地舒单抗治疗儿童成骨不全症的疗效和安全性分析

Efficacy and safety of denosumab in the treatment of osteogenesis imperfecta in children

目的回顾性观察地舒单抗治疗儿童成骨不全症(OI)患者的疗效和安全性,为地舒单抗作为OI的一种新替代治疗提供参考和证据支持。方法选取2021年1月1日至2022年12月31日北京协和医院首次接受地舒单抗治疗且年龄≤12岁的OI患儿为研究对象,比较治疗后6个月和12个月与治疗前的生长发育情况、骨代谢和生化指标改善情况、骨密度(BMD)变化,以及地舒单抗相关的ADR情况。结果共纳入27例患儿,中位年龄为8岁,1例在治疗6个月随访时未进行相关检查,地舒单抗用法为30 mg或60 mg,每5.5~6.0个月1次,皮下注射。与治疗前相比,治疗后6个月患儿的身高增加,血Ca水平及L2~4、股骨颈和全髋BMD均显著提高,差异有统计学意义(P<0.05);治疗后12个月患儿的身高和体质量显著增加,L2~4、股骨颈、大粗隆和全髋BMD均显著提高,差异有统计学意义(P<0.05)。14例患儿报告治疗期间曾发生可能与地舒单抗相关的不良反应,其中8例出现关节和肌肉疼痛,5例血Ca升高。结论儿童OI患者接受地舒单抗治疗后6个月及12个月,腰椎和股骨近端BMD提高,血Ca升高、关节和肌肉疼痛是其主要不良反应,临床可在密切监测血Ca等不良反应的情况下谨慎用于儿童OI患者。

Objective To retrospectively observe the efficacy and safety of denosumab in pediatric patients with osteogenesis imperfecta(OI)to provide reference and evidence support for denosumab as a new alternative option for treatment of OI.Methods From January 1,2021 to December 31,2022,all OI children aged≤12 years old who received disulizumab for the first time in Peking Union Medical College Hospital were selected as subjects.The growth and development,improvements in bone metabolism,biochemical indices and changes in bone mineral density(BMD)after 6 months and 12 months of treatment were compared with baseline,and denosumab-related adverse drug reactions were retrieved.Results A total of 27 children were included,with a median age of 8 years.One patient did not undergo relevant examinations during the 6-month follow-up period.The dosage of desucumab was 30 mg or 60 mg,once every 5.5 to 6.0 months,and was injected subcutaneously.Compared with before treatment,the height,blood Ca level,L2-4,femoral neck and total hip BMD significantly increased of children 6 months after treatment,with a statistically significant difference(P<0.05).At 12 months after treatment,the height and body mass of the children were significantly increased,and the L2-4,femoral neck,greater trochanter and total hip BMD were significantly increased,with statistical significance(P<0.05).Fourteen patients reported possible denosumab-related adverse reactions during treatment,8 cases had joint and muscle pain and 5 cases had elevated blood Ca.Conclusion After 6 months and 12 months of treatment with denosumab in children with OI,the BMI of lumbar spine and proximal femur is increased,and the main adverse reactions are increased blood Ca and joint and muscle pain.Denosumab should be used with caution in children with OI with close monitoring of adverse reactions such as blood calcium.