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

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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.

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Acknowledgements

We thank the staff and participants of Columbia University Medical Center and Bronx-Lebanon Hospital Center. This work was supported by National Institutes of Health Grants DK65511, AI065200 (ES), AI059884 (MY), and HL55646 (JL), the Angelo Donghia and Hagedorn Funds (JL), and the Thomas L. Kempner and Katheryn C. Patterson Foundation (ES).

Conflicts of interest

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, 630 w168th street, PH8-876, New York, NY, 10032, USA

    M. T. Yin

  2. Division of Endocrinology, Department of Medicine, Columbia University Medical Center, New York, NY, USA

    E. Shane, D. J. McMahon, C. A. Zhang & S. Cremers

  3. Division of Hematology-Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    R. Modarresi, F. Santiago & J. Laurence

  4. Division of Infectious Diseases, Department of Medicine, Bronx-Lebanon Hospital Center, Bronx, NY, USA

    D. C. Ferris

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  1. M. T. Yin
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Correspondence to M. T. Yin.

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Yin, M.T., Modarresi, R., Shane, E. et al. Effects of HIV infection and antiretroviral therapy with ritonavir on induction of osteoclast-like cells in postmenopausal women. Osteoporos Int 22, 1459–1468 (2011). https://doi.org/10.1007/s00198-010-1363-6

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  • DOI: https://doi.org/10.1007/s00198-010-1363-6

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