Unveiling the basis of ART-induced osteopenia

Objectives: Osteopenia is frequent in HIV infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis. Design: We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a 3-drug regimen, and Atazanavir, which was widely utilized in the past. Results: We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, while Darunavir exerts no effect. Conclusions: Atazanavir and Dolutegravir impair osteogenesis. It is essential to early diagnose impaired osteogenesis and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients and put it in the context of a correct antiretroviral combination.