The aim of this systematic review and meta-analysis was to investigate the cardiovascular safety profile of Zoledronic acid, a commonly used treatment for primary osteoporosis.

The study focused on randomized controlled trials (RCTs) involving subjects suffering from osteoporosis who were administered Zoledronic acid or a placebo. The systematic search encompassed databases like ICTRP, ClinicalTrials.gov, PubMed, Chinese National Knowledge Infrastructure, Embase, Web of Science, Scopus, and Cochrane CENTRAL. Adhering to PRISMA guidelines, two investigators extracted data on study characteristics, risk of bias, and endpoints of interest.

The search yielded 32,361 records. Following the exclusion of irrelevant entries, nine RCTs were incorporated. The overall risk ratio [RR] for cardiovascular events linked with Zoledronic acid in primary osteoporosis, compared with placebo, was 1.15 (95% CI 1.05-1.26, I2=12%).

But, the risk of major adverse cardiovascular events (MACE) with Zoledronic acid (RR 1.03, 95% CI 0.89-1.18, I2=21%) did not reach significance, possibly due to atrial fibrillation (RR 1.21, 95% CI 0.99-1.47, I2=0%), in contrast to the increased relative risk of arrhythmia (RR 1.30, 95% CI 1.11-1.52, I2=34%).

In summary, while the overall cardiovascular risk of Zoledronic acid for primary osteoporosis was not significant, the elevated relative risks of atrial fibrillation and arrhythmias warrant additional investigation.

Among women battling primary osteoporosis, Zoledronic acid escalated the risk of atrial fibrillation  and arrhythmias compared to placebo, irrespective of MACE, angina, and heart failure. Caution was advised when interpreting results for men having primary osteoporosis due to the small sample size. Zoledronic acid's cardiovascular risk in this population remained uncertain.