PROJECT 1: LONGITUDINAL STUDIES

项目 1：纵向研究

• 批准号: 10478158
• 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/10478158
• 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; treatment response

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.

项目总结(OI纵向研究) 脆性骨病罕见疾病临床研究联盟(BBD RDCRC)纵向 对成骨不全(OI)的研究试图1)描述OI的表型 寿命，2)了解各种问题对OI患者的影响，3)评估对常规的反应 临床护理。导致BBDS的基因超过18个，它们具有多效性，导致广泛的 一系列身体和健康的挑战和生活经历。生物化学和分子机制研究进展 单倍体缺乏型I型胶原OI，显性阴性I型胶原OI，I型病变 胶原蛋白翻译后修饰，I型胶原运输障碍，以及一些新出现的 信号异常引起的紊乱。我们很有必要了解这些生物的自然历史。 条件以及将基因类型与表型相关联，以定义护理标准和改善 治疗选择。根据我们迄今在BBDC第1-5年的经验，我们确定了以下几点 需要进行纵向评估的重要问题： 1)评估患有以下疾病的患者在表型、疾病进展和治疗反应方面的差异 OI的显性和隐性形式评估这些疾病的自然病史。 2)描述I型胶原单倍体不足的椎体骨折发生率(OI-HI或OI类型) 通过前瞻性、多中心观察性研究，评价临床易感因素的影响 浅谈偶发椎体骨折的发展 3)描述各种形式的OI的脊柱侧弯的自然病史，并评估易患OI的特征 畸形进展、脊柱侧弯对肺功能、活动度和生活质量的影响 脊柱侧弯干预措施(支具、手术等)关于脊柱侧弯和肺功能。 4)利用患者报告结果工具评估导致焦虑和疼痛增加的因素 对成人和儿童OI的干预，以制定提高生活质量的干预措施。 5)通过分析妊娠期和哺乳期对OI妇女骨健康的影响 妊娠后骨密度和含量与骨折发生率。 6)评估牙齿错牙合和颅面畸形，并确定其随时间的动态变化 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个临床地点进行。V.里德·萨顿 贝勒医学院的弗兰克·劳赫和蒙特利尔施林纳儿童医院的弗兰克·劳赫将成为共同的PI 整个纵向研究的结果。