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Relationship of Total and Free 25-Hydroxyvitamin D to Biomarkers and Metabolic Indices in Healthy Children

Christine A SimpsonJane H ZhangDirk VanderschuerenLei FuTeresita C PennestriRoger BouillonDavid E C ColeThomas O Carpenter

The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 4, April 2020, dgz230,



Vitamin D status is usually assessed by serum total 25-hydroxyvitamin D (t25-OHD). Whether free 25-hydroxyvitamin D measures better correlate with various clinical outcomes is unclear.


To identify correlations between t25-OHD, calculated and direct measures of free 25-OHD, and to identify associations of these measures with other outcomes in children, across the 6 common GC haplotypes.


Healthy urban-dwelling children underwent measurement of relevant variables.


Academic medical center.


The study included 203 healthy, urban-dwelling children, aged 6 months to 10 years, predominantly of Hispanic background and representative of all common GC haplotypes.



Main Outcome Measures

Total and free 25-OHD and 1,25(OH)2D, calcium, phosphate, parathyroid hormone (PTH), glucose, insulin, aldosterone, and renin.


Mean t25-OHD [26.3 ± 6.7ng/ml; 65.8 ± 16.8nmol/L] were lowest in the GC2 genotype. Mean t1,25(OH)2D [57.6 ± 16.5pg/ml; 143.9 ± 41.3pmol/L], were lowest in GC1f/1fGC1f/2, and GC2/2 groups. T25-OHD correlated strongly with calculated free 25-OHD (cf25-OHD) (r = 0.89) and moderately with directly measured free 25-OHD (dmf25-OHD) (r = 0.69). Cf25-OHD correlated with dmf25-OHD (r = 0.69) (P < 0.001 for all). t25-OHD inversely correlated with body mass index (BMI) (r=-0.191; P = 0.006), skin reflectometry, and systolic blood pressure. T25-OHD correlated with fasting insulin and the homeostatic model assessment for insulin resistance (HOMA-IR), however significance for these correlations was not evident after adjustment for BMI. PTH inversely correlated with all measures of 25-OHD, but most strongly with t25-OHD.


Measures of circulating total and free 25-OHD are comparable measures of vitamin D status in heathy children. Correlations are similar with other outcome variables, however t25-OHD remains the strongest correlate of circulating PTH and other variables. These data argue against routine refinement of the t25-OHD measure using currently available assessments of free 25-OHD.