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Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays

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Abstract

Summary

A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D.

Introduction

This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations.

Methods

DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21–80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D.

Results

Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r s = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (−0.34, p < 0.001) versus free/bioavailable 25(OH)D (−0.18/−0.24 depending on DBP assay, p ≤ 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites.

Conclusions

The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

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Funding sources

This project was supported by NIH Grants K23 DK093556 (MRD), K24 DK076808 (MBL and JS), R01DK064966 (MBL), and T32DK060455 (TJ). Dr. Denburg was also funded by The Nephcure Foundation–American Society of Nephrology Research Grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Baker is supported by a Veterans Affairs Clinical Science Research & Development Career Development Award. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States Government. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript.

Disclosures

Dr. Denburg receives/received funding (not related to this work) from Genentech, Inc, Mallinckrodt Pharmaceuticals, and the National Kidney Foundation/Amgen KDOQI Research Fellowship. Dr. Denburg has a consultancy agreement with Infiniti Medical. Dr. Leonard’s consultancy agreements include Amgen, Inc., Johnson & Johnson, and Novartis. She also serves/served as an Associate Editor for the Journal of the American Society of Nephrology and Journal of Bone and Mineral Research, on the American Society of Pediatric Nephrology Council, on the Scientific Advisory Board of Marodyne Medical, and an NIH Data Safety and Monitoring Board.

Conflict of interest

Thomas Jemielita, Joshua Baker, Samir Sayed, Babette Zemel, Justine Shults, and Rita Herskovitz declare that they have no conflict of interest.

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Authors and Affiliations

  1. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    T. O. Jemielita & J. Baker

  2. Stanford University School of Medicine, Stanford, CA, USA

    M. B. Leonard

  3. Philadelphia VA Medical Center, Philadelphia, PA, USA

    J. Baker

  4. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    S. Sayed & R. Herskovitz

  5. The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, 34th Street and Civic Center Blvd, Philadelphia, PA, 19104, USA

    B. S. Zemel, J. Shults & M. R. Denburg

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  1. T. O. Jemielita
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Jemielita, T.O., Leonard, M.B., Baker, J. et al. Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays. Osteoporos Int 27, 617–626 (2016). https://doi.org/10.1007/s00198-015-3296-6

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