Bone turnover markers, and growth and bone parameters in infants participating in a vitamin D intervention study

Amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-I) are markers of bone metabolism. We examined the effect of vitamin D3 supplementation on these markers and their relationship with growth and bone parameters in 12-month-old infants. In a randomized, double-blinded, vitamin D intervention in infants (VIDI) study, 987 infants received daily vitamin D3 supplementation of 10 μg (group-10) or 30 μg (group-30) from age 2 weeks to 24 months. We conducted a secondary analysis of the original VIDI trial. At 12 months of age, P1NP (n = 812) and CTX-I (n = 786) concentrations were analyzed, and anthropometrics and total bone mineral content, volumetric bone mineral density, cross-sectional area and polar moment of inertia of tibia were measured by peripheral quantitative computed tomography. The growth rate in weight and length was calculated from birth to 12 months. The vitamin D dose did not influence mean (SD) levels of CTX-I (group-10: 0.90 (0.31); group-30: 0.89 (0.31) (P > 0.53)). The mean difference of P1NP (CI 95%) comparing group-10 with group-30 was 35 (-103, 33) ng/mL (P = 0.31) in boys and -63 (-4, 130) ng/mL (P = 0.064) in girls. In group-10, girls had higher mean (SD) value of P1NP (1509 (362) ng/mL) than boys (1407 (297) ng/mL) (P = 0.003); no sex differences were observed in group-30 (girls: 1446 (359); boys: 1442 (359), P = 0.91) or CTX-I. P1NP associated positively with the growth rate in length (B (CI 95%) 0.0003 (0.0001, 0.001), P = 0.022) in the whole cohort but not in subgroups divided by the intervention group or sex, adjusted for birth size and parental heights and corrected for multiple testing. P1NP associated positively with the growth rate in weight (0.01 (0.0003, 0.01), P < 0.001). An inverse association was observed between CTX-I and length (cm) in the whole cohort (-0.90 (-1.40, -0.40), P = 0.005) and in group-30 (-1.05 (-1.72, -0.39), P = 0.011). Furthermore, CTX-I associated negatively with weight (SDS) in the whole cohort (-0.33 (-0.55, -0.12), P = 0.015) and the growth rate in weight (-0.43 (-0.66, -0.20), P = 0.005), persisting in group-30 and in boys but not in group-10 or in girls. Neither marker was associated with bone parameters. The observed sex difference in P1NP might suggest that a higher vitamin D dose resulted in a small decrease in bone collagen matrix formation in girls but not in boys. P1NP and CTX-I associate with growth and body size but not with bone mineralization in infancy.