The largest joint in the human body, the knee is a complex system of bones, muscles, cartilage, ligaments and tendons. It bends and extends a leg, propelling us forward, backwards, and side-to-side. It allows us to sit, stand, and pivot. It absorbs the impacts of walking, running and jumping. It enables us to leap, lunge, peddle, schuss, swim, climb and kick.
Yet, the knee is so fragile and vulnerable. Each year across the U.S., about 2.5 million people present to emergency departments with knee injuries, according to National Institutes of Health data. The injured are typically teenage athletes and young adults, 13-44 years old. Regardless of age, people whose injury includes a torn anterior cruciate ligament (ACL) —which connects the femur to the tibia—will likely develop post-traumatic osteoarthritis (PTOA) of the knee within 10-15 years post-injury, causing severe pain, joint stiffness, and disability. About 5.6 million young people in the United States currently suffer from PTOA.
Osteoarthritis (OA) occurs because the load bearing surfaces of the knee—such as the articular and meniscus cartilage—wears out. Cartilage acts as a shock absorber, allowing bones to withstand weight-bearing movements. When knee cartilage wears out, OA sets in. Although researchers have been investigating this for decades, the biological mechanism responsible for progression from ACL tear to OA is not well-understood, says Bruce Beynnon, Ph.D., professor of orthopaedics and rehabilitation and director of research in the McClure Musculoskeletal Research Center at ¶¶Ňő̽̽.
“We’ve made huge advances in the treatment of the injury, but not in the prevention of the [OA] disease,” Dr. Beynnon says. His research examines risk factors for knee and ankle injuries and the body’s response at various stages after an injury. “It’s the ligament that gets injured initially, but then the cartilage wears away and leads to arthritis. If we can understand the early mechanism, maybe we can develop interventions to prevent loss of cartilage.”
Six students in the medical class of 2027 joined Beynnon in the musculoskeletal research center last summer to explore the risk factors that predispose people to knee trauma and investigate how ACL tears lead to OA. Mentored by Beynnon and Nic Fiorentino, Ph.D., assistant professor of engineering and mathematical science, each student pursued a separate research topic, fueled by their personal passions, experiences, and curiosities. The students presented their research at a poster session during the Dean’s Celebration of Excellence In Research in September, and they will submit their work for publication in orthopedic research journals.
Differences in Female and Male Quadriceps Muscle
As a ballet dancer, Marie Lim understands the suffering and setbacks associated with leg injuries. She experienced chronic shin pain that hindered dancing and witnessed a good friend rupture an ACL during ballet class. These experiences made Lim curious about the factors that precipitate injuries and why some people are more prone to injury than others.
As a medical student, Lim is channeling her curiosity into research analyzing quadriceps muscle tissue in limbs that experienced ACL ruptures and reconstruction surgery. She is evaluating muscle stiffness, or fibrosis, that occurs after ruptures and comparing the differences that may exist between females and males aged 18 to 37. She hypothesizes that fibrosis in the quadriceps alters a person’s gait and impacts loading of the knee joint, which may be associated with onset and progression of PTOA.
“What excites me about this topic is that the findings could have large implications for developing effective rehabilitation programs,” Lim says. “It is possible that current physical therapy exercises could be further improved by tailoring them based on one’s sex and understanding that a one-size-fits-all approach should not necessarily be the paradigm.”
Predicting ACL Tear Risk Through Characterization of Cartilage Geometry
Rupturing an ACL substantially increases the risk of a secondary injury, including an ACL tear on the opposite knee, known as a contralateral ACL (CACL) tear. Aaron Dees knows this well: Starting as a teenager and into adulthood, he tore ACLs in both of his knees while playing basketball. His research aims to determine whether geometric measurements of tibial articular cartilage surface can help predict whether CACL tears will occur in people who have experienced ACL reconstruction surgery and return to sport.
Dees analyzed a subgroup of MRI scans of tibial articular cartilage from 200 individuals who underwent ACL reconstruction surgery. He then used polynomial equations to characterize the cartilage geometry and is determining how the geometric characteristics are related to ACL injury and repeated injury of the same kind.
“Insights from this study could lead to improved injury prevention and patient management strategies.” – AARON DEES
“Such advancements would not only benefit athletes by extending their active careers, but also decrease health care costs associated with these injuries, offering more personalized approaches based on individual risk profiles derived from knee cartilage geometry.”
Adaptive Response of Bone and Cartilage to ACL Disruption
After an ACL ruptures, changes occur in the affected leg’s muscles, bones, and knee cartilage. Scientist do not fully understand these changes, Jowkar says, and better understanding may help improve treatment to prevent PTOA onset. His research aims to illustrate the adaptive changes that occur in skeletal muscle size and function, bone architecture, and articular cartilage in response to ACL rupture.
“These knowledge gaps make it significantly more difficult to develop effective treatment options,” he says. The sooner we can understand the pathophysiology of these factors leading to the severity of PTOA, the sooner we can begin advancing treatments.”
Jowkar examined MRI scans of injured knees and healthy contralateral knees shortly after ACL injury and prior to ACL reconstruction. He conducted post-processing statistical analysis to assess changes in thickness and matrix components of articular cartilage in the injured knee and examined the data to see if alterations in cartilage thickness and matrix components correlated with concurrent injuries to the meniscus, the patient’s sex, body mass index and knee joint geometry. The findings may contribute to the development of PTOA treatment strategies.
Changes in Cartilage Thickness After ACL Trauma
Cassandra Chin was 14 years old the first time she injured her knee. As a soccer athlete, she sustained two ACL tears and knew many teammates with this injury. Chin has long wanted to better understand the factors that lead to ACL trauma and affect return to sport.
“It took me more than two years and three surgeries to get back to playing soccer. During that experience, I spent a lot of time around orthopedics and doctors who gave me back my ability to be active. I want to be able to give others the same,” Chin says. “Over a decade later, it’s really cool to see the advances in ACL procedures from the perspective of a medical student.”
Chin’s research projected investigated articular cartilage changes in the knee following ACL injury with and without additional injury to the meniscus. She made measurements on baseline magnetic resonance imaging (MRI) scans of injured knees using medical imaging software called OsirX. The measurements were processed into three-dimensional thickness maps and matrix components of the cartilage on the ends of the femur and tibia. These measurements will help illuminate the effects of injury on the cartilage before the subjects undergo surgery.
Left-to-Right and Visit-to-Visit Repeatability
Oona Davies worked as a scribe, medical assistant, and manager at orthopedic clinics in Virginia and Utah prior to attending medical school. Through these experiences, she learned about the musculoskeletal system and became curious about how doctors can track meniscal degeneration and the onset of OA.
Davies endeavored to determine whether a series of MRI scans of a healthy meniscus can produce reliable biomarkers for monitoring OA progression. She examined left and right knee MRI scans of 10 participants with no known history of knee injury. Each knee was scanned without load, and then with a 40 percent body weight load. Davies segmented the anterior and posterior horns (where they attach to the knee joint) of both menisci, and calculated correlation coefficients with an aim to quantify repeatability of imaging in left and right legs, and from visit to visit. Preliminary results show a low visit-to visit reliability, says Davies. Her next steps will quantify repeatability from visit-to-visit and between left-to-right knees. She says that this project has kindled her passion for research to prevent, treat, and diagnose disease.
Risk Factors for Contralateral ACL (CACL) Injury
A lifelong skier, Ivan Davis understands the prevalence of ACL injuries: His mother and his sister tore their ACLs while skiing. He wants to learn more about this injury, and why after the index injury the risk of tearing the ACL in the opposite knee is 30 to 40 times higher after ACL reconstruction.
Davis investigated risk factors for contralateral injury focusing on geometric characteristics of the femoral notch (a shallow groove at the junction of the femur that surrounds the ACL). He examined MRI images of knees taken on 199 athletes ages 13-26 who underwent ACL reconstruction and measured femoral notch width, ridge thickness, and volume. His next steps will be to perform a statistical analysis and interpret the data to identify geometric risk factors.
As a future doctor, Davis wants to support patients in keeping their musculoskeletal systems healthy: “Spending time in the orthopedic department has definitely spurred my interest in pursuing orthopedics in the future.”
While the medical students wrap up their research projects, the quest to understand the biology of the knee continues. Each individual investigation contributes to better understanding of the body’s response to knee trauma and the post-traumatic osteoarthritis disease process. Ultimately, these insights will improve injury prevention, rehabilitation methods and optimal long-term health of people’s knees, to keep us leaping, lunging, peddling, pivoting, standing up and stepping forward.
Read the full story in the Fall/Winter 2024 issue of Vermont Medicine Magazine.