PMR Feature: Novel Approaches to Knee Osteoarthritis

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The following was featured in the PM&R on Point newsletter, which taps the brainpower of our clinicians, scientists and alumni to highlight our specialty from every angle. Our goal: to deliver actionable insights and valuable takeaways to your inbox — on time, on topic and on point.

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By splitting his time between the clinic and the lab, Prakash Jayabalan, MD, PhD, physician-scientist director, Nancy W. Knowles Strength + Endurance Lab, Shirley Ryan AbilityLab, said he gets the best of both worlds — the emotional connection from treating patients and the thrill of pursuing scientific discovery and solving problems to improve care.

Dr. Jayabalan has long pondered why more non-operative treatment options aren’t available to patients with knee osteoarthritis (OA), particularly because it is the most common cause of disability in the United States.

“Doctors perform approximately 1 million surgical knee replacements each year,” he said. “Of course, a proportion of these people need surgery. However, I’ve always felt that a lot of patients with OA are getting knee replacements much sooner in life than needed.”

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This question — how to help patients with knee OA feel better without surgery — has prompted two research projects Dr. Jayabalan leads at Shirley Ryan AbilityLab: one is a new test to identify OA earlier, and the second is the novel use of equipment to help patients with OA get the full benefits of exercise without pain.

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Earlier Identification of Knee OA

Staying active is the best way for a patient to keep OA from getting worse. Yet, one of the biggest challenges of current knee OA treatment practices is that diagnosis typically happens only after a patient is in such severe pain that activity is difficult.

“Right now, I can diagnose patients with knee OA using an X-ray and send them for physical therapy, pain management and maybe injections,” Dr. Jayabalan said. “However, by that point, the OA is already far down the line. I don’t have anything to prescribe that will prevent its progression.”

To help doctors diagnose knee OA much earlier, Dr. Jayabalan and his lab team are developing a new protocol that he describes as a “cartilage stress test.”

“We have the patient exercise to put stress on the joints, and then we measure the body’s responses to that stress by looking at blood- or synovial-based biomarkers,” he said.

The design of the cartilage stress test relies on two novel aspects to measure the metabolic state of joints. First, it uses a real-time approach. Dr. Jayabalan’s team takes blood during periodic intervals using an IV line while the patient is on the treadmill, instead of relying on blood taken pre- and post-evaluation.

Second, the test uses a special treadmill that provides a mediolateral tilt of up to 10 degrees. This angle creates individualized stress loads on each joint. Preliminary results show that by testing for biological markers in the patient’s blood and synovial fluids during tilted treadmill walking, Dr. Jayabalan’s team can not only identify evidence of OA — but also differentiate its severity.

“For the first time, I’m able to tell someone, metabolically, how this type of exercise is affecting their joint disease,” he said.

This new protocol could lead to individualized treatment plans for OA patients while they are still relatively healthy, years before their joints start hurting. Ideally, early intervention will delay, or even eliminate, the need for joint replacements.

“In physiatry, our current OA prescription is very much a one-size-fits-all approach,” he said. “We generally tell patients to walk 30 minutes a day, five times per week. However, my goal is to identify an optimal prescription for each patient that would prevent disease progression. With early diagnosis, we could prescribe an individualized, preventive exercise program.”

Similarly, the framework of this diagnostic tool for determining prevalence and severity of OA could be applied to other rehabilitation populations. For instance, Dr. Jayabalan is testing use of the protocol in diagnosing knee OA in people with anterior cruciate ligament (ACL) injuries occurring within two years of reconstructive surgery. This patient population has been shown to have a high likelihood of developing knee OA.

In another study, funded by a translational pediatric research grant from Shirley Ryan AbilityLab, Dr. Jayabalan researched joint disease in people with cerebral palsy — a high-incidence population for the development of OA — looking at how the biomarkers of joint disease correlate to mobility status.

“When measuring even baseline markers in these individuals, without getting study participants to walk, we were able to see significant relationships between some of these biomarkers and differences in functional mobility status,” he said. “The number of these markers in the bloodstream correlated very well with level of mobility.”

Taking the Load Off

For patients with joint pain caused by advanced knee OA, an exercise prescription consisting of even the simplest tasks, such as walking for 30 minutes, can present an overwhelming challenge. Dr. Jayabalan’s lab is pursuing a hopeful alternative — use of an anti-gravity treadmill that allows knee OA patients to walk longer without increasing joint pain, while still reaping the full cardiac benefits.

Anti-gravity treadmills are increasingly more common in physical therapy regimens for patients recovering from ACL and other knee injuries. These devices enclose the patient’s lower body in a vacuum, and allow the therapist to vary the body-weight load that patients feel as they walk or run on the treadmill.

In a recent pilot study, Dr. Jayabalan’s team observed 30 patients with knee OA over the course of two 30-minute sessions. In one session, research subjects attempted to walk for 30 minutes on a treadmill at their full body weight. In the second, they attempted the same goal on an anti-gravity treadmill, set to reduce their body weight by 50 percent. Study results were overwhelmingly positive.

“We’ve had subjects who felt they could not walk 15 minutes on a flat surface — but when they were walking on the anti-gravity treadmill, and we reduced their body weight, they were able to walk the full 30 minutes,” he said. “The reduced body weight enabled them to walk longer due to significantly less joint pain, and they got the full cardiovascular benefit of 30-minutes’ exercise. Additionally, their biomarker responses indicated significantly less stress placed on their cartilage and improved gait parameters.”

Dr. Jayabalan said future clinical trials could explore additional benefits of using these special treadmills in treating knee OA patients (e.g., whether it increases strength and improves biological processes within the knee joint).

Clearly, anti-gravity treadmills are showing promise for these patients, but they are expensive. The good news, Dr. Jayabalan said, is that there is a much simpler, more affordable and readily available way to reduce load on arthritic joints — aquatic therapy.

“A pool can un-weight the patient, too,” he said. “Buoyancy affords significant biological and biomechanical benefits that potentially could allow someone with knee OA to walk without joint pain for longer.”

Upcoming for Dr. Jayabalan: New Research & Physiatry ’22 Honor

Dr. Jayabalan — along with his Shirley Ryan AbilityLab colleague R. James Cotton, MD, PhD, clinician-researcher — recently received a grant from the NIH-funded Restore Center. Drs. Jayabalan and Cotton will collaborate to investigate specific baseline gait metrics and biological markers as predictors of patients' responses to injections for knee OA. The Restore Center is based out of Stanford University, and is one of six centers that form the Medical Rehabilitation Resource Network.

Additionally, at the upcoming Association of Academic Physiatrists’ annual meeting (rescheduled for May 24–28), Dr. Jayabalan will receive the AAP Early Career Academician Award in recognition of his research, teaching and mentorship.

“Of those three aspects, the one that has given me the most satisfaction is mentorship,” he said. “It is my major passion, and the residents in my lab have been critical to my success.”

Currently, 12 residents from the McGaw Medical Center of Northwestern University/Shirley Ryan AbilityLab PM&R Residency Program work in Dr. Jayabalan's lab on studies focused on physical activity and function in chronic musculoskeletal conditions. Residents have voted him Mentor of the Year for four consecutive years.

“I’m getting this award at the AAP conference, but I’m much more excited about the fact that I have 12 trainees presenting abstracts there — three of which are podium presentations,” Dr. Jayabalan said. “I can’t wait to witness their excitement.”