Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
Calcium supplementation, without coadministration of vitamin D, is associated with a modest increased incidence of myocardial infarction, which warrants a reassessment of its use in the management of osteoporosis.
In adults aged 40 years and older, does calcium supplementation as compared with placebo increase the risk of myocardial infarction?
The authors searched three electronic databases and two clinical trial registries for study literature published from 1966 to March 2010. They followed a defined protocol. Two independent authors assessed trial quality and extracted data. The authors included studies that were randomized, double-blind, placebo-controlled trials that administered =500 mg/day of elemental calcium administered per day. Studies were excluded if vitamin D was given only in the intervention group, but included if also given in the control group. The lead authors of eligible trials supplied additional data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates.
The authors included 11 RCTs to evaluate calcium supplementation and cardiovascular events. In 5 RCTs (8,151 participants) that had a median follow-up time of 3.6 years (2.7 to 4.3 years), 143 participants taking calcium had a myocardial infarction compared to 111 participants taking placebo (hazard ratio, 1.31; 95 percent confidence interval [CI], 1.02 to 1.67; P = 0.035). Nonsignificant increases occurred in the incidence of stroke (Hazard Ratio: 1.20, CI, 0.96 to 1.50, P = 0.11) with the end point of myocardial infarction, stroke, or sudden death (Hazard Ratio: 1.18, CI, 1.00 to 1.39; P = 0.057), and death (Hazard Ratio: 1.09, CI, 0.96 to 1.23; P = 0.18). Six RCTs (3,770 participants) with mean duration of 4.0 years showed similar results: 166 participants taking calcium had myocardial infarctions compared to 130 participants on placebo (pooled relative risk [RR] 1.27; CI, 1.01 to 1.59; P = 0.038).
Calcium supplements (without coadministered vitamin D) are associated with a modest increased risk of myocardial infarction. The widespread use of calcium supplements may put a large percentage of the population at modest increased risk of developing cardiovascular disease. This warrants a reassessment of the role of calcium supplements in the management of osteoporosis.
Source of Funding:
Health Research Council of New Zealand and the University of Auckland School of Medicine Foundation.
Importance and Context:
Osteoporosis is a major cause of morbidity and mortality in the older population. Calcium supplements marginally reduce the risk of fracture. Most guidelines have recommended increased calcium intake as an integral part of the prevention or treatment of osteoporosis. (1) Some studies suggest calcium supplements have increased vascular calcification and mortality in patients with renal failure. A recent five-year RCT of calcium supplements reported that rates of myocardial infarction and cardiovascular events increased in healthy women taking calcium supplements. A systematic review is warranted to evaluate the association of calcium supplements to an increased risk of myocardial infarction.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehensive search, defined inclusion and exclusion criteria, and no language restrictions. Publication bias was assessed using Funnel plots and Egger's regression model. Common tests for heterogeneity were used. The authors declared no conflict of interest with the funding or research results.
Strengths and Weaknesses of the Evidence:
Of 11 studies used to evaluate cardiovascular events, only seven studies stated the method of randomization and four described the allocation concealment. Only two of the trials had data adjudicated by blinded trial investigators. One large study (5,292 participants) included subjects taking calcium plus vitamin D compared with vitamin D as the control. One study (563 participants) compared calcium plus alendronate with alendronate. None of the trials had cardiovascular outcomes as the primary end points, and data on cardiovascular events were not gathered in a standardized manner. Incomplete or no data on cardiovascular outcomes were available for seven trials, comprising 15 percent of the total number of participants. No significant statistical heterogeneity existed between any trials.
Implications for Dental Practice:
Calcium supplementation increases bone density and decreases the risk of bone fractures by 10 percent. (2) Many chewable antacid tablets contain calcium carbonate which also is an effective calcium supplement. Since calcium supplementation increases the risk of myocardial infarction by about 30 percent, the future role of calcium supplements may be reassessed for the management of osteoporosis. Further research is needed to evaluate if vitamin D provides a protective effect, since no increased risk of myocardial infarction was reported when calcium supplements are taken in conjunction with vitamin D. (3,4)
1. Rosen C. Postmenopausal osteoporosis. N Engl J Med. 2005; 353:595- 603. 2. Recker RR, Hinders S, Davies KM, Heaney RP, Stegman MR, Lappe JM, et al. Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J Bone Miner Res 1996;11:1961-6. 3. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730-7. 4. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-11.