Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations

Janice B. Schwartz, John Christopher G. Gallagher, Rolf Jorde, Vivian Berg, Jennifer Walsh, Richard Eastell, Amy L. Evans, Simon Bowles, Kim E. Naylor, Kerry S. Jones, Inez Schoenmakers, Michael Holick, Eric Orwoll, Carrie Nielson, Martin Kaufmann, Glenville Jones, Roger Bouillon, Jennifer Lai, Davide Verotta, Daniel Bikle

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis . nursing home residents . patients with prediabetes . outpatients . pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

Original languageEnglish (US)
Pages (from-to)3278-3288
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number9
DOIs
StatePublished - Sep 1 2018

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Nursing
Haplotypes
Outpatients
Nursing Homes
Hazards and race conditions
Health
Body Mass Index
Population
Glomerular Filtration Rate
Liquid chromatography
Analysis of variance (ANOVA)
Parathyroid Hormone
Vitamin D
Fibrosis
Mass spectrometry
Outcome Assessment (Health Care)
Albumins
Assays
Creatinine
Carrier Proteins

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. / Schwartz, Janice B.; Gallagher, John Christopher G.; Jorde, Rolf; Berg, Vivian; Walsh, Jennifer; Eastell, Richard; Evans, Amy L.; Bowles, Simon; Naylor, Kim E.; Jones, Kerry S.; Schoenmakers, Inez; Holick, Michael; Orwoll, Eric; Nielson, Carrie; Kaufmann, Martin; Jones, Glenville; Bouillon, Roger; Lai, Jennifer; Verotta, Davide; Bikle, Daniel.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 9, 01.09.2018, p. 3278-3288.

Research output: Contribution to journalArticle

Schwartz, JB, Gallagher, JCG, Jorde, R, Berg, V, Walsh, J, Eastell, R, Evans, AL, Bowles, S, Naylor, KE, Jones, KS, Schoenmakers, I, Holick, M, Orwoll, E, Nielson, C, Kaufmann, M, Jones, G, Bouillon, R, Lai, J, Verotta, D & Bikle, D 2018, 'Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 9, pp. 3278-3288. https://doi.org/10.1210/jc.2018-00295
Schwartz, Janice B. ; Gallagher, John Christopher G. ; Jorde, Rolf ; Berg, Vivian ; Walsh, Jennifer ; Eastell, Richard ; Evans, Amy L. ; Bowles, Simon ; Naylor, Kim E. ; Jones, Kerry S. ; Schoenmakers, Inez ; Holick, Michael ; Orwoll, Eric ; Nielson, Carrie ; Kaufmann, Martin ; Jones, Glenville ; Bouillon, Roger ; Lai, Jennifer ; Verotta, Davide ; Bikle, Daniel. / Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 9. pp. 3278-3288.
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abstract = "Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95{\%} of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis . nursing home residents . patients with prediabetes . outpatients . pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.",
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T1 - Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations

AU - Schwartz, Janice B.

AU - Gallagher, John Christopher G.

AU - Jorde, Rolf

AU - Berg, Vivian

AU - Walsh, Jennifer

AU - Eastell, Richard

AU - Evans, Amy L.

AU - Bowles, Simon

AU - Naylor, Kim E.

AU - Jones, Kerry S.

AU - Schoenmakers, Inez

AU - Holick, Michael

AU - Orwoll, Eric

AU - Nielson, Carrie

AU - Kaufmann, Martin

AU - Jones, Glenville

AU - Bouillon, Roger

AU - Lai, Jennifer

AU - Verotta, Davide

AU - Bikle, Daniel

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis . nursing home residents . patients with prediabetes . outpatients . pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

AB - Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis . nursing home residents . patients with prediabetes . outpatients . pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

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