Denosumab is a potent anti-resorptive agent that inhibits osteoclast maturation and activity by binding to receptor activator of nuclear factor kappa-B ligand (RANKL). Its use in adult osteoporosis is well established, using six-monthly dosing, which results in minimal drug accumulation with recovery of bone turnover between doses. Monthly dosing leads to continuous suppression of bone turnover and is used for treatment of giant cell-rich bone tumours, bone metastases from solid tumours and hypercalcaemia of malignancy. There is also an emerging role for treatment of symptomatic fibrous dysplasia lesions refractory to standard therapy.
The efficacy and safety of the monthly, higher-dose denosumab regimen has been shown in adults and skeletally-mature adolescents in phase 2 and 3 clinical trials, leading to its regulatory approval in these populations. Evidence for its use in children and adolescents before skeletal maturity is much scarcer. The case reports and series available describe similar efficacy when used for giant cell-rich bone tumours, but safety concerns have been far greater. The most significant of these is the hypercalcaemia observed during the rebound of bone turnover after denosumab cessation, which can be severe and invariably requires treatment with intravenous bisphosphonates or further denosumab. Nevertheless, for unresectable bone tumours, the benefits may outweigh the risks and international collaboration is underway to improve the evidence base for the paediatric use of denosumab.
This presentation will cover the use of denosumab in non-osteoporotic conditions with a focus on RANKL-mediated focal bone lesions and the management considerations for paediatric use.