Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Abstract

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. Summary 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.

Giant cell tumours of bone treated with denosumab: histological, immunohistochemical and H3F3A mutation analyses

“…1 Previous studies found instances of sarcomatous transformation arising in GCTBs treated with denosumab, 23,24 and there have been several suggestions regarding the ideal length of denosumab therapy and monitoring procedures. 22,[25][26][27] Further studies are required to determine the best therapeutic strategy.…”

Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

“…Denosumab, a monoclonal antibody that blocks RANKL interaction with RANK, inhibits bone resorption by inhibiting osteoclast maturation and function. It has been approved for the treatment of osteoporosis, multiple myeloma, skeletal metastasis, and recently GCTB . RANK and RANKL expression was observed in ABCs as well as GCTBs, chondroblastoma, and myelomas using immunohistochemistry and real‐time PCR methods .…”

Severe Primary Hyperparathyroidism Caused by Parathyroid Carcinoma in a 13‐Year‐Old Child; Novel Findings From HRpQCT

“…Given the severity of the initial presentation, hungry bone syndrome was anticipated despite the use of bisphosphonates, which have been implicated to reduce the risk of this postsurgical complication in patients with hyperparathyroidism . An interesting consideration in the use of denosumab, given its half‐life of 30 days and mechanism of action, is whether it might prolong postsurgical hypocalcemia. The duration and requirement for i.v.…”