What type of osteoarthritis do I have? with Prof Francis Berenbaum

hello and welcome to this edition of joint action [Music] this podcast is dedicated to all those out there who have osteoarthritis on the show we unpack the truth and demystify the myths about the disease and its management if you have joint pain and want to know more about how to manage it from the world's best experts you've come to the right place without further ado it is time to welcome your host david hunter hello and welcome to this edition of join action this week we have the privilege of talking about osteoarthritis phenotypes many people wonder

why they got osteoarthritis why it differs from someone else with osteoarthritis and why sometimes it responds to treatment for you where it doesn't for someone else for anyone who has osteoarthritis there are many reasons why it might develop in the first place the progression of the disease can vary dramatically between different individuals and their response to different treatments can similarly be quite distinct with a greater understanding of the genesis of osteoarthritis osteoarthritis can often be described as a spectrum of disease composed of different phenotypes some people have even described this as a mixed bag of

disorders all falling under the osteoarthritis umbrella by characterizing osteoarthritis into phenotypes it helps to improve our knowledge of the disease and ultimately enables targeted treatment based on the phenotype that a patient presents with on this episode of joint action we will be speaking to dr francis sperenbaum to learn more about osteoarthritis phenotypes how they are identified and how this affects the management of osteoarthritis dr berenbaum is professor of rheumatology at sorbonne university and is the director of the department of rheumatology at saint antoine hospital in paris france he's the national representative of bone and joint

diseases at aviasan the french alliance for the life science and health dr berenbaum leads an experimental team at the insome institute his basic research institutes include the understanding of relationships between metabolic diseases and osteoarthritis and his clinical research focuses on new targeted therapies for treating symptoms and structural changes in osteoarthritis hello and welcome to the show francis and thank you so much for coming along hello david a pleasure to be here thank you now it's it's great to have you on the show today francis but before we actually get into the main content of today's

topic i just wonder if you could share with the listeners a little bit more about your background and what a typical day looks like for you yes i'm a rheumatologist so i'm at the head of the department of rheumatology in paris sorbonne university saturn hospital and i also have a research team working on osteoarthritis looking for new targets based on animal models cell culture and so on so i have both hats i would say a typical day starts around 7 30 i arrive at my office i take a coffee and then i have two hours

which are very quiet the quietest period of the day and so that's the time where i look for emails with fast answers and i look at some table of contents of journals to pick up some interesting news in the field uh not only in on oa and not only in the field of rheumatology and then for the rest of the day it really depends i have an outpatient consultation two times a week i have also some addition works because i'm an associate editor of the announce of the rheumatic disease for the lab i have the

lab meeting journal clubs and so on so that's fantastic because there is not one day which is like the next so um yeah very very exciting variety is the spice of life and i'm i'm sure as we both mature in our careers having that variety is is fantastic oh yes really now more importantly when you're not doing your day job what is it that you like to do i like cycling i started not so long ago maybe it was less than 10 years ago because i was repeating to my patients you should do cycling and

so on but i didn't so i started citing by by myself and then i really liked that it's outside and and so that's what i prefer and i also like cooking but really cycling is not sport it's physical activity cycling yes yeah i know it's it's it's wonderful i um have been a road cyclist in triathlete for many years when i was much younger um and actually was fortunate enough to spend a bit of time in france and have climbed up one of your sacred mountains called but more recently i've actually taken up mountain biking

and i love it just being out there wilderness it's superb now francis if you had to describe yourself in five words what would they be that's really a very difficult question so i will pick up five words that comes from my friends and family so of course it's quite positive i'm not sure that that's always positive but the one i would pick up is first i'm very optimistic always even if there is something quite negative i'm very very optimistic enthusiastic also because i do what i love innovative also i like having some crazy ideas and

then uh tolerant and sociable that's the words that comes from from my friends once again for my enemies maybe not the same i think it's good good to listen to your friends and good to listen to your enemies in very small doses but i think the optimistic innovator are some great great qualities for someone who's engaged at the front of their field as you are francis now before we get into the main content of today about phenotypes i'm just wondering if you could actually start by explaining what that term actually means so what is a

phenotype so maybe you have blue eyes i have grown eyes this is a different phenotype so this is very simple example for disease it's the presentation of the disease the the definition of a phenotype so it could be a characteristic it could be a trait it could be a behavior whatever the difference will be a phenotype it's what you observe this results on different possibilities for phenotyping someone and also this is resulting from the genetics from the environment and so all together this this is the definition of a phenotype so that's a great explanation now

you've been pivotally involved in this field for a long while and really been leading some important work around metabolic or inflammatory changes that occur in the context of osteoarthritis now there's been a well-established link between being overweight or obese in the development of osteoarthritis and weight-bearing joints like the hip or the knee can you explain to us a little bit more about what is the metabolic osteoarthritis phenotype and how it is associated with the development of osteoarthritis yes this is a long long history in fact maybe 20 years ago osteoarthritis was seen as a disease

of tear and wear only and so when you have overweight of course this will increase the pressure on the cartilage and so you have the consequence which is osteoarthritis and 20 years ago came the discovery that the adipose tissue from obese patients was able to release inflammatory mediators inflammatory molecules inflammation into the blood and at the same period maybe 15 years ago or something like that came the first epidemiological studies showing that the patient with obesity had two-fold increase in symptomatic hand osteoarthritis so these two new discoveries lead to the possibility that the inflammatory molecules

coming from the adipose tissue from the fat tissue was able to reach the joints and by this way could lead to inflammation into the joints leading to the osteoarthritis so this was the first step in this story and then maybe you you are aware that in fact having obesity could also be associated with other metabolic factors the metabolic factors are the factors that could lead to cardiovascular problems and these factors are diabetes hypertension repeat abnormalities and there are some cohorts of patients showing that the patient with these metabolic factors have an increased risk of osteoarthritis

over the obesity and by this way came the hypothesis that these metabolic factors could have an independent impact on osteoarthritis so this is really the the story leading to this phenotype of oa that is metabolic osteoarthritis what we have just to keep in mind that the majority of the studies of these studies were in symptomatic osteoarthritis meaning the patients with pain into their joint and now it's possible that this specific phenotype could really due to the pain meaning the association could be with the pain and we know that the patient with obesity have an increased

sensitivity to pain so we do not know a lot about pain in a way which is very strange because this is really the the main feature of this disease and the reason why the patient with oahuf pain is very not well known and this aspect now is in the research in order to have a better understanding on that yeah so important and as you've just alluded to a lot of these discoveries both around the importance of the mechanics of obesity the consequences in terms of inflammatory molecules and other associated uh conditions like diabetes high blood

pressure and high cholesterol have all really occurred over the last 10 to 20 years but as you're just alluding to there's also a lot more that we don't currently know both about the onset of pain and what can be done about reducing the impact of those metabolic changes now once as you've discussed metabolic osteoarthritis but are there different types of osteoarthritis other than that yes as a very easy example is the past trauma osteoarthritis if you have a ski accident at 20 years old you may have a problem on your ligaments or meniscus instability of

the joint or leading to a meniscectomy meaning you release a part of the meniscus and then some years after that trauma this could lead to uh osteoarthritis and so that's what we call the past trauma oh this is really one other phenotype aging also it's a disease which is correlated to aging of course and this also could be a specific phenotype in the sense that not being too complicated but by research we know now that there are some cells that could be old that what we call the senescent cells and these old cells are able

to release mediators uh molecules that could have a deleterious impact on the joint so there are this kind of phenotypes based on risk factors that's fantastic and you know i think it's i guess most important to one for the listeners out there to understand that there's lots of different ways a person can get to that development of osteoarthritis and it's not just by one root and more often than not people have a couple of different types of factors predisposing to their osteoarthritis now how have people gone about identifying these different phenotypes yes so you see

what we have discussed now is a fashion to phenotype which is based on the risk factors we know the risk factors and we consider that one risk factor equal to one phenotype so this is one uh possibility which is based on this epidemiological studies showing that when you are obese you increase your risk of oa when you have a trauma you increase your real risk in a way and so on but in fact there are many other possibilities to to phenotype the patients another way is the localization handaway neo way are two phenotypes this is

another possibility a more recent one has been based on imaging when you perform an mri you see that in some patients there is some abnormalities into the bone what we call the bone marrow lesion and some patients have more inflammation in the sign of your tissue the membrane which are around our joints and these are two possibilities two phenotypes one bone phenotype the other one is the sign of your phenotype there are another possibilities which are the progresses what does it mean if you take 100 patients with oa after five years only 20 will progress

in the disease 80 will not progress into the disease so these are two phenotypes the progressors and the non-progressors so you see that this other possibility to phenotype the patient all these opportunities for phenotyping the patients are based on hypotheses so that what we call the hypothesis-driven phenotyping but now there are new methodological possibilities new statistical possibilities giving the possibility to phenotype to grouping the patient without any hypothesis and this is very complicated to explain how but just you give to the computer many many variables many many parameters of the patient and at the end

the machine the computer is able to group the patient because they are very close each other and in fact sometimes this could lead to a new phenotyping which is not based on your hypothesis and this is very very interesting because this really opened your mind on what could be the oa process yeah and it's so important and particularly the latter part of what you were just saying there with regards distinguishing between i guess historically the the traditional way many people have defined these uh groups or phenotypes of people has been based on their own theories

their own hypotheses but more recently using data and as you suggested machine learning methodologies to identify those phenotypes where it obviously is not necessarily dependent upon a scientist or an investigator's beliefs about what is causing the disease are we finding much if any difference between the historical ways of defining the disease using theoretical or hypothesis-driven research versus uh the machine learning methodology for instance so i think we are at the beginning of the story what i have in mind for that is for the pain phenotype because the people with osteoarthritis have different sort of pain

it's not always the same fashion the patients describe their pain and where is the pain whether it's only on the joint or whether it's more widespread pain and so on and i think that we are doing progresses in in the field of non driven hypothesis phenotyping in this field and so this could have a big impact because then you can choose the pharmacological and non-pharmacological approach of the patient based on this new phenotyping way so i think this is one example easy to to to understand i think that we are really going to a more

personalized medicine in the field of oa also thanks to these new methods to find this new way of phenotyping the patient yeah that's superb and i think it's a good segue into where i wanted to go next so you're someone who both does research but also works as a clinician and with regards to the phenotyping methodologies themselves has they changed at all the way your clinical practice runs has has it had any impact in terms of what you say to patients in terms of how they develop disease the prognosis or the progression of the disease

or the selection of treatments that you use in clinical practice yeah of course today tomorrow we will see but but today the fact that we are able to phenotype the patient according to the risk factor lead to the possibility to treat the patient according to these risk factors so the messages will not be the same if you are speaking to a patient with a metabolic or phenotype compared to someone with a past trauma or a phenotype just this example of course for the trauma you will try to find ways for preventing the trauma it could

be in sports it could be at work whereas for the metabolic phenotype of course you will work a lot with the patient in order to to find ways for weight loss to increase the physical activity so the ways you will speak to the patient give advices to the patient will be based on this kind of phenotyping that's based on obviously our existing knowledge about the importance of those different phenotypes and as you just alluded to obviously influences the way you both communicate to the patient but also the selection of treatment now you've given us a

great overview of the different phenotypes that are out there and how they've been identified is there anything that listeners out there with osteoarthritis or without osteoarthritis can do to reduce their risk of having an osteoarthritis phenotype or if they do already have reduced their risk of developing osteoarthritis completely oh oh yes a lot to do and not not based on drugs in a way overall the way to decrease the risk of progression of a way or initiation of a way is based on non-pharmacological advices and treatment the first one is the physical activity now it's

very very well known that whatever the phenotype the physical activity will have a positive impact it will have a positive impact for pain it will have a positive impact on inflammation a positive impact also in order to to resume a sport once you have a trauma and possibly this is not sure but possibly also it could delay the process of away so all together the first message is moving moving moving this is very very important of course when you are in a flare of the disease this message could be difficult to listen and at this

stage of course when you are in a flare you you will decrease your physical activity but i this could be completely understandable but just to keep in mind that once the flare has finished then it's really important for your joints that you resume physical activity and the second message is to eat healthy in order to have the right weight and maybe more than that because we do not know everything around what you eat and the consequence for the joints but it's clear that this is a very very important so the two messages are here the

physical activity and to eat healthy then the drugs uh nsaids analgesics and so on will just be there when it's a flare or something that's really neat for just a couple of days to have a an effect but just keep in mind that the most important way is the non-pharmacological approach so important for everybody to hear is that you know those core treatments that we speak about for osteoarthritis are eminently applicable to someone who's at risk of developing the disease very much focused obviously on keeping people active and trying to attain a healthy weight as

well now is there anything else that you wanted to say about the phenotype topic before i move on to probing you a little bit more with some more provocative questions i think that we have to to be very positive for the future because we now have very new methodologies very new ways to phenotype the patient that's what we call the androtypes that means that now we can go up to the the tissue to the cells in order to see how the cells works and maybe the the cells from one tissue of one person works in

another way than another patient in the same tissue and the same cells it means that we can find what we call signatures like for the tumors in cancer we are now able to find specific signatures of the tumors in order to give the right drug and now in many many chronic diseases and oa is part of that we try now to find these new signatures into the tissues leading to a new ways for phenotyping the patients and all together maybe it will be in ten years i don't know but in a whole couple of years

i don't know but with these progresses you will have what we call the deep phenotyping so it means that we will integrate all the environment factors around a patient everything also the dosage in the blood and so on and in parallel having the signature of the tissue and all together with this new very modern methodologies all together this will lead to very very accurate phenotyping of the patient one patient with one phenotype and then one specific ways to personalize the treatment i think this is really the future yeah it's very exciting and as you just

alluded to the um the scientific ability to do that is already with us but the roll out of that to the individuals that come along for clinical practice is another thing altogether so maybe a couple of years away yet now again just more in closing and this is me just trying to learn a little bit more about you frenzies but if you could do anything to improve health and healthcare what would you do to improve health i think that i will try to give the message that it's very very important to consider osteoarthritis as a

whole of a person it's not just the joint is the whole person and once again having this physical activity having these healthy meals non-smoking not drinking too much and so on all that will have a positive impact on your health and then you will see the life really different i know that it's not so easy when you have these habits but step by step not by changing everything on one day but just very little steps very little steps then the result is here yeah simple advice but hopefully many people out there will lead that now

how do you continue to learn in order to stay off of things within your role to continue to learn we have to keep interactions to keep to discuss read read read i think this is very very important and discuss discuss and discuss again and with your colleagues with your patients because you're with your patient you can learn a lot also because we discussed on pain as an example the fashion that the patient explained their pain will give you a lot of information that will help you then in your research so this is so important to

keep all these interactions not only being in your office on that seat but try to discuss with the patients and your colleagues very very important that's the reason why of course we are so disappointed today uh with this epidemic leading to much less interactions due to the all these meetings and so the interactions are not so so high but we try to keep that but this is really frustrating yeah yeah oh it's uh as you say it's changed a lot with covert and shifted more online and obviously like this podcast we're using different ways to

communicate but it's not not quite the same as the real thing face-to-face and i look forward to seeing you again soon at some point in a conference in the not too distant future but without a personal interest why do you do what you do what motivates you ah that's a very good question i think my motivation was first that when i was 10 years old i heard about uh cardiac transplantation for me it was incredible amazing and so that was my first motivation was to try to to do something for the patient and then because

of of interaction with my patients and and specifically in in the field of osteoarthritis they are so disappointed because they heard a lot of discoveries in many other diseases and they really suffer from from their disease because they are they consider that they're really isolated the media the politics are not really considering osteoarthritis as a problem and of course we know by speaking with them every day that the quality of life is so disturbed by the disease so my motivation is to find new ways to decrease this impact of the disease so important that we

listen to our patients and it sounds like they've been wonderful advocates both for their own disease but hopefully also their peers in stimulating you to make some of the important discoveries and work that you're doing both in the research and the clinical space now just in closing francis is there any one piece of advice knowledge or wisdom that you'd like to give to people out there with osteoarthritis yeah my advice is you don't have a disease of an old person you are not old because you have a way oa is really a disease it's not

the equivalent of wrinkles or the white hair it's not a fatality yeah things can be done to fight the disease and these things to do are much more efficient that what we what you could think it's not because we do not have drugs that it means that there are nothing to do so please keep that in mind it's not a fatality and that's a great way to finish it sounds like your optimistic tray shone through in a very positive closing there francis really really appreciate your time and thank you very much for spending a little

bit of time with me and discussing a topic that you are leading in this field thank you david it was really a pleasure to be with you do you know what type of osteoarthritis you have and why it developed have you been less responsive to some interventions than you otherwise might have expected osteoarthritis phenotypes are observable characteristics of a disease with the implication of a mechanism that might play a role in disease development or its progression there are different types of phenotypes including metabolic dramatic and aging the identification of these phenotypes will lead to targeted

treatment in osteoarthritis and hence we need a much better understanding of phenotypes thank you very much for joining me this week thanks for listening to joint action with david hunter if you like our show and want to know more check out www.jointaction.info if you have any questions you can email us at hello at joint action.info and follow us on twitter at jointactionorg this podcast was hosted by david hunter edited by vicky dwong music produced by jordan hunter the information posted on this podcast is not intended to diagnose treat cure or prevent disease anyone seeking medical

advice should consult a health professional you