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Menopause Live - IMS Updates
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Date of release: 08 February, 2010

Vitamin D supplementation for prevention of fractures


The rationale for using vitamin D in older people to prevent fractures exists beyond doubt but both the dose of vitamin D and the need for co-supplementation with calcium are not exactly clear. Conflicting results have been reported from various randomized trials examining the effect of vitamin D supplementation (with or without calcium) on the incidence of fractures.


 


The DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group has recently published an analysis using pooled data from 68,500 participants from seven major randomized, vitamin D fracture trials in the USA and Europe [1]. The criteria for inclusion of a study in their analysis included that it must have at least 1000 participants, have at least one interventional arm using vitamin D, and have fracture as an outcome. Logistic regression and the Cox’s hazards model were used for data analysis to identify significant interactions. The results of individual patient data analysis showed that vitamin D alone in doses of 10–20 µg (400–800 IU) was not effective in preventing fractures. On the other hand, vitamin D given with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86–0.99; p = 0.025).

Comment

Vitamin D deficiency may contribute to increased risk of falls and fractures by causing secondary hyperparathyroidism, bone loss and impaired neuromuscular function. There are conflicting results in some randomized, controlled trials examining the effect of vitamin D on the incidence of fractures. A meta-analysis in 2005 indicated that lower doses (10 µg, 400 IU) were ineffective in preventing fractures [2]. Several recent meta-analyses have also shown that a combination of calcium and vitamin D reduces hip and non-vertebral fractures but vitamin D alone does not [3, 4]. Vitamin D given alone was not shown to be effective [5, 6]; this may have been due to low bioavailability of the preparation, different methods and routes of administration of vitamin D, a long interval between doses, or enrolment of higher-aged women in these studies. Using serum vitamin D levels as a marker for determining the right dose to achieve the recommended target level and maximal efficacy may be the optimal clinical approach. For many people taking 20 µg (800 IU) vitamin D/day may still be a too low dose to achieve the optimal serum levels. Calcium and vitamin D are more effective in decreasing parathyroid hormone levels, improving bone density, and reducing fractures. If calcium is not co-administered, higher doses of vitamin D may be needed to suppress bone turnover. As analysis of individual patient’s data improves the statistical power, the results of the DIPART group become important. I also feel that both calcium and vitamin D be recommended together for the prevention of fractures.

Comentario

Neelam Aggarwal
Senior Consultant, Department of Obstetrics & Gynecology, PGIMER, Chandigarh, India

    References

  1. DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010;340:b5463. Published online January 12, 2010.
    http://www.ncbi.nlm.nih.gov/pubmed/20068257

  2. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005;293:2257-64.
    http://www.ncbi.nlm.nih.gov/pubmed/15886381

  3. Boonen S, Lips P, Bouillon R, et al. Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2007;92:1415-23.
    http://www.ncbi.nlm.nih.gov/pubmed/17264183

  4. Avenell A, Gillespie WJ, Gillespie LD, OConnell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009;(2):CD000227.
    http://www.ncbi.nlm.nih.gov/pubmed/19370554

  5. Smith H, Anderson F, Raphael H, et al. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women a population-based, randomized, double-blind, placebo controlled trial. Rheumatology 2007;46:1852-7.
    http://www.ncbi.nlm.nih.gov/pubmed/17998225

  6. Grant AM, Avenell A, Campbell MK, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo controlled trial. Lancet 2005;365:1621-8.
    http://www.ncbi.nlm.nih.gov/pubmed/15885294