Denosumab in pediatric patients with fibrous dysplasia/McCune-Albright syndrome: a single-center, open-labeled study

Context: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder frequently manifesting in childhood, often leading to progressive bone lesions, pain and functional impairment. Denosumab as a monoclonal antibody targeting RANKL has emerged as a potential therapeutic option, while its safety and efficacy in pediatric population remains poorly defined. Objective: Investigate the efficacy and safety of denosumab in pediatric FD/MAS population. Design: 12-month single-arm study. Setting: Single center study at Peking Union Medical College Hospital. Patients: FD/MAS patients under 18. Interventions: Denosumab 1mg/kg with a maximum dosage of 60mg every 3 months for 12-month follow-up. Main outcome measures: Tc-MDP bone scintigraphy, bone mineral density. Results: In 5 pediatric FD/MAS patients treated with denosumab, significant clinical improvements were observed, including alleviation of FD-associated bone pain, reductions in bone turnover markers, and regression of FD lesions. Alkaline phosphatase levels dropped to an average of 41.8% of baseline, accompanied by concurrent reductions in C-terminal telopeptide and type 1 N-terminal pro-peptide levels. Adverse events particularly hypercalcemia following treatment cessation occurred in 2 of the 5 patients, indicating a relatively high incidence of rebound hypercalcemia and highlighting the need for careful monitoring and cautious use of denosumab in pediatric patients. Conclusions: Denosumab appears to be effective in pediatric FD/MAS patients, however safety concerns remain. Comprehensive pre-treatment evaluation and close monitoring throughout the treatment course are essential. Further prospective studies and randomized controlled trials are needed to determine optimal dosing strategies and establish long-term safety in this population.