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

Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say?
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.
Calcium, Cardiovascular, Epidemiology, Magnesium, Osteoporosis, Strontium
1594-0667
479-494
Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145

Curtis, Elizabeth, Cooper, Cyrus and Harvey, Nicholas (2021) Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say? Aging Clinical and Experimental Research, 33 (3), 479-494. (doi:10.1007/s40520-021-01799-x).

Record type: Review

Abstract

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.

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bc nch CaMgSr ACER 2021_01_11 - Accepted Manuscript
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Accepted/In Press date: 13 January 2021
e-pub ahead of print date: 9 February 2021
Published date: March 2021
Additional Information: Funding Information: We would like to thank the Medical Research Council (UK), National Institute for Health Research, Wellcome Trust, Versus Arthritis, Royal Osteoporosis Society Osteoporosis and Bone Research Academy and International Osteoporosis Foundation for supporting this work. This article reproduces, with permission and modification [1]: Harvey NC, et al., Osteoporos Int. 2017 Feb;28(2):447?462. Publisher Copyright: © 2021, The Author(s).
Keywords: Calcium, Cardiovascular, Epidemiology, Magnesium, Osteoporosis, Strontium

Identifiers

Local EPrints ID: 446706
URI: http://eprints.soton.ac.uk/id/eprint/446706
ISSN: 1594-0667
PURE UUID: 60968601-09a8-4a5a-aff8-5e43dcf63ca5
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 18 Feb 2021 17:31
Last modified: 18 Mar 2024 03:38

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