Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials

Wu, Feitong; El-Hajj Fuleihan, Ghada; Cai, Guoqi; Lamberg-Allardt, Christel; Viljakainen, Heli T.; Rahme, Maya; Grønborg, Ida M.; Andersen, Rikke; Khadilkar, Anuradha; Zulf Mughal, M.; Mølgaard, Christian; Larnkjær, Anni; Zhu, Kun; Riley, Richard D.; Winzenberg, Tania

Abstract

Background
Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D–deficient children are unclear.

Objectives
This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D–deficient individuals.

Methods
This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1–19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup.

Results
Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty.

Conclusions
Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets).

This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772

Citation

Wu, F., El-Hajj Fuleihan, G., Cai, G., Lamberg-Allardt, C., Viljakainen, H. T., Rahme, M., …Winzenberg, T. (2023). Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition, 118(3), 498-506. https://doi.org/10.1016/j.ajcnut.2023.05.028

• Journal Article Type: Article
• Acceptance Date: May 23, 2023
• Online Publication Date: Aug 8, 2023
• Publication Date: 2023-09
• Deposit Date: Feb 1, 2024
• Journal: The American Journal of Clinical Nutrition
• Print ISSN: 0002-9165
• Publisher: American Society for Nutrition
• Peer Reviewed: Peer Reviewed
• Volume: 118
• Issue: 3
• Pages: 498-506
• DOI: https://doi.org/10.1016/j.ajcnut.2023.05.028
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0002916523639565?via%3Dihub