Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials

Abstract

Objective: To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals.

Data sources: We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion.

Results: Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94).

Conclusions: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Fig 1 Quorum flow chart. RCT=randomised controlled trial

Fig 2 Fall prevention with high dose (700-1000 IU a day) and low dose (200-600 IU a day) of supplemental vitamin D. Boxes represent relative risks, and the size of the boxes is proportional to the size of the high dose supplemental vitamin D trials included in the primary analysis. Error bars represent 95% confidence intervals. Shaded boxes indicate trials with vitamin D_3, and white boxes indicate those with vitamin D₂

Fig 3 Fall prevention by dose and achieved 25(OH)D concentrations. Circles represent relative risks and error bars represent 95% confidence intervals. Trendline is based on series of effect sizes (circles). There were three trials with 800 IU D₃,^{w5 w6 w7} so the effect size for 800 IU D₃ is the pooled result from these three trials. Likewise, the effect size for 1000 IU D₂ is the pooled result from the two trials with 1000 IU D₂.^{w3 w4} We have listed the same dose D₂ and D₃ separately in the graph to account for their potential different impact on fall reduction. As there were two data points from the Broe et al trial that reached 48 nmol/l,^w1 two trials that reached 60 nmol/l,^{w1 w3} and two trials that reached 66 nmol/l,^{w6 w7} we pooled each of the sets. On the basis of visual inspection of figure 3, the benefits of vitamin D for fall risk started at a dose of 700 IU a day