Biomarkers to Advance Clinical Phenotypes of Low Back Pain (BACk)

促进腰痛 (BACk) 临床表型的生物标志物

• 批准号: 9755361
• 负责人: Adam Goode
• 金额: $ 59.81万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-07 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755361
• 关键词: Address; Back; Behavioral; Biochemical; Biological Markers; Biology; Biometry; Brain-Derived Neurotrophic Factor; CXCL6 gene; Cessation of life; Chronic low back pain; Clinical; Communities; County; Data; Degenerative polyarthritis; Development; Diagnosis; Diagnostic radiologic examination; Disease; Epidemiologist; Epidemiology; Etiology; Facet joint structure; Fibrinogen; Funding; Future; Genetic; Goals; Grouping; Image; Incidence; Individual; Infection; Inflammation; Inflammatory; Interleukin-17; Intervention; Keratin-19; Knowledge; Lead; Link; Literature; Longitudinal Studies; Low Back Pain; Measures; Mechanics; Metabolism; Methods; Musculoskeletal; N-Cadherin; NIH Program Announcements; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Operative Surgical Procedures; Orthopedics; Pain; Pain Measurement; Pain Threshold; Patient Self-Report; Patient-Focused Outcomes; Patients; Pharmacologic Substance; Phenotype; Principal Investigator; Process; Public Health; Quality of life; RANTES; Recommendation; Recording of previous events; Research; Research Personnel; Rheumatology; Risk Factors; Sensory; Serum; Source; Specificity; Specimen; Structure; Subgroup; Symptoms; Synovial joint; Testing; Training; United States; Validation; Vertebral column; base; clinical diagnostics; clinical imaging; clinical phenotype; cohort; cost; epidemiology study; improved; inflammatory marker; inflammatory pain; intervention cost; intervertebral disk degeneration; longitudinal analysis; lumican; multidisciplinary; novel; pain sensitivity; personalized intervention; physical therapist; population based; predictive marker; predictive modeling; pressure; radiologist; sample collection; specific biomarkers

Project Summary/Abstract Intervertebral disc degeneration (IDD) and facet joint osteoarthritis (FOA) result in a combined collective cost of over $40 billion per year in interventions because of their strong association with chronic low back pain (cLBP). A large proportion of these costs are for interventions without significant improvement in patient quality of life. A major reason for this clinical problem is due to the limited understanding of the etiological process for both IDD and FOA that is needed to develop a clinically valid method for phenotyping patients into groups, such as mechanical, inflammatory or heightened pain sensitivity. The overall goal of this research is to define phenotypes of IDD or FOA that lead to cLBP. The objective of this project is to conduct the first and largest longitudinal analyses of biomarkers ever performed in the lumbar spine by capitalizing on extant data from two large existing cohorts: the Johnston County Osteoarthritis Project (development cohort) and Genetics of Generalized Osteoarthritis Study (external validation cohort). The rationale for this proposed research is that: 1) cLBP is a heterogeneous diagnosis that can result from mechanical, inflammatory or pain sensitivity sources and these sources can be identified by biomarkers 2) there is a subgroup of individuals that can be identified with biochemical and quantitative sensory biomarkers with heightened pain sensitivity and 3) there are risk factors that can be identified to predict incidence and progression of lumbar spine disease with and without symptoms. The findings from this study would lead to the development and testing of pharmaceutical, behavioral, physical or surgical interventions by biomarker identified lumbar spine phenotypes. In Aim I, we will demonstrate the degree to which biochemical biomarkers predict the incidence or progression of radiographic IDD and FOA. In Aim II, we will determine longitudinal relationships between pain and quantitative sensory biomarkers and symptomatic radiographic IDD or FOA."In Aim III, because imaging and cLBP can be discordant we will identify combinations of risk factors (i.e., demographic, clinical, self-reported and biomarkers) that differentiate symptomatic from asymptomatic IDD and/or FOA. To achieve these aims, we will conduct the largest (n=4,167) longitudinal study to date of biomarkers from two large community based studies with and without lumbar spine IDD or FOA. Specimen collection, lumbar spine radiographs, and LBP were consistently measured in both studies. The multidisciplinary team includes collaborative and productive researchers with expertise in OA, cLBP, epidemiology, rheumatology, biomarkers, IDD biology and biostatistics. The Principal Investigator is a New and Early Stage Investigator with advanced training as a musculoskeletal epidemiologist and a physical therapist with a productive history of scholarly activity and funding in low back pain and lumbar spine research. "

项目概要/摘要 椎间盘退变 (IDD) 和小关节骨关节炎 (FOA) 导致的综合成本 由于干预措施与慢性腰痛 (cLBP) 密切相关，因此每年投入的干预措施费用超过 400 亿美元。 这些成本的很大一部分用于干预措施，但患者的生活质量没有显着改善。 造成这一临床问题的主要原因是对这两种疾病的病因过程了解有限。 IDD 和 FOA 需要开发一种临床有效的方法来对患者进行表型分组，例如 机械性、炎症性或疼痛敏感性增强。这项研究的总体目标是定义 导致 cLBP 的 IDD 或 FOA 表型。该项目的目标是进行第一个也是最大的 利用两个项目的现有数据对腰椎生物标志物进行纵向分析 现有的大型队列：约翰斯顿县骨关节炎项目（开发队列）和遗传学 广义骨关节炎研究（外部验证队列）。这项拟议研究的基本原理是： 1) cLBP 是一种异质性诊断，可能由机械、炎症或疼痛敏感性来源引起 并且这些来源可以通过生物标志物来识别 2) 有一个可以识别的个体亚组 生化和定量感觉生物标志物具有较高的疼痛敏感性，并且 3) 存在风险 可以确定的因素来预测腰椎疾病的发病率和进展，无论有无 症状。这项研究的结果将导致药物的开发和测试， 通过生物标志物识别腰椎表型进行行为、物理或手术干预。在目标一中，我们将 证明生化生物标志物预测放射学疾病发生或进展的程度 IDD 和 FOA。在目标 II 中，我们将确定疼痛与定量感觉之间的纵向关系 生物标志物和有症状的影像学 IDD 或 FOA。”在 Aim III 中，因为影像学和 cLBP 可以 如果不一致，我们将识别风险因素的组合（即人口统计、临床、自我报告和 生物标志物）区分有症状和无症状 IDD 和/或 FOA。为了实现这些目标，我们将 对来自两项大型社区研究的生物标志物进行迄今为止最大规模（n=4,167）的纵向研究 有或没有腰椎 IDD 或 FOA。标本采集、腰椎X线片和LBP 两项研究中的测量结果一致。多学科团队包括协作和富有成效的 具有 OA、cLBP、流行病学、风湿病学、生物标志物、IDD 生物学和 生物统计学。首席研究员是一位新的早期研究员，接受过高级培训 肌肉骨骼流行病学家和物理治疗师，具有丰富的学术活动历史和 资助腰痛和腰椎研究。 ”