LONGITUDINAL STUDY OF OSTEOPOROSIS IMPERFECTA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 摘要 成骨不全（OI）是一种罕见的骨脆性增加的疾病，最常见的是由于I型胶原蛋白异常。 由于这种疾病的罕见性和疾病的泛种族性，OI个体没有地理聚集性，因此没有中心有足够数量的OI患者单独进行充分的把握度研究。 迄今为止，尚未进行关于OI自然史或管理的大型临床研究。 在过去的几十年里，医疗保健的大多数进步都是由针对特定疾病的自然史、药物或设备的大型多中心研究提供信息的。 对于罕见疾病，多中心模型对于获得足够个体的足够信息以使研究有效至关重要。 为此，OI基金会已投入资源，以发展相关的临床研究中心。 在第一年的资助中，将有三个中心（贝勒医学院，休斯顿，得克萨斯州;该研究所，巴尔的摩，马里兰州和俄勒冈州健康科学大学，波特兰，俄勒冈州）和一个数据收集和分析中心（南佛罗里达大学医学院，坦帕，佛罗里达）。 预计每个中心将在资助的前12个月招募至少40名患者。 我们预计，在LCRC计划的第五年，将在随后的几年中增加更多的中心，大约有24个参与中心。 最初的重点将是进行OI的自然史研究，预计将由此开发重点研究问题，以观察医疗和手术管理的结果，包括新治疗文章的临床试验。 I. 假设 一个纵向的多学科调查的自然史，发病率和死亡率的人与成骨不全将改善治疗和这种毁灭性的疾病的结果。 二. 具体目标 本方案的目的是对OI患者的自然史、当前治疗干预、发病率和死亡率进行纵向多学科研究。 研究问题是： a. 在纵向队列中，疾病严重程度的特定病理指标的患病率如何，包括骨折、疼痛和功能/活动性，以及与各种形式的OI相关的病死率？ B. 各种基因型与疾病严重程度和进展之间有何关系？ C. 目前使用的和新的OI疗法的安全性和有效性如何？

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Osteogenesis Imperfecta (OI) is a rare disorder of increased bone fragility that is most often due to abnormalities in type I collagen. Because of the rarity of this disorder and the pan-ethnicity of the disorder, there is no geographic clustering of individuals with OI and therefore there are no centers that have sufficient numbers of patients with OI to perform adequately powered studies alone. To date, large clinical research studies on the natural history or management of OI have not been performed. The majority of advances in medical care in the last few decades are informed by large, multicenter studies of natural history, drugs or devices for particular disorders. For rare disorders, the multicenter model is critical for obtaining enough information on enough individuals for a study to be valid. Toward this end, the OI Foundation has committed resources to the development of linked clinical research centers. There will be three centers in the first year of funding (Baylor College of Medicine, Houston, Texas; The Kennedy-Kreiger Institute, Baltimore, Maryland and Oregon Health Science University, Portland, Oregon) and a data collection and analysis center (University of South Florida College of Medicine, Tampa, Florida). It is expected that each center will enroll a minimum of 40 patients in the first 12 months of funding. We anticipate that additional centers will be added in subsequent years with around two dozen participant sites at year five of the LCRC initiative. The initial focus will be on performing a natural history study of OI and it is anticipated that from this, focused research questions will be developed to look at outcomes of medical and surgical management, including clinical trials of new therapeutic articles. I. HYPOTHESIS A longitudinal multidisciplinary investigation of the natural history, morbidity, and mortality in people with osteogenesis imperfecta will improve treatment and outcome of this devastating disorder. II. SPECIFIC AIMS The objective of this protocol is to conduct a longitudinal multidisciplinary investigation of the natural history, current therapeutic interventions, morbidity, and mortality in people with OI. The research questions are: a. In the longitudinal cohort, what is the prevalence of specific morbid indicators of disease severity, including fractures, pain, and functionality/mobility, as well as case-fatality associated with the various forms of OI? b. What is the relationship between various genotype and disease severity and progression? c. What is the safety and efficacy of currently used and new OI therapies?