When Steve Messier started researching how to best treat pain caused by knee osteoarthritis, there was no cure for the debilitating condition.

More than 30 years later, that’s still the case—so the biomechanics expert and professor of Health and Exercise Science at Wake Forest University wants to prevent it.

Through a series of clinical studies, Messier’s team has confirmed that exercise reduces pain and improves function in older adults with knee osteoarthritis (OA). They have found that weight loss plus exercise can reduce pain better than diet or exercise alone.

Now, The Osteoarthritis Prevention Study (TOPS), with $17.1 million in funding, will determine if the same treatments can help women at risk avoid developing knee OA.

What is knee OA and why do you study it?

Knee osteoarthritis is a degenerative disease where joint cartilage breaks down and is accompanied by inflammation of the joint’s soft tissue, causing pain, stiffness, and reduced mobility. There are two pathways to knee osteoarthritis: One is an increase in load on the joint, and the other is inflammation. Obesity, which is a major risk factor for osteoarthritis, impacts both of these pathways. Obesity increases the load on the joint, and the excessive fat that accompanies obesity includes pro-inflammatory cytokines that increase joint inflammation. 

Osteoarthritis is the leading cause of disability in adults. It affects an estimated 50 million people in the U.S. Risk factors for developing knee osteoarthritis include injury, being overweight, and being female. Approximately seventy percent of the people who have knee osteoarthritis are female. As we age, there’s also an increased risk of developing osteoarthritis. 

My first grant from the National Institutes of Health was determining the causes of overuse injuries and runners. We tested 300 runners in that study. The very last person that came in happened to be a fellow in rheumatology, a young researcher and physician, and he asked me if I had thought about doing this work with older people with arthritis. So we did a little study, it got published right away, and it changed my life. 

What has your study of knee OA found?

We’ve had a number of clinical trials over the last three decades. In the beginning, we tried to see if exercise was better than no exercise in reducing knee pain. That first study was called the Fitness Arthritis and Seniors Trial. In the late 1980s, many physicians who treated people with knee osteoarthritis would tell people to take it easy, don’t hurt yourself. It made sense, that if moving hurts you should stop moving. But it was the worst advice you could give someone with knee osteoarthritis, however we didn’t know it at the time. In FAST,  we showed that both walking and strength training were superior to a control group in reducing pain, improving function and quality of life. This groundbreaking work, led by the late Dr. Walter Ettinger and Dr. William Applegate, was the beginning of decades of research on reducing pain and improving function through exercise and diet.

Over half the people that participated in FAST were overweight or had obesity. We thought, maybe if we combine diet with exercise, we’d have a better impact on reducing pain. In the ADAPT study, we compared the effect of a 5% weight loss plus exercise, either separately or in combination, to a control group. Sure enough, the diet plus exercise group overwhelmed the other groups in reducing pain and improving function. After that study we thought that If a little weight loss is good, maybe twice as much may be even better. So we did the next study, which examined the effect of 10% weight loss plus exercise. The people in the 10% weight loss plus exercise group had twice the improvement as people in the previous study who had a 5% weight loss. NIH recommends 10% weight loss as the gold standard now. 

All of that work has been great. But you know what? At the end of each study, the participants still had osteoarthritis. They felt better, they reduced their pain, they improved their function, and their quality of life was better. But they still had osteoarthritis. Unfortunately, there is currently no cure for osteoarthritis. So we started thinking, maybe prevention is better than treatment. And that’s what The Osteoarthritis Prevention Study or TOPS is all about.

Tell us about TOPS.

We have four clinical sites internationally, one in Boston at Brigham and Women’s Hospital, one in Chapel Hill at the University of North Carolina, one here at Wake Forest, and one in Sydney, Australia. We’re recruiting people who are at risk for having knee osteoarthritis but don’t have it yet—that is, women 50 years old or older who have obesity. We are recruiting 1,230 people, and they go through X-rays and MRIs. Eligible women have at least one knee that does not have osteoarthritis. Half of those women will be randomized to a diet and exercise group, and the other half will be in a healthy lifestyle group. 

We’re predicting at least 30% fewer people in the diet plus exercise group will have knees that progress to osteoarthritis within four years compared to the control group. 

This study is as much about behavioral change as it is about diet and exercise, right?

A big part of our intervention is behavioral or psychological, to increase participants’ self-efficacy, the belief that you can really do something. In this case, it’s the belief that you can lose the weight and keep it off. We can get people to lose weight pretty easily. It’s the keeping it off part that becomes really difficult. I’ve had people stand up in a meeting at the end of their intervention with us and say, why didn’t my doctor tell me I just needed some help? We’re there for them on this journey to a healthier lifestyle as much as they need. It’s the emphasis on behavioral change that often separates us from other trials.

When we recruit people to be in the study, we recruit them in waves. So women in each wave will be together in this weight loss journey, and it’s this group dynamic that I think is really important. They actually motivate each other. We even allow spouses to accompany their wives during the trial. They are not officially part of the study, but they may join their spouse during the exercise sessions. It’s really helpful for the spouse that is in the study to have that emotional support. 

How is this research changing people’s lives?

Osteoarthritis has been thought of for many, many years as inevitable: As I get older, I’m going to get osteoarthritis. Well, maybe that’s not true. Maybe you can do things, reduce your weight, exercise, improve the quality of your life, live a healthier lifestyle, and maybe not get osteoarthritis at all. We’re trying to prove that.

The major symptom of osteoarthritis is pain. Pain can govern your life. The pain changes your lifestyle, makes it more narrow. We try to expand their lifestyle again so they can play with their grandkids, get in and out of a car, go up to the second and third floors of their home. People with knee osteoarthritis have narrowed their lives because of the pain associated with the disease. If we can reduce that pain, we can give them a lot of their life back.

So what’s next? The real key here is something called implementation science, taking what we know works and getting it into healthcare systems. That would be the ultimate for us, to actually get what we know works into healthcare systems so it can be utilized by more than just the people who are in our studies.