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Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency *

Background Antifracture efficacy with supplemental vitamin D has been questioned by recent trials.

Methods We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (≥65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose × adherence) for each trial.

Results The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (−29%) and institutionalized older individuals (−15%), and its effect was independent of additional calcium supplementation.

Conclusion Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.

The antifracture benefits of vitamin D have been questioned by several recent trials,1- 4 leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation. Two 2007 meta-analyses5- 6 included most of these trials and concluded that vitamin D may not reduce fractures significantly or may do so only in combination with calcium and primarily among institutionalized older individuals. A third 2007 meta-analysis7 concluded that calcium with or without vitamin D may reduce total fracture risk by 12%, a result that was questioned by a more recent meta-analysis8 of high-quality trials of calcium supplementation alone in which calcium had a neutral effect on nonvertebral fractures and a possible adverse effect on hip fracture risk. Apart from the mixed data on calcium, the recent meta-analyses with vitamin D did not consider heterogeneity by received dose (incorporating adherence) or achieved level of 25-hydroxyvitamin D.

A dose-response relationship between vitamin D and fracture reduction is supported by epidemiologic data showing a significant positive trend between serum 25-hydroxyvitamin D concentrations and hip bone density9 and lower extremity strength.10- 11 In addition, greater antifracture efficacy with higher achieved 25-hydroxyvitamin D levels was documented in an earlier meta-analysis of high-quality primary prevention trials with supplemental vitamin D.12 Factors that may obscure a benefit of vitamin D are low adherence to treatment,2 low dose of vitamin D, or the use of less potent ergocalciferol (vitamin D2).13- 14 Furthermore, open study design trials1 may bias results toward the null because vitamin D supplementation is available over the counter.

Our 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 RCTs. In addition, we specifically addressed antifracture efficacy by received dose, achieved 25-hydroxyvitamin D levels, and in predefined subgroups.

* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 06-22-2013