Zoledronic Acid Induced Hepatotoxicity: A Review of Case Studies to Identify Possible Mechanisms of Toxicity

Nova Southeastern University, Davie, Florida, USA

Objectives: This study examined evidence from case studies to reinforce hepatotoxicity as a rare but serious possible adverse reaction to zoledronic acid. Background: Zoledronic acid, a bisphosphonate derivative, is a potent inhibitor of bone resorption. It is mainly used to prevent osteoporosis in postmenopausal women, treatment of Paget’s and Behcet’s disease, and bone metastases. Methods: A search was made on PubMed for english, peer-reviewed case studies, published between 2013 through 2019. The keywords were “zoledronic acid”, “hepatotoxicity”, and “case reports”. Four cases studies met the inclusion criteria. Results: Hepatotoxicity after intravenous infusion of zoledronic acid was found in all four case reports. All patients were postmenopausal women whom received zoledronic acid for prevention of osteoporosis due to menopause, Paget's disease or Behcet's disease. In all four cases, patients experienced signs of hepatotoxicity evidenced by elevated AST, ALT, and GGT levels between 1 to 3 days post intravenous infusion of zoledronic acid. In one case, the patient received zoledronic acid on two additional occasions, with concomitant administration of liver protective agents, within a 1-year interval. There was a slight increase in AST, ALT and GGT levels after the second infusion, but levels remained normal after the third infusion. Conclusion: Zoledronic Acid induced hepatotoxicity is a rare adverse event that may occur in postmenopausal women. The pathogenesis of hepatic injury is postulated to be a specific immune mediated response. Liver function enzymes should be monitored before and after administration, and the drug should be used with caution in patients with liver disease.