Pseudogout attack following zoledronic acid treatment in primary hyperparathyroidism

Abstract Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, clinically known as pseudogout (PG), is an acute inflammatory arthritis that may rarely occur following bisphosphonate (BP) exposure. Zoledronic acid (ZA) is widely used for osteoporosis and hypercalcemia; however, crystal-induced arthritis is an uncommon adverse event. We describe a 65-year-old woman with primary hyperparathyroidism (PHPT) presenting with persistent hypercalcemia. Initial laboratory evaluation showed calcium of 11.1 mg/dL (SI: 2.78 mmol/L) (reference range, 8.8-10.2 mg/dL SI: 2.20-2.55 mmol/L) and parathyroid hormone of 89.31 pg/mL (SI: 9.47 pmol/L) (reference range, 15-65 pg/mL SI: 1.6-6.9 pmol/L). Imaging failed to localize a parathyroid lesion. Due to uncontrolled hypercalcemia and osteoporosis, intravenous ZA was administered. Three days later, she developed nausea, diffuse musculoskeletal pain, and laboratory findings consistent with acute kidney injury, requiring hospitalization. On the third hospital day, acute pain, swelling, warmth, and restricted movement occurred in the right elbow. Septic arthritis was excluded after negative cultures. Rheumatologic evaluation confirmed PG. Corticosteroid therapy led to rapid improvement. Advanced age, PHPT, baseline hypercalcemia, and a rapid calcium decline likely contributed to the CPPD crystal flare. Clinicians should consider PG after bisphosphonate use.