Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone as Functional Biomarkers of Bone Mass in Early Childhood

The 25-hydroxyvitamin D (25(OH)D) concentration at which parathyroid hormone (PTH) concentration plateaus has been considered to benchmark vitamin D deficiency. However, in young children, there is limited evidence for a suppression point in the 25(OH)D-PTH relationship or its relevance to bone mass accrual.

To determine whether the threshold of 25(OH)D at PTH suppression in young children is corroborated by associations of 25(OH)D (or PTH) with bone mineral content (BMC) and areal bone mineral density (aBMD).

In a cross-sectional secondary analysis of data from the BONe and mUScle health in Kids (BONUSKids) study of 4-y-old children in Bangladesh, serum 25(OH)D and intact PTH (iPTH) were analyzed by liquid chromatography-tandem mass spectrometry and a chemiluminescent immunoassay, respectively. BMC and aBMD were measured by dual-energy X-ray absorptiometry. Associations between 25(OH)D, iPTH, and bone outcomes (BMC, BMC z-score, aBMD, and aBMD z-score) were modeled using multivariable-adjusted linear regression and spline models. Model fit was compared using Akaike's Information Criteria.

Of 534 participants (51% female), 28% had 25(OH)D concentrations <25 nmol/L and 34% had iPTH >6.7 pmol/L. Model fit of the inverse relationship between 25(OH)D and iPTH was optimized with an inflection point at 25 nmol/L [<25 nmol/L: -0.16 pmol/L per 1 nmol/L increase in 25(OH)D; 95% confidence interval (CI): -0.22, -0.10; P < 0.001), above which the slope attenuated (≥25 nmol/L: -0.02 pmol/L; 95% CI: -0.04, -0.003; P = 0.019]. However, the positive linear associations between 25(OH)D and bone mass outcomes were monotonic (P < 0.05), and iPTH was not associated with any bone outcome in adjusted models (P > 0.05 for all). Associations were similar in males and females.

Among 4-y-old children in Dhaka, Bangladesh, we did not identify a 25(OH)D threshold to define vitamin D deficiency based on its association with bone mass. However, efforts to raise 25(OH)D to ≥25 nmol/L may be warranted based on the relatively strong inverse association of 25(OH)D with iPTH below this threshold. This trial was registered at clinicaltrials.gov as #NCT03537443.