Become a Creator today!Start creating today - Share your story with the world!
Start for free
00:00:00
00:00:01
Associations Between Periodontitis and Rheumatoid Arthritis with Dr. Jeffrey B. Payne
98 Plays11 days ago
Listen to Dr. Effie Ioannidou and Dr. Jeffrey Payne discuss the associations among periodontal pathogens, serum antibodies, and rheumatoid arthritis. In Dr. Payne's study, researchers assessed serum samples from individuals with rheumatoid arthritis and osteoarthritis controls to investigate the relationships between periodontal health measures, alveolar bone loss, and antibody levels. Listen in for a fascinating discussion!
Read the full article here. https://aap.onlinelibrary.wiley.com/doi/10.1002/JPER.23-0604
This podcast is produced by the American Academy of Periodontology (AAP). To learn more visit perio.org
The views expressed in this podcast episode are those of the participants and not necessarily those of the AAP.
Music Credit: Groove Nation by OctoSound
Recommended
Transcript
Introduction to Periodontal Research
00:00:00
Speaker
Whether you're in training, in practice, or in research, the Journal of Periodontology and Clinical Advances in Periodontics have something new for you.
Biological Plausibility: Periodontitis & Rheumatoid Arthritis
00:00:34
Speaker
Hello, everybody. ah Today we are discussing how exploring the biological plausibility behind the association of periodontitis and rheumatoid arthritis ah becomes a very interesting topic. So hello, I'm Dr. Efio Anido, the editor-in-chief of the Journal of Periodontology and the Clinical Advances in Periodontology, and I'm here with you at Probing Perio. This is amazing. The podcast that explores and dives into the clinical and translational work in periodontology and implant industry. Friends, colleagues, residents, ah membership of the AEP. If you have ah enjoyed Probing Perio, please help us by rating the podcast, Apple Podcasts, Spotify, or wherever you listen to your podcast.
00:01:30
Speaker
And please leave us a review. This is really important to leave a review. It's important for us to communicate with you, get your feedback, improve, and and bring to you back great episodes. and What an honor honor to have today here.
Guest Introduction: Dr. Jeff Payne's Research Journey
00:01:44
Speaker
An amazing guest. um The paper that we have selected from the October 2024 Journal of Periodontology issue, um Dr. Jeff Payne from the University of Nebraska.
00:01:59
Speaker
It will be a great conversation because we are going to dive into the association and the biological plausibility between periodontitis and the rheumatoid arthritis, a discussion that has started maybe 100 years ago in the speaks the big spectrum of the connection between oral and systemic diseases in the field of periodontology. And I think it has expanded in many different directions. I think today,
00:02:27
Speaker
We are talking about the association. Perhaps we are touching upon the causation too. It will be a great discussion. So let's kick it off and let's introduce the senior author of the paper, Dr. Payne. Again, University of Nebraska. ah Welcome to Probing Periods F.
00:02:45
Speaker
Oh, thank you very much. It's an honor to be here, and I'm looking forward to our conversation. I know. I love it. It's exciting. ah But before we start, um we we have kind of decided not to introduce our guests and give their bio, but allow them to speak for for themselves. So tell us a little bit about you, how you started with Pero, where you train, what you do in Nebraska, and just a brief short bio.
Research Collaborations and Methodologies
00:03:11
Speaker
Sure. I went to dental school at State University of New York at Stony Brook School of Dental Medicine. I did research at Stony Brook with Vince Iacono when I was a dancer. Oh, wow. So we did some salivary research on histidine-rich polypeptides. I then went to Yukon, where I trained. And obviously, we have that commonality. Yeah, they do.
00:03:35
Speaker
And Frank Nichols was my ah my advisor for my graduate research. I did work on monocyte secretory function ah with with Frank. i you Frank hasn't changed, by the way, parentheses. Whoever the listeners that are out there and know Frank Nichols, he hasn't changed.
00:03:54
Speaker
A bit. he is exactly He looks exactly the same as he used to look in the 80s. Which is pretty extraordinary because I know that. I haven't seen him for a while, but we speak on the phone periodically. and He hadn't grayed the last time I had seen him. I don't know if his hair is still dark, but it's pretty amazing he maintained. I mean gray. Yeah, a little bit. Okay. Yeah. um But we worked together, published some papers in some good basic science journals. And then I stayed on for two years and what Frank calls his informal postdoc with me. So, yeah um and then I went to the University of Nebraska Medical Center back in 91, where I carried out some additional work on monocyte secretory function in response to tobacco, ah smokeless tobacco and nicotine.
00:04:41
Speaker
and then went to the NIDCR Clinical Research a Symposium back in like, I think it was 96, January of 96, and decided to go in in a more clinical direction. I collaborated with Dr. Larry Golub for many years. We had a clinical trial on low dose taxi cyclin in osteopenic women. um and And during that same time, I ended up establishing a collaboration with a rheumatologist at UNMC, Ted Michaels. And interestingly, that began
00:05:16
Speaker
when I had gone to a tetracycling conference in in Garden City in Long Island and I met Jim Odell at UNMC who's a prominent rheumatologist and he ultimately introduced me to Ted and and the rest of it is is kind of history. We've been collaborating for about 20 years And that collaboration with Ted Michaels led us to this publication that we're going to talk about today. Yeah, that's an interesting publication. But, you know, it isn't amazing how, you know, I think this is a ah point that we should make for ah junior investigators, junior faculty.
00:05:54
Speaker
uh perhaps graduate students you just mentioned that's that's such a long story right it has been very long
Study Hypotheses and Logistic Challenges
00:06:03
Speaker
collaboration 20 years working on the topic so because people now nowadays the the younger generation if you will they are so used to this kind of speedy feedback and speedy um lifestyle that they think that you know research and and and ah investigative work can be equally speedy, but it takes time, right? Well, it's really interesting you say that because I think back to my collaboration with Ted, you know, you came down to Lincoln, he and Jim Odell back in 2004. Our first paper wasn't published till 2009. Right. It just turns out getting things off the ground.
00:06:40
Speaker
Our first grant was not funded till 2010. So you're looking at a six year lag there. yeah So um patience was important. um We knew we're we were going on the right path and and and it's just taken a while, but it's been very fruitful. So sometimes um that gratification has to be delayed a little bit.
00:06:59
Speaker
Yeah, no, very good point. Absolutely, I agree. ah but Patience and perseverance. Right, right. night having Having thick skin because... And thick skin, resilience. Yes, yes. Yeah, never give up. But anyway, so tell me a little bit about, let's discuss ah how the ah you you gave us now the background of the team, how the team came together and how come you came up up with the idea.
00:07:23
Speaker
But I would like to hear a little bit more um about the the the story and specifically about I was very interested in the location, the fact that you decided to do the Durand study in the VA and obviously the University of Nebraska. But give us a little bit of the behind the scenes.
00:07:39
Speaker
Sure. um So um Ted Michaels has an appointment at the VA, and I've done some consulting at the VA. And during the course of our funding, we had some of our funding from the Veterans Administration. I had a research appointment there as well. So that appointment sort of opened the door to some things.
00:07:57
Speaker
And they enabled us to get funding ah through that mechanism. So TED-Ed collaborators at the Dallas VA, Salt Lake City VA. Yeah, you have four sites in the VA. That's great. And OMA, which was really great. And then, you of course, UNMC, where we saw 200 of the 617 or so patients in that clinical study.
00:08:18
Speaker
The challenge in doing a multi-center study is getting everybody on board. And and as you you see in the paper, you know we had clinical measurements that were made. um I calibrated all the examiners. Everybody flew to Omaha. ah We had calibration here. um Radiographically, we used panoramic films um because it was easier to calibrate on those. And our radiologist on the study, Dr. Shawning Gonzalez, traveled to each of the study centers to calibrate everybody in doing that. So you know you're doing these multi-center studies it's critical to have that calibration. The other thing was we had one dental examiner at each site so that we didn't have the worry of having intra, inter examiner error at the same clinical center. um But yeah, so
Key Findings and Research Narrative
00:09:03
Speaker
that sort of the VA a was really a result of Dr. Michaels work. He's established a registry of ah VA a patients with rheumatoid arthritis. So that sort of got our foot in the door with that.
00:09:14
Speaker
and and And for our listeners, let's go back to the study and just ah highlight for us the the hypothesis. So the the objective of the study was give us a little bit of a brief summary, exactly what you were planning to do, and then we can talk about the findings. Yeah. So what we hypothesized were that periodontal clinical measures we're going to be associated with serum autoantibodies. The autoantibody in this study is is anti-malinaldehyde, acetaaldehyde, and I'll just call that. Two miles of reward here. It's easier. And the the other hypothesis was that alveolar bone loss, um as measured in posterior teeth on panoramic radiographs, would be associated with autoantibodies, tumor.
00:10:04
Speaker
MAH is not used diagnostically at this point in in rheumatoid arthritis, but it is, has been found to be associated with rheumatoid arthritis. It's a biomarker of oxidative stress, which we see in RA. And so um um we decided to look at this biomarker specifically and its relationship to some periodontal clinical measures and measures of alveolar bone loss and some of that was predicated on previous work we had done.
00:10:34
Speaker
And then you also looked, if I'm not mistaken, I put a paper next to me, but you also looked at antibodies to specific periodontal bacteria, correct? Correct. We looked at antibodies to P. gingivalis, P. intermedia, and F. nucleatum, all of which have some association in this relationship between RA and periodontitis.
00:10:55
Speaker
P. gingivalis has a unique enzyme, peptidial arginine deaminase, that results in the generation of citrullinated antigens. Those antigens in susceptible patients can serve as auto antigens and are involved in the pathogenesis of RA. And one of the and and um antibodies that is used in the diagnosis of RA is ACPA, or anti-citrullinated protein antibodies and and the fact that P. ging is the only eukaryot or prokaryotic ah organism that can generate um these citrullated antigens through the enzyme pad.
00:11:39
Speaker
um positions that organism rather uniquely among the 600 or 700 organisms that exist in the royal cavity. P. intermedia also has a role not exactly the same way, but um through production of pads indirectly, through neutrophil extracellular traps. And and F. nucleotum also has had some role, um more so as a bacterial species that co-aggregates with pea change.
00:12:09
Speaker
I just want to highlight here, Jeff, and I really appreciate it. at the the And for again, for readers and for junior authors, I think it's important to to point out how nicely you built up your introduction.
00:12:25
Speaker
Now I speak like as the the editor of the journal. I really like the fact that you ah my my although my my my research is in the perio-systemic broad field,
00:12:41
Speaker
I'm not that informed and you know the the science changes weekly. So I'm not informed about the rheumatoid arthritis specifically on the biological plausibility that you built up here. So I really like the fact that you started with epidemiological evidence and you built up on the why specifically this bacteria, what this means and why you looked at this antibody. So I think it's important for the junior authors to to understand that even the in the studies where you know we look at the associations, it's really important to
Future Research and Gender Considerations
00:13:17
Speaker
bring this piece of plausibility so that the reader can make the connection.
00:13:22
Speaker
Exactly, and I felt you know when we wrote this paper that we have to tell the story yeah because um Readers may not be familiar with this and quite frankly um By not keeping up with this you can get behind pretty quickly So we felt we needed to bring the leadership up and by writing it in such a way that it was clear And and that we had a strong fundamental foundation to carry out the work we did Yeah, that that was great. and We spoke about the the sites. It was a two-year study. Now, in your ah i I don't want to speak about methodology. that Our listeners can can go to the paper and we will have the link on there um on the podcast, ah but but I would like to speak about the results and also speak not only about the major results, but if you had any surprises, like was there anything that you found and you were like, huh, look at this, I never expected.
00:14:20
Speaker
Well, you know I think you know it's interesting. We were debating when we put this together, what should we have as our primary outcome? and And we had some previous evidence that alveolar bone loss was associated with ACPA, the antibody ah that is measured as part of the diagnosis of RA.
00:14:43
Speaker
The fact that this also fit that story so nicely was was a pleasant surprise. The clinical measurements did not associate with anti my antibody. um we We expected that in our hypothesis, but I guess we could say that that's probably related to the fact that there's not a relationship with soft tissue changes. you know yeah um We saw the change in the alveolus, which suggested to us that perhaps the alveolus is acting acting as an extra-articular site or as another joint per se. yeah okay So I think the Alveolar Bone Loss Association was exciting to us. It sort of verified previous work. And I know it's one of those things when you see the results unfold and the fact that
00:15:27
Speaker
Those results diverged between RA and OA patients was the most exciting thing for us. and As you look at the figure in the paper, figure one,
00:15:38
Speaker
um It's pretty compelling in terms of um the antima antibody has a very strongly and statistically significantly positive association with alveolar bone loss, while the OA association is negative and not significant. um you know And the fact that RA is an inflammatory autoimmune disease, OA is more of a wear and tear disease from,
00:16:06
Speaker
um You know, some comorbidities such as obesity. So the fact that if you look at figure one, I remember when we had the discussion in our in our Zoom meeting, because Ted's in Omaha, ah Joyce Lee, who's the resident that I work with, she was a great resident, published a couple of papers during the course of her time here. So when we were discussing these data,
00:16:27
Speaker
hey We started sketching out the results, and we're pretty excited to see the way the data fell out in figure one, that you know there was a definite difference between the RA group and the OA group in terms of the association between antilaw antibodies and alveolar bone loss. For sure. Yeah, I also pay the attention to this figure, and I think it's very informative.
00:16:48
Speaker
um Can you speak a little bit about the selection of the control group? i had ah i was not the you know I completely understand where you come from. As you said, the the rheumatoid arthritis inflammatory disease, you wanted to look at similar condition that doesn't have the inflammatory component and it's the wear and tear of you know the regular osteoarthritis. But did you consider, did you debate about using a systemically healthy group at all as a if you were in negative control?
00:17:19
Speaker
You know, we did talk about that early on when we designed this, but going back to the literature looking at prevalence of periodontitis in RA patients versus healthy controls, if you look at other publications, they were pretty different in terms of prevalence. so we yeah what let's Let's choose a non-healthy control, yeah because if there's truly a difference in prevalence, this was a paper we published in 2014,
00:17:43
Speaker
if in arthritis and rheumatology, if there's truly a difference in prevalence, even in spite of the fact that we have a sick control group. I mean, this control group was obese, hypertensive, diabetic. And in spite of that, we still saw a higher prevalence of periodontitis in the RA versus OA group. And so we're able to find these associations. That was sort of a rationale of not having a healthy control by choosing a non-healthy group.
00:18:13
Speaker
and I like this. And I also like the fact that your population was very pragmatic. The selection was very pragmatic. So you didn't have the sterile non-smokers, non-diabetics, just dermatoid arthritis. And I don't even know if these people exist.
Study Limitations and Future Directions
00:18:27
Speaker
But in theory. So I like the fact that it was ah you know a really a very, as I said, pragmatic selection of of the sample that really reflected the the people that we see out there in our practices.
00:18:42
Speaker
Right. And you know, it's interesting in terms of putting this together because we had the rheumatological side and we had the period on Titus side. So yeah I wrote an operations manual for the period on Titus side. Ted Michaels and his team wrote for the rheumatological side and then we merged them together. And and one of the things that came up was the number of joints, you know, in RA, you're looking at disease activity scores and 28 joints. And I remember when we were putting together the probing depths and and the attachment levels and and so forth. And I was trying to impress upon Dr. Michaels the number of sites we measure in periodontitis. And when when he saw the database, he was ah surprised and overwhelmed by, you know, 20, 18, six sites per teeth. That's 168 measurements for probing depth, you know, recession, bleeding on probing and plaque. So we had a pretty large database for the periodontal measurements, which was much to the surprise of my rheumatology colleague.
00:19:37
Speaker
No, I think that people that are not familiar with a mouse yes um I think they are shocked when they see the first spreadsheet with exactly what we measure, how many variables we have, how many sites, what the numbers mean. And and then and I find that it's amusing when when you start collaborating, for example, with a biostatistician that has never done oral orally health research and they're like, wait, what?
00:20:08
Speaker
Exactly. exactly and And we've been fortunate to work with statisticians over the years who've done quite a bit of training for them to understand how these sites are in the same person, but act independently of one another, which makes our work very unique. No, it's really um it's really interesting. so um I would go back and and now you will understand why I brought up the VA. So when I was looking at the table ah for with my little knowledge on rheumatoid arthritis, I said, wait, isn't this more prevalent on female patients? I yeah remember that. so um And I know that you bring this up very nicely in the discussion and the limitations. And again, I want to highlight the fact that you built up a very nice conversation there in the discussion and you highlight
00:20:59
Speaker
very I always give ah advice to junior authors and I say in the discussion you have to be true to yourself and and and you know compare yourself ah to the to what is out there. and they And you acknowledge this and I'm sure it's a limitation that comes out of the selection of this. ah you know The VA traditionally has probably more um I want to assume more male patients. than That's correct. that's correct so So tell me a little bit how um what are your thoughts ah about future approaches and if you think that this might be um an important factor to ah to to examine in details.
00:21:39
Speaker
Yeah, I think it's an important factor. You know, it's interesting. I think we found 62% of our patients, I believe, were were male. Yeah. In in in the um general population, it's a three to one ratio yeah prevalent female to male. So, um you know, the outcomes could very well be different, you know, in in female patients.
00:22:01
Speaker
um So by using a VA population, that's a limitation, but also gives us some insights into the disease in a population that's predominantly male. But I agree with you that if the opportunity were to arise, that investigating a population that represented the general population better would be optimal.
00:22:22
Speaker
You know what, I give you an idea. Since you have so many patients, how about you go back and you do a secondary data analysis and you ah and you see how stratifying by by but sex biology and maybe see if there are any differences. And I know that you used sex and gender in the, um in them I think so, in the regression analysis probably.
00:22:46
Speaker
But I think it might be interesting to test this in the data. I mean, it will be another paper. Bring it to JPerio. Right, right. thank you You've got a good point there. um That's something when I have my next Zoom meeting we can discuss. I know we'd be underpowered, probably. Probably, And you're absolutely right. It's something that we always say that you know if if you have something in mind like this, it's always important to plan for this ahead of the game. But but ah you know as an exploratory analysis, it may be worth it. I don't know. I thought when I was reading in the paper, I'm like, ah, you know, this is
00:23:22
Speaker
There is something here, and like I know that it's, as we said, 3 to 1
Research Contributions and Career Impacts
00:23:27
Speaker
ratio. Here it's the reverse, but um still you find the evidence of bond laws associated. So who knows what you will find if you stratify.
00:23:37
Speaker
Right, right. I know I agree that's certainly worthy of of looking at it, you know. Yeah, so our population is is pretty unique in that regard, because if you look at most of that literature, you'll see a female preponderance. But any work with the VA population is just going to be, you know, the opposite of that. Yeah, yeah, for sure.
00:23:55
Speaker
Do you think that that is there anything else that you would like to point out about the paper? any um ah You said that the the first author is a resident, has graduated. Is he staying in research? Is he going to practice? like Because when you when they get this flavor and the taste of what it means to go through this and put it out in the publication, I think it's it's very ah satisfying. so Yeah, I know. i know you So the resident is Dr. Joyce Lee. She finished in June of 2024. She's practicing in St. Paul, Minnesota. She published another paper prior to this in in in a rheumatology journal ah that we published with a different database. So Joyce learned a lot in her three years. But the problem we're finding with students is you know they have such a huge debt load.
00:24:49
Speaker
of they feel they have to go into practice to sort of offset and they always say to me well maybe in 20 years off you know I have to give you ah ah to to kudos for the fact that that ah she was able to work so hard and be committed and put two papers out many residents to some, ah you know, perhaps a little bit lighter research work during residency and there is no hard outcome out of it, right? There is maybe a thesis or something that states in turn that this work is really, i have to I have to congratulate both you as a mentor and her that was persistent to do this.
00:25:25
Speaker
Yeah, and I appreciated her drive in doing this. You know, she also won the Clinical Research Award at the poster competition at the AAP meeting. I'm excited. And the Clinical Impact Award too. So, you she worked really hard, as you know, in a three year residency when the clinical demands are so high.
00:25:42
Speaker
She spent a lot of time on evenings and weekends and and working together with me on this.
Conclusion and Listener Engagement
00:25:47
Speaker
So I was obviously very proud of her um for accomplishing that goal. Obviously I worked hard with mentoring her, but it was good to have a solid student to work with.
00:25:57
Speaker
This is great, and I'm glad that she had the recognition at the AAP for her work. That's great. Listen, Zef, this was a pleasure. I really enjoyed it. I hope it was informative for our audience, too. I don't know if you want to say anything in the conclusion.
00:26:15
Speaker
Um, yeah, I said this, this work, you know, we've enjoyed doing this. Um, we have another study with another resident. I can't give too many details at this point, but we're looking at, um, additional biomarkers in this patient base so we can further elucidate this mechanism of this very intriguing association between periodontitis and rheumatoid arthritis. bring it the do j perio By the way. Okay. please do This is good work. You guys are great team. It's going to be nice.
00:26:43
Speaker
ah probably a couple years away but yes we are here we're not going anywhere we are next year we are celebrating the 95th so yeah 95 years journal of periodontology which is incredible it's incredible for sure thank you Jeff thank you so much this was a pleasure um People that are listening, don't forget to like the episode. Don't forget to share it with your friend. Subscribe to the podcast. Do everything that you need to do. Let's work on promoting the Journal of Periodontology. Send us your reviews. Send us your ideas. Follow us on social media. Thank you, Jeff. It was a pleasure to have you.
00:27:22
Speaker
It was a pleasure for you to include me and I want to congratulate you and your team for the work you do for the Journal of Perio and and why it's one of the it's the preeminent journal in our field. Thank you. Thank you so much. Thank you. Thank you for joining our episodes today. If you like this episode, share it with a friend. Don't forget to subscribe to the podcast wherever you're listening so you get the latest episodes.