A comparison of free and total 25-hydroxyvitamin D levels as functional indicators of bone health in healthy children

Context: The “free hormone” hypothesis suggests that the free
25-hydroxyvitamin D (25OHDFree) level may usefully indicate bone
health.

Objective: To
determine
which vitamin D measure is optimally correlated with clinical and bone
parameters in healthy children.

Design and Participants: A
cross-sectional study including 146 healthy children (71 boys, 9.5±1.9 years)
at a tertiary medical center.

Main Outcome Measures: We used a multiplex liquid
chromatography-tandem mass spectrometry-based assay to simultaneously measure
vitamin D metabolites. The 25OHDFree level was directly measured
(m-25OHDFree) or calculated using genotype-constant or
genotype-specific affinity coefficients of vitamin D-binding proteins
(con-25OHDFree or spe-25OHDFree). Bone
mineral content (BMC) and density (BMD) were assessed via dual-energy X-ray
absorptiometry.

Results: The concentrations
of total 25OHD
(25OHDTotal), the three forms of 25OHDFree, and
24,25-dihydroxyvitamin D3 correlated with parathyroid hormone levels
(all p<0.01). Serum 25OHDTotal and m-25OHDFree levels reflected
age, puberty, season, body mass index (BMI), daylight hours, and vitamin D
intake (all p<0.05). The con-25OHDFree level
better reflected puberty and daylight hours than did the spe-25OHDFree
level (both p<0.01). The association between the 25OHDTotal
level and bone parameters varied according to the BMI (interaction p<0.05).
In 109 normal-weight children, the con-25OHDFree level correlated
with BMC and BMD (both p<0.05), but the 25OHDTotal and
24,25-dihydroxyvitamin D3 levels were associated with BMC (both
p<0.05). No association was found in overweight or obese children.

Conclusions: In healthy children, total and free 25OHD levels comparably reflected
lifestyle factors. In normal-weight children, the con-25OHDFree level reflected BMC and BMD,
whereas the 25OHDTotal level was associated with BMC.