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

H A Bischoff-Ferrari, B Dawson-Hughes, H B Staehelin, J E Orav, A E Stuck, R Theiler, J B Wong, A Egli, D P Kiel, J Henschkowski, H A Bischoff-Ferrari, B Dawson-Hughes, H B Staehelin, J E Orav, A E Stuck, R Theiler, J B Wong, A Egli, D P Kiel, J Henschkowski

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.

Conflict of interest statement

Competing interests: None declared.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787496/bin/ferh608828.f1_default.jpg
Fig 1 Quorum flow chart. RCT=randomised controlled trial
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787496/bin/ferh608828.f2_default.jpg
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 D3, and white boxes indicate those with vitamin D2
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787496/bin/ferh608828.f3_default.jpg
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

References

    1. Blake AJ, Morgan K, Bendall MJ, Dallosso H, Ebrahim SB, Arie TH, et al. Falls by elderly people at home: prevalence and associated factors. Age Ageing 1988;17:365-72.
    1. Graafmans WC, Ooms ME, Hofstee HM, Bezemer PD, Bouter LM, Lips P. Falls in the elderly: a prospective study of risk factors and risk profiles. Am J Epidemiol 1996;143:1129-36.
    1. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701-7.
    1. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003;18:343-51.
    1. Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 2004;19:265-9.
    1. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 2000;66:419-24.
    1. Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet 1976;1:626-9.
    1. Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 2009;20:315-22.
    1. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000;15:1113-8.
    1. Bischoff-Ferrari HA, Dawson-Hughes B, Willett CW, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004;291:1999-2006.
    1. Law M, Withers H, Morris J, Anderson F. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Age Ageing 2006;35:482-6.
    1. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326:469.
    1. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 2007; 92: 2058-65.
    1. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged >=60 y. Am J Clin Nutr 2004;80:752-8.
    1. Heikinheimo RJ, Haavisto MV, Harju EJ, Inkovaara JA, Kaarela RH, Kolho LA, et al. Serum vitamin D level after an annual intramuscular injection of ergocalciferol. Calcif Tissue Int 1991;49:S87.
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408-12.
    1. Cook DJ, Sackett DL, Spitzer WO. Methodologic guidelines for systematic reviews of randomized control trials in health care from the Potsdam Consultation on Meta-Analysis. J Clin Epidemiol 1995;48:167-71.
    1. Jongen MJ, Van Ginkel FC, van der Vijgh WJ, Kuiper S, Netelenbos JC, Lips P. An international comparison of vitamin D metabolite measurements. Clin Chem 1984;30:399-403.
    1. Jongen MJ, van der Vijgh WJ, van Beresteyn EC, van den Berg H, Bosch R, Hoogenboezem T, et al. Interlaboratory variation of vitamin D1 metabolite measurements. J Clin Chem Clin Biochem 1982;20:753-6.
    1. Lips P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements. Osteoporos Int 1999;9:394-7.
    1. Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med 1995;14:395-411.
    1. Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med 2002;21:1559-73.
    1. Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med 1999;18:2693-708.
    1. Egger M, Smith GD, Altman DG. Systemic reviews in health care: meta-analysis in context. BMJ Publishing Group, 2001.
    1. Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 2001;86:3618-28.
    1. Dukas L, Bischoff HA, Lindpaintner LS, Schacht E, Birkner-Binder D, Damm TN, et al. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. J Am Geriatr Soc 2004;52:230-6.
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
    1. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455-63.
    1. Boland R. Role of vitamin D in skeletal muscle function. Endocr Rev 1986;7:434-447.
    1. Sorensen OH, Lund B, Saltin B, Andersen RB, Hjorth L, Melsen F, et al. Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Colch) 1979;56:157-61.
    1. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337:670-6.
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck A, Staehelin HB, Orav JE, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 2009;169:551-61.
    1. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 1996;124:400-6.
    1. Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res 2002;17:709-15.
    1. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-83.
    1. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327:1637-42.
    1. Cranny A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess 2007;158:1-235.
    1. Jackson C, Gaugris S, Sen SS, Hosking D. The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM 2007;100:185-92.
    1. Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Holick MF. Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997;82:4111-6.
    1. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003;22:142-6.

Source: PubMed

3
Iratkozz fel