Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial
Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial
复制标题
DOI：
10.1016/s0140-6736(13)61091-0
复制
发表时间：
2013-10-26
期刊：
影响因子：
168.9
通讯作者：
Steiner, Robert D.
中科院分区：
文献类型：
--
作者：
Bishop, Nick;Adami, Silvano;Steiner, Robert D.
背景：儿童成骨不全常采用静脉注射双膦酸盐治疗。我们的目的是评估利塞膦酸盐，口服第三代双膦酸盐，在儿童与疾病的安全性和有效性，在这个多中心，随机，平行，双盲，安慰剂对照试验，儿童年龄4-15岁的骨生成障碍和骨折风险增加随机分配电话随机系统在2：1比率接受每日利塞膦酸钠（2.5或5 mg）或安慰剂1年。研究治疗对患者、研究者和研究中心工作人员设盲。此后，所有儿童在开放标签扩展中接受了额外2年的利塞膦酸钠治疗。主要疗效终点是1年时腰椎区域骨密度（BMD）的百分比变化。通过ANCOVA进行主要疗效分析，治疗、年龄组和汇总中心作为固定效应，基线作为协变量。分析基于意向治疗人群，包括随机分配并接受至少一剂分配的研究治疗的所有患者。该试验在ClinicalTrials.gov注册，编号NCT 00106028。结果在147名患者中，97名被随机分配到利塞膦酸钠组，50名被随机分配到安慰剂组。利塞膦酸钠组的3名患者和安慰剂组的1名患者未接受研究治疗，意向治疗人群中分别留下94名和49名患者。1年后，利塞膦酸钠组腰椎区域BMD平均增加16.3%，安慰剂组增加7.6%（差异8.7%，95%CI 5.7-11.7; p
Background Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease.Methods In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4-15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2: 1 ratio to receive either daily risedronate (2.5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov, number NCT00106028.Findings Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16.3% in the risedronate group and 7.6% in the placebo group (difference 8.7%, 95% CI 5.7-11.7; p