ahead and get started. I want to welcome everybody to AAP Virtual Didactics today. We're really excited for both of our lectures today. As always, we want to start by recognizing and appreciating those who have been kind of on the front lines of this epidemic. We recognize that not all of us have been affected equally, so we appreciate those of you who have been personally or professionally impacted more than the rest of us. If there's anything we can do to further support you, please let us know. As always, we've got to go through some goals and some housekeeping type of things. So the goals of this are to augment didactic curricula that are already ongoing at your home institutions, to offload overstretched faculty, and provide learning opportunities for off-schedule residents as necessitated by some of the logistical challenges that have come with the COVID-19 pandemic, to develop further digital learning resources and support physiatrists in general during the COVID-19. We're going to keep everybody video and audio muted. This is both for bandwidth and distraction, so it's not personal. If you see us mute you for whatever reason, that's why. If you have any questions, you can look me up. My name is Sterling Herring. I'm a PGY3 at Vanderbilt, and so if you click on participants, you should see me up near the top of the list, Sterling Herring. You can double click my name and send me a message via the chat, and I will ask our lecturer at appropriate times. If you have any general questions, suggestions, anything like that, there's Candice's email at AAP, and of course you can find us on Twitter. So without further ado, we're really excited to have our lecturer today. Welcome, and thank you for joining us. Hi Sterling, thanks so much for the opportunity. I'm just going to share my screen in a second. Perfect, thank you. Hopefully that's up on the screen, is that? Yeah, okay. Awesome. Thanks so much Sterling. And really want to thank you actually for, I know it's a lot of work as a resident to be putting this lecture series together. So thanks so much. And thanks Candice as well from the AAP. So for those of you that don't know me, I'm Prakash J Bal and I'm a clinician and director of musculoskeletal research at the Shirley Ryan Ability Lab. And my research really focuses on knee osteoarthritis as my primary clinical care, as well as general sports medicine. So when Sterling asked me to talk today, I didn't want to make my talk really research heavy. I really wanted to make it relevant with some sprinkles of research to residents and medical students and most of you guys on the call today. So we're going to really break it down into six parts. So we're going to talk about the biology of knee osteoarthritis, which is really more my research focus and using biological markers for diagnosis and treatment. We'll talk about exercise, joint loading strategies, biological strategies. Full disclosure, we're not going to be talking a lot about regenerative medicine, though I will have some pearls for you to think about as a societary residents or incoming societary students. Some pearls to just think about in terms of looking at outcomes of some of these procedures and then potentially some talk about the future. So as I said, there'll be some sprinkles of research, but we won't be focusing a lot of my research for this talk. I think really the three takeaways that I want you to get away from this is sort of biomechanical strategies, joint loading strategies, some of the pharmacological treatments that are being developed, and also some of the biological processes that you need to think about as students and societists managing these going forward. So I'm British. Hopefully my accent gives it away. But my first thing that I want to point out is I always put a cricket player or something British in my talks. So I want you to imagine a clinical scenario that you'll see no matter what stage you are at in your training. So imagine you have a 68 year old former cricket player who presents with a seven to eight month history of medial sided knee pain. And our typical paradigm in clinic is really to examine this patient, perform radiographs on them, and then in turn diagnose them with osteoarthritis of their knee. Now, then we start thinking about what our treatment strategy is. And so our treatment strategy most commonly involves managing pain because that's what our patients are presenting with. So usually we're thinking about analgesic medications such as Tylenol, non-steroidal medications. We'll talk about weight loss, exercise, rehabilitation, and we'll talk about that during this talk today. And then those are sort of my first go-tos when I'm seeing a patient for the first time in clinic. So in this talk, I sort of want to give you my practical pearls as well as my educational pearls. But usually I'm not talking about injections on the first visit in a clinic, but injections are potentially the next step. And so we'll talk about, we'll think about sort of injections such as visco supplementation, such as hyaluronic acid, medications such as CINVAS-1 or other pharmaceutical treatments, injections such as steroids. And generally, I'll think about steroids as being more in the acute management of pain and injections. Now, these are not optimal treatments by any means, but they're the only ones currently right now, at least in our practice that are covered by insurance. So that's why I mentioned them. And there's definitely some controversy in both of their use. And then that leads all the way to arthroplasty. So where we use essentially metals and plastics and total joint replacements. And our goal as sort of non-operative physicians is really to try and optimize the left side of the screen to try and prevent and negate the need for total joint replacement. Now we certainly do send patients to total joint replacement eventually when all of these sort of left side of the screen treatments have been exhausted. So that's something important to remember. But when we go back to our case, these are sort of the things that I think about. So from a research perspective, as well as a clinical perspective. So we diagnosed our patient, but could we have diagnosed him earlier? That's really a good research question. How do we decide what is the best treatment for this specific patient? What level of physical activity should we recommend? And what sort of rehabilitation regimen should we prescribe for this patient? And those are some of the things I want you to think about, both in terms of this presentation, but also in your future careers in managing those patients in knee osteoarthritis. The problems we have with OA is that we really don't have a great way or early way to detect the disease, staging the disease, predicting who's going to respond to treatment well, monitoring the progression, monitoring compliance, and determining who's going to most benefit from a treatment. So those are sort of things in the back of your mind. And sometimes I will have to counsel patients on this and say that we're not 100% certain whether a treatment is necessarily going to work, but it's sort of a best averages approach in trying to, in trying to come up with a treatment strategy for our patients. The other important thing to remember is that knee osteoarthritis, if I ask most medical students or residents, what is knee osteoarthritis? Most will say that it's wear and tear in the joint because of overloading within the joint. And that's because we think that it's essentially this normal biomechanics in the joint. But I also, if there's one takeaway from my talk today is that there's abnormal biological processes that are also going on in the joint and those have a complex interplay with the abnormal biomechanics. So there's this sort of inflammatory and degradative cascade that is fueled by both the abnormal biomechanics, as well as the abnormal biology. And we target these with our treatment. So we'll use medications to sort of limit the inflammatory processes. So anti-inflammatories that we commonly use, actually try and limit that inflammatory cytokine release in our patients, as well as medications that are being developed, which targets some of those degradative enzymes called MMPs in the knee joint. So those are important to remember. But also studies have shown that weight loss, which we'll talk about, has both a biomechanical effect as well as a biological effect. And that's important to remember, as does modifying the activity of our patients. So as I said, if there's one takeaway from this talk today, knee OA is not just a wear and tear disease process, but it has both abnormal biomechanics, which interfaces with abnormal biological processes in the joint. And that's what I really want you to remember going forward in your careers with managing knee osteoarthritis. And that really speaks to the fact that the knee joint, or any joints in our body, is an organ. It's an organ just like the heart, liver, lungs, in the sense that it's essentially composed of different types of cells, which are encapsulated within a membrane. And the knee joint is no different compared to many of the other organs in your body. So we think about the knee joint, most practitioners will think about cartilage that's being abnormal, but there are many other different parts of the joint. So we have the synovium, which basically surrounds the knee joint, and it produces hyaluronic acid, which actually sits on the surface of the articular cartilage and provides it some, which actually provides it some health, as well as some of the nutrients that go into the synovial fluid, which spades the cartilage. And that's also very important to the health of the cartilage. We also know that the subchondral bone, so that's the bone underneath the cartilage, actually has a big impact on the health of the cartilage. And that there's this crosstalk that's been described in the literature that occurs between the subchondral bone and the articular cartilage on top. So that's also important to remember. And then the synovial fluid itself also has a function, and this is the fluid that's within the knee joint. And studies have shown that in people with osteoarthritis, they actually have more acidic content of their synovial fluid, as well as a difference in the biological content of the synovial fluid as a whole. And then that leads overall to articular cartilage. And the challenge with us as non-operative practitioners is that articular cartilage, which is that cartilage which is in the knee joint, is avascular, alymphatic, and aneural. So that means that it doesn't have a blood supply. And so when it's damaged, it has a limited reparative potential. And also it's aneural, so that when it's initially damaged or when cartilage is thinning, the patient may not really know about it unless there's an associated bony injury with that cartilage damage. So that's important to remember as well when you're managing these processes. And that's why many of our patients really present very late in the game. Also in the healthy knee joint, there's an optimal balance between catabolic and anabolic processes. Now we know what happens in a way is that there's damage to the articular cartilage and other portions of the joint, such that as the patient bears weight over time, there's basically a thickening of the synovium or inflammation of the synovium. There's osteophyte formation. But there's also some other parts of the joint that are also impacted. And we know that there's also the release of inflammatory cytokines and cartilage degradative enzymes into the joint, which over time potentiate that joint damage leading to bone-on-bone motion, which leads to pain. And we also know that that balance in the healthy joint gets tipped in the unhealthy joint towards catabolic processes occurring into the joint as opposed to anabolic processes. So this really leads to sort of the research goal that I'm going to describe, which is using these biomarkers for diagnosis and treatment. And the challenge that we have, particularly as non-operative practitioners, is that we don't have great imaging studies for knee osteoarthritis. So the most common imaging study that's used for osteoarthritis is a radiograph. And we'll talk about findings in a radiograph of knee OA shortly. But the problem is that if I have a patient in clinic who I'm diagnosing with knee osteoarthritis based on their radiographs, they're already quite far down the line. And we know that radiographs really have a poor sensitivity to early disease. And by the time someone presents with radiographic knee osteoarthritis, there are potentially less interventional options for this patient. And as we know, particularly as societists, is that we want our imaging studies ideally to really correlate to functional symptoms in our patients. And radiographs have been shown to notoriously not be great at that. Now, the other options are sort of MRI. And I rarely order an MRI for a patient to diagnose knee osteoarthritis. They're expensive. They don't always provide, particularly early on, information on the potential pain generator. And many of our patients won't have access to many of the novel scanning protocols, which look at cartilage health based on MRI. So that's also important to remember. And then the final thing is really arthroscopy. So many of our surgical colleagues used to perform arthroscopy. And you'd have patients who'd say, oh, I'm going to have my knee washed out for my knee drain. And they're going to clean out the osteoarthritis. Really, there's no evidence that that really occurs. And arthroscopy is an invasive, expensive procedure. And just even from a biological standpoint, it's basically, arthroscopy is where they take a camera into the knee joint and look at the knee joint articular surfaces. And you're only really looking at the surface cartilage layer. You don't really know the biological standing of that articular cartilage. So that's also a practical issue with arthroscopy. So really that's gone out of favor and isn't done for knee osteoarthritis management. So as a podiatrist, and particularly as a researcher in this realm, my research really focuses on, can we be fortune tellers of individuals with knee osteoarthritis? Can we tell someone, diagnose someone earlier on with knee osteoarthritis and then prognosticate how they're going to do with treatment? And though I'm not going to focus on research too much, that's questions that really need to be addressed in managing knee osteoarthritis. And what we're after is essentially some sort of test, which is basically similar to a PSA test, where we'll be able to tell someone the extent of their disease and potentially prognosticate how they're going to respond to specific treatment. In getting to that, I think it's important also to remember, and particularly those of you in medical school will know this, the structure of cartilage, because you probably have to learn this, unfortunately, for many of the step exams. But cartilage essentially consists of a chondrocyte, which is the cell in cartilage surrounded by an extracellular matrix. And that extracellular matrix has water as a primary component, but also consists of collagen, which is essentially a triple helix, which gives cartilage its tensile strength, and glycosaminoglycans, which hold water and give cartilage its compressive strength. And so we know in osteoarthritis that there's damage to that extracellular matrix. And also that synovium, which surrounds the knee joint, as we talked about, releases macrophages, which actually cause the release, in turn, of some of those cartilage degradative enzymes, which clean up some of those breakdown products and also potentiate some of the damage further. And we know from some studies that we're able to measure some of these breakdown products in patients' blood or synovial fluid from their joints. And so that's also some of the pathophysiological processes that are occurring in cartilage injury in our knee joint. So that's important to remember. From a research perspective, the advantage of measuring some of these biological markers is that we know some of these biological processes. If we think about the time course of knee osteoarthritis, and on the right here is an individual with joint replacement, and just before that is radiographical NeoA, and then there's sort of pre-radiographic NeoA that you can diagnose using some of those imaging modalities we talked about, though they are expensive. We also know that some of these biological markers can be measured earlier on in the disease process in our individuals in knee osteoarthritis. So that also shows that there's biological processes that are occurring in knee osteoarthritis before even the patient knows about it or presents with symptoms. And that's some of the epidemiological studies have shown. So really thinking about sort of treatment strategies in the future, the hope is in the field of knee osteoarthritis that we can preemptively treat patients on the bottom part of the screen earlier on than later on in the disease process at the top half of the screen. And that's really the goal of knee osteoarthritis treatment as well as research going forward in our patients. So the next phase of this talk is really to talk about some of our treatment strategies. And so the first is really to talk about biology and exercise and really talk about the biological effects of exercise and what you will prescribe as potential for dietary resonance as well as students. And so the biggest treatment that we'll probably prescribe for our patients is weight loss. And there's a significant relationship between obesity or being overweight, clinically overweight, and the presence of osteoarthritis. And this really speaks to what we said at the beginning, which is that osteoarthritis is not just wear and tear. So there is a concept that for every pound of weight that you lose, you lose four pounds of pressure from each individual knee. So that's an important thing to potentially mention to your patients in trying to get them to buy into losing weight. But the other thing that I'll commonly also tell my patients is not just losing weight takes pressure off your knee joints. There are actually studies which suggest that losing weight is also anti-inflammatory. And osteoarthritis has been suggested to be a chronic inflammatory state. We know this because in individuals who are overweight or obese, they actually have a higher incidence of hand osteoarthritis. And the hand is obviously not a weight-bearing joint like the knee. And the thought is that it's because of the systemic inflammation that people who are overweight actually have that leads to the presence of osteoarthritis. And so that really speaks again to the fact that osteoarthritis is not just this wear and tear or chronic overloading of the joints, but there is also biological processes that are also at play. The other thing that's also interesting is that, and this is probably particularly pertinent with what we're seeing with COVID-19, for example, is that there is this increased amount of cytokines, inflammatory cytokines in individuals who are overweight. And we're seeing that even with individuals who are having severe symptoms from COVID-19. But osteoarthritis, as we just talked about, has an inflammatory component to it. And there's studies that have shown that the amount of white adipose tissue that you have in your belly actually correlates with some inflammatory mediators and adipokines that are associated with chronic inflammatory diseases, such as rheumatoid arthritis, insulin resistance, as well as osteoarthritis. So weight loss potentially has an anti-inflammatory effect that's important to also remember when we're prescribing it for patients with knee osteoarthritis. The other thing is rehabilitation. So, and this is something that you'll commonly prescribe as someone in society for knee osteoarthritis. And our goal in sort of prescribing physical therapy is to improve the biomechanics of the joints. And the goal is to strengthen some of the musculature around the joints with the goal to sort of offload the joint to some extent and also improve function and decrease pain. And we did a study to essentially see how, whether there's any correlation between some of these functional metrics and to an individual's markers. And so what we found was that the ability of an individual to perform a leg press or a knee extension exercise actually had a significant correlation to certain urinary biomarkers. So MMP9, which is a cartilage degradative enzyme and IL-8, which is an inflammatory cytokine. We actually found that the more amounts that individuals with NeoA had in their urine of these two markers, they actually had less strength and less power when performing a leg press. Similarly, we found that when you're thinking about functional motion, when they actually rise from a seated position, which we call the sit to stand time or the chair rise time, what we found was that there was a significant positive correlation to these two markers. So the more amounts of these two markers they had in their urine, the longer it took for them to rise from a seated position. Now, we didn't find that actually rehabilitation caused a significant reduction in these markers. So it did show that there was some biological relationship between these markers and the functional abilities of some of our patients. And so in the field, there probably, there aren't many studies currently that show that rehabilitation as a whole maybe has an anti-inflammatory effect. So that's something that I know that many labs are potentially gonna look at. The other part is then prescribing exercise, which is a big part of being a podiatrist managing OA. And I put this quote of what we describe typically as an athlete. And so when we're prescribing exercise, I really like to think of all of my patients as being athletes. And even though I'm sort of sports medicine trained, it doesn't matter whether you're sort of Cristiano Ronaldo here on the left, or you're sort of my older patient with knee osteoarthritis on the right, or me in the middle, who's clearly not very, who's not very athletic. Someone who's physically active and is fit and is regularly involved in sport or leisure activity is what I would describe as an athlete. And so what can we prescribe these athletes and how do we develop an exercise program for someone with knee osteoarthritis? So it really comes down to many of the societary principles that we've learned. And the ACSM guidelines for individuals with knee osteoarthritis are sort of the cornerstone of how I prescribe exercise for someone with knee OA. 30 minutes of moderate intensity exercise, four to five times a week. And we'll talk about some of the problems with that prescription in a second, but I still use that as the cornerstone of my prescription. And many patients, when you see them for the first time in clinic will say, well, am I developing knee osteoarthritis because I was exercising two months? And there really is conflicting literature on this, but overall, I would say that exercise is protective because of some of the other things we talked about. People who generally exercise are probably in better shape, less overweight, and are probably making good lifestyle decisions that potentially do decrease their risk of development of the disease. So to say necessarily that exercise leads to the development of knee OA isn't probably correct at this point. And then when you're evaluating some patients in clinic, these are some of the things that you want to evaluate in terms of an exercise prescription. Their impairments, their strength, range of motion that you'll get from their physical exam, their balance, and their overall aerobic fitness, as well as their fitness goals. And so exercise goals are probably a big part of also deciding what is the best exercise prescription for someone with knee osteoarthritis. The other things that I'll also talk about are sort of precautions for these individuals. So discomfort during exercise can be normal. I mean, most of us who exercise regularly do feel some level of discomfort. But what I would say is, and it's not a hard and fast rule, but I would say is if the pain and swelling in any joint sort of is prolonged to greater than two hours, that suggests that that exercise may have been a bit too much and may require some modification of that program. Some other things I'll discuss with them is footwear, which we'll talk about, warming up, cooling down, graded increase in frequency and duration, joint loading strategies that we'll talk about, and also potentially injectable treatments or also biologics. And this really speaks to then our exercise, most common exercise recommendation, which is greater than 30 minutes of moderate intensity activity five times a week. And one of the biggest challenges that you'll have as physiatrists who may be prescribed this is that this is really based on cardiac health. We don't know what impact this has on an individual's knee joint long-term. And that's important to remember when you're prescribing this. So what we actually, what I'll commonly do is sort of think about step counts as well. And so one of the ways to sort of monitor someone's exercise prescription is to just ask them if they wear a smartwatch or something like that, or have an iPhone, and really think about monitoring their exercise themselves and holding them accountable. So if I was to tell a very sedentary individual to go and exercise 30 minutes of moderate intensity exercise, they probably aren't gonna listen. But one thing that I would do is to really start with a simple prescription, which would be using step counts at 6,000 steps per day, and increasing by either 1,000 steps per day or 1,000 steps per week to try and get to that potential 10,000 steps. Now, the important thing to remember is 10,000 steps is sort of this magical figure that we use, but it really doesn't speak to the intensity of the exercise. But studies have shown with this sort of exercise prescription of sort of 6,000 steps per day, with that graded increase, you can decrease functional limitations of patients by up to about 18%. And also with a significant decrease potentially in pain in these individuals. Now, these studies haven't really been used in very athletic individuals, but still, this is a potential methodology to use in our patients. Now, if we get back to our patient with this sort of exercise prescription of 30 minutes per moderate intensity exercise, the problem is and the challenge we have as individuals managing knee osteoarthritis is that we really don't know how that impacts the knee joints and my lab really focuses on the development of similar to a cardiac stress test where essentially you get someone on a treadmill, you look at EKG changes to stratify risk of coronary artery disease. We're trying to develop a cartilage stress test. So this is where you basically provide someone a biomechanical stimulus such as walking and you load the joint obviously during walking and you can measure certain biological markers of cartilage stress in these individuals while they're walking using an IV. And this has been suggested to have certain diagnostics of prognostic value. And the opportunity, the nice thing about this is that we can potentially use it to measure real time cartilage stress response by measuring these biological markers while they're on the treadmill. And studies have shown that this sort of type of treadmill walking for 30 minutes and measuring the sort of biological marker response acutely has been able to predict cartilage thickness at five years down the line on an MRI. We did a simple study just comparing, taking individuals in knee osteoarthritis and walking them continuously on a treadmill for 45 minutes and comparing them to individuals where we do an interval walking regimen where they do the same duration of walking of 45 minutes but it's interspersed with two breaks of one hour a piece of rest where they're not loading their joints at all. And the marker that we measure just so you know is a marker of cartilage stress called COMP which is in the extracellular matrix. And essentially what it does is it transduces that mechanical signal every time you take a step on your knee joint from the extracellular matrix to the contracellular. Now I don't want to get too much into the science of this but the important thing to remember is that cartilage is mechanosensitive. If I take any of you guys and I put you in space and you don't put weight on your joints you actually have the propensity to develop knee osteoarthritis. The cartilage doesn't require some loading to maintain its health and COMP is important to that. So we know that increased COMP is essentially analogous to increased cartilage stress. And what we found in this study was that when you get individuals to walk continuously on a treadmill they actually have a significant increase in COMP which is this red line here compared to an interval walking regimen where they take the rest breaks. What we also found is that when they walk at 30 minutes on the treadmill there's also a significant increase in knee joint contact force when they walk continuously on the treadmill as opposed to walking with an interval walking regimen. What does this mean? It's important thing to remember is that when we're prescribing exercise for our patients we'll say 30 minutes of exercise but maybe actually breaking up that exercise could have both a benefit in making sure that the patients are actually continuing with the exercise we're prescribing but also could have some potential benefits to our patients going forward. All right, so next I wanna talk about joint loading strategies. And so we really talked about research and that'll probably, we won't talk about as much about some of the biology going forward but this is probably the bread and butter of most physiatrists who are managing knee osteoarthritis. And there are many, the first thing to remember is that there are certain situations that lead to changing the mechanics of the joints in our patients. So obesity, prior history of joint trauma, certain occupations in sports, joint deformity and malalignment as well as abnormal gait mechanics. So abnormal joint deformity and malalignment statically is really sort of varus valgus, particularly varus angulation of the knee joint and abnormal gait mechanics. So when you watch someone walking, for example, they have a high degree of varus thrust that puts them at risk of potentially the development of knee osteoarthritis. So those are things that you can sort of get from either your physical exam as well as your history from the patient. And these potentially will lead to increased risk for the development of knee osteoarthritis. The other thing that's important to remember is that as we just talked about, healthy cartilage really responds positively to loading. It needs some sense of loading to actually maintain its health. But what they found is that in people with osteoarthritis, they actually respond negatively to higher loading compared to that in the healthy state. And what we also know is that each one of us on this call today, the distribution of cartilage within our knee joints is different and it's really influenced by our knee kinematics when we were younger. Some of us may have more articular cartilage in certain parts of the joint compared to others just because of the loading pattern of our joint. But what happens in knee osteoarthritis is that we know that certain parts of the joint that can't handle certain joint stress is suddenly get this increased load because of the change in mechanics. And so that's important to remember. So one of the first things that I'll do in sort of evaluating someone with knee osteoarthritis is thinking about their level of exercise or how they're loading their joint. So for example, if they are a high-level soccer player or were a high-level soccer player, soccer is notorious for actually putting a significant amount of stress on the knee joint. So I may think about changing them to a type of exercise. If they're open to it, there may be more of a moderate to lower level of joint loading. Similarly, if they were a running back in football, running backs in football are notorious for also developing knee osteoarthritis at a higher rate than other positions. And although they may not want to change their position, it may be a thought to actually think about going to a different sport if they're getting provocation of symptoms in the amateur level of any of these sports. So that's important to remember is thinking about the level of joint loading in these individuals and maybe thinking about changing to a different sport that could actually put lower impact on their knee joint. The next is really thinking about their evaluation. And many patients, when we go back to that case at the beginning and evaluating that patient, is sort of, we'll sort of do radiographic findings. And I just want to take a quick aside, as sort of a high yield topic that many of you will be tested on in the future, is sort of some of the radiographic findings of knee osteoarthritis. So it's really four cardinal radiographic findings in knee osteoarthritis. The first thing before even mentioning that is that most people will develop knee osteoarthritis in the medial compartment of their joints. And we'll talk about why that is in a second. But the four cardinal features essentially joint space narrowing, osteophytes, which are these bone spurs that you'll see on the margin, and they're called marginal osteophytes because they're essentially on the marginal aspect of the joint. Subchondral sclerosis, which you may not be able to see so well here, but it's essentially this white line that you'll sometimes see just on the edge of the bony surface of the joint, on the articular surface of the joint. And essentially that increased density of the bone because of bony injury here. And then subchondral cysts, which are essentially pockets of fluid that are in the subchondral regions, so underneath the cartilage that you'll sometimes see, and these are usually pockets of fluid with inflammatory materials such as blood or other synovial fluid that's in this area that you'll sometimes see. So those are the four cardinal features that all of you should remember as a take home from this talk as well. So why do people with knee osteoarthritis develop medial compartment knee OA more so than lateral? And this is again, another take home message from this talk. And this really speaks to the knee adduction moment. And the knee adduction moment, as we'll see here, so typically the ground reaction force when someone is taking a step on the knee joint goes medial to the knee joint. But what happens when someone has a varus angulation, so that's bow-leggedness to their knee joints, is that that lever arm at the knee joint is increased. It puts more strain on this medial compartment of the knee joint due to this increase in this moment lever arm. And so what we, what studies have shown is that in individuals with sort of bow-leggedness, for example, the medial tibiofemoral joint contact force, which is this force on the medial side of the knee joint, are 2.5 times greater than lateral forces during walking. And studies have shown that this knee adduction moment that I'm describing is an indicator of medial joint load. And it's also a marker, a surrogate marker, of severity of knee osteoarthritis and potential progression of knee osteoarthritis down the line. So what we're gonna talk about now is potential biomechanical strategies that many of you would have heard of that really try and target the knee adduction moment. And these are some of those common targeted treatments. So knee bracing, foot orthotics, footwear, gait modification. We won't talk about weight loss in this sense, but it's just as divisive. But these are typical biomechanical strategies that you will prescribe as a psychiatrist in this population. So one of the most commonly used initially was sort of this medial unloader brace. And the goal of the medial unloader brace is really to try and get the knee into a more neutral posture. And what it tries to do is just, again, try and take the force of the medial aspect of the joint by limiting the knee adduction moment. Now, the biggest challenge with this brace that you'll see here is that these are pretty large braces and compliance in many patients can be really, really challenging. And studies have shown really compliance can range anywhere from 45% to 100%. But practically speaking, I would say many of my patients don't tolerate it very well. And that's why some of the Cochrane reviews which have looked at this really have shown no benefit or limited benefit because of patients not continuing to wear the brace. So that's important to remember with this. The other thing that is a common sort of board type question or a question you may get asked in clinic is what type of insole to use in patients. So the challenge is the typical answer is to say a lateral wedge insole. And the reason is, is again, it sort of puts that knee into more of a neutral alignment as opposed to various alignments as shown here on the top image. And it's generally been associated with up to about a 12% reduction in that knee adduction moment. And it really is tolerated better than the knee brace that we just talked about. But again, the studies haven't shown a great outcome from using the lateral wedge insole compared to those who've had a neutral insole. And again, it might be a compliance issue. It might be that the size of the wedge is also important things to remember. And also patients tolerating it, particularly those who maybe have pes planus may not tolerate this type of insole very well compared to those who don't. So that's also important to remember. The other thing to also remember is the type of footwear that your patients use. And so this used to be the really hot type of shoe people used to use is these types of shoes with sort of minimalist shoe or barefoot type running. And that was because there was some studies that suggested that shoes actually increase that knee adduction moment. And it's actually also a group that has developed sort of variable stiffness shoes where one side of the shoe actually has a different level of stiffness compared to the other. And these did show that they can reduce knee adduction moment in individuals with less severity of knee OA. But the studies haven't been really great in sort of showing a longer term outcome. The other thing also to remember is high heel. So this is something that I will definitely counsel my patients on as well is that high heels do increase that knee adduction moment that in turn can increase the, dependent on the heel, can also increase the peak knee adduction moment at the medial joint surface of the knee. So, and it does depend on the size of the heel. So that's also important to remember. The other thing that we can also prescribe as we just talked about is a sort of physical therapy. And one thing that physical therapy will certainly try and change or manage is sort of gait modification. And there are studies suggesting that potentially speeds while someone's walking can increase the knee adduction. So when someone walks faster, they can increase that peak knee adduction moment up to about 35%. But then studies conversely, where they actually try and slow someone's speed as an intervention haven't decreased the knee adduction moment significantly. So that's, the jury's still out on that as a treatment. But the other part let's also remember is that many of our patients also have weak hips. So they will also have sort of a trunk lean and trying to manage that trunk lean can also reduce some of the knee adduction moments. It's strengthening their hips can be beneficial. And also thinking about other gait modifications such as a step width can also reduce the adduction moment. The important thing to remember is that longitudinally following patients who've had these gait modifications, there are many studies looking at that. And so we don't know long-term whether these have a significant benefit in terms of outcome, but hypothetically speaking, obviously reducing that knee adduction moment could be of benefit. And then finally, from a biomechanical strategy, sort of single point cane. So this is something that I will prescribe my patients. And what I want you to put important things to remember is that we commonly prescribe the cane for the contralateral side to the knee joint, to that knee that painful or the knee that has osteoarthritis. And that's because again, studies have shown that knee adduction moment increases significantly when someone uses the cane on the same side as their pathology compared to if they use it for the other side. So that's important to remember. Just a more practical thing is that, of course, if someone has hand osteoarthritis and you're gonna prescribe them a cane, you may exacerbate their hand away. So that's important to also remember and counsel patients when you're prescribing this as a treatment. Now, the other thing that you all get asked by your patients is radiographic, is exercise gonna worsen my knee away down the line? And we did a study actually trying to look at radiographic progression of knee osteoarthritis. And there's a nationally available cohort of individuals with knee osteoarthritis called OAI. And essentially what we wanted to look at is, and these are individuals with knee osteoarthritis who had baseline activity monitoring. And what they wanted to look at was, how does their knee away progress down the line radiographically four years down the line? And so what we looked at was, if someone has mild osteoarthritis at the beginning, what factors actually were associated with progression of knee osteoarthritis down the line, four years down the line? And what we found was sort of factors that you would think would be associated with knee osteoarthritis. So being older, female sex, which is commonly associated with the presence of knee osteoarthritis, having higher BMI, and having higher baseline pain were associated with radiographic progression. What we did not find was actually being physically inactive. So being the lowest level of physical activity or the highest level of physical activity, having a prior knee surgery or prior knee injury. This is prior to incorporation in the study. Those are often not associated with radiographic progression. That doesn't mean that prior knee surgery and prior knee injury aren't associated with the presence of knee osteoarthritis. So I just wanna make that distinction in this study. The last two parts we're gonna talk about is just pharmacological treatments. And we'll breeze through this. Just mainly to say that the commonly prescribed medications for knee osteoarthritis are these, sort of Tylenol, NSAID, SNRIs, duloxetine, intra-articular injections, such as steroids, hyaluronic acid. And I only mentioned those because those are the typical ones covered by insurance. They all don't have the best efficacy and side effects. And I will say that there is, particularly in the pharmaceutical literature, there's a whole move towards some of the biological aspects of knee osteoarthritis. And managing those going forward is really, really important. So we've talked about some of those processes. And also sometimes even managing some of the central aspects of pain with medications such as NGF, which is a nerve growth factor. That actually, an antibody too, that is being developed to potentially prevent against the pain associated with osteoarthritis. So really speaks to some of the biological principles that we talked about. All right, so we've talked, I just want to summarize what we've got to so far. So we talked about the biology of knee osteoarthritis, suggesting that it's not just wear and tear. We've talked about some of the, we talked about some of the exercise treatments, the rehabilitation, weight loss, as well as exercise prescriptions. And then we've also talked about some of the joint loading strategies that you'll employ as a podiatrist in managing knee osteoarthritis. So I sort of want to end with sort of biological strategies. And this is the concept of sort of regenerative medicine or orthobiologics. And I think for knee osteoarthritis, certainly it's sort of still somewhat of a gray area. There isn't sort of a magic bullet of a study that suggested that all of us should be having, prescribing orthobiologics for knee osteoarthritis. So there is some potential. What I want to sort of leave you with is just to think about some of the important issues that are there if you're thinking about orthobiologic procedures. So one of the most commonly used is PRP, which essentially is platelet-rich plasma, which essentially is concentrated platelets, which contain growth factors. And these are taken from the patients themselves, and these can be injected into the knee joint. And some of these growth factors are here. So there's TGF-beta, platelet-derived growth factor, VEGF. I won't go into that. And the hypothesis in using these is basically, the hope is that it will stimulate some growth of cartilage, some of the pathways that are associated with growth of cartilage as well. The challenge is that there aren't many studies right now which have really looked at other aspects of the knee joint, such as the synovium and the subchondral bone. And I think going forward, that's definitely where the field is moving, is to sort of not just document some of the cartilage changes that you see following regenerative medicine procedures, but also potentially other aspects of the joint that are also being affected by the procedure. The other parts that are also important to remember is that when we're thinking about regenerative medicine, it's also important to remember about the cell source. So we're typically taking it from older patients, and you want to make sure that the type of cell, if it's a stem cell, or even if it's a PRP, you want to make sure that it's optimal. You want to make sure that the biological properties of the cell or the cartilage you're trying to produce actually are the same as the native cartilage. And also the other thing importantly to remember is that we're injecting some of these treatments into a joint, and the joint isn't always a healthy environment, going back to what we talked about at the beginning. And so it might be that certain individuals may respond better to regenerative medicine procedures just because of the environment of their knee joint. That's also important to remember. So these are some of the state, the evidence, some studies that suggested that the studies for PRP for soft tissue injuries aren't optimal. And certainly there are many laboratories in the US, particularly in sodiatry, which are doing great jobs of trying to improve some of the evidence for it, and some of the potential for it. Some of the questions that you will get asked as sodiatry residents, and you should ask, is the age of your patients. In general, it's being shown that younger patients tend to be better for knee osteoarthritis and some of these regenerative medicine procedures. The stage of OA, so milder, younger patients are important to remember. And then the other part that is not clear is really an opportunity for us as sodiatrists is sort of the post-injection protocol, the rehab protocol, seems to vary. And I think that's something that's definitely being looked at in the future. Some of these other factors are things that we also need to think about. I won't go into this too much, but the other thing to remember is many of the things I've talked about in this talk today, as sort of weight loss, physical therapy, physical activity, do have biological effects, going back to the beginning of the talk. So there was a study in 2015 out of Wake Forest, which suggested that diet and exercise intervention over 18 months significantly decreased joint contact forces and inflammation. A physical therapy program out of Finland, where they did progressive aquatic resistance program, actually improved the biochemical content of cartilage. And then physical activity as a whole, sort of those individuals who had the highest level of physical activity actually had an increase in extracellular matrix constituents over 12 months. So just the other important thing to remember is that many of the treatments that are our bread and butter as sodiatrists also do have a biological effect, so we may not be thinking that. So in conclusion, I would say the sort of future is sort of, well, this was really my conclusion, but I wanna end with one sort of opportunity as well, but managing patients in knee osteoarthritis is not clear. It's not just managing sort of wear and tear, but there are other parts to it as well that are important. And so they are, and one thing that could be important to mention is the sort of genetic clock. And this is the concept that we each have chromosomes and at the end of chromosomes are telomeres. And telomerase is essentially an enzyme which maintains our telomeres length. And when we think about a young cell, in most of you on this call, not me, you have long telomeres and they eroded at the rate of about 100 to 200 base pairs per division. But they've actually found that when you erode these base pairs beyond six kilobase pairs, it actually leads to chondrocyte senescence. This means that your cells will not respond to growth factors in the same way. And also after puberty, you actually lose that enzyme telomerase in your chondrocyte. So this is a potential opportunity also to show as to why certain individuals may not respond to orthobiologics the same way. So our lab is really looking to how we can harness this signal. So finally, I just want to say my hope for the future management of knee osteoarthritis, we went through a lot. And certainly, please feel free to go back to the webinar and look through it in your own leisure. But what I would say is that the future of knee osteoarthritis probably in management, not just of examining a patient and doing imaging studies, but potentially looking at their biology, as well as certain psychosocial factors that may also be at play. And treating every patient as an individual, which we all know as podiatrists. These are all sort of my lab folks and people who I work with and collaborate with and my funding sources. Feel free to email me directly if you have questions, if anyone's interested in the research we're doing, or if you want to follow me on Twitter as well, that's totally fine as well. But feel free to contact me. And that's it. I'll take any questions. Thank you so much. This was really helpful and very informative. We do have some questions. First, what, if any, role do you see of sex hormones in progression of Neo-A? It's a great question, actually. And so I do think that there is certainly an anabolic component to sex hormones, particularly post-menopausal, that changes. So obviously we know that the post-menopausally, there's a change in sort of estrogen and progesterone and some of the sex hormones concentrations in women. And there is some suggestion that not only does that impact sort of bone health, but that bone that's underneath the cartilage may also be impacted. There are some studies also suggest that there are estrogen receptors on cartilage that essentially, if they're not stimulated, they also impact the health of cartilage. So the reason that women may develop osteoarthritis at a higher rate than men may not just be a sort of mechanical reason because of anatomy, but it also may be due to a biological reason. So that's a great question. That's interesting. I think there's a lot about cartilage, I think, for me to learn. I think for everyone to learn. Absolutely. Another question. So you noted the impact of rehab and exercise on some of these biomarkers you were referring to. Any research on mental health or stress management on some of these same biomarkers? Yeah, so there is some studies suggesting that, so IL-6, which is commonly an acute phase reactant, cytokine, is also a biomarker of stress, I mean, sort of mental health type stress. And so there are studies suggesting that individuals with high levels of IL-6 at baseline tend to have potentially a worsening response to sort of pain management treatment. There are some studies, particularly in the spine literature that have shown that. So that's actually an interesting thing to look at. So yeah, there potentially are. One of our studies, we did actually measure endorphin levels with exercise and see if there's any relationship with outcome. And we did find that individuals who exercise tend to have higher levels of beta-endorphins, but we didn't correlate it to symptoms. So, but I think, yes, I think definitely individuals with high inflammatory load, particularly IL-6, it's suggestive of those who tend to have higher levels of mental health strain or stress. Interesting. So from a practicing sports medicine physician, he says he worries a lot in some of his athletes, he worries more about knee valgus than varus and focuses on hip abduction. Is lateral knee OA more common in athletes or is there something else you might attribute to the difference? As far as I'm aware, I still think it holds the same. I think that's a great question though, because it's probably more challenging to manage someone with lateral knee OA, just because it's not as common in my experience, at least. And most of the biomechanical strategies that I just talked about are really targeted more towards medial knee OA. And so that's what makes it probably a little bit more challenging to manage sort of lateral knee OA. So I think there aren't, as far as I'm aware, I don't know if there are differential studies looking at in athletes, comparing the incidence of lateral versus medial knee OA, just most studies, just epidemiological studies have in general found higher levels of medial knee OA, but that's a great point. And I think one thing we didn't mention that the question really brings up or the person asking the question brings up is also everything's connected. So when we're managing knee OA, we're not just talking about managing the knee, which I focused on today. We're also managing the hips as well and the ankle. And so those are important things to remember when you're managing. I'm evaluating those things as well in my patients with knee OA. That's a great point as well. Are you familiar with the GLAD program for OA? Any thoughts on that in terms of approach to exercise? I'm not aware of that. Does the speaker wanna elaborate? Oh, the person asking the question wanna elaborate? I don't know that program myself. We'll give him an opportunity to kind of tell us a little bit more about it. If not, maybe he can reach out to you after the- That sounds great. Yeah, that sounds great. One more question that came up just as kind of I was thinking about this. I was thinking about the correlation between obesity and knee osteoarthritis, the prevalence of medial knee osteoarthritis, but also the correlation between obesity and pes planus in general. And I would anticipate based on some of the mechanics that you were going into, that pes planus and just kind of hyperpronation in general would tend toward a reduced KAM, right? The knee abduction moment, and then would kind of reduce or kind of push the opposite direction of the medial knee? Yeah, that's a good question. Honestly, I'm not sure about that. I haven't done with sort of obesity and medial knee OA, hasn't really been a focus of a lot of the treatments. I really don't, I haven't used as many of the joint loading strategies with my obese population, I'll be honest. I tend to talk more about sort of the exercise strategies we talked about and weight loss strategies, rather than because they, in my experience, getting individuals to sort of buy into many of the biomechanical strategies are tough enough as it is, that getting someone who's overweight to do that can be really challenging. So I'm not aware of that as well, of how the biomechanics change when you're talking about what you're describing. It's a great point though, but that's definitely something that we can look at as well. Well, thank you. We have a couple of questions about enzymes. I think we're about out of time. I don't know if you want to address these briefly. Yeah, sure. Yeah, no problem. So one is addressing kind of the use of NSAIDs, reducing inflammatory mediators and enzymes. Any thought as opposed to, for opposing the use of NSAIDs to allow enzymes to kind of debride the knee? Yeah, so this really comes down to the big question, which is always, is inflammation necessarily a bad thing or a good thing? You know, inflammation is important for repair. In people with knee OA, I would say overall, they probably have a overload of inflammation. So particularly when they're far down the line with knee OA, that's fine. One thing I want to make clear is that when I talk about anti-inflammatory, so NSAIDs, they're not really targeting the degradative cascade. They're really targeting the inflammatory.

knee osteoarthritis

management

exercise

pharmacological treatments

regenerative medicine

biomechanics

weight loss

physical therapy

research