Meta-analysis Quantifies Fracture Risk Reduction With Calcium, Vit D

A modest reduction in risk for fracture was noted with calcium plus vitamin D supplements, but the effect on cardiovascular outcomes was unclear.

Although the effect size was modest, calcium plus vitamin D supplements reduced the risk for fracture in a meta-analysis of randomized controlled trials and post-hoc analyses. The risk for myocardial infarction (MI) and stroke among patients taking the supplements, however, remained uncertain.

“Among old people, calcium plus vitamin D supplements — at the population level — are likely to reduce fracture risk without a detectable increase in cardiovascular risk,” Tuan Nguyen, PhD, of the Garvan Institute of Medical Research and the University of Technology Sydney, Australia, said in an interview.

Dr Nguyen and fellow researchers presented their findings at the American Society for Bone and Mineral Research (ASBMR) 2016 Annual Meeting.

According to Dr Nguyen, in 2011, a re-analysis of Women’s Health Initiative data suggested that calcium supplements with or without vitamin D were associated with an increased risk for MI and stroke, but the effect sizes and P values were marginal. “It has been shown that at least 30% of findings with a P value of roughly .05 are false positives,” he said. “Subsequent meta-analyses yielded conflicting results regarding the benefit and risk of calcium and vitamin D supplements. However, previous analyses focused on either calcium alone or calcium with vitamin D.

Influenced by the late Dr Robert Heaney who thought that biologically, to have a skeletal effect, calcium and vitamin D must go together, we asked a specific question: Do calcium and vitamin D supplements reduce fracture risk and increase cardiovascular outcomes?”

The final analysis included 11 primary randomized controlled trials (n=56 569) on the efficacy of calcium plus vitamin D on fracture risk, and 7 post-hoc analyses (n=46 526) of randomized controlled trials examining the association between calcium plus vitamin D and cardiovascular disease (CVD) outcomes. With these data, researchers synthesized a Bayesian random-effects meta-analysis.

Dr Nguyen and researchers reported that calcium plus vitamin D supplements led to a 15% reduction in the risk for fragility fracture, with the probability that the supplements reduced total fracture risk by ≥10% of 0.85.

However, the evidence of calcium plus vitamin D supplements’ effect on hip fracture was unclear (relative risk [RR], 0.95; 95% CI, 0.67-1.35), which was also the case with MI or ischemic heart disease (RR, 1.09; 95% CI, 0.69-1.88). In addition, there was a reduction in the risk for stroke or cerebrovascular disease with calcium plus vitamin D supplements (RR, 0.89; 95% CI, 0.35-1.94), although the association was not clear-cut, according to the researchers.

Following adjustment for the incidence and utilities linked with each outcome, the probability of calcium plus vitamin D supplementation benefiting fracture prevention was 8.7 times higher than the likelihood of being harmed by MI or ischemic heart disease.

Dr Nguyen cautioned, however, that the effect of calcium plus vitamin D supplements on fracture risk reduction observed in the study was modest. “Even with the most optimistic belief, the existing data suggest that there is only a 53% chance that calcium plus vitamin D supplementation reduces fracture risk by 20% or more,” he said.

Disclosure: Dr Nguyen reports no relevant financial disclosures.

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  1. Frost S, Phan K, Thach T, Eisman J, Nguyen T. Abstract 1008. Calcium plus vitamin D supplementation, fracture, and cardiovascular outcomes: A Bayesian meta-analysis. Presented at: ASBMR 2016 Annual Meeting; September 16-19, 2016; Atlanta, Georgia. 

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This article originally appeared on Endocrinology Advisor