Comparative effects of calcium, vitamin D, and combined supplementation on growth and bone mineral density in healthy children and adolescents: a systematic review and network meta-analysis
Abstract
Calcium and vitamin D are central to skeletal development in childhood, yet the relative effects of calcium alone, vitamin D alone, and their combination on somatic growth and bone mineral density (BMD) in healthy children and adolescents remain unclear. Eight databases were searched from inception through June 2026 for randomized controlled trials of oral calcium and/or vitamin D supplementation. Random-effects pairwise meta-analyses and Bayesian network meta-analysis (NMA) evaluated monthly height growth, monthly weight gain, and BMD at the lumbar spine, femoral neck, and total body. Sixteen RCTs involving approximately 2,100 participants were included. Supplementation did not significantly affect monthly height growth (MD = 0.0441 cm/month, 95% CI [−0.0114, 0.0996]) or monthly weight gain (MD = 0.0075 kg/month, 95% CI [−0.0064, 0.0214]). Small positive differences were observed for lumbar spine BMD (MD = 0.0145 g/cm 2 , 95% CI [0.0040, 0.0249]), femoral neck BMD (MD = 0.0101 g/cm 2 , 95% CI [0.0064, 0.0138]), and total body BMD (MD = 0.0110 g/cm 2 , 95% CI [0.0049, 0.0170]), with substantial heterogeneity for lumbar spine and total body outcomes. Age-subgroup findings were exploratory, and no significant subgroup differences were found by intervention duration. The NMA did not establish consistent superiority of any active regimen. Calcium and/or vitamin D supplementation did not appreciably accelerate height or weight gain. Small site-specific increases in aBMD were observed, but their clinical significance remains uncertain and they do not establish benefits for bone strength or fracture prevention. Supplementation should primarily address inadequate intake, biochemical deficiency, or other clinical indications rather than routine growth promotion. https://www.crd.york.ac.uk/prospero/ , identifier CRD420261388414.