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Author Notes:

Kehmia Titanji, PhD, ktitanj@emory.edu.

We would like to thank all the study participants for their generous contributions to this study.

We would also like to thank Laura Ward for database management and Sara Sanford for study coordination.

Authors declared no conflicts of interest.


Research Funding:

Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health under Award Numbers R01AR059364, R01AR068157, and R01AR070091); and by the National Institute on Aging (NIA) under Award Number R01AG040013 to M.N.W. and I.O.

M.N.W. is also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105);and by NIAMS grant R01AR056090.

K.T. is also supported by the National Heart, Lung and Blood Institute (NHLBI)(1K01HL131333).

The authors gratefully acknowledge services provided by the Emory Center for AIDS Research (CFAR) funded through NIADID (P30AI050409) ;and the Georgia Clinical and Translational Science Alliance (Georgia CTSA), funded through the National center for Advancing Translational Sciences (UL1TR002378).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • Virology
  • bone loss
  • HIV
  • HIV-induced bone loss
  • osteoprotegerin
  • eceptor activator of nuclear factor-kappa B ligand
  • T cells

T-cell receptor activator of nuclear factor-kappa B ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4(+) T-cell counts


Journal Title:



Volume 32, Number 7


, Pages 885-894

Type of Work:

Article | Post-print: After Peer Review


Objective: Higher incidence of osteopenia and osteoporosis underlie increased rates of fragility fracture in HIV infection. B cells are a major source of osteoprotegerin (OPG), an inhibitor of the key osteoclastogenic cytokine receptor activator of nuclear factor-κB ligand (RANKL). We previously showed that higher B-cell RANKL/OPG ratio contributes to HIV-induced bone loss. T-cell OPG production in humans, however, remains undefined and the contribution of T-cell OPG and RANKL to HIV-induced bone loss has not been explored. Design: We investigated T-cell OPG and RANKL production in ART-naive HIV-infected and uninfected individuals in relation to indices of bone loss in a cross-sectional study. Methods: T-cell RANKL and OPG production was determined by intracellular staining and flow cytometry, and plasma levels of bone resorption markers were determined by ELISA. Results: We demonstrate for the first time in-vivo human T-cell OPG production, which was significantly lower in HIV-infected individuals and was coupled with moderately higher T-cell RANKL production, resulting in a significantly higher T-cell RANKL/OPG ratio. T-cell RANKL/OPG ratio correlated significantly with BMD-derived z-scores at the hip, lumbar spine and femur neck in HIV-infected individuals with CD4+ T-cell counts at least 200 cells/μl but not in those with lower counts. Conclusion: Our data suggest that T cells may be a physiologically relevant source of OPG and T-cell RANKL/OPG imbalance is associated with HIV-induced bone loss in CD4+ T-cell-sufficient patients. Both B and T lymphocytes may thus contribute to HIV-induced bone loss.

Copyright information:

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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