Evolving Use of Denosumab in Severe Cherubism: Updates, Fragility Fractures, Rebound Hypercalcemia, and Lessons from Two Cases

Cherubism is a rare autosomal dominant disorder characterized by proliferative fibro-osseous lesions of the maxilla and mandible. Surgical management varies by disease severity and symptom burden, often resulting in substantial operative burden in pediatric patients. Denosumab, a monoclonal antibody targeting RANKL, offers potential off-label therapy to suppress osseous overgrowth and reduce surgical morbidity. The authors previously reported early success with denosumab in 1 patient ; however, during long-term treatment, the patient developed multiple long-bone fragility fractures and severe rebound hypercalcemia. This report updates that patient and describes treatment modifications in a second patient with cherubism, supporting denosumab as a disease-suppressive therapy with refined dosing and metabolic surveillance.