Denosumab as a treatment for pediatric hypercalcemia—a multicenter experience

Abstract

Denosumab, a monoclonal antibody against receptor activator of NF-κB ligand, is frequently used to manage hypercalcemia and has recently been recommended as first-line therapy in adults with hypercalcemia of malignancy. Despite this, its use in the pediatric population is not well described for this indication. Our case series illustrates a multicenter experience using denosumab in the management of acute and chronic hypercalcemia. Patients had an age range of 2 mo to 16 yr of age. They had varying causes of hypercalcemia, including hypercalcemia of malignancy, the ketogenic diet, and Williams syndrome. Peak hypercalcemia ranged from 3.29 to 5.04 mmol/L and treatments trialed included intravenous fluids, calcitonin, and glucocorticoids. All patients received multiple doses of denosumab, with an individual dose range of 0.125-0.5 mg/kg, which successfully improved hypercalcemia. In two patients, denosumab was used as bridging therapy until acute renal impairment improved before giving bisphosphonates. Two patients experienced mild hypocalcemia which was managed with oral supplementation. Denosumab may be considered in the management of hypercalcemia, where other treatment has not been effective or where there is concomitant renal impairment and bisphosphonate therapy is contraindicated. Multiple doses of denosumab may be required and children must have their serum calcium monitored closely during therapy.