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

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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. "