Endocrine Abstracts

JOINT1856

Background: Denosumab is a monoclonal anti-RANK-L receptor antibody used to treat a wide range of bone lesions, including fibrous dysplasia, osteogenesis imperfecta, aneurysmal bone cysts, giant cell granuloma (GCG) and giant cell tumor of bone (GCTB) in both adults and children. The use of denosumab in pediatric patients is associated with a high risk of rebound hypercalcemia upon discontinuation. This condition often requires hospitalization and, in some cases, bisphosphonates to normalize calcium levels. Based on the clinical course of two patients with GCG treated with denosumab, we propose a preventive approach to rebound hypercalcemia.

Case presentation: Patient 1 was a 7-year-10-month-old boy who presented with maxillary swelling. MRI revealed a left maxillary mass (50x50x57mm), and pathology confirmed the diagnosis of GCG. Neoadjuvant treatment with denosumab (120 mg) was initiated with loading doses at T0, followed by doses at T15 and T45. T8 was not performed due to phosphaturia. Loading doses were followed by monthly doses of 100 mg for 8 months. The dose was gradually reduced to 20 mg over 6 months and discontinued after a total of 16 months of treatment. Follow-up MRI showed size reduction of the lesion to 45x54x37mm. Despite the tapering, the patient developed severe rebound hypercalcemia 2 months after discontinuation (total serum calcium increased to 15.8 mg/dl), requiring hospitalization and treatment with intravenous hydration, furosemide, oral glucocorticoids and endovenous zoledronate (dose 0.05 mg/kg/dose). Patient 2 was a 16-year-2-month-old boy referred for a costal lesion, which was diagnosed as GCTB after biopsy. Denosumab treatment was started with a dose of 120 mg at T0, followed by 100 mg (due to hypophosphatemia) at T8 (T15 was not performed due to hypophosphatemia) and T45. Monthly doses were then administered and reduced to 40 mg within 3 months. One month after suspension, the patient received 2 mg (dose 0.03 mg/kg/dose) of intravenous zoledronate. Follow-up CT scan showed a stable size of the lesion with increased calcification. Six months after discontinuation, the patient successfully underwent surgical removal of the lesion, and his serum calcium levels remained within the normal range.

Discussion: Prevention of rebound hypercalcemia after suspension of denosumab may be challenging and tapering alone may not suffice. We propose a stepwise approach to the adverse events associated with denosumab involving strict monitoring for hypocalcemia and hypophosphatemia (which should be promptly corrected), and the administration of zoledronate at least one month after suspension to prevent rebound hypercalcemia.