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.