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Meta-Analysis
. 2007 Mar 9:8:26.
doi: 10.1186/1471-2474-8-26.

Fracture prevention with vitamin D supplementation: considering the inconsistent results

Gerbrand J Izaks  1
Affiliations
Meta-Analysis

Fracture prevention with vitamin D supplementation: considering the inconsistent results

Gerbrand J Izaks. BMC Musculoskelet Disord. .

Abstract

Background: A meta-analysis found that high dose vitamin D, different from low dose, decreased fracture risk by 23% for any nonvertebral fracture and by 26% for hip fracture. Unfortunately, however, this effect was not confirmed by recent trials. The aim of this paper is to explore if this inconsistency can be attributed to publication bias or heterogeneity of the trials.

Methods: The meta-analysis was extended with recent randomised controlled trials (RCTs) that were identified by a systematic review. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from raw data. A funnel plot was used to explore the possibility of publication bias. Forest plots were used to investigate if vitamin D dose, concurrent use of calcium and target population were sources of heterogeneity. Linear regression analysis of log RR on adherence rate and achieved vitamin D level was used to study whether these variables were associated with fracture risk.

Results: A total of eleven trials was included: seven RCTs from the meta-analysis and four recently published. For any nonvertebral fracture, the funnel plot was asymmetrical because two small RCTs showed a large positive effect. This was not found for hip fracture. As reported in the meta-analysis, low dose vitamin D (<400 IU daily) was not effective. In contrast to the meta-analysis, however, the effect of high dose vitamin D (> or =700 IU daily) seemed to be dependent on target population. For any nonvertebral fracture, the pooled RR was 0.80 (95% CI, 0.70-0.90) in institutionalised persons, and 0.88 (95% CI, 0.75-1.04) in the general population; for hip fracture, pooled RR 0.72 (95% CI, 0.59 to 0.88) and 1.04 (95% CI, 0.72-1.50), respectively. Other sources of heterogeneity were not clearly found. In the meta-analysis, pooled RRs were mainly based on small trials that showed a large effect or trials in institutionalised persons.

Conclusion: It is likely that the inconsistency between the meta-analysis and the recent trials is, at least partially, due to publication bias and differences in target population. High dose vitamin D may be effective in institutionalised persons but probably is not effective in the general population.

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Figures

Figure 1
Figure 1
Risk ratio for any nonvertebral fracture in a comparison of vitamin D supplementation (treatment) with placebo. The trials are ordered according to year of publication. Bars represent 95 percent confidence intervals. Pooled risk ratio, 0.94 (95 percent confidence interval, 0.89 to 0.98).
Figure 2
Figure 2
Funnel plot of randomised controlled trials on the prevention of any nonvertebral fracture with vitamin D supplementation. Open symbols: trials included in the meta-analysis. Solid symbols: recent trials. Dashed line: pooled risk ratio (RR, 0.94; 95 percent confidence interval, 0.89 to 0.98).
Figure 3
Figure 3
Risk ratios for any nonvertebral fracture according to target population, vitamin D dose and concurrent use of calcium. Bars represent 95 percent confidence intervals.
Figure 4
Figure 4
Risk ratios for any nonvertebral fracture according to adherence to the trial medication. Slope: slope of the regression line. 95%CI: 95 percent confidence interval. Pearson correlation coefficient: -0.56 (p = 0.10).
Figure 5
Figure 5
Risk ratios for any nonvertebral fracture according to achieved vitamin D level. Slope: slope of the regression line. 95%CI: 95 percent confidence interval. Pearson correlation coefficient: -0.54 (p = 0.17). Multiply values by 0.40 to convert 25-OH-vitamin D to ng/ml.
See this image and copyright information in PMC

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