QD Clinic: How Weight Loss Changes the Course of Knee OA Save

Hello everyone. This is Bella Mata. I'm a rheumatologist in New York and I will discuss a case of a patient with knee osteoarthritis. We as rheumatologists see these patients almost all the time. And I will talk about this particular patient who was this man in his late 40s who presented with progressive worsening bilateral knee pain. His BMI was 34. He also had developed type 2 diabetes and over the past several years I think things got just worse with his pain. In the knees it was around 6 on 10, goes up to 8 on 10, and it substantially limited his quality of life. He avoided recreational activities with his family, could no longer exercise regularly, and reported sort of problems with stairs especially going downstairs and walking extended distances.

So when I first saw him the X-rays demonstrated a KL grade three bilaterally with definite joint space narrowing medially and some osteophytes. So again, typically what we see in these OA patients, he had already attempted many standard therapies. He had NSAIDs, he had gone to physical therapy a number of times, and received corticosteroid injections. Now these injections did seem to help and mainly all of these interventions did provide temporary relief. Did go from like 6 on 10 to 4 on 10, maybe 2 on 10 sometimes the pain, but it was still something that would worry him. Again the KL score was grade three and he would ask me, he's like oh it's just grade three and not grade four. And I'm also too young for eventual joint replacement. But I always would talk to him and this is another point that I make to all my patients — saying KL grades in knee osteoarthritis may not correspond to the amount of pain the patient has, because pain is so multifactorial and the joint damage may not completely contribute to the pain, joint damage on an X-ray.

So we were trying to manage this patient with conservative treatment because he did not want a joint replacement, which made sense. And at a routine visit with his endocrinologist he was started on semaglutide to improve glycemic control. Again I think they tried to get some of the other GLP-1s but then insurance approved the semaglutide. So over the following year he experienced substantial weight loss and improved metabolic health. His BMI went from like 34 to like 28. And his knee pain dramatically improved. What surprised him was not just simply the change in his weight but overall the kind of energy that he had. He reported walking longer distances, returning back to exercise, participating in activities that he previously avoided, and his pain declined to like around 1. He then did not need as much NSAIDs — maybe he would still take it occasionally. But we particularly stopped giving him the corticosteroid injections because he was doing fine.

Again, I think that this sort of tells us that even with that KL grade three, once his weight was reduced it did help his pain component for his knee OA. And primarily we thought obesity contributed to knee OA through excess mechanical loading across the joint, across the knee — which is like, for every 1 kg increase in weight I was taught your knees have to sort of take in 4 kg to compensate. So certainly biomechanics matter, but that explanation is incomplete, and especially seeing these dramatic effects we know more. We now recognize that obesity is associated with metabolic inflammation and changes throughout the entire joint. And fat cells produce inflammatory mediators which can influence overall the whole joint outcomes, pain sensitization, bone remodeling, all of these things that affect quality of life. This explains why obesity is associated not only with knee OA but also with OA in joints that are not particularly exposed to substantial mechanical loading. For example, hand OA — there are some early studies showing that patients who have substantially lost weight, their hand OA symptoms have also gotten better. So obesity is not simply making the knee work harder but also changing the biological milieu within the joint itself.

And the other thing I take away from this is that as the patient lost more weight it was not just the number on the scale — the number on the scale of the weight as well as the number on the pain — but also function, which is sometimes not talked about enough I feel in our field. So he returned to exercise, reduced his pain medications, and started doing activities that were getting increasingly difficult prior because of his OA. So his experience actually is like if you
take a trial patient from the STEP 9 trial which was the original NEJM trial which talks about how patients with knee OA improved after getting GLP-1s. He's basically like one of the prototypes within those curves on the STEP trials where it shows that patients who were on this improved pain significantly versus those who were on a placebo. Um again, you know, they found the delta or the clinically meaningful finding which was pretty large in those patients who were on these drugs.

Um again, you know, there are recent imaging and mechanistic studies that have shown that improvement in inflammatory as well as structural features including changes in the synovium and the cartilage have been associated with the GLP-1 drugs, but again these are small studies in different models, mice models or whatnot. Um again there's some data, you know, again very few patients in these studies with MRI showing there's changes, there's more to come, and you know we will see more and more data emerge out of this.

But I think that the idea that obesity treatment will have biological effects in a disease like OA, in addition to the mechanical effects of course, are great. And even with a disease like OA that we feel has less or not many DMOADs, or things that change trajectory, you know treatment of obesity can change trajectory. And even though his radiographs did not normalize obviously because he had some damage, some osteophytes, his function and pain improved, his daily life changed.

So you know the conversation of the patient's health trajectory changes if there's a motivated patient, if things work right. And the goal is not necessarily to reverse the osteoarthritis. It is just to help patients have less pain, move better, and slow the progression of the joint damage getting worse.

So you know again we think of obesity as a comorbidity but I think we should start thinking about it as something that we can disease-modify using this. And for many patients with knee osteoarthritis, obesity is more than a risk factor. And as our understanding of osteoarthritis evolves we are moving away from this concept of osteoarthritis being a purely mechanical disease and more towards something that affects the whole joint.

And it's influenced by many factors. Weight or obesity is the big one. But metabolism, inflammation, body composition, all of that contribute. And treating the patient thinking about all of this together might be something that would help improve outcomes. So with that this is Bella Ma signing off and please follow me on Twitter at Bella_Ma. Thank you.