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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。双膦酸盐是焦磷酸盐的合成类似物，已被广泛用于治疗患有骨丢失和骨脆性的成年人。最近对双膦酸帕米磷酸钠治疗严重成骨不全儿童的研究表明，早在治疗开始六周后，骨密度就明显增加。无一例外，骨密度的增加超过了健康儿童的预期。骨疼痛的迹象在接受双膦酸盐治疗后的几天内消失，尽管由于活动能力增加而受伤的风险较高，但骨折发生率明显下降。这是对CZOL446H2 202的一项为期一年的研究，该研究是一项多中心有效性和安全性试验，比较了静脉注射唑来膦酸和静脉注射帕米磷酸钠治疗严重成骨不全儿童的疗效和安全性。这项扩展研究是一项国际性、多中心、随机、开放标签、安全性和有效性的试验，评估两种不同剂量的唑来膦酸持续治疗的安全性：一年一次或一年两次。通过对耐受性、肾脏安全性、一般安全性和不良事件的监测，将显示唑来膦酸治疗儿童严重成骨不全的安全性。疗效评估将包括骨密度测量、脊柱和左手的X光检查、评估骨吸收和形成的专门血清测试、骨骼疼痛评估和握力测量。

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.