TY - JOUR
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, Christopher
AU - Jorde, Rolf
AU - Berg, Vivian
AU - Walsh, Jennifer
AU - Eastell, Richard
AU - Evans, Amy L
AU - Bowles, Simon
AU - Naylor, K E
AU - Jones, Kerry S
AU - Schoenmakers, Inez
AU - Holick, Michael
AU - Orwoll, Eric
AU - Nielson, Carrie
AU - Kaufman, 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(D) status is unknown.
Objective: Directly measure circulating free 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: 1661 adults: (healthy(n=211), pre-diabetic(n=479), outpatients(n=783), cirrhotic(n=90), pregnant(n=20), nursing home(n=79))
Interventions: Merge research data on circulating free 25(OH)D (directly measured immunoassay), total 25(OH)D (LC/MS/MS), D binding protein (DBP by radial (polyclonal) immunodiffusion assay)), albumin, creatinine, iPTH 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, eGFR, BMI and other covariates).
Results: Free 25(OH)D was 4.7±1.8 pg/mL (mean ±SD) in healthy and 4.3 ±1.9 pg/mL in outpatients with 0.5-8.1 pg/mL and 0.9-8.1 pg/mL encompassing 95% of healthy and outpatients, respectively. Free 25(OH)D was higher in cirrhotics (7.1 ±3.0 pg/mL, p<.0033) and nursing home residents (7.9± 2.1pg/mL, p<.0033) compared to other groups and differed between whites and blacks (p<.0033) and between DBP haplotypes (p<.0001). Mixed effects modeling of relationships between free and total 25(OH)D identified clinical conditions (cirrhotic>nursing home>prediabetic > outpatient > pregnant), 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(D) status is unknown.
Objective: Directly measure circulating free 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: 1661 adults: (healthy(n=211), pre-diabetic(n=479), outpatients(n=783), cirrhotic(n=90), pregnant(n=20), nursing home(n=79))
Interventions: Merge research data on circulating free 25(OH)D (directly measured immunoassay), total 25(OH)D (LC/MS/MS), D binding protein (DBP by radial (polyclonal) immunodiffusion assay)), albumin, creatinine, iPTH 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, eGFR, BMI and other covariates).
Results: Free 25(OH)D was 4.7±1.8 pg/mL (mean ±SD) in healthy and 4.3 ±1.9 pg/mL in outpatients with 0.5-8.1 pg/mL and 0.9-8.1 pg/mL encompassing 95% of healthy and outpatients, respectively. Free 25(OH)D was higher in cirrhotics (7.1 ±3.0 pg/mL, p<.0033) and nursing home residents (7.9± 2.1pg/mL, p<.0033) compared to other groups and differed between whites and blacks (p<.0033) and between DBP haplotypes (p<.0001). Mixed effects modeling of relationships between free and total 25(OH)D identified clinical conditions (cirrhotic>nursing home>prediabetic > outpatient > pregnant), 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.
U2 - 10.1210/jc.2018-00295
DO - 10.1210/jc.2018-00295
M3 - Article
VL - 103
SP - 3278
EP - 3288
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
SN - 0021-972X
IS - 9
ER -
