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Mechanisms of acute hypercalcemia in pediatric patients following the interruption of Denosumab
Journal of Endocrinological Investigation ( IF 5.4 ) Pub Date : 2021-07-03 , DOI: 10.1007/s40618-021-01630-4
A Deodati 1 , D Fintini 1 , E Levtchenko 2 , M Rossi 3 , G Ubertini 1 , H Segers 2 , G Battafarano 3 , M Cappa 1 , A Del Fattore 3
Affiliation  

Purpose

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.

Methods

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.

Results

Increase of CD16CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis.

Conclusion

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.



中文翻译:

地诺单抗中断后儿科患者急性高钙血症的机制

目的

地诺单抗是一种全人源单克隆抗 RANK-L 抗体,临床用于抵消破骨细胞活性加剧引起的骨丢失。事实上,它与 RANK-L 的结合阻止了 RANK-L/受体 RANK 的相互作用,这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丢失疾病,包括双膦酸盐,但狄诺塞麦非常有效,因为它可以减少骨侵蚀。在儿科患者中使用是安全的。然而,一些担忧与治疗的中断有关。事实上,在这项研究中,我们报告了两名儿科患者的高钙血症和循环破骨细胞前体的改变。

方法

外周血单个核细胞 (PBMC) 从 2 名 Denosumab 中断后患有高钙血症的儿科患者和 10 名对照中分离出来。进行了细胞荧光分析和体外破骨细胞生成实验。

结果

在患者的 PBMC 中发现CD16 - CD14 + CD11b +细胞增加,反映了体外破骨细胞生成的增强。

结论

我们的数据表明,当狄诺塞麦治疗中断时必须采取预防措施,并逐渐减少剂量和/或治疗时间。为防止可能处于停药阶段的高钙血症的发生,应进行 PBMC 的细胞荧光分析以评估破骨细胞前体。

更新日期:2021-07-04
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