Persia Sabrina, Holmlund-Suila Elisa, Valkama Saara, Enlund-Cerullo Maria, Rosendahl Jenni, Andersson Sture, Mäkitie Outi, Hauta-Alus Helena
Endocr Connect. 2024 Dec 20;14(1). doi: 10.1530/EC-24-0482. Print 2025 Jan 1.
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.
1型前胶原氨基端前肽（P1NP）和1型胶原羧基端交联末肽（CTX-I）是骨代谢标志物。我们研究了补充维生素D3对这些标志物的影响，以及它们与12月龄婴儿生长和骨骼参数的关系。在一项婴儿维生素D干预（VIDI）随机双盲研究中，987名婴儿从2周龄至24月龄每天补充10μg维生素D3（10μg组）或30μg维生素D3（30μg组）。我们对原VIDI试验进行了二次分析。在12月龄时，分析了P1NP（n = 812）和CTX-I（n = 786）浓度，并通过外周定量计算机断层扫描测量了人体测量指标以及胫骨的总骨矿物质含量、体积骨矿物质密度、横截面积和极惯性矩。计算了从出生到12个月的体重和身长增长率。维生素D剂量不影响CTX-I的平均（标准差）水平（10μg组：0.90（0.31）；30μg组：0.89（0.31）（P>0.53））。10μg组与30μg组相比，P1NP的平均差异（95%CI）在男孩中为35（-103，33）ng/mL（P = 0.31），在女孩中为-63（-4，130）ng/mL（P = 0.064）。在10μg组中，女孩的P1NP平均（标准差）值（1509（362）ng/mL）高于男孩（1407（297）ng/mL）（P = 0.003）；在30μg组（女孩：1446（359）；男孩：1442（359），P = 0.91）或CTX-I中未观察到性别差异。在整个队列中，P1NP与身长增长率呈正相关（B（95%CI）0.0003（0.0001，0.001），P = 0.022），但在按干预组或性别划分的亚组中不相关，校正了出生大小和父母身高并进行了多重检验校正。P1NP与体重增长率呈正相关（0.01（0.0003，0.01），P<0.001）。在整个队列中（-0.90（-1.40，-0.40），P = 0.005）以及在30μg组中（-1.05（-1.72，-0.39），P = 0.011），观察到CTX-I与身长（cm）呈负相关。此外，在整个队列中（-0.33（-0.55，-0.12），P = 0.015）以及体重增长率方面（-0.43（-0.66，-0.20），P = 0.005），CTX-I与体重（标准差分值）呈负相关，在30μg组和男孩中持续存在，但在10μg组或女孩中不存在。两种标志物均与骨骼参数无关。观察到的P1NP性别差异可能表明，较高剂量的维生素D导致女孩骨胶原基质形成略有下降，而男孩则没有。P1NP和CTX-I与婴儿期的生长和体型有关，但与骨矿化无关。
