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: 9445928
• 负责人: Adam Goode
• 金额: $ 56.74万
• 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/9445928
• 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; intervertebral disk degeneration; longitudinal analysis; lumican; multidisciplinary; novel; 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. "

项目总结/摘要 椎间盘退变（IDD）和小关节骨关节炎（FOA）导致以下综合成本： 每年超过400亿美元的干预措施，因为它们与慢性腰痛（cLBP）密切相关。 这些费用中有很大一部分用于干预，而患者的生活质量没有显著改善。 这一临床问题的一个主要原因是由于对两者的病因学过程的了解有限 IDD和FOA，需要开发一种临床有效的方法，用于将患者表型分型成组，如 机械、炎症或疼痛敏感性增强。本研究的总体目标是确定 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 通过利用两个文献中的现有数据，对腰椎生物标志物进行了纵向分析， 现有的大型队列：约翰斯顿县骨关节炎项目（发展队列）和 全身性骨关节炎研究（外部验证队列）。这项拟议研究的理由是： 1)cLBP是一种异质性诊断，可由机械、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）存在可以被识别的个体的亚组 与生物化学和定量感觉生物标志物具有高度的疼痛敏感性，以及3）存在风险 可以确定的因素，以预测腰椎疾病的发病率和进展， 症状这项研究的发现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Aim I中，我们将 证明生物化学生物标志物预测放射学检查的发生或进展的程度 IDD和FOA。在目标II中，我们将确定疼痛和定量感觉之间的纵向关系， 生物标志物和有症状的放射学IDD或FOA。“在Aim III中，由于成像和cLBP可以 我们将识别风险因素的组合（即，人口统计学、临床、自我报告和 生物标志物）区分有症状与无症状IDD和/或FOA。为达致这些目标，我们会 对来自两项大型社区研究的生物标志物进行迄今为止规模最大的（n= 4，167）纵向研究 伴有或不伴有腰椎IDD或FOA。标本采集、腰椎X线片和LBP 在两项研究中一致测量。多学科团队包括协作和生产力 具有OA、cLBP、流行病学、流变学、生物标志物、IDD生物学和 生物统计学主要研究者是一名新的早期研究者，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， 资助下背痛和腰椎研究。 "