Denosumab: an Emerging Therapy in Pediatric Bone Disorders.

PURPOSE OF REVIEW: Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand (RANKL), and has emerged as an important novel therapy for skeletal disorders. This article examines the use of denosumab in children.

RECENT FINDINGS: Considerable safety and efficacy data exists for denosumab treatment of adults with osteoporosis, bone metastases, and giant cell tumors. Pediatric data is limited; however, evidence suggests denosumab may be beneficial in decreasing bone turnover, increasing bone density, and preventing growth of certain skeletal neoplasms in children. Denosumab's effect on bone turnover is rapidly reversible after drug discontinuation, representing a key difference from bisphosphonates. Rebound increased bone turnover has led to severe hypercalcemia in several pediatric patients. Denosumab is a promising therapy for pediatric skeletal disorders. At present, safety concerns related to rebounding bone turnover and mineral homeostasis impact use of denosumab in children. Research is needed to determine if and how these effects can be mitigated.