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Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV

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Abstract

Summary

Rationale: To see if vitamin D and antiretroviral therapy are associated with bone mineral density (BMD) in people with HIV. Result: Lower hip BMD was associated with tenofovir (an antiretroviral medicine) in those with 25(OH)D ≥50 nmol/L. Significance: The relationship between antiretroviral therapy and hip BMD differs depending on vitamin D status.

Introduction

People with HIV have an increased risk of low BMD and fractures. Antiretroviral therapy contributes to this increased risk.

The aim of this study was to evaluate associations between vitamin D metabolites and antiretroviral therapy on BMD.

Methods

The simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine trial (STEAL) was an open-label, prospective randomised non-inferiority study that compared simplification of current nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose combination tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine. Serum 25(OH)D and 1,25(OH)2D were measured in 160 individuals (90 receiving TDF-FTC, 70 receiving other NRTIs) at baseline from this study. Multivariable linear regression models were constructed to evaluate the covariates of 1,25(OH)2D and BMD.

Results

Protease inhibitor use (p = 0.02) and higher body mass index (BMI) (p = 0.002) were associated with lower 1,25(OH)2D levels in those with 25(OH)D <50 nmol/L. However, TDF-FTC use (p = 0.01) was associated with higher 1,25(OH)2D levels, but only in those with 25(OH)D ≥50 nmol/L.

White ethnicity (p = 0.02) and lower BMI (p < 0.001) in those with 25(OH)D <50 nmol/L and with TDF-FTC use (p = 0.008) in those with 25(OH)D ≥50 nmol/L were associated with lower hip BMD. TDF-FTC use, higher serum calcium and serum βCTX, winter, and lower bone-specific alkaline phosphatase (BALP) and BMI were associated with lower lumbar spine BMD.

Conclusion

TDF-FTC use (versus non-TDF-FTC use) was associated with lower hip BMD, and this difference was more pronounced in those with 25(OH)D ≥50 nmol/L. Serum 25(OH)D <50 nmol/L was associated with lower hip BMD in all participants. Therefore, the associations between antiretroviral therapy and hip BMD differ depending on vitamin D status.

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Abbreviations

25(OH)D:

25-Hydroxyvitamin D

1,25(OH)2D:

1,25-Dihydroxyvitamin D

ABC-3TC:

Abacavir-lamivudine

BALP:

Bone-specific alkaline phosphatase

βCTx:

C-terminal cross-linking telopeptide of type 1 collagen

BMD:

Bone mineral density

BTM:

Bone turnover marker

CI:

Confidence interval

ART:

Antiretroviral therapy

NNRTI:

Non-nucleoside reverse transcriptase inhibitor

NRTI:

Nucleoside reverse transcriptase inhibitor

NtRTI:

Nucleotide reverse transcriptase inhibitor

P1NP:

Procollagen type 1N-terminal propeptide

PI:

Protease inhibitor

TDF-FTC:

Tenofovir-emtricitabine

VDR:

Vitamin D receptor

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Acknowledgments

The content is solely the responsibility of the authors, and the views expressed in this publication do not necessarily represent the position of the Australian Government.

Dr. Andrew Turner is acknowledged for his performance of vitamin D metabolite assays and Dr. Hila Haskelberg for her assistance with preparing the data.

STEAL Study Group (as listed in [18])

STEAL study investigators are Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert Finlayson, Michelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, Ban Kiem Tee, Ian Woolley.

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Authors and Affiliations

  1. Department of Medicine, University of Melbourne, Victoria, 3021, Australia

    K. M. Klassen & P. R. Ebeling

  2. Melbourne Sexual Health Centre, Alfred Health, 580 Swanston Street, Carlton, Melbourne, Victoria, Australia

    K. M. Klassen

  3. Central Clinical School, Alfred Centre, Monash University, Melbourne, 3004, Australia

    C. K. Fairley & C. K. Fairley

  4. AusSun Research Lab, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

    M. G. Kimlin

  5. The Kirby Institute, University of New South Wales, Sydney, Australia

    S. Emery

  6. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

    P. H. Anderson

  7. Department of Medicine, School of Clinical Sciences, Monash University, Monash Health, Clayton, 3168, Victoria, Australia

    P. R. Ebeling

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on behalf of the STEAL Study Group

Corresponding author

Correspondence to K. M. Klassen.

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Funding

This work was supported by The Kirby Institute (formerly the National Centre in HIV Epidemiology and Clinical Research) funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. The Kirby Institute is affiliated with the Faculty of Medicine, University of New South Wales. Funding for the vitamin D metabolites and researcher time was provided by the NHMRC Centre for Research Excellence in Sun and Health. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. No additional external funding was received for this study.

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Klassen, K.M., Kimlin, M.G., Fairley, C.K. et al. Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV. Osteoporos Int 27, 1737–1745 (2016). https://doi.org/10.1007/s00198-015-3432-3

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  • DOI: https://doi.org/10.1007/s00198-015-3432-3

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