PROJECT 1: LONGITUDINAL STUDIES

项目 1：纵向研究

• 批准号: 10017034
• 负责人: Brendan Lee
• 金额: $ 110.39万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-06 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017034
• 关键词: Adolescent; Adult; Anxiety; Area; Biochemical; Biological Markers; Bone Density; Bone Mineral Contents; Characteristics; Child; Clinical; Clinical Research; Clinical Trials; Collagen Type I; Compression Fracture; Craniofacial Abnormalities; DNA analysis; Data; Deformity; Dental; Development; Disease; Disease Progression; Dominant-Negative Mutation; Dual-Energy X-Ray Absorptiometry; Enrollment; Etiology; Evaluation; Female of child bearing age; Foundations; Fracture; Funding; Future; General Population; Genes; Genotype; Goals; Impairment; Incidence; Individual; Intervention; Lactation; Lead; Life Experience; Longevity; Longitudinal Studies; Lung diseases; Malocclusion; Measures; Medicine; Molecular; Mutation; Natural History; Observational Study; Operative Surgical Procedures; Oral health; Orthodontic; Osteogenesis Imperfecta; Osteoporosis; Outcome; Outcome Measure; Pain interference; Patient Outcomes Assessments; Patients; Pediatric Hospitals; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Post-Translational Protein Processing; Predisposing Factor; Predisposition; Pregnancy; Pregnancy Complications; Pulmonary function tests; Quality of life; Rare Diseases; Reporting; Risk; Signal Transduction; Spinal Fractures; Structural defect; Therapeutic; Time; Woman; base; biobank; bone; bone health; bone imaging; bone loss; clinical care; clinical research site; college; experience; health related quality of life; improved; parity; physical conditioning; pleiotropism; prospective; pulmonary function; response; scoliosis; social; spine bone structure; standard of care; tool

PROJECT SUMMARY (Longitudinal Study of OI) The Brittle Bone Disorders Rare Disease Clinical Research Consortium (BBD RDCRC) longitudinal study of Osteogenesis Imperfecta (OI) seeks to 1) characterize the phenotypes of OI that occur across the lifespan, 2) understand how various issues effect individuals with OI and 3) assess the response to routine clinical care. There are over 18 genes that cause BBDs and they have pleiotropic effects resulting in a broad spectrum of physical and health challenges and life experiences. Biochemical and molecular mechanisms of OI include haploinsufficient type I collagen OI, dominant negative type I collagen OI, disorders of type I collagen post-translational modification, disorders of type I collagen transport, and an emerging number of disorders due to abnormal signaling. There is great need to understand the natural histories of these conditions as well as correlating genotypes with phenotypes to define a standard of care and improve therapeutic options. Based on our experience to date in the BBDC years 1-5, we have identified the following important issues in need of longitudinal assessment: 1) Evaluate the difference in phenotype, disease progression and response to therapies in individuals with dominant and recessive forms of OI to assess the natural history of these disorders. 2) Describe the incidence of vertebral fractures in type I collagen haploinsufficient OI (OI-HI or OI type I) through a prospective, multi-center observational study, and evaluate the impact of clinical susceptibility factors on the development of incident vertebral fractures 3) Describe the natural history of scoliosis in various forms of OI and assess the characteristics predisposing to progression of the deformity, effects of scoliosis on pulmonary function, mobility & quality of life and impact of scoliosis interventions (bracing, surgery, etc.) on scoliosis and pulmonary function. 4) Utilize patient reported outcomes tools to assess factors that contribute to increased anxiety and pain interference in adults and children with OI, in order to develop interventions to improve quality of life. 5) Characterize the effect of pregnancy and lactation on bone health in women with OI by analyzing pre- and post-pregnancy bone mineral density and content and fracture incidence. 6) Evaluate dental malocclusion & craniofacial abnormalities and determine the dynamic changes over time and impact upon oral-health related quality of life. The BBD RDCRC longitudinal study will be performed by all 11 clinical sites of the consortium. V. Reid Sutton at Baylor College of Medicine and Frank Rauch at the Montreal Shriners Hospital for Children will be the co-PIs of the overall longitudinal study.

项目摘要（OI 纵向研究） 脆性骨疾病罕见疾病临床研究联盟 (BBD RDCRC) 纵向 成骨不全症 (OI) 研究旨在 1) 描述发生在整个骨骼中的 OI 表型特征 寿命，2) 了解各种问题如何影响成骨不全症患者，3) 评估对日常生活的反应 临床护理。有超过 18 个基因可导致 BBD，它们具有多效性，可导致广泛的影响 一系列身体和健康挑战以及生活经历。生化和分子机制 OI 包括单倍体不足的 I 型胶原蛋白 OI、显性失活 I 型胶原蛋白 OI、I 型疾病 胶原蛋白翻译后修饰、I 型胶原蛋白运输障碍以及新兴数量的 由于信号异常而导致的疾病。非常需要了解这些自然历史 条件以及将基因型与表型相关联，以确定护理标准并改善 治疗选择。根据迄今为止 BBDC 1-5 年的经验，我们确定了以下内容 需要纵向评估的重要问题： 1) 评估患有以下疾病的个体在表型、疾病进展和治疗反应方面的差异 显性和隐性成骨不全症的形式，以评估这些疾病的自然史。 2）描述I型胶原单倍体不足OI（OI-HI或OI I型）椎体骨折的发生率 通过前瞻性、多中心观察研究，评估临床易感因素的影响 椎体骨折事件的发展 3) 描述各种成骨不全症中脊柱侧凸的自然病程并评估诱发脊柱侧弯的特征 畸形的进展、脊柱侧凸对肺功能、活动能力和生活质量的影响以及 针对脊柱侧弯和肺功能的脊柱侧弯干预措施（支具、手术等）。 4) 利用患者报告的结果工具来评估导致焦虑和疼痛加剧的因素 对患有成骨不全症的成人和儿童进行干预，以便制定干预措施来改善生活质量。 5) 通过分析怀孕前和哺乳期的情况来描述怀孕和哺乳期对成骨不全女性骨骼健康的影响。 怀孕后骨矿物质密度和含量以及骨折发生率。 6) 评估牙齿咬合不正和颅面异常并确定随时间的动态变化 以及对口腔健康相关生活质量的影响。 BBD RDCRC 纵向研究将由该联盟的所有 11 个临床中心进行。 V·里德·萨顿 贝勒医学院的教授和蒙特利尔圣地兄弟会儿童医院的 Frank Rauch 将担任联合 PI 总体纵向研究。