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Antifracture efficacy with supplemental vitamin D has been questioned by several trials published in the last 4 years, leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation. A recent meta-analysis confirms the efficacy of oral supplemental vitamin D in preventing non-vertebral and hip fractures among older individuals (≥ 65 years) [1]. The meta-analysis compared oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, the dose was multiplied by the percentage of adherence to estimate the mean received dose (dose × adherence) for each trial. The primary goal was to determine the antifracture efficacy of oral vitamin D supplementation among individuals aged 65 years or older by performing a systematic review of the literature and meta-analysis of high-quality, double-blinded, randomized, controlled trials (RCTs). Twelve double-blind RCTs for non-vertebral fractures (n = 42,279) and eight RCTs for hip fractures (n = 40,886) were included, among them the data from the Women’s Health Initiative trial. In addition, the analysis specifically addressed the antifracture efficacy by received dose, achieved 25-hydroxyvitamin D levels and in predefined subgroups.

The authors reported the following results. The pooled relative risk (RR) was 0.86 (95% confidence interval (CI) 0.77–0.96) for prevention of non-vertebral fractures and 0.91 (95% CI 0.78–1.05) for the prevention of hip fractures. However, there was a significant heterogeneity for both endpoints. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both endpoints. Consistently, pooling trials with a higher received dose of more than 400 IU/day vitamin D resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI 0.72–0.89; n = 33,265 subjects from nine trials) for non-vertebral fractures and 0.82 (95% CI 0.69–0.97; n = 31,872 subjects from five trials) for hip fractures. The higher dose reduced non-vertebral fractures in community-dwelling individuals (−29%) and institutionalized older individuals (−15%), and its effect was independent of additional calcium supplementation.

It was concluded that non-vertebral fracture prevention with vitamin D is dose-dependent and that a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.


  • Martin Birkhäuser
    Professor Emeritus, Division of Gynecological Endocrinology and Reproductive Medicine, Department of Obstetrics & Gynecology, University of Berne, Switzerland


  1. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. [i]Arch Intern Med[/i] 2009;169:551-61. Published March 23, 2009.
  2. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. [i]N Engl J Med[/i] 1992;327:1637-42.
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  5. International Position Paper on Womens Health and Menopause: a comprehensive approach. National Heart, Lung and Blood Institute, Office of Research on Womens Health, National Institute of Health, and Giovanni Lorenzini Medical Science Foundation. NIH publication no. 02-3284, July 2002.
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  7. Mithal A, Wahl DA, Bonjour J-P, et al. on behalf of the IOF Committee of Scientific Advisors, Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. [i]Osteoporos Int[/i] 2009 Jun 19. [Epub ahead of print].
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