DIVERSITY SUPPLEMENT: BRITTLE BONE DISORDERS CONSORTIUM OF THE RARE DISEASE CLINICAL RESEARCH NETWORK

项目总结(总体) 这是一份延续脆性骨疾病罕见疾病联盟的续签申请 6-10年的临床研究网络(BBDC RDCRN)。BBDC专注于罕见的骨骼疾病 是由成骨细胞分化和/或功能缺陷引起的，这种缺陷导致质量和/或 骨的数量缺陷、生物材料特性的改变，如矿化，和/或下游细胞 骨细胞和破骨细胞的变化。这些都以不同类型的成骨作用为代表 不完美(OI)。虽然OI经常与BBD互换使用，但表型谱很快 正在扩张。此外，了解这些表型的自然历史还有一个重要的未得到满足的需求。 根据他们的分子遗传病因分层。这些不同的突变是如何最终导致脆性骨骼的 仍然不清楚，各种疾病发病率的适当干预措施和生物标记物是什么 公开的问题。在BBDC的第1-5年，我们在7个方案中有6个达到或超过了应计目标。我们 已发表或正在审阅描述我们横断面数据的12篇手稿。重要的是，我们的 在之前的纵向研究、妊娠研究、颅面研究、试点胶原交联剂中的发现 生物标记物研究和PROMIS试点研究使新元素的设计和纳入成为可能 目前的纵向研究(项目1)，治疗OI错牙合的正畸临床试验(项目2)，以及 生长的纵向生物标志物研究(项目3)。BBDC将由12个临床站点组成，涵盖 美国和加拿大。BBDC的具体目标是：i)在以下领域开展合作临床研究 脆性骨病，包括上述三个临床项目；ii)培训和吸引一批 临床骨研究的研究人员将从本科生、学士学位后、研究生、 医学生、住院医生/研究员和初级教员；以及iii)与成骨 不完美基金会(OIF)扩展可用于广泛教育的培训材料工具箱 患者、家属和医疗保健提供者拥有广泛的专业知识。

PROJECT SUMMARY (OVERALL) This is a renewal application to continue the Brittle Bone Disorders Consortium of the Rare Diseases Clinical Research Network (BBDC RDCRN) for years 6-10. The BBDC is focused on rare bone diseases that are caused by defects in osteoblast differentiation and/or function which leads to qualitative and/or quantitative defects of bone, altered biomaterial properties such as mineralization, and/or downstream cellular changes in osteocytes and osteoclasts. These are represented by the different types of Osteogenesis Imperfecta (OI). While OI is often used interchangeably with BBD, the phenotypic spectrum is rapidly expanding. Moreover, there is a significant unmet need to understand the natural history of these phenotypes stratified by their molecular genetic etiologies. How these different mutations ultimately lead to brittle bone remains unknown and what are appropriate interventions and biomarkers of various disease morbidities are open questions. In years 1-5 of the BBDC, we met or exceeded accrual targets in 6 out of 7 protocols. We have published or have under review 12 manuscripts describing our cross sectional data. Importantly, our findings in the previous longitudinal study, pregnancy study, craniofacial study, pilot collagen crosslink biomarker study, and the PROMIS pilot study have empowered the design and inclusion of new elements in the current longitudinal study (Project 1), orthodontic clinical trial to treat malocclusion in OI (Project 2), and longitudinal biomarker study of growth (Project 3). This BBDC will be composed of 12 clinical sites covering the U.S. and Canada. The Specific Aims of the BBDC are: i) To perform collaborative clinical research in brittle bone disorders including the three clinical projects listed above; ii) To train and attract a cohort of investigators in clinical bone research who will be recruited from undergraduate, post-baccalaureate, graduate, medical student, resident/fellow, and junior faculty ranks; and iii) to collaborate with the Osteogenesis Imperfecta Foundation (OIF) to expand a tool box of training materials that can be used to broadly educate patients, families, and healthcare provider across a broad spectrum of expertise.