Effective interventions for osteoarthritis (OA) are limited, and innovative research approaches are needed to advance the detection, prevention, and treatment of this common and disabling disease. Injury-mediated OA provides a unique model of OA, one in which the onset of joint metabolism changes can be clearly identified (the time of injury) and where progression to OA is faster than via non-injury pathways. Abnormal human movement biomechanics and biochemical marker levels may be critical identifiers of individuals at high risk for injury-mediated OA who would benefit from interventions such as neuromuscular training programs preor post-injury. We have the remarkable opportunity to examine the course of OA among large existing cohort with Anterior Cruciate Ligament (ACL) injury. The proposed study will advance our understanding of key markers (biochemical and biomechanical) associated with OA and ofthe role of injury in accelerafing the onset of OA. This proposal benefits from: 1) existing serum samples and epidemiological, injury, and biomechanical data from a large cohort of young military cadets, and 2) well-established collaborations between prolific epidemiologic, biomechanics, biomarker, and osteoarthritis investigators.
Specific Aims of the project are: 1) Determine whether serum biomarkers of joint metabolism are associated cross-sectionally with movement biomechanics in subjects with no ACL injury; 2) Determine longitudinally whether serum biomarkers of joint metabolism are altered following incident ACL injury, relative to pre-injury levels in the same subjects, and in comparison to non-injured participants; 3) Quantify the increase in the risk of radiographic ipsilateral knee OA following incident ACL injury; 4) Determine whether longitudinal changes in serum biomarkers associated with ACL injury predict risk of ipsilateral knee OA (in subjects with incident ACL injury). This study is timely, innovative, cost-efficient, and of great signficance in the quest to understand mechanisms underiying the development of OA in response to joint injury.

Public Health Relevance

Osteoarthrifis (OA) is a painful and disabling condition. Some OA is linked to knee injuries. To learn about this relafionship, we will follow a group of military cadets from a previous study, some whom have had severe knee injuries. We will determine who has developed post-injury OA, and will relate the presence of OA to data on their human movement patterns (biomechanics) and biological chemicals present in their blood (biomarkers).

National Institute of Health (NIH)
Comprehensive Center (P60)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Chapel Hill
United States
Zip Code
An, H; Marron, J S; Schwartz, T A et al. (2016) Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women. Osteoarthritis Cartilage 24:640-6
Loeser, R F; Pathmasiri, W; Sumner, S J et al. (2016) Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study. Osteoarthritis Cartilage 24:1479-86
Scanzello, Carla R; Loeser, Richard F (2015) Editorial: inflammatory activity in symptomatic knee osteoarthritis: not all inflammation is local. Arthritis Rheumatol 67:2797-800
Rini, Christine; Porter, Laura S; Somers, Tamara J et al. (2015) Automated Internet-based pain coping skills training to manage osteoarthritis pain: a randomized controlled trial. Pain 156:837-48
Hsu, Yi-Hsiang; Liu, Youfang; Hannan, Marian T et al. (2015) Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans. J Med Genet 52:762-9
Barbour, K E; Hootman, J M; Helmick, C G et al. (2014) Meeting physical activity guidelines and the risk of incident knee osteoarthritis: a population-based prospective cohort study. Arthritis Care Res (Hoboken) 66:139-46
Goode, Adam P; Shi, Xiaoyan A; Gracely, Richard H et al. (2014) Associations between pressure-pain threshold, symptoms, and radiographic knee and hip osteoarthritis. Arthritis Care Res (Hoboken) 66:1513-9