Relationship of total and calculated free 25-hydroxyvitamin D to biomarkers and metabolic indices in healthy children

ABSTRACT Context:  Vitamin D status is usually assessed by serum
total 25-hydroxyvitamin D.  Whether free 25-hydroxyvitamin D
measures better correlate with various clinical outcomes is unclear.
Objective:  To identify correlations between total
25-hydroxyvitamin D (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. Design:  Healthy
urban-dwelling children underwent measurement of relevant variables.
Setting: Academic medical center Participants: Healthy, urban-dwelling
children, 6 months to 10 yrs old, predominantly of Hispanic background and
representative of all common GC haplotypes. Intervention: None Main
Outcome Measures: Total and free 25-OHD and 1,25(OH)2D, calcium,
phosphate, PTH, glucose, insulin, aldosterone, and renin. Results: 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/1f, GC1f/2, and GC2/2 groups. T25-OHD correlated
strongly with circulating free 25-OHD (cf25-OHD) (r=0.89) and 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 BMI (r=-0.191; p=0.006), skin reflectometry, and systolic
blood pressure. T25-OHD correlated with fasting insulin and HOMA-IR,
however significance for these correlations were not evident after
adjustment for BMI. PTH inversely correlated with all measures of 25-OHD,
but most strongly with t25-OHD. Conclusions:  Measure 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.