblast differentiation.