HEALTH NEWS

Study Title:

Vitamin D Reduces Fractures

Study Abstract

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 x 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.

From press release:

Oral vitamin D supplements at a dose of at least 400 international units per day are associated with a reduced risk of bone fractures in older adults, according to results of a meta-analysis published in the March 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

"The anti-fracture benefits of vitamin D have been questioned by several recent trials, leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation," the authors write as background information in the article. "Factors that may obscure a benefit of vitamin D are low adherence to treatment, low dose of vitamin D or the use of less potent ergocalciferol (vitamin D2)."

Heike A. Bischoff-Ferrari, Dr.P.H., of the University of Zurich, University Hospital, Zurich, Switzerland, and colleagues performed a meta-analysis on 12 previously published clinical trials of oral vitamin D supplements among adults age 65 or older. These double-blind randomized controlled trials involved 42,279 participants (average age 78) and looked at non-vertebral (non-spinal) fractures, including eight trials of 40,886 participants specifically studying hip fractures.

When the results of the trials were pooled, vitamin D supplements decreased the risk of non-vertebral fractures by 14 percent and of hip fractures by 9 percent. The authors then pooled the results of only the nine trials in which participants received doses of more than 400 international units per day. At this dosage, vitamin D supplements reduced non-vertebral fractures by 20 percent and hip fractures by 18 percent. Doses of 400 international units per day or lower did not reduce the risk of either fracture type. A greater reduction in risk was also seen among trial participants whose blood levels of 25-hydroxyvitamin D (a commonly used measure of blood vitamin D levels) achieved a greater increase.

Among individuals taking high doses of vitamin D, additional calcium did not appear to have any further protective effect against fractures. "Physiologically, the calcium-sparing effect of vitamin D may explain why we did not see an additional benefit of calcium supplementation at a higher dose of vitamin D," the authors write.

"The greater fracture reduction with a higher received dose or higher achieved 25-hydroxyvitamin D levels for both any non-vertebral fractures and hip fractures suggests that higher doses of vitamin D should be explored in future research to optimize anti-fracture efficacy," they conclude. "Also, it is possible that greater benefits may be achieved with earlier initiation of vitamin D supplementation and longer duration of use. Our results do not support use of low-dose vitamin D with or without calcium in the prevention of fractures among older individuals."

Study Information

Heike A. Bischoff-Ferrari; Walter C. Willett; John B. Wong; Andreas E. Stuck; Hannes B. Staehelin; E. John Orav; Anna Thoma; Douglas P. Kiel; Jana Henschkowski.
Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency: A Meta-analysis of Randomized Controlled Trials.
Arch Intern Med.
2009 March
Center on Aging and Mobility and Department of Rheumatology and Institute of Physical Medicine, University of Zurich, University Hospital, Zurich, Switzerland.