Bilici M E, Siklar Z, Unal E, Tacyildiz N, Aycan Z, Ozsu E, Uyanik R, Berberoglu M
Zonguldak Bulent Ecevit University School of Medicine, Department of Pediatric Endocrinology.
Ankara University School of Medicine, Department of Pediatric Endocrinology.
Acta Endocrinol (Buchar). 2024 Apr-Jun;20(2):231-235. doi: 10.4183/aeb.2024.231. Epub 2025 Jan 18.
Denosumab,a monoclonal IgG2 antibody directed against RANK-L,is used as a neoadjuvant therapy for inoperable or metastatic giant cell tumor of bone. Many side effects like as hypocalcemia during treatment and rarely severe hypercalcemia especially in children after discontinuation of denosumab occurred. The unpredictable onset and recurrent episodes of severe hypercalcemia increase the duration of hospitalization and the risk of complications. Persistent hypercalcemia and difficulties in management have prompted the search for different more effective therapeutic options.
To share our experience with the use of oral bisphosphonate in acute and long-term therapy of severe hypercalcemia following high-dose denosumab therapy and to review the literature on this subject.
We report the management of a case of severe hypercalcemia that developed 4 months after the completion of 18-month denosumab treatment in a 9-year-old girl who was followed up with a giant cell bone tumor for 6 years. Based on an evaluation aiming to determine etiology, hypercalcemia was considered as "rebound-linked" upon denosumab discontinuation. Severe hypercalcemia attacks recurring with an interval of 2 weeks were treated with IV bisphosphonate, but when mild hypercalcemia developed again, treatment with 70 mg per week of oral bisphosphonate was planned. After the second dose of alendronate, the calcium level always remained below 10.5 mg/dl. In the 14-month follow-up, no hypercalcemia attack was observed again.
Rebound hypercalcemia can occur as an unpredictable recurrent episode at any time after denosumab cessation. Thus, the patient should be closely monitored especially in childhood due to rapid bone cycle. In long-term follow-up, oral biphosphonates can be used effectively to reduce hospitalization time and the management of especially life-threatening recurrent attacks.
地诺单抗是一种靶向核因子κB受体活化因子配体（RANK-L）的单克隆IgG2抗体，用作不可切除或转移性骨巨细胞瘤的新辅助治疗。治疗期间会出现许多副作用，如低钙血症，停药后尤其是儿童中很少会出现严重高钙血症。严重高钙血症的发作不可预测且反复发作，增加了住院时间和并发症风险。持续性高钙血症及管理困难促使人们寻找更有效的不同治疗方案。
分享我们在大剂量地诺单抗治疗后严重高钙血症的急性和长期治疗中使用口服双膦酸盐的经验，并回顾关于该主题的文献。
我们报告了一名9岁女孩的严重高钙血症治疗情况，该女孩因骨巨细胞瘤接受了6年随访，在完成18个月的地诺单抗治疗后4个月出现严重高钙血症。基于旨在确定病因的评估，高钙血症被认为是地诺单抗停药后的“反弹相关”。每2周复发一次的严重高钙血症发作采用静脉注射双膦酸盐治疗，但当再次出现轻度高钙血症时，计划采用每周70毫克的口服双膦酸盐治疗。在服用第二剂阿仑膦酸钠后，钙水平始终保持在10.5毫克/分升以下。在14个月的随访中，未再次观察到高钙血症发作。
地诺单抗停药后，反弹高钙血症可能在任何时间以不可预测的复发形式出现。因此，由于儿童骨转换迅速，应特别密切监测患者。在长期随访中，口服双膦酸盐可有效减少住院时间，并管理尤其是危及生命的复发发作。
