Elsevier

Maturitas

Volume 69, Issue 4, August 2011, Pages 289-295
Maturitas

Review
Calcium supplementation: Balancing the cardiovascular risks

https://doi.org/10.1016/j.maturitas.2011.04.014Get rights and content

Abstract

Calcium supplementation has been widely accepted as a key strategy in the prevention and treatment of osteoporosis. Its role has been undermined, to some extent, by its disappointing effects on fracture in randomised controlled trials, but its use has continued to be encouraged on the grounds that it is physiologically appealing, and is unlikely to cause harm. The latter assumption is now under threat from accumulating evidence that calcium supplement use is associated with an increased risk of myocardial infarction and, possibly, stroke. The latest data, based on meta-analysis of trials involving 29,000 participants, indicate that this risk is not mitigated by co-administration of vitamin D, and that the number of cardiovascular events caused is likely to be greater than the number of fractures prevented. These findings indicate that calcium supplementation probably does not have a role as a routine preventative agent and that dietary advice is the appropriate way to attain an adequate calcium intake in most situations. Patients at high risk of fracture need to take interventions of proven anti-fracture efficacy. Available evidence suggests that this efficacy is not dependent on the co-administration of calcium supplements.

Introduction

Calcium supplements have been regarded as a cornerstone of the prevention and treatment of osteoporosis, over the last 50 years. Calcium supplements have been promoted on the grounds that calcium is a major constituent of the skeleton, so more calcium should lead to a stronger skeleton. This paradigm treats the skeleton as being akin to a stalagmite in a limestone cave, expected to grow more rapidly if we drip more calcium-rich fluid onto it. This ignores the reality that bone is a collagen-based connective tissue and that bone mass is determined by the balance between the activity of the bone forming cells (osteoblasts) and that of bone resorbing osteoclasts. While substrate deficiency would be expected to have a negative impact on bone mass, oversupply of calcium should not, ipso facto, be expected to increase the bone mass.

In the last 20 years a solid evidence base has been built describing the skeletal effects of calcium, both through bone density measurements and through assessments of fracture risk. While beneficial effects have been found, they have been relatively modest, and low compliance has been a consistent feature of the large scale studies of calcium supplementation. Many physicians have continued to encourage calcium use on the grounds that it should be beneficial and there is no reason to think it does any harm. The latter assumption is now called into doubt by accumulating evidence that calcium supplement use increases the risk of cardiovascular disease. This suggestion requires that we carefully consider the balance of risk and benefit with calcium supplement use, as we would with any pharmaceutical intervention.

Section snippets

How important is calcium for bone health?

Very low calcium intakes have been associated with impaired mineralisation of the skeleton because the critical calcium-phosphate product is not reached adjacent to the mineralising osteoid [1]. However, most studies have shown remarkably little correlation between dietary calcium intake and either bone density [2], [3], [4] or fracture rates [5], [6] (Fig. 1). Indeed, some of the lowest fracture rates internationally are observed in Africa and Asia, where dietary calcium intakes of 300 mg/day

Calcium monotherapy

During the period that trials have been undertaken to determine the skeletal effects of calcium supplements, there has also been interest in the possibility that calcium supplements might have an impact on vascular disease. The outcome most frequently studied is blood pressure, where a consistent body of evidence has developed showing small reductions in both systolic and diastolic pressures from the introduction of calcium supplements [16], [17], [18]. There have also been reports that calcium

Conclusion

The consistent message from the meta-analyses of clinical trials is that calcium supplements probably carry a small but significant adverse effect on cardiovascular risk. Their beneficial effect on fractures is also small, so it is likely that there is no net benefit from their use. This suggests that we need to look elsewhere for strategies for preventing postmenopausal bone loss. Lifestyle interventions should include smoking cessation, weight maintenance, and moderation of alcohol intake.

Contributors

The article was drafted by IRR, then critically revised by the other authors.

Conflict of interests

IRR has received research support from and acted as a consultant for Fonterra and had study medications for clinical trials of calcium supplementation supplied by Mission Pharmacal. The other authors have no conflicts.

Provenance and peer review

Commissioned and externally peer reviewed.

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