Metaphyseal band fractures in pediatric patients treated with denosumab

Abstract

OBJECTIVE: Denosumab, a potent antiresorptive agent targeting receptor activator of nuclear factor kappa-B ligand (RANKL), is increasingly used off-label in RANKL-mediated pediatric bone disorders, but concerns remain regarding rebound hypercalcemia and altered bone modeling and remodeling. This study describes clinical, biochemical, and radiological features of metaphyseal sclerotic band fractures in children on denosumab and assesses risk factors with focus on timing and occurrence of rebound hypercalcemia. DESIGN AND METHODS: We conducted a retrospective multicenter study. Clinical, biochemical, and X-ray data were reviewed. High-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis were performed in 1 case to assess bone microarchitecture. RESULTS: Five pediatric patients (aged 7-18 years) were included: 4 received denosumab for RANKL-mediated bone lesions, and 1 for secondary osteoporosis. Fractures occurred 1.5-7.7 years after starting denosumab, involving the distal radius, ulna, femur, clavicle, and rib. All followed low- or moderate-impact trauma and involved zones of metaphyseal sclerosis. Rebound hypercalcemia occurred in all patients (1 to >16 episodes); in 4 cases, it preceded the fracture by 0-4 months, while 1 case first developed hypercalcemia 3 weeks postfracture. HR-pQCT in a single patient revealed markedly increased trabecular volumetric bone mineral density and stiffness within the sclerotic band plus reduced estimated failure load. Bisphosphonates were used, albeit variably, for prevention or treatment of hypercalcemia. CONCLUSIONS AND RELEVANCE: Fractures through sclerotic metaphyseal bands may represent a distinct complication of denosumab therapy in children. Rebound hypercalcemia and fractures can co-occur, underscoring the need for close monitoring and management by pediatric bone specialists throughout treatment.