Assessing the Impact of Osteogenesis Imperfecta on Non-Skeletal Systems

描述（由申请人提供）：成骨不全症（Osteogenesis imperfecta， OI）是一种罕见的异质结缔组织疾病，在美国影响约30,000人。这种疾病是由负责生产I型胶原蛋白的基因缺陷引起的，导致骨基质和结缔组织缺陷。成骨不全的主要表现是骨脆性；然而，这种疾病可能影响几乎所有含有胶原蛋白丰富组织的器官系统。因此，成骨不全患者可能会出现牙列受损、关节松弛、听力丧失和各种心脏问题。关于突变的胶原蛋白对这些组织的具体影响，有许多悬而未决的问题，对患者护理有重要意义。虽然文献提供了关于这些问题的广泛案例研究，但这种疾病的低患病率及其遗传变异意味着，很少有论文是基于足够大的人群来给出各种非骨骼并发症的风险或范围的清晰图景。因此，对于初级保健医生或面临处理成骨不全对主要健康问题（如心血管疾病、胃肠道疾病和癌症的适当治疗）影响的成年人来说，很少或根本没有指导。没有专门研究该疾病的中心，收集研究所需数据的机制过于昂贵，无法为临床医生和研究人员提供指导治疗决策和促进培训所需的结果证据。拟议会议“评估成骨不全对非骨骼系统的影响”的参与者将回顾与成骨不全相关的胶原缺陷如何影响非骨骼结构的现有知识，包括心血管、肺、胃肠道和妇科系统。与会者将在2010年成骨不全症基金会（OIF）科学会议的基础上建立势头，改善成骨不全症患者的肌肉骨骼预后，该会议部分由R-13基金支持，并由2010年OIF两年一次会议上举行的焦点小组支持。拟议的2012年会议将标志着在确定需要研究的领域和有希望的新治疗目标方面向前迈出了一大步。与会者将包括主要的成骨不全研究人员和临床医生（包括五个成骨不全相关临床研究中心和其他成骨不全诊所的代表），他们还将制定一项战略，与临床医生、研究人员、家长和成骨不全患者广泛分享知识。

DESCRIPTION (provided by applicant): Osteogenesis imperfecta (OI) is a rare, heterogeneous disease of connective tissue that affects about 30,000 persons in the United States. The disorder is caused by gene defects responsible for the production of Type I collagen, resulting in defective bone matrix and connective tissue. The primary manifestation of OI is bone fragility; however, the disease may affect virtually all organ systems that contain collagen-rich tissues. Thus, individuals with OI may experience impaired dentition, joint laxity, hearing loss, and a wide range of cardiac problems. There are many unanswered questions about the specific effect of mutated collagen on these tissues, with significant implications for patient care. While the literature offers a wide range of case studies on these problems, the low prevalence of the disease, combined with its genetic variation, means that few papers are based on a population that is sufficiently large to give a clear picture of the risk or range of th varied nonskeletal complications of OI. As a result, little or no guidance is available for the primary care physician or the adult who is faced with addressing the implications of OI on major health questions, such as the appropriate treatment of cardiovascular disease, gastrointestinal diseases, and cancers. Absent centers specializing in the disease, mechanisms to gather the data needed for research are too expensive to give clinicians and researchers the evidence on outcomes they need to guide treatment decisions and facilitate training. Participants in the proposed meeting, Assessing the Impact of Osteogenesis Imperfecta on Nonskeletal Systems, will review current knowledge on how the collagen defects associated with OI affect nonskeletal structures, including the cardiovascular, pulmonary, gastrointestinal, and gynecological systems. Attendees will build on the momentum created by the 2010 Scientific Meeting of the Osteogenesis Imperfecta Foundation (OIF), Improving Musculoskeletal Outcomes for Individuals with Osteogenesis Imperfecta, which was supported in part by an R-13 grant, and by focus groups held at the 2010 OIF Biennial Meeting. The proposed 2012 meeting will mark a major step forward in the identification of areas needing research and of promising targets for new treatments. Attendees, who will include leading OI researchers and clinicians (including representatives of the five OI Linked Clinical Research Centers and other OI clinics), will also develop a strategy for sharing knowledge broadly with clinicians, researchers, parents, and adults with OI. PUBLIC HEALTH RELEVANCE: The best known aspect of osteogenesis imperfecta (OI), a rare disorder of connective tissue, is fragile bones ("brittle bones"), but OI may also affect a wide range of other organ systems, including the heart, lungs, hearing, vision, and teeth. To date there has been little research on how to treat the varied complications of OI. Assessing the Impact of Osteogenesis Imperfecta on Nonskeletal Systems will bring together leading OI researchers and clinicians, as well as adults living with OI, to review current knowledge regarding the impact of OI on a wide range of bodily systems during the aging process, identify major information gaps, and make recommendations to expand the OI research agenda.