Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children. Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025mg/kg, aimed at preventing rebound hypercalcaemia. Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6months in three patients and 12months in one patient. Three patients developed symptomatic hypercalcaemia 4-5months and one patient asymptomatic hypercalcaemia 7months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment. Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.