AN INTERNATIONAL, MULTICENTER, RANDOMIZED, OPEN-LABEL, SAFETY AND EFFICACY TR

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。双膦酸盐，焦磷酸盐的合成类似物，已被广泛用于治疗成人骨质流失和骨质脆弱。最近对患有严重成骨不全症的儿童使用双膦酸盐帕米膦酸盐的研究表明，早在治疗开始六周后，骨密度就明显增加。无一例外，骨密度的增加比健康儿童预期的增加要大。骨痛的症状在接受双膦酸盐治疗的几天内消失，骨折率显著降低，尽管由于活动能力的增加，受伤的风险更高。这是CZOL446H2202的一项为期一年的研究延伸，这是一项多中心疗效和安全性试验，比较静脉注射唑来膦酸和静脉注射帕米膦酸治疗严重成骨不全症儿童。该研究扩展是一项国际、多中心、随机、开放标签、安全性和有效性试验，评估两种不同剂量唑来膦酸持续治疗方案的安全性：每年一次或每年两次。唑来膦酸治疗儿童严重成骨不全症的安全性将通过耐受性、肾脏安全性、一般安全性和不良事件的监测来证明。疗效评估将包括骨密度测量、脊椎和左手x光片、评估骨吸收和形成的专门血清测试、骨痛评估和握力测量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bisphosphonates, the synthetic analogs of pyrophosphate, have been widely used for the treatment of adults suffering from bone loss and bone fragility. Recent studies of the bisphosphonate, pamidronate, in children with severe osteogenesis imperfecta show an increase in BMD evident as early as six weeks after the start of treatment. Without exception, this gain in BMD has been greater than the increase expected in healthy children. Signs of bone pain disappear within days of receiving the bisphosphonate and a marked decrease in fracture rate is observed despite a higher risk of injury due to increased mobility. This is a one-year study extension to CZOL446H2202, a multicenter efficacy and safety trial that compared intravenous zoledronic acid to intravenous pamidronate in children with severe osteogenesis imperfecta. This study extension is an international, multicenter, randomized, open-label, safety and efficacy trial, evaluating the safety of continued treatment with two different dosing regimens of zoledronic acid: once yearly or twice yearly. The safety of zoledronic acid for the treatment of severe osteogenesis imperfecta in children will be shown through the monitoring of tolerability, renal safety, general safety, and adverse events. Efficacy assessments will include bone mineral density measurements, x-rays of vertebral spine and left hand, specialized serum tests to evaluate bone resorption and formation, bone pain assessment, and grip strength measurements.