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However, despite these three elements being closely chemically related, there is marked heterogeneity\u00a0of their\u00a0characteristics in relation\u00a0to 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.<\/jats:p>","DOI":"10.1007\/s40520-021-01799-x","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T05:18:04Z","timestamp":1612934284000},"page":"479-494","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Cardiovascular safety of calcium, magnesium and strontium: what does the evidence say?"],"prefix":"10.1007","volume":"33","author":[{"given":"Elizabeth M.","family":"Curtis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"1799_CR1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00198-016-3773-6","volume":"28","author":"NC Harvey","year":"2017","unstructured":"Harvey NC, Biver E, Kaufman JM et al (2017) The role of calcium supplementation in healthy musculoskeletal ageing: an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF). 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Harvey has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, UCS, Shire, Consilient Healthcare, Kyowa Kirin and Internis Pharma; C. Cooper has received consultancy, lecture fees and honoraria from AMGEN, GSK, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Medtronic and Roche. E.Curtis reports honoraria\/travel support from Eli Lilly, UCB and Amgen outside the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}