Vitamin D and Calcium Supplementation Reduces Fracture Risk

Joe Barber Jr, PhD

December 19, 2011

December 19, 2011 — Combined supplementation with vitamin D and calcium can reduce the risk for fracture, according to the findings of a meta-analysis.

Mei Chung, PhD, MPH, from Tufts Medical Center in Boston, Massachusetts, and colleagues published their findings in the December 20 issue of the Annals of Internal Medicine.

The authors mention that active forms of vitamin D participate in a number of biological processes in addition to their indirect effects on bone mineralization. "For example, as recently noted, 1,25-(OH)2D inhibits parathyroid hormone secretion and promotes insulin secretion, inhibits adaptive immunity and promotes innate immunity, and inhibits proliferation and stimulates differentiation of cells," the authors write. "These functions suggest a possible role of vitamin D in cancer prevention."

In this meta-analysis, the authors included 137 studies to address 4 questions regarding the effects of vitamin D supplementation on fracture and cancer risk. Compared with placebo, combined vitamin D and calcium supplementation reduced the risk for fracture (pooled relative risk ratio, 0.88; 95% confidence interval [CI], 0.78 - 0.99), although vitamin D supplementation alone did not reduce this risk (pooled relative risk ratio, 1.03; 95% CI, 0.84 - 1.26). The effect of combined vitamin D and calcium supplementation was significantly stronger in the institutional setting than in the community setting (institutional setting: relative risk ratio, 0.71 [95% CI, 0.57 - 0.89]; community setting: relative risk ratio, 0.89 [95% CI, 0.76 - 1.04]; P = .07).

The authors searched the MEDLINE and Cochrane Central Register of Controlled Trials databases through July 2011 for studies limited to human participants, published in English-language journals. The search terms included vitamin D, 25-hydroxyvitamin D, calcium, and text terms and Medical Subject Heading terms related to cancer or neoplasms, fracture, and bone mineral density.

Compared with placebo, randomized controlled trials reported hazard or risk ratios for the incidence and mortality of colorectal, breast, or total cancer ranging from 0.55 to 1.09. Among randomized controlled trials evaluating combined vitamin D and calcium supplementation vs placebo regarding cancer risk, a trend of no effect of supplementation was identified, although one smaller study reported that combined vitamin D and calcium supplementation reduced the incidence of total cancer by 60% (95% CI, 18% - 80%).

Despite the findings of this meta-analysis, the authors mention that challenges remain in confirming the benefits of vitamin D supplementation in the general population. "No methods are currently available to quantify the contribution of endogenous vitamin D synthesis resulting from sun exposure on an individual or a group, and serious limitations remain in accurately estimating dietary vitamin D intake because of the incompleteness of nutrient databases for both vitamin D–fortified food and vitamin D supplements," the authors state.

"Future study is needed to evaluate the appropriate dose and dosing regimens of vitamin D supplementation for bone health outcomes."

The study and several authors were supported by the Agency for Healthcare Research and Quality. The authors have disclosed no relevant financial relationships.

Ann Intern Med. 2011;55:827-838. Full text

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