Acute Phase Reactions in Osteoporotic Patients receiving Intravenous Zoledronic Acid: A Multi-Centre Retrospective Cohort Study

Background Intravenous Zoledronic Acid (IV ZA) is a third-generation bisphosphonates used for osteoporosis with once-yearly administration demonstrating benefits in improvement of bone mineral density and fracture risk reduction. However, acute phase reactions (APRs) pose challenges, often leading to treatment discontinuation. This study aims to assess APR incidence in osteoporotic patients who received IV ZA and associated risk factors. Methods A retrospective review of all patients aged over 50 years receiving IV ZA between the periods of May 2018 and May 2022 across Gosford and Wyong Hospitals, in NSW, Australia. Data on demographics, comorbidities, and adverse reactions were collected from electronic medical records. Logistic regression analysed associations between variables and APRs. Results Among 212 patients receiving IV ZA, 41% experienced APRs, predominantly in the form of flu-like symptoms. Patients starting IV ZA within 1–3 months of fracture onset were significantly more likely to develop APRs. Most APRs lasted 1–3 days, but 21% persisted over 1 week, with 15% resulting in a period of patient immobility. Despite APRs, 83% continued ZA treatment. Timing of ZA from fracture onset did not affect BMD improvement at 1 year. Conclusion This study highlights a higher APR risk with earlier ZA initiation from fracture onset. Notably, there are no significant BMD differences observed based on ZA timing at 1 year. In conclusion, early initiation of IV ZA post-fracture increased APR risk without affecting BMD outcomes, emphasising need for further prospective trials to optimise treatment protocols to reduce risk of APRs. Clinical Trial number: not applicable