Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis.

Context: There is still controversy over the effect of vitamin D3 supplementation on bone health.

Objective: The effects of vitamin D3 supplementation on bone mineral density (BMD) and markers of bone turnover, as well as the dose-response relationship between vitamin D3 and bone health in adults, were evaluated.

Data Sources: The PubMed, Scopus, Cochrane, Web of Science, and AGRIS databases were searched for articles published through April 30, 2022. Thirty-nine of the 6409 records identified met the inclusion criteria.

Data Extraction: Data were extracted from articles by 2 authors, and data extraction was cross-checked independently. A random-effects model was used to estimate the pooled effect size and the associated 95%CI for the effect of vitamin D3 for each outcome. A one-stage random-effects dose-response model was used to estimate the dose-response relationship between vitamin D3 supplementation and BMD.

Data Analysis: Results of meta-analysis showed a beneficial effect of vitamin D3 at the lumbar spine (standardized mean difference [SMD] = 0.06; 95%CI, 0.01-0.12) and femoral neck (SMD = 0.25; 95%CI, 0.09-0.41). Dose-response analysis revealed a linear relationship between vitamin D3 supplementation doses and BMD at the femoral neck, lumbar spine, and total hip sites. No significant effect of vitamin D3 supplementation on whole-body or total hip BMD was observed (P > 0.05). Vitamin D3 supplementation significantly decreased BMD at both proximal and distal forearm (SMD = -0.16; 95%CI, -0.26 to -0.06). The variables of ethnicity, age, baseline 25-hydroxyvitamin D (25[OH]D), menopause status, vitamin D3 dosing frequency, and bone health status (P interaction = 0.02) altered the effect of vitamin D3 supplementation on BMD. Additionally, a nonlinear relationship between vitamin D3 supplement doses and markers of bone turnover was found.

Conclusion: A protective effect of vitamin D3 supplementation on BMD of the lumbar spine, femoral neck, and total hip is implicated.

Systematic Review Registration: PROSPERO registration number CRD42017054132.