Differences in overlapping meta-analyses of vitamin D supplements and falls

Overlapping meta-analyses on the same topic are common and often report discordant results. An Endocrine Society (ES) meta-analysis reported that vitamin D with calcium reduced the risk of falls, whereas vitamin D monotherapy had no effect. Despite meta-analyzing an overlapping set of trials, we concluded that vitamin D with or without calcium had no effect on falls.

The objective of the study was to determine the reasons for the different conclusions from the two meta-analyses.

We extracted raw data from the 25 randomized controlled trials included in the ES meta-analysis, calculated the treatment effect for each trial, compared them with the published ES meta-analysis, and determined the reason for any differences.

Of the 25 trials, there were differences in 14 results (56%) between the two meta-analyses. In the ES meta-analysis, data were used from a subset of falls or participants (four trials), from trial completers (three trials), or were imputed from fracture data (one trial). Other differences resulted from use of adjusted results from original papers (two trials), differences in incorporating data from multiarm and factorial studies (three trials), and inconsistent group numbers reported in original papers (two trials). In a reanalysis of the ES meta-analysis using unadjusted analyses and all randomized participants, there was a marginal effect of vitamin D with or without calcium on falls [relative risk (RR) 0.95, 95% confidence interval (CI) 0.90-1.00], with the subgroup analysis showing no effect of vitamin D monotherapy (RR 1.00, 95% CI 0.92-1.08) or vitamin D with calcium vs the placebo/controls (RR 0.95, 95% CI 0.88-1.02), but a modest effect of vitamin D with calcium vs calcium (RR 0.84, 95% CI 0.76-0.92) was shown.

Methodological differences in utilizing data from the same trials directly led to substantially different conclusions between meta-analyses about the efficacy of vitamin D supplements on falls. More detailed reporting of meta-analyses is necessary to allow readers to understand the discordant results from overlapping meta-analyses.