Electrocardiogram Changes Following Intravenous Bisphosphonate Infusion: A Systematic Review and Meta-Analysis.

Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients receiving bisphosphonates, however, uncertainty remains as to if electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting electrocardiogram findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE from inception until January 14, 2023, for studies reporting electrocardiogram parameters following intravenous bisphosphonate infusion. We excluded studies that only reported atrial fibrillation. 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 standardised mean difference (SMD) with 95% confidence intervals (95%CI). We found 1,083 unique records, of which 11 met our inclusion and exclusion criteria. Studies had a low to low/moderate risk of bias. Six prospective cohort studies were included in the meta-analysis. 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 in children with osteoporosis secondary to cerebral palsy. Study populations ranged from n=15 to n=116. QTc was significantly longer post-infusion (SMD = 0.46 milliseconds [95%CI: 0.80 to 0.11]; n=67 patients, k=2 studies, τ 2 = 0). There were no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc, QTc (maximum), QTc (minimum) and QTc dispersion. The correlation between pre- and post-infusion QTc was not significant (p=0.93). Overall, there is a weak association between intravenous bisphosphonate infusion and a QTc interval prolongation. However, there is insufficient evidence to support an association between intravenous bisphosphonate and any ECG variable changes, which may precipitate atrial fibrillation. This article is protected by copyright. All rights reserved.