AOSSM’s Award Goes to Constance Chu, M.D. and Colleagues

Constance R. Chu, M.D. is professor and vice chair of research, in the Department of Orthopedic Surgery at Stanford University. She and her colleagues have just been recognized for their work on the knee center of rotation after anterior cruciate ligament reconstruction (ACLR), winning the O’Donoghue Sports Injury Award from the American Orthopaedic Society for Sports Medicine (AOSSM).

Dr. Chu told OTW, “There is tremendous clinical need for early warning signs of joint deterioration in order to reduce the massive health and societal burden of pain and disability from osteoarthritis [OA]. During my first year in practice 16 years ago, I was surprised to see patients in their 30s and 40s seeking cartilage repair and transplantation who had bone on bone osteoarthritis to where knee replacement was their only surgical option. I soon noticed that many of these patients had undergone anterior cruciate ligament (ACL) reconstructions 10 or more years before seeing me.

“Remembering that I had helped a postdoctoral fellow perform ACL transections in rabbits during my residency to test hyaluronic acid for treatment of osteoarthritis, I started to wonder whether I could find cures for human osteoarthritis by studying people who had torn their ACLs. I also knew that meniscus tears increased osteoarthritis risk. Back then, I sought new clinical means to provide early warning of osteoarthritis risk by identifying the early structural and biological changes to articular cartilage after ACL and meniscus injury using novel imaging techniques such as Optical Coherence Tomography and quantitative MRI T2 and ultrashort echo time enhanced (UTE) T2* mapping. My hypothesis was that if we could identify injury and degeneration prior to breakdown of the articular surface, that the cartilage could heal and prevent or delay the onset of osteoarthritis. This led to my first research project grant from the National Institutes of Health (NIH R01). Since moving to Stanford in 2013, I have been able to collaborate with Tom Andriacchi [Ph.D.] to include mechanical risk factors into a systems based approach to evaluating osteoarthritis development. Matt Titchenal, the first author, is a Ph.D. student we are mentoring together. This award winning paper evaluates the potential utility of a multi-dimensional mechanical marker of knee kinematics called Knee Center of Rotation (KCOR) in predicting patient reported outcomes eight years after ACL reconstruction.

“The most interesting findings were that the change in knee kinematics 2 and 4 years after ACLR appeared to predict how patients were doing at longer term follow-up. We found that recovery of knee function diverged greatly between subjects in that 62% of patients moved towards kinematic symmetry with the contralateral uninjured knee while 38% showed greater differences in how they were using the ACL reconstructed knee compared to the uninjured knee 2 and 4 years after surgery. When Jenny Erhart-Hledik [Ph.D.] looked at the patient reported outcomes 8 years after surgery, we found that earlier change in mechanics correlated to longer term changes to measures of pain and function. This is particularly interesting because when these patients were recruited 2 years after ACLR, they were all doing well and had clinically successful ACL reconstructions. This means that the mechanical changes provided early warning of movement patterns placing the knee at greater risk for poorer clinical outcomes over time. Furthermore, our data shows that recovery of knee function after ACLR continues for much longer than the 6 months to 1 year time frame for clinical follow-up and return to sports or work that is typically seen in current clinical practice. These findings argue for longer follow-up. More importantly, they open a potential window for early intervention to address deteriorating kinematics that can improve longer term outcomes for ‘at risk’ patients.

“We are planning radiographic follow-up at 10 years in these subjects to determine whether these same metrics actually predict development of premature osteoarthritis. More importantly, we are recruiting new and larger cohorts and combining mechanical evaluations with structural and biochemical assessments of the same patients to more definitively evaluate the spectrum of changes over time in this population as well as the predictive potential of our mechanical, structural and biochemical metrics for predicting long term outcomes and providing early warning of the risk for premature OA. This comprehensive information will be critical to developing disease modifying strategies for the prevention of osteoarthritis, a major global health issue.”