Hypercalcaemia after treatment with denosumab in children: bisphosphonates as an option for therapy and prevention?

BACKGROUND Pharmacologic options for treatment of osteolytic diseases especially in children are limited. Although not licensed for use, denosumab, a fully humanized antibody to RANKL, is used in children with good effects. Among others, one possible indication are giant cell tumors and aneurysmatic bone cysts. However, there are reports of severe hypercalcemia during weeks to months after termination of denosumab, that are rarely seen in adults. METHODS We collected~data of four patients, aged 6-17~years, who~experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment. The detailed case information were described. RESULTS One patient was treated with long-term, high-dose steroid therapy, leading to typical Cushing's syndrome. Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop. Finally, in two patients, hypercalcemia ceased definitely after treatment with bisphosphonates. However, several applications were necessary to stabilize calcium levels. CONCLUSIONS There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children. Therapeutic and, preferably, preventive strategies are needed. Bisphosphonates seem to be an option for both, but effective proceedings still remain to be established

Needle-free and needle-based growth hormone therapy in children

$\bf Background:$ Treatment with growth hormone (GH) is standard clinical practice in children with GH deficiency (GHD) or Turner syndrome (TS). Hitherto, no long-term data on auxological outcome and safety of Zomacton® have been published. Data comparing needle-free administration (NF) and needle injection (NI) of GH are very sparse. $\bf Aims:$ To analyse longitudinal auxological outcome and safety data of GH treatment-naïve patients diagnosed with GHD or TS and to compare NF and NI in a real-life setting. $\bf Methods:$ Pooled auxological data and safety information from three consecutive prospective observational Zomacton® studies covering 22 years of treatment were analysed and NF was compared to NI. $\bf Results:$ The safety cohort comprised 1,595 patients who received at least one GH dose. The auxological outcome cohort comprised 856 treatment-naïve patients with follow-up data $\geq$ 12 months. Height-SDS and height velocity improved significantly during the first 3 years of treatment. Documented choice of device was available for 658 patients (NF 69.1%, NI 30.9%). NF administration was non-inferior to NI. No previously unknown safety signals occurred. $\bf Conclusion:$ Real-life data show that treatment with Zomacton® improves auxological outcome parameters without new safety concerns. NF administration of GH represents a useful alternative to NI in children with growth disorders