Effects of intermittent or single high-dose vitamin D supplementation on risk of falls and fractures: a systematic review and meta-analysis.

UNLABELLED: Previous randomized controlled trials have reported inconsistent findings regarding the effects of high-dose vitamin D supplementation on a risk of falls and fractures. This meta-analysis of 15 trials shows that intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.

PURPOSE: Randomized controlled trials (RCTs) have reported controversial findings regarding the associations between intermittent or single high-dose vitamin D supplementation and a risk of falls and fractures in adults. This study aimed to investigate those associations using a systematic review and meta-analysis.

METHODS: We searched PubMed, EMBASE, and Cochrane Library from inception to May 25, 2022. Data were extracted for a random-effects meta-analysis to calculate a pooled relative risk (RR) with a 95% confidence interval (CI).

RESULTS: Out of 527 articles, a total of 15 RCTs were included in the final analysis. In a meta-analysis of RCTs, intermittent or single high-dose vitamin D supplementation showed no significant beneficial effect in the prevention of either falls (RR, 1.03 [95% CI, 0.98-1.09]; I2  = 56.6%; n = 11) or fractures (RR, 0.99 [95% CI, 0.87-1.14]; I2  = 48.3%; n = 11). Among the subgroup meta-analyses by various factors, intermittent or single high-dose vitamin D supplementation reduced the risk of fractures in the subgroup meta-analysis of RCTs that included fewer than 1000 participants (RR, 0.74 [95% CI 0.57-0.96]; I2  = 0.0%; n = 5). However, its beneficial effect was not observed in those including 1000 or more participants (RR, 1.06 [95% CI 0.92-1.21]; I2  = 57.5%; n = 6). In contrast, intermittent or single high-dose vitamin D3 supplementation increased the risk of falls on the borderline of statistical significance (RR, 1.06 [95% CI 0.99-1.15]; P = 0.051; I2  = 50.0%; n = 7).

CONCLUSIONS: Intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.