Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review

BACKGROUND AND OBJECTIVE: Denosumab is a valuable and safe therapy for skeletal disorders in adults and has received regulatory approval to treat osteoporosis and bone metastases. However, denosumab is not licensed for pediatric use due to a lack of high-quality prospective research on children. This study aimed to describe and discuss the benefits and disadvantages of denosumab in treating bone diseases in children and to summarize the current understanding of the role of denosumab therapy in children. METHODS: A narrative review was conducted using the literature retrieved from the PubMed, Embase, and Cochrane Library databases. KEY CONTENT AND FINDINGS: In children with type 6 osteogenesis imperfecta (OI), juvenile Paget disease (JPD), and secondary osteoporosis who show poor response to bisphosphonate, the use of denosumab has been reported to improve osteoporosis and increase bone mineral density (BMD). Moreover, for those with relapse, progressive and refractory aneurysmal bone cyst (ABC), fibrous dysplasia (FD), giant cell tumor of bone (GCTB), and central giant cell granuloma (CGCG) lesions, denosumab can improve pain symptoms, control disease progression, and reduce serious adverse events. Although there have been sporadic reports of adverse events such as hypocalcemia during medication and rebound hypercalcemia after discontinuation, early prevention, monitoring, and timely intervention can prevent children from experiencing severe adverse events. CONCLUSIONS: The published data indicate that denosumab has efficacy in alleviating disease in multiple refractory bone lesions in children.