Deodati A, Fintini D, Levtchenko E, Rossi M, Ubertini G, Segers H, Battafarano G, Cappa M, Del Fattore A
Endocrinology Unit, University Pediatric Clinical Department, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Department of Pediatrics, University Hospitals Leuven, 3000, Leuven, Belgium.
J Endocrinol Invest. 2022 Jan;45(1):159-166. doi: 10.1007/s40618-021-01630-4. Epub 2021 Jul 3.
Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors.
Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed.
Increase of CD16CD14CD11b cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis.
Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.
地诺单抗是一种全人源单克隆抗核因子κB受体活化因子配体（RANK-L）抗体，临床上用于对抗因破骨细胞活性增强引起的骨质流失。实际上，它与RANK-L结合可阻止RANK-L/受体RANK之间的相互作用，而这种相互作用对破骨细胞生成和骨吸收活性至关重要。尽管有许多药物可用于治疗骨质流失疾病，包括双膦酸盐类药物，但地诺单抗非常有效，因为它可减少骨侵蚀。在儿科患者中使用是安全的。然而，一些问题与治疗中断有关。实际上，在本研究中，我们报告了两名儿科患者出现高钙血症以及循环破骨细胞前体的改变。
从两名地诺单抗中断治疗后出现高钙血症的儿科患者和10名对照者中分离外周血单个核细胞（PBMC）。进行细胞荧光分析和体外破骨细胞生成实验。
患者PBMC中CD16CD14CD11b细胞增加，这反映了体外破骨细胞生成增强。
我们的数据表明，中断地诺单抗治疗时必须采取预防措施，应逐渐减少剂量和/或治疗时间。为防止在停药阶段可能出现的高钙血症，应进行PBMC的细胞荧光分析以评估破骨细胞前体。
