This is Dr.Young.
It is truly rare that a scientific journal like the Journal of Periodontology will publish a tribute edition to one man but it did so recently. I find these types of publications extremely useful because they give me an opportunity to step away from the monthly publication of research and look at it from the perspective of an individual scientist/researcher’s life or career. Also, it helps link different studies which may at first-view cause students and clinicians to question their benefit and allow them to be able to see them in a deeper context. Plus, sometimes a single researcher will move from one area of interest to another and it may seem sudden, but understanding their evolving understanding of the principles behind their research can help us begin to see what it was they saw and that there are principles and links behind things we never before knew existed.
So, what I would like to do in this podcast is to introduce you to a man who passed away in 2018 and who has been credited by the periodontic scientific and academic community as the Father of Periodontal Medicine.
His name is Steven Offenbacher and he was born in 1950. In August 2018 while on a vacation cruise he passed away suddenly. On October 4, 2019 in Chapel Hill, North Carolina where he had been working within the dental school, there was held a day of celebration consisting of presentations on research by some of his colleagues and former residents which was then compiled into the tribute edition recently published this October 2020.
I did not know Dr. Offenbacher personally, but I do know many of the others who wrote about him and who are also tremendous scientists and periodontists who have influenced me more directly. However, I have been impacted by this gentleman’s research along with the entire specialty since my residency days in the mid 1980’s.
Now, it is completely understandable if you, who are listening to me, have never heard of Dr. Offenbacher, and this simply reflects the importance of specialists like myself to sometimes provide an introduction. It isn’t important that you will necessarily remember his name later, but I would like all of us to better appreciate where some of the information that has been discovered over the past many decades in the field of periodontics that have actually contributed to other areas of dentistry and medicine has come from.
After completing his undergraduate degree at Boston University, Dr. Offenbacher received his DDS and PhD degrees in a combined program at Virginia Commonwealth University/Medical College of Virginia. He then returned to Boston for a periodontology certificate, an MMSC degree in oral biology, and a postdoctoral fellowship in pharmacology at Harvard University and Forsyth. During his time as a junior faculty member at Emory, he worked along with others on the pathogenesis of periodontitis. Pathogenesis is defined most simply as the manner of development of disease. What are the steps that take someone from health to a specific presentation of disease? His work ultimately culminated in a reclassification of periodontal disease as an inflammatory disease. This moved it from being an infectious disease or caused principally by certain pathogenic bacteria to being a destructive process involving the interaction of bacteria with the body’s immune response. At the same time, he began to extrapolate his studies of oral infections in animal models both pregnant and non-pregnant to ask the question whether maternal periodontal disease (periodontal disease in a pregnant woman) might increase the risk of preterm birth, smaller than expected for their gestation age deliveries, and pre-eclampsia.
Pre-eclampsia is a potentially dangerous pregnancy complication characterized by high blood pressure.
Pre-eclampsia usually begins after 20 weeks of pregnancy in a woman whose blood pressure had been normal. It can lead to serious, even fatal, complications for both mother and baby.
There may be no symptoms. High blood pressure and protein in the urine are key features. There may also be swelling in the legs and water retention, but this can be hard to distinguish from normal pregnancy.
Pre-eclampsia can often be managed with oral or IV medications until the baby is sufficiently mature to be delivered. This often requires weighing the risks of early delivery versus the risks of continued pre-eclampsia symptoms.
Dr. Offenbacher was the first to establish that periodontal disease is an independent risk factor for abnormal pregnancy outcomes in humans.
How can this be? Well, when the mother has advanced severe infections and inflammation occurring in the mouth, it easily moves into the blood stream and begins to affect the biochemistry, including hormone production related to the pregnancy. I have heard some state that severe periodontal inflammation is equivalent to a golf-ball sized infection found anywhere else in the body. His work pointed out that periodontal disease is linked to other medical concerns and is not a trivial matter. Even more specifically, Prostaglandin E2 is well known to begin the pregnancy delivery sequence and it is also a marker for periodontal disease found in the gingival crevicular fluid.
He continued this work after his move to University of North Carolina where he began collaborating with new associates. This culminated in 69 publications. He then began to look at other medical problems like cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and kidney disease. This work resulted in 60 additional publications and provided mechanistic insight to observed population-based associations between periodontal disease and stroke and myocardial infarction independent of traditional risk. These findings resulted in new international consensus recommendations and changes in healthcare policy. Many Americans now have insurance coverage for periodontal care for conditions including diabetes and pregnancy that is predicated upon these seminal findings.
Although many people associate Dr. Offenbacher with his work in periodontal medicine, much of his research was focused on periodontal disease itself.
Thus far I have used as my outline a biography found at the front of this tribute supplement to the Journal of Periodontology October 2020 written by two of Dr. Offenbacher’s colleagues and I hope it has more or less been clear to you who have a background in periodontics provided by your dental or dental hygiene education. Others listening may have been lost to what we have been talking about long before now.
However, now, if I were to simply continue reading this article to you, it would be necessary, I think, to begin to interpret multiple times a sentence.
So, instead of doing that I am going to step back and try and explain where much of periodontal research is at this time in a general way. And to do this I am going to step way back and take a long run at it. It won’t take me long.
Earliest periodontal research was clinical observations – recording what was happening to people and their mouths. Some of this obviously came before the invention of the microscope and the knowledge that organs were made of tissues and tissues made of cells. Also, this came before we knew that bacteria existed.
This changed with the invention and research around the microscope which led to culturing bacteria in laboratories.
In the area of periodontal disease research, we found that there were some organisms we could see but not culture and this resulted in work in the area of anaerobic organisms and how to grow them in the laboratory. Incidentally, this aided other medical areas of research, one of these being research in the disease of Syphilis. We also studied histologic slides and attempted to explain the pathogenesis of disease from them. This resulted in a lot of theories that were eventually discarded.
As scientists became comfortable at the microscopic level including the electron microscopic level, interest turned to the parts of the cell. What was the cell doing? How did the cell work and how did the cell – both single celled organisms and multi-celled organisms like ourselves reproduce cells and tissues normally and during healing from injury and disease processes?
Now biochemistry became important and useful and we began to see how DNA and RNA worked in transmitting information. The public is learning more about this from Covid because this particular virus injects it’s own RNA into cells that then produce the virus rather than continue their intended functions.
Some of this information left the cell not in the form of RNA, but as cytokines which I will describe in more detail in a moment. This is where Dr. Offenbacher’s work contributed so much. He helped scientists begin to see that conditions like pregnancy, diabetes, heart disease, Alzheimer’s disease and the rest are actually involved with conditions occurring elsewhere like in the mouth and the digestive tract. I will have more to say about all of this in future podcasts.
Dr. Offenbacher was the first to publish a biological model of how periodontal disease becomes systemic.
The answer, as I mentioned a moment ago, has to do with the transmission of cytokines.
What is a cytokine? Consider this your big word for the day and listen very carefully.
Cytokines are a broad and loose category of small proteins (~5–20 kDa) important in cell signaling. Cytokines are peptides (short chains of between two and fifty amino acids, linked by peptide bonds) and cannot cross the lipid bilayer of cells to enter the cytoplasm.
Knowledge in this area is continuing to expand, that’s why I think you will hear about cytokines in the future.
Because of Dr. Offenbacher’s interest in molecular epidemiology, he worked with multiple epidemiologists in using large data sets and samples analyzed in his laboratory. Two important contributions demonstrated that periodontal disease is associated with elevated serum C-reactive protein (CRP) and high serum CRP is a predictor of incident type 2 diabetes.
Incident T2D is defined as fasting serum glucose ≥126 mg/dL, HbA1C ≥6.5%, or use of medication for T2D during follow-up.
His early work on examining the central role of prostaglandin E2 (PGE2), and later other inflammatory biomarkers including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha and an array of inflammatory mediators in humans and animal models, has helped to define the central role of the innate immune response in demonstrating that the magnitude of the inflammatory response to the infectious challenge is a critical determinant of disease severity, irrespective of microbial burden.
So, allow me to put this in my own words for you.
Cells send signals. These signals can be a response to other cells sending cytokine signals. These can be a response to chemicals emitted by bacteria and also from trauma. Some research is directed at understanding these signals in order to understand more accurately the pathogenesis of disease. But there are other avenues that this sort of research can take. One would be diagnostic markers. Are there some blood tests or saliva tests that could tell us that someone has or is at risk for diseases? Most specific to us would be tests for periodontal disease. Another area of investigation would be therapeutics. Can we introduce medications that will change the course of disease? What happens when we lower the immune response – not only locally, but systemically? What happens when we stop inflammation in one part of the body to other parts of the body? And if we aren’t that keen on systemic or even local chemical mediators, what about electro-magnetic energy? How does this turn on the signaling of cells?
As I read the literature it more and more pulls me into the world of cytokines in order to be able to interpret whether or not different therapeutic options are ready for clinical practice. As best I can, I will let you know what I find.
This has been the Perio Hygienist Podcast episode
Entitled “The Father of Periodontal Medicine”
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