帕米膦酸二钠治疗儿童成骨不全症的疗效和安全性分析

Analysis of the Efficacy and Safety of Pamidronate Disodium in the Treatment of Osteogenic Imperfecta in Children

关键词:  成骨不全症  帕米膦酸二钠  儿童  罕见病

Key words:  osteogenic imperfecta  pamidronate  children  rare disease

摘要:

目的 回顾性分析帕米膦酸二钠(pamidronate，APD)治疗儿童成骨不全症(osteogenesis imperfecta，OI)的疗效和安全性。方法 选取2014年1月1日—2023年6月30日重庆医科大学附属儿童医院首次使用APD的儿童患者为研究对象，比较治疗前后的生长发育情况、骨代谢和生化指标改善情况、骨密度(bone mineral density，BMD)和骨折变化，以及不良反应(adverse drug reactions，ADR)发生情况。结果 共纳入14例患儿，中位年龄为5.16岁。所有患儿无论治疗持续时间长短(1，2年及≥3年)，与治疗前相比，身高、体质量、腰椎BMD均显著提高，年平均骨折次数显著下降，差异有统计学意义(P<0.05)；治疗1年后，碱性磷酸酶(alkaline phosphatase，ALP)显著增加(P=0.024)；治疗2年后，总25-羟维生素D₃(T-25OHD₃)明显提高(P=0.014)；治疗3年后，身高Z值明显改善(P=0.036)。最常见ADR为发热、骨骼肌肉疼痛、低钙血症和低磷血症等。结论 OI患儿接受APD治疗的耐受性良好，腰椎BMD和BMD Z值增加，骨折率降低，生长发育改善。

Abstract:

OBJECTIVE To retrospectively analyze the efficacy and safety of pamidronate disodium(APD) in the treatment of osteogenic imperfecta(OI) in children. METHODS Children who first used APD at the Children's Hospital Affiliated to Chongqing Medical University from January 1, 2014 to June 30, 2023 were selected as the research subjects. The growth and development status, improvement of bone metabolism and biochemical indicators, changes in bone density(BMD) and fractures, and occurrence of adverse drug reactions(ADRs) before and after treatment were compared. RESULTS A total of 14 pediatric patients were included, with a median age of 5.16 years. All children, regardless of the duration of treatment(1, 2 years, 3 years or more), showed significant improvements in height, body mass, and lumbar BMD compared to before treatment, while the average number of fractures per year decreased significantly(P<0.05). After 1 year of treatment, the alkaline phosphatase significantly increased(P=0.024). After 2 years of treatment, the total 25-hydroxyvitamin D₃(T-25OHD₃) significantly improved(P=0.014). After 3 years of treatment, the Z-value of height significantly improved(P=0.036). The most common ADR were fever, skeletal muscle pain, asymptomatic hypocalcemia and hypophosphatemia. CONCLUSION Pediatric patients with OI have good tolerance to APD treatment, with increased lumbar BMD and BMD Z values, reduced fracture rates, and improved growth and development.