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

Abstract

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.

• Authors: M T Yin, R Modarresi, E Shane, F Santiago, D C Ferris, D J McMahon, C A Zhang, S Cremers, J Laurence
• Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (Osteoporos Int) Vol. 22 Issue 5 Pg. 1459-68 (May 2011) ISSN: 1433-2965 [Electronic] England
• PMID: 20683705 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• HIV Protease Inhibitors
• Ritonavir

Topics

• Adult
• Biomarkers (blood)
• Bone Density (physiology)
• Bone Remodeling (physiology)
• Cell Differentiation (drug effects)
• Cells, Cultured
• Cytokines (blood)
• Female
• HIV Infections (blood, drug therapy, physiopathology)
• HIV Protease Inhibitors (pharmacology)
• HIV-1
• Humans
• Leukocytes, Mononuclear (drug effects, pathology)
• Middle Aged
• Osteoclasts (drug effects, pathology)
• Pilot Projects
• Postmenopause (blood)
• Ritonavir (pharmacology)