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


BACKGROUND
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.
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MT
Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, 630 w168th street, PH8-876, New York, NY 10032, USA. mty4@columbia.edu
Modarresi
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Shane
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Santiago
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Ferris
D C
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McMahon
D J
DJ
Zhang
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CA
Cremers
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Laurence
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D000328:Adult; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010865:Pilot Projects; D017698:Postmenopause / Q000097:blood; D019438:Ritonavir / Q000494:pharmacology*
D015415:Biomarkers; D016207:Cytokines; D017320:HIV Protease Inhibitors; D019438:Ritonavir