Osteophyte Formation in Post-Traumatic Osteoarthritis

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease that affects approximately 5.6 million Americans, with incidence projected to increase over the next decade [1]. Traumatic injuries, such as anterior cruciate ligament (ACL) rupture, greatly increase the risk of PTOA development 10-20 years post-injury. PTOA leads to significant pain, stiffness, and loss of joint function, all of which can severely impact the quality of life of patients. Osteophytes, or bone spurs, are a common radiographic finding during PTOA, but their role in disease progression and the factors that contribute to their development are not well understood. In these studies, we used a noninvasive mouse model of ACL rupture to examine osteophyte development, its role in PTOA development, and factors that contribute to their formation. The aim of this work was to: examine the role of osteophytes as mechanical stabilizers after ACL rupture; compare osteophyte development with that of another bony stabilizer, fracture calluses; and determine if current nonsurgical therapies after ACL rupture impact long term osteophyte development. In this study, we used a noninvasive mouse model of ACL rupture developed by our lab to induce PTOA and study osteophyte formation. We used this model to correlate osteophyte growth with changes in anterior-posterior (AP) joint laxity and range of motion (ROM) after injury, as well as compare osteophyte and fracture callus development. We also paired this model with a tail suspension model of hindlimb unloading to study the effects of mechanical unloading on osteophyte formation. We evaluated inflammatory protease activity using fluorescence reflectance imaging (FRI), mineralized osteophyte volume using micro-computed tomography (µCT), and chondro/osteophyte area with histology.

We found that chondro/osteophyte growth is inversely correlated with AP joint laxity and ROM after ACL rupture, and that early time points post-injury are vital for examining osteophyte formation. Additionally, we compared osteophyte and fracture callus development to find that both structures go through similar developmental milestones, though at different time scales and through different biological pathways. Long-term osteophyte development was also shown to be affected by non-steroidal antiinflammatory drug (NSAID) administration and temporary unloading immediately after injury.

These results increase scientific knowledge of osteophyte and PTOA development after ACL rupture, and may inform future clinical approaches to treating traumatic joint injuries.

Year	Entry
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2013	Jilka RL. The relevance of mouse models for investigating age-related bone loss in humans. J Gerontol A Biol Sci Med Sci. October 2013;68(10):1209-1217.
2008	Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.
2010	Glasson SS, Chambers MG, Van Den Berg WB, Little CB. The OARSI histopathology initiative: recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage. October 2010;18(suppl 3):S17-S23.
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Year

Entry

1998

Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. October 1998;355(suppl):S7-S21.

2013

Jilka RL. The relevance of mouse models for investigating age-related bone loss in humans. J Gerontol A Biol Sci Med Sci. October 2013;68(10):1209-1217.

2008

Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.

2010

Glasson SS, Chambers MG, Van Den Berg WB, Little CB. The OARSI histopathology initiative: recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage. October 2010;18(suppl 3):S17-S23.

2004

Doblaré M, García JM, Gomez MJ. Modelling bone tissue fracture and healing: a review. Eng Fract Mech. September 2004;71(13-14):1809-1840.