Assessing the Impact of Osteogenesis Imperfecta on Non-Skeletal Systems

描述(申请人提供)：成骨不全(OI)是一种罕见的异质性结缔组织疾病，在美国约有30,000人患病。这种疾病是由负责产生I型胶原的基因缺陷引起的，导致骨基质和结缔组织缺陷。OI的主要表现是骨骼脆弱；然而，这种疾病可能会影响到几乎所有含有丰富胶原组织的器官系统。因此，OI患者可能会经历牙列受损、关节松弛、听力丧失和广泛的心脏问题。关于突变的胶原蛋白对这些组织的具体影响，还有许多悬而未决的问题，这对患者护理具有重要意义。虽然这些文献提供了关于这些问题的广泛的案例研究，但这种疾病的低患病率，加上它的遗传变异，意味着很少有文献是基于足够大的人群来清楚地描述OI的各种非骨骼并发症的风险或范围。因此，对于面临OI对重大健康问题的影响的初级保健医生或成年人，如心血管疾病、胃肠道疾病和癌症的适当治疗，几乎没有或没有指导。如果没有专门研究这种疾病的中心，收集研究所需数据的机制成本太高，无法为临床医生和研究人员提供他们需要的关于结果的证据，以指导治疗决策和促进培训。这次会议的与会者将评估成骨不全对非骨骼系统的影响，他们将回顾与OI相关的胶原蛋白缺陷如何影响非骨骼结构的现有知识，包括心血管、肺、胃肠和妇科系统。与会者将利用2010年成骨不全基金会(OIF)科学会议创造的势头，改善成骨不全患者的肌肉骨骼结果，部分由R-13赠款支持，并由2010年OIF两年一度的会议上的焦点小组提供支持。拟议的2012年会议将标志着在确定需要研究的领域和新疗法的有希望的目标方面向前迈出了重要的一步。与会者将包括领先的OI研究人员和临床医生(包括五个与OI相关的临床研究中心和其他OI诊所的代表)，还将制定一项战略，与临床医生、研究人员、父母和患有OI的成年人广泛分享知识。 与公共卫生相关：成骨不全(OI)是一种罕见的结缔组织疾病，最为人所知的方面是脆性骨骼，但OI也可能影响广泛的其他器官系统，包括心脏、肺、听力、视力和牙齿。到目前为止，关于如何治疗OI的各种并发症的研究很少。评估成骨不全对非骨骼系统的影响将把OI的主要研究人员和临床医生以及OI的成年人聚集在一起，审查目前关于OI在衰老过程中对广泛身体系统的影响的知识，确定主要的信息差距，并提出扩大OI研究议程的建议。

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.