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

项目摘要/摘要 椎间盘退行性变(IDD)和小关节骨关节炎(FOA)导致的总成本为 由于它们与慢性下腰痛(CLBP)密切相关，每年用于干预的资金超过400亿美元。 这些费用中的很大一部分是用于在患者生活质量没有显著改善的情况下进行干预。 这一临床问题的一个主要原因是由于对两者的病因过程了解有限。 IDD和FOA，需要开发一种临床上有效的方法将患者分成不同的组，例如 机械性、炎症性或疼痛敏感度升高。这项研究的总体目标是确定 导致慢性LBP的IDD或FOA表型。这个项目的目标是进行第一个也是最大的 利用现有数据对腰椎曾进行过的生物标志物的纵向分析 大型现有队列：约翰斯顿县骨性关节炎项目(发展队列)和 全面性骨关节炎研究(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、炎症或疼痛敏感源引起 这些来源可以通过生物标记物来识别2)可以识别的个体亚群 生物化学和定量感觉生物标记物具有高度的疼痛敏感性和3)有风险 可确定的预测有无腰椎疾病发生和发展的因素 症状。这项研究的发现将导致药物的开发和测试， 生物标记物的行为、身体或手术干预确定了腰椎表型。在Aim I中，我们将 说明生化标志物预测放射学发病率或进展的程度 IDD和FOA。在AIM II中，我们将确定疼痛和定量感觉之间的纵向关系 生物标记物和有症状的放射学IDD或FOA。 不协调我们将确定风险因素的组合(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的IDD和/或FOA。为了实现这些目标，我们将 开展迄今规模最大(n=4,167)的纵向研究，研究生物标志物来自两个大型社区的研究 有或没有腰椎IDD或FOA。标本收集、腰椎X线片和LBP 在两项研究中都得到了一致的测量。多学科团队包括协作性和生产力 具有OA、cLBP、流行病学、风湿学、生物标记物、IDD生物学和 生物统计学。首席调查员是一名新的和早期的调查员，接受过高级培训， 肌肉骨骼流行病学家和物理治疗师，有丰富的学术活动和 为下腰痛和腰椎研究提供资金。 “

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. "