PROJECT SUMMARY/ABSTRACT The objectives of this longitudinal outcome study are to evaluate the progression of post-traumatic osteoarthritis (PTOA) following surgical reconstruction of the anterior cruciate ligament (ACL) in male and female patients 15 years after surgery, and to determine if the initial tension applied to the graft at the time of surgery and if sex influences long-term outcomes related to arthrosis. Disruption of the ACL is a common injury that usually requires surgical reconstruction to restore function and prevent PTOA. The “initial graft tension” applied at the time of surgery modulates joint contact mechanics, which in turn, may promote PTOA. However, the effects of low- and high-initial graft tensions on PTOA development are unknown. It is also known that sex is a risk factor for ACL injury and subsequent graft failure. Thus, it is likely that females are at increased risk for PTOA following surgery. The proposed work will leverage a cohort of ACL reconstructed patients that were previously enrolled in a randomized control trial to study the effects of initial graft tension. Patients, who were candidates for ACL reconstruction with an autograft, were randomized into one of two treatment groups: 1) initial graft tension set such that the anterior-posterior (AP) laxity of the reconstructed knee was equal to that of the contralateral normal knee (the “low-tension” treatment; n=46), and 2) initial graft tension set to reduce AP knee laxity by 2 mm relative to that of the contralateral knee (the “high-tension” treatment; n=44). An additional group of subjects without evidence of knee injury (n=60) was recruited to serve as an uninjured control. In the previous funding cycle, we found differences in several outcome measures starting to emerge between the two initial graft tension groups at 7-year follow-up that were not present at 3-year follow-up. In this proposal, the follow-up of this patient cohort and its matched control group will be extended to 15 years, a time point that will enable us to clearly identify those patients who present with both radiographic and symptomatic PTOA. The first hypothesis is that tibiofemoral joint space width of the reconstructed knees of the “high-tension” cohort will be equal to that of the control group, while that of the “low-tension” cohort will be less than that of the control group 15 years after ACL reconstruction. The second hypothesis is that decreases in medial joint space width after ACL reconstruction will be greater in female patients compared to male patients. The comprehensive set of outcomes to be used include imaging modalities to monitor PTOA development and other validated patient- reported, clinical, and functional measures. X-ray measures of joint space width are considered the only validated indicator of PTOA progression for clinical trials of the knee, and will serve as the primary outcome measure for the proposed study. Radiographic assessment of joint health (OARSI score) and a MR-based measure of joint health (WORMS) will serve as secondary imaging outcomes. The Knee Osteoarthritis Outcome Score (KOOS) will be used to identify which patients have symptomatic PTOA. The comprehensive set of outcomes will allow us to establish the long-term effects of initial graft tension, and to systematically evaluate the effects of sex on PTOA development following ACL reconstruction surgery. The proposed study is novel as the ACL reconstructed cohort is comprised of patients with isolated unilateral ACL injuries at the time of injury, includes the long-term follow-up required to assess PTOA development in these patients, and includes a matched control group in order to compare arthrosis development in the uninjured population.

PROJECT NARRATIVE Anterior cruciate ligament (ACL) injuries have reached epidemic proportions and place the patient at high risk for post-traumatic arthritis (PTOA). The proposed study will establish the long-term incidence of PTOA following ACL surgery, and will determine if a modification in the surgical technique can reduce cartilage degeneration. It will also evaluate potential factors placing the knee at increased risk for PTOA. Therefore these data will impact the future care of the ACL injured patient and reduce the economic burden of PTOA associated with this injury.