Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA development in the C57BL/6 strain of mice. A species of mice (MRL/MpJ) was found that is protected from PTA after AF. Further work identified key differences between mouse strains that did and did not develop PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1 receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that successfully prevented PTA following AF. This success in preventing PTA in the murine model has elucidated several important clinical implications: 1) Pro-inflammatory cytokines play an important role in the development of PTA after joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after an AF, and 3) The murine AF model of joint injury provides a novel means of studying mechanisms of PTA development.