Severe Systemic Inflammatory Response Syndrome with Multi-Organ Failure Following Zoledronic ACID Infusion

ABSTRACT Objective: We report a new, life-threatening adverse effect of zoledronic acid. One of the adverse effects of zoledronic acid is acute phase reaction (APR). Mild APR is characterized by arthralgia, myalgia, headache, and fever, which are usually self-limiting. Here, we present a case of severe systemic inflammatory response syndrome (SIRS) following zoledronic acid infusion, leading to multi-organ failure. Methods: A 63-year-old female presented to the emergency department with fever, headache, and myalgia within hours after zoledronic acid infusion. Approximately 24 hours later, she developed progressive weakness and confusion. She was febrile, tachycardic, and tachypneic on presentation. Subsequently, she developed acute respiratory distress syndrome, stress or Takotsubo cardiomyopathy, shock with hypotension, and acute tubular necrosis with acute kidney failure. Results: All infectious work-up was unrevealing. She was diagnosed with severe SIRS leading to multi-organ failure. She needed aggressive supportive therapies, including mechanical ventilation, multiple vasopressors, and renal replacement therapy. She was treated with systemic steroids. She gradually improved over the next 4 weeks. Conclusion: Mild APRs are common with administration of nitrogen-based bisphosphonates. However, to date, severe life-threatening APR as seen in the above-mentioned case has not been reported. It is important for clinicians to be aware of the possibility of such adverse effects. This case highlights the need for further investigation related to underlying mechanisms of APR by bisphosphonates and identification of patients at risk so that alternative treatments may be considered. Abbreviations: APR acute phase reaction; FPPS farnesyl pyrophosphate synthase; IPP isopentenyl pyrophosphate; IV intravenous; UTI urinary tract infection