Abstract

Abstract Bisphosphonates are the first-line treatment for several bone and mineral disorders. Randomized trials and cohort studies have reported increased rates of atrial fibrillation in patients receiving bisphosphonates, however, uncertainty remains as to whether other electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting ECG findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE on 06/01/2022 for studies reporting ECG parameters following administration of intravenous bisphosphonates. We excluded studies that only reported atrial fibrillation, case reports and animal or cell-based studies. Study quality was assessed using the Newcastle-Ottawa Scale. Continuous data were meta-analysed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95%CI). Heterogeneity was determined by the I 2 statistic. All data were computed using R (4.1.1). We found 1,123 records of which six met our inclusion and exclusion criteria, of which five had data for meta-analysis. Studies were of low to moderate quality. Five studies used zoledronic acid while one study used pamidronate. Most studies [n=4] were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases and one study was conducted in children with cerebral palsy and osteoporosis. Most studies [n=4] reported outcomes in the sub-acute (>24 hours) phase. Study populations ranged from n=15 to n=116. There was a significant difference in QTc dispersion (SMD= -0.456 milliseconds [95%CI: -0.800 to -0.113]; I 2 = 0%; n= 67 patients; k= 2 studies) but no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc (maximum), QTc (minimum), or QTc. The correlation between pre- and post-infusion QTc dispersion was rho= 0.981 (p=0.866). Results were unchanged when analysing studies reporting acute or sub-acute phase ECG changes. Overall, there is insufficient and low quality evidence to support an association between intravenous bisphosphonate administration and acute phase dysrhythmias. These data underscore the importance of performing a pre-infusion ECG to evaluate potentially unreported conduction abnormalities. Presentation: No date and time listed

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