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Vitamin D supplementation and falls: a trial sequential meta-analysis

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Summary

Background

Vitamin D supplementation is often recommended to prevent falls, although vitamin D trials and meta-analyses of these trials have reported conflicting results for this outcome. We aimed to assess if there was a need for further research.

Methods

We explored the value of doing further randomised controlled trials assessing the effects of vitamin D supplements on falls with trial sequential analysis with a risk reduction threshold of 15%. All analyses were done using the numbers of participants who had a fall in intention-to-treat analyses. Trial sequential analysis performs a cumulative meta-analysis, but reduces the risk of false-positive results from repetitive statistical testing by maintaining the overall risk of type 1 error at 5%.

Findings

In 20 existing randomised controlled trials (n=29 535), the effect estimate for vitamin D with or without calcium on falls lay within the futility boundary, providing evidence that vitamin D supplementation does not alter the relative risk by 15% or more. In a sensitivity analysis using a risk reduction threshold of 10%, the effect estimate also lay within the futility boundary. In subgroup analyses using a risk reduction threshold of 15%, the effect estimate also lay within the futility boundary for trials of vitamin D supplementation (16 trials, n=22 291) and trials of vitamin D with calcium (six trials, n=9919).

Interpretation

In pooled analyses, supplementation with vitamin D, with or without calcium, does not reduce falls by 15% or more. Future trials with similar designs are unlikely to alter these conclusions. At present, there is little justification for prescribing vitamin D supplements to prevent falls.

Funding

Health Research Council of New Zealand.

Introduction

Vitamin D supplementation has long been advocated for maintaining and improving musculoskeletal health.1 More recently, the association between vitamin D insufficiency and a variety of non-skeletal disorders has led to calls for broader use of vitamin D supplements.2, 3 However, findings from several recent systematic reviews and meta-analyses of randomised controlled trials do not support such recommendations. Vitamin D supplementation (without coadministered calcium supplements) has no clinically relevant effect on bone mineral density,4 no effect on total fracture or hip fracture,5, 6 and no effect on a broad range of non-skeletal endpoints.7, 8 One of the remaining recommendations for vitamin D supplementation is in the prevention of falls, even though recent meta-analyses on this topic have reported conflicting results.9, 10, 11, 12, 13

Recently, we reported the results of a trial sequential meta-analysis of vitamin D supplements on fracture, cardiovascular events, cancer, and mortality.8 Trial sequential analysis complements traditional meta-analysis by permitting an estimation of the point at which the body of evidence is sufficiently large and consistent to make further trials futile, because of the low probability that they will affect the results of the existing meta-analysis.14, 15 This approach is similar to the early termination of a clinical trial when interim analyses suggest that continuing the trial is highly unlikely to alter the interim result, although there is more certainty that later data will be similar to earlier data for a trial than in a trial sequential analysis. Using this technique, we concluded that existing trials reliably show that vitamin D supplementation, with or without calcium, does not produce clinically relevant effects on fracture, cardiovascular events, cancer, and mortality in unselected community-dwelling individuals, and that future trials with similar designs were unlikely to change these conclusions.8 Here, we extend these trial sequential analyses to the most recent meta-analyses of vitamin D supplementation on falls.

Section snippets

Search strategy

We searched PubMed in January, 2014, with the terms “vitamin D”, “systematic review”, and “meta-analysis” and identified ten trial-level meta-analyses of the effects of supplementation with vitamin D, with or without calcium, on falls published since January, 2009 (appendix).9, 10, 11, 12, 13, 16, 17, 18, 19, 20 We also reviewed the recent report on vitamin D intake by the Institute of Medicine.21 We identified all randomised trials included in any of these meta-analyses that studied vitamin D

Results

We obtained falls data from 20 trials (table 1).22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 The risk of bias in the trials is described in the appendix. All trials were randomised, 17 were double-blind, placebo-controlled trials,22, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, 36, 37, 38, 40, 41 13 described the random sequence generation explicitly,22, 23, 24, 27, 28, 31, 32, 34, 35, 37, 39, 40, 41 and 14 described the methods of allocation concealment.22, 23,

Discussion

Supplementation with vitamin D, with or without calcium, had no effect on falls in traditional meta-analysis. Trial sequential analysis suggests that vitamin D supplementation, with or without calcium, does not decrease falls by 15% or more, and that results from similar future trials are unlikely to alter this finding. A sensitivity analysis suggests that similar conclusions apply when considering a 10% risk reduction. The results of the traditional meta-analyses and the trial sequential

References (43)

  • A Avenell et al.

    Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis

    Cochrane Database Syst Rev

    (2009)
  • Patient level pooled analysis of 68500 patients from seven major vitamin D fracture trials in US and Europe

    BMJ

    (2010)
  • HA Bischoff-Ferrari et al.

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

    BMJ

    (2009)
  • YL Michael et al.

    Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the US Preventive Services Task Force

    Ann Intern Med

    (2010)
  • MH Murad et al.

    Clinical review: the effect of vitamin D on falls: a systematic review and meta-analysis

    J Clin Endocrinol Metab

    (2011)
  • ID Cameron et al.

    Interventions for preventing falls in older people in care facilities and hospitals

    Cochrane Database Syst Rev

    (2012)
  • LD Gillespie et al.

    Interventions for preventing falls in older people living in the community

    Cochrane Database Syst Rev

    (2012)
  • K Thorlund et al.

    User manual for trial sequential analysis (TSA)

    (2011)
  • M Chung et al.

    Vitamin D and calcium: a systematic review of health outcomes

    Evid Rep Technol Assess (Full Rep)

    (2009)
  • RR Kalyani et al.

    Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis

    J Am Geriatr Soc

    (2010)
  • CJ Rosen et al.

    The nonskeletal effects of vitamin D: an Endocrine Society scientific statement

    Endocr Rev

    (2012)
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      The calcium dose ranged between 360-1,200 mg/d. The outcome of interest was the number of falls [18,20–24,26] and/or the number of patients suffering from one or more falls (number of fallers) [19–21,23–25]. The duration of the intervention in the included studies extended from 1 to 60 months [19,20,22–26] (see Table 1 [18–30], Appendix 1 [18–30]).

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