Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say?

Calcium, magnesium and strontium have all been implicated in both musculoskeletal and cardiovascular health and disease. However, despite these three elements being closely chemically related, there is marked heterogeneity of their characteristics in relation to cardiovascular outcomes. In this narrative review, we describe the relevant evidential landscape, focusing on clinical trials where possible and incorporating findings from observational and causal analyses, to discern the relative roles of these elements in musculoskeletal and cardiovascular health. We conclude that calcium supplementation (for bone health) is most appropriately used in combination with vitamin D supplementation and targeted to those who are deficient in these nutrients, or in combination with antiosteoporosis medications. Whilst calcium supplementation is associated with gastrointestinal side effects and a small increased risk of renal stones, purported links with cardiovascular outcomes remain unconvincing. In normal physiology, no mechanism for an association has been elucidated and other considerations such as dose response and temporal relationships do not support a causal relationship. There is little evidence to support routine magnesium supplementation for musculoskeletal outcomes; greater dietary intake and serum concentrations appear protective against cardiovascular events. Strontium ranelate, which is now available again as a generic medication, has clear anti-fracture efficacy but is associated with an increased risk of thromboembolic disease. Whilst a signal for increased risk of myocardial infarction has been detected in some studies, this is not supported by wider analyses. Strontium ranelate, under its current licence, thus provides a useful therapeutic option for severe osteoporosis in those who do not have cardiovascular risk factors.