Department of Pediatric Endocrinology, Dr. v. Haunersches Children's Hospital, Ludwig-Maximilian-University of Munich, Lindwurmstr. 4, 80337, Munich, Germany.
Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany.
World J Pediatr. 2020 Oct;16(5):520-527. doi: 10.1007/s12519-020-00378-w. Epub 2020 Aug 10.
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.
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.
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.
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.
治疗溶骨性疾病的药物选择，尤其是儿童患者，非常有限。地舒单抗是一种完全人源化的 RANKL 抗体，虽然尚未获得批准用于儿童，但在儿童中的应用效果良好。其中一个可能的适应证是骨巨细胞瘤和动脉瘤样骨囊肿。然而，有报道称在停药数周到数月后会出现严重的高钙血症，这种情况在成人中很少见。
我们收集了 4 名年龄在 6-17 岁的患者的数据，他们在接受地舒单抗治疗不可切除的骨巨细胞瘤或骨动脉瘤样骨囊肿后出现严重的高钙血症，并描述了他们的治疗方法。
1 名患者接受了长期、大剂量的类固醇治疗，导致典型的库欣综合征。另一名患者因每次停药后高钙血症复发而反复重新开始使用地舒单抗。最后，在 2 名患者中，高钙血症在使用双膦酸盐治疗后确实停止，但需要多次应用以稳定血钙水平。
地舒单抗治疗儿童后出现高钙血症的不良反应风险相当大。需要治疗和（最好）预防策略。双膦酸盐似乎是一种选择，但有效的治疗方法仍有待确定。
