T O Jemielita1, M B Leonard2, J Baker1,3, S Sayed4, B S Zemel5, J Shults5, R Herskovitz4, M R Denburg6. 1. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 2. Stanford University School of Medicine, Stanford, CA, USA. 3. Philadelphia VA Medical Center, Philadelphia, PA, USA. 4. The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 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. 6. 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. denburgm@email.chop.edu.
Abstract
UNLABELLED: 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.
UNLABELLED: 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.
Entities:
Keywords:
Bone mineral density; Parathyroid hormone; Vitamin D; Vitamin D-binding protein
Authors: A M Grant; A Avenell; M K Campbell; A M McDonald; G S MacLennan; G C McPherson; F H Anderson; C Cooper; R M Francis; C Donaldson; W J Gillespie; C M Robinson; D J Torgerson; W A Wallace Journal: Lancet Date: 2005 May 7-13 Impact factor: 79.321
Authors: Maja Christiansen; Charlotte S Jørgensen; Inga Laursen; Daniel Hirschberg; Peter Højrup; Gunnar Houen Journal: Biochim Biophys Acta Date: 2007-02-12
Authors: Shanna Nesby-O'Dell; Kelley S Scanlon; Mary E Cogswell; Cathleen Gillespie; Bruce W Hollis; Anne C Looker; Chris Allen; Cindy Doughertly; Elaine W Gunter; Barbara A Bowman Journal: Am J Clin Nutr Date: 2002-07 Impact factor: 7.045
Authors: Michelle R Denburg; Heidi J Kalkwarf; Ian H de Boer; Martin Hewison; Justine Shults; Babette S Zemel; David Stokes; Debbie Foerster; Benjamin Laskin; Anthony Ramirez; Mary B Leonard Journal: Pediatr Nephrol Date: 2013-06-02 Impact factor: 3.714
Authors: Camille E Powe; Catherine Ricciardi; Anders H Berg; Delger Erdenesanaa; Gina Collerone; Elizabeth Ankers; Julia Wenger; S Ananth Karumanchi; Ravi Thadhani; Ishir Bhan Journal: J Bone Miner Res Date: 2011-07 Impact factor: 6.741
Authors: Ishir Bhan; Camille E Powe; Anders H Berg; Elizabeth Ankers; Julia B Wenger; S Ananth Karumanchi; Ravi I Thadhani Journal: Kidney Int Date: 2012-03-07 Impact factor: 10.612
Authors: Rene F Chun; Ivan Hernandez; Renata Pereira; Leon Swinkles; Tonnie Huijs; Rui Zhou; Nancy Q Liu; Albert Shieh; Miriam Guemes; Sanjay M Mallya; John S Adams; Martin Hewison Journal: Endocrinology Date: 2016-07-11 Impact factor: 4.736
Authors: Michael T Yin; Ellen S Chan; Todd T Brown; Pablo Tebas; Grace A McComsey; Kathleen M Melbourne; Andrew Napoli; William R Hardin; Heather J Ribaudo; Edgar T Overton Journal: AIDS Date: 2017-11-13 Impact factor: 4.177
Authors: Albert Shieh; Rene F Chun; Christina Ma; Sten Witzel; Briana Meyer; Brandon Rafison; Leon Swinkels; Tonnie Huijs; Sam Pepkowitz; Brett Holmquist; Martin Hewison; John S Adams Journal: J Clin Endocrinol Metab Date: 2016-05-18 Impact factor: 5.958
Authors: Michelle R Denburg; Andrew N Hoofnagle; Samir Sayed; Jayanta Gupta; Ian H de Boer; Lawrence J Appel; Ramon Durazo-Arvizu; Krista Whitehead; Harold I Feldman; Mary B Leonard Journal: J Bone Miner Res Date: 2016-06 Impact factor: 6.741
Authors: Albert Shieh; Christina Ma; Rene F Chun; Sten Witzel; Brandon Rafison; Hannah T M Contreras; Jonas Wittwer-Schegg; Leon Swinkels; Tonnie Huijs; Martin Hewison; John S Adams Journal: J Clin Endocrinol Metab Date: 2017-04-01 Impact factor: 6.134