Bisphosphonates and cardiac electrophysiology: should the red flag be raised higher?
Bisphosphonates and cardiac electrophysiology: should the red flag be raised higher?
复制标题
双磷酸盐和心脏电生理学：是否应该提高危险信号？
DOI：
10.1111/jce.12349
复制
发表时间：
2014
影响因子：
2.7
通讯作者：
Avula,UmaMaheshR
中科院分区：
文献类型：
--
作者：
Kalifa,Jérôme;Avula,UmaMaheshR
双膦酸盐被广泛用于以破骨细胞介导的骨吸收增加为特征的疾病，如老年性骨质疏松症，以减少骨质流失。虽然通常耐受性良好，但副作用如急性炎症期反应，颌骨骨坏死，胃肠道疾病或低钙血症已被描述。此外，关于心房颤动（AF）与使用双磷酸盐之间的关联的相互矛盾的报告导致了令人困惑的陈述，并向医生和患者传递了混淆的信息。关于这些相互矛盾的观察结果的细节在之前发表的综述文章中进行了总结。1-3有趣的是，已经提出了几种将双膦酸盐与房颤发病联系起来的假设：促炎细胞因子的急性增加、钙稳态紊乱或细胞外基质重塑。然而，到目前为止，这些前提都没有经过测试，双磷酸盐可能影响心脏电生理的机制尚不清楚，截至2008年底，美国食品和药物管理局未能确定两者之间的明确联系，并得出结论，没有必要改变处方做法。1,2在这一期的《心血管电生理学杂志》上，Bonilla等人提出了一项多方面的研究，描述了双膦酸盐诱发心律失常的可能机制。他们的结果具有实质性的机制深度，尽管具有挑衅性，但对先前关于双膦酸盐与心律失常之间关系的现状提出了质疑。
Bisphosphonates are widely employed to decrease bone loss in disorders characterized by increased osteoclast-mediated bone resorption, such as senile osteoporosis. 1 While generally well tolerated, side effects such as an acute inflammatory phase reaction, osteonecrosis of the jaw, gastro-intestinal disorders or hypocalcemia have been described. 1 Also, contradictory reports of an association between atrial fibrillation (AF) and the use bisphosphonates has led to confusing statements and sent mixed messages to practitioners and patients. 2 Details on these conflicting observations are summarized in previously published review articles. 1-3 Interestingly, several hypotheses linking bisphosphonates to the onset of AF have been formulated: an acute increase in pro-inflammatory cytokines, disturbances in calcium homeostasis or extra-cellular matrix remodeling. 2 To date, however, none of these premises have been tested, the mechanisms by which bisphosphonates may impact cardiac electrophysiology are unknown, and as of late 2008, the Food and Drug Administration failed to identify a clear association and concluded that no change in prescribing practices was warranted. 1, 2In this issue of the Journal of Cardiovascular Electrophysiology, Bonilla et al. present a multi-faceted investigation describing plausible mechanisms for bisphosphonates-induced cardiac arrhythmias. Their results have substantial mechanistic depth and, albeit provocative, put at question the previous status quo on an association between bisphosphonates and cardiac arrhythmias.