Effects of HIV infection and antiretroviral therapy with ritonavir on induction of osteoclast-like cells in postmenopausal women.

SUMMARY: Ritonavir (RTV) is a commonly used antiretroviral associated with bone loss. We show that peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-positive women on RTV are more likely to differentiate into osteoclast-like cells when cultured with their own sera than PBMCs and sera from HIV- women or HIV+ on other antiretrovirals. INTRODUCTION: RTV increases differentiation of human adherent PBMCs to functional osteoclasts in vitro, and antiretroviral regimens containing RTV have been associated with low bone mineral density (BMD) and bone loss. METHODS: BMD, proresorptive cytokines, bone turnover markers (BTMs), and induction of osteoclast-like cells from adherent PBMCs incubated either with macrophage colony-stimulating factor (MCSF) and receptor activator of nuclear factor κB ligand (RANKL) or with autologous serum were compared in 51 HIV- and 68 HIV+ postmenopausal women. RESULTS: BMD was lower, and serum proresorptive cytokines and BTMs were higher in HIV+ versus HIV- women. Differentiation of osteoclast-like cells from adherent PBMCs exposed to either MCSF/RANKL or autologous serum was greater in HIV+ women. Induction of osteoclast-like cells was greater from PBMCs exposed to autologous sera from HIV+ women on RTV-containing versus other regimens (172 ± 14% versus 110 ± 10%, p < 0.001). Serum-based induction of osteoclast-like cells from adherent PBMCs correlated with certain BTMs but not BMD. CONCLUSIONS: HIV infection and antiretroviral therapy are associated with higher BTMs and increased differentiation of osteoclast-like cells from adherent PBMCs, especially in women on regimens containing RTV. HIV+ postmenopausal women receiving RTV may be at greater risk for bone loss.