Beyond 25(OH)D: Carboxylated Osteocalcin and the Undercarboxylated/Carboxylated Osteocalcin Ratio as Superior Biomarkers for Vitamin D Recovery in Offspring Affected by Maternal Deficiency.

Abstract

: Maternal vitamin D deficiency (VDD) compromises fetal skeletal development. The impact of postnatal vitamin D supplementation on osteocalcin (OC) carboxylation, converting undercarboxylated (ucOC) to carboxylated osteocalcin (cOC), in offspring remains unclear, given conflicting reports on the correlation between serum 25-hydroxyvitamin D (25(OH)D) and specific OC forms. This study investigated OC profile recovery in a mouse model of maternal VDD.: Female C57BL/6J mice were fed a VDD diet from four weeks pre-conception through lactation. Weaned offspring were maintained on the VDD diet and randomized to three groups: control (saline), standard-dose (1500 IU/kg), or high-dose (4500 IU/kg) vitamin D supplementation. Serum 25(OH)D, cOC, and ucOC were quantified via ELISA at 1, 2, and 4 weeks post-intervention.: Controls remained vitamin D-deficient (<13 ng/mL). Supplementation dose-dependently increased serum 25(OH)D (< 0.05). Crucially, while absolute ucOC levels remained stable across all groups, supplementation significantly upregulated cOC and total osteocalcin at all time points (< 0.05). Consequently, the ucOC/cOC ratio significantly decreased in supplemented groups. Partial correlation analysis revealed a strong positive correlation between 25(OH)D and cOC (r= 0.718) and a negative correlation with the ucOC/cOC ratio (r= -0.433), but no correlation with ucOC (r= -0.102).: In offspring affected by maternal VDD, vitamin D supplementation improves the osteocalcin carboxylation profile primarily by driving carboxylated osteocalcin synthesis rather than reducing the undercarboxylated pool. Serum cOC and the ucOC/cOC ratio serve as superior functional biomarkers to ucOC for monitoring therapeutic efficacy in this early-life developmental model.