UI orthopedics researchers aim to improve long-term outcomes after ACL injury

Two new clinical studies aim to prevent post-traumatic osteoarthritis

Oct 31, 2023 - 04:07 p.m. by Jennifer Brown

Twist. Pop. Pain.

It’s a combination that any athlete—young or old, professional or weekend warrior—knows and dreads as a likely indication of a torn ACL.

Rupture of the anterior cruciate ligament (ACL), which stabilizes the knee joint, is an extremely common injury, affecting between 100,000 to 200,000 people in the U.S. every year. It is also a significant injury, often requiring surgery and months of rehabilitation.

Although many people recover fully and can resume high-level activity again, the joint injury can have long-term consequences. In particular, ACL injuries increase the risk for post-traumatic osteoarthritis (PTOA), a type of osteoarthritis that develops after a joint injury. PTOA is painful and disabling in many cases. Treatments for PTOA are limited, and they only address symptoms, they do not cure arthritis.

It is estimated that nearly six million people in the United States have their lives substantially impacted by PTOA, and it is the most common cause of disability in military service personnel injured in combat and other military service. In addition, the annual financial burden on the U.S. economy is about $12 billion.

“Despite advances in joint imaging and surgery, the risk of OA following a variety of joint injuries has not declined substantially in the last 25 years,” says Don Anderson, PhD, UI professor of orthopedics and rehabilitation and the Richard and Jan Johnston Chair of Orthopedic Biomechanics. “This is especially troubling because joint injuries disproportionately occur in younger individuals, which means that associated pain and disability may limit their ability to work and stay physically active.”

UI orthopedics researchers have long-standing expertise in studying the causes and potential treatments for PTOA. Their overall goal is to develop and test therapies that can prevent the condition.

It’s exciting to study cutting-edge interventions that can potentially lower reinjury rates and head off future knee PTOA that some ACL patients have after their injury.

- Brian Wolf, professor of orthopedics and rehabilitation and the John and Kim Callaghan Chair in Sports Medicine

Leading the research team are Anderson and Brian Wolf, MD, professor of orthopedics and rehabilitation and the John and Kim Callaghan Chair in Sports Medicine. Their current focus lies with two clinical studies aimed at identifying and preventing PTOA from developing after ACL repair. Both are studies funded by the Arthritis Foundation.

Lateral tightening study

The first study is analyzing patients with an ACL injury treated surgically at University of Iowa Health Care. In this unique trial, participants receive either the current standard of care ACL reconstruction, or standard ACL reconstruction plus an extra procedure to tighten the lateral side of the knee. The lateral tightening, referred to as LET, has been shown to reduce reinjury rates in high-risk patients. The study aims to determine if the additional tightening of the knee during ACL reconstruction surgery alters the knee joint in a way that could increase the risk of PTOA in the long-term. UI researchers use a weight-bearing CT scanner to monitor the width of the joint space while standing upright, as well as knee joint function, in the months after ACL reconstruction as early indicators of PTOA. Around 70 patients have already been enrolled in the trial, which has been in progress for about two years.

PIKASO study

The Post-Injury Knee Arthritis Severity Outcomes (PIKASO) Trial is a randomized phase 2 clinical trial testing the ability of the off-patent drug metformin to slow or prevent knee OA in patients who are at high-risk for developing PTOA after major knee injury and subsequent ACL reconstruction.

University of Iowa Health Care is one of nine leading research centers participating in this first-of-its-kind clinical trial. The trial will measure changes in joint structure using advanced imaging techniques and functional improvements using innovative biomechanics measurements. Positive results from this trial could enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression or fully prevent PTOA.

“We have a long history of studying both PTOA and outcomes of ACL injury. It’s exciting to study cutting-edge interventions that can potentially lower reinjury rates and head off future knee PTOA that some ACL patients have after their injury,” Wolf says. “These studies represent fresh new ways to identify early which knees are at risk for developing PTOA after ACL injury and new interventions aimed at preventing this disabling outcome.”

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