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Their mechanism of action is through inhibiting osteoclast\u2010induced bone remodeling, and they also possess calcium sequestering properties. Common side effects involve the gastrointestinal system and rare but serious side effects, including osteonecrosis of the jaw. However, a link between BPs and atrial fibrillation (AF) has been proposed, with early clinical trials, such as the Fracture Intervention Trial and the HORIZON Pivotal Fracture Trial, reporting that BPs are associated with increased risk of AF. Nevertheless, subsequent studies have reported contrasting results, ranging from no effect of BPs to antiarrhythmic effects of BPs. Preclinical and electrophysiological studies on any proarrhythmic effect of BPs are limited in scope and number, but suggest possible mechanisms that include antiangionesis\u2010related myocardial remodeling, calcium handling abnormalities, and inflammatory changes. Contrastingly, some studies indicate that BPs are antiarrhythmic by inhibiting fibrotic myocardial remodeling. In order to continue established clinical prescribing of BPs within absolute margins of safety, it will be necessary to systematically rule in\/rule out these mechanisms. Thus, we discuss these studies and examine in detail the potential mechanistic links, with the aim of suggesting further avenues for research.<\/jats:p>","DOI":"10.1111\/nyas.14332","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T18:39:55Z","timestamp":1585075195000},"page":"15-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Bisphosphonates and atrial fibrillation: revisiting the controversy"],"prefix":"10.1111","volume":"1474","author":[{"given":"Ibrahim T.","family":"Fazmin","sequence":"first","affiliation":[{"name":"Faculty of Health and Medical Sciences University of Surrey  Guildford United Kingdom"},{"name":"School of Clinical Medicine University of Cambridge  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.\u2010H.","family":"Huang","sequence":"additional","affiliation":[{"name":"Physiological Laboratory University of Cambridge  Cambridge United Kingdom"},{"name":"Department of Biochemistry University of Cambridge  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamalan","family":"Jeevaratnam","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences University of Surrey  Guildford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr413"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-3007-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.12.225"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1402.052"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60752-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00221"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-018-00512-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3657"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1346.041"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68891-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djq114"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05812.x"},{"key":"e_1_2_9_14_1","unstructured":"Joint Formulatory Committee.2019. 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