ESPE Abstracts

Background: Hypercalcaemia has various etiologies and treatment is often challenging. Therapeutic options include aggressive fluid management, loop diuretics and antiresorptive drugs. Since both hypercalcaemia and bisphosphonates can cause acute kidney injury (AKI), bisphosphonates are not recommended in patients with renal impairment. Denosumab, an antiresorptive human monoclonal antibody, is not associated with AKI and offers a temporary treatment option. However, osteoclastic activity will recover after a few weeks to months with the risk of rebound hypercalcaemia. Treatment of hypercalcaemia with denosumab in the setting of renal impairment may be an alternative to bisphosphonates.

Methods: We reached out to international colleagues, including the ESPE working group on bone and growth plate, experienced with the use of denosumab for hypercalcaemia in paediatrics and collated cases using a custom-made case report form.

Results: Five patients were included in the analysis, with a mean age of 12 years (range 8.2 to 17.7). Indications for denosumab were hypercalcaemia secondary to immobility (n=2), malignancy (n=1), sarcoidosis (n=1) and an undiagnosed genetic condition (n=1). All had renal concerns, including AKI (n=3), solitary kidney (n=1) or bilateral dysplastic kidneys (n=1). The mean serum calcium level before denosumab administration was 3.51 mmol/l (range 3.27 to 3.81) and all patients were vitamin D replete. Denosumab was given at a mean dose of 1.36 mg/kg (range 0.25 to 2.9). Mean time to normalization of serum calcium was three days (range 2 to 4). One patient developed hypocalcaemia (serum calcium 1.7 mmol/l), which resolved by intravenous calcium infusion and oral calcitriol. In one patient hypercalcaemia recurred 47 days after the first denosumab dose (serum calcium 3.84 mmol/l). This patient received a second dose of denosumab 60 days after the first and three months later two sealing doses of zoledronic acid (first dose 0.0125 mg/kg, second dose 0.02 mg/kg) 25 days apart. Two patients stayed normocalcaemic. In two patients, no statement can be made regarding recurrence of hypercalcemia, since they died of their underlying condition.

Discussion: Denosumab effectively lowered serum calcium in all hypercalcaemic patients, but the interindividual dosages used were quite different. Whether recurrence of hypercalcaemia in one of the patients was due to rebound phenomenon or because the underlying cause had not resolved remains unclear. More research is needed to explore safety, dosing and management of hypercalcemia, and of rebound hypercalcaemia, for the paediatric use of denosumab.