Bisphosphonates (BPs) are widely prescribed drugs used to treat osteoporosis, commonly arising in postmenopausal women and in chronic glucocorticoid use. Their mechanism of action is through inhibiting osteoclast-induced 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-related 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.

中文翻译：

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双膦酸盐和心房颤动：重新审视争议

双膦酸盐 (BPs) 是广泛用于治疗骨质疏松症的处方药，通常出现在绝经后妇女和慢性糖皮质激素使用中。它们的作用机制是通过抑制破骨细胞诱导的骨重塑，并且它们还具有钙螯合特性。常见的副作用涉及胃肠系统和罕见但严重的副作用，包括颌骨坏死。然而，已经提出了 BP 与心房颤动 (AF) 之间的联系，早期临床试验，如骨折干预试验和 HORIZON 枢轴骨折试验，报告称 BP 与 AF 风险增加有关。然而，随后的研究报告了对比结果，范围从 BP 的无作用到 BP 的抗心律失常作用。关于 BP 的任何促心律失常作用的临床前和电生理学研究的范围和数量都有限，但提出了可能的机制，包括抗血管生成相关的心肌重构、钙处理异常和炎症变化。相比之下，一些研究表明 BP 通过抑制纤维化心肌重构而具有抗心律失常作用。为了在绝对安全范围内继续制定 BP 的临床处方，有必要系统地排除/排除这些机制。因此，我们讨论这些研究并详细研究潜在的机制联系，目的是提出进一步的研究途径。和炎症变化。相比之下，一些研究表明 BP 通过抑制纤维化心肌重构而具有抗心律失常作用。为了在绝对安全范围内继续制定 BP 的临床处方，有必要系统地排除/排除这些机制。因此，我们讨论这些研究并详细研究潜在的机制联系，目的是提出进一步的研究途径。和炎症变化。相比之下，一些研究表明 BP 通过抑制纤维化心肌重构而具有抗心律失常作用。为了在绝对安全范围内继续制定 BP 的临床处方，有必要系统地排除/排除这些机制。因此，我们讨论这些研究并详细研究潜在的机制联系，目的是提出进一步的研究途径。