UNC Perio 2017 Expo
At the recent UNC Perio Expo, panomics and big data made bold strides toward precision periodontal medicine
Steven Offenbacher, DDS, PhD, MMSc; and James D. Beck, PhD
An exceptional event was held in Chapel Hill, North Carolina, that did not involve basketball. This last May, 2017, approximately 270 scientists, students, and dental alumni attended the UNC Perio 2017 Expo in celebration of the 50th year of the University of North Carolina’s residency program in Periodontology, the 20th anniversary of the Sunstar oral-systemic disease conference, and the 20th year of the Center for Oral and Systemic Disease. The 2-day program was supported by an educational grant from Sunstar. The diverse exposition of contemporary periodontology included hands-on workshops in computer-aided implant treatment planning, 3D printing for surgical stents, methods in clinical research, calibration of clinical examiners, informatics and data management for clinical trials, laboratory demonstrations for cytokine measurements, genotyping, molecular epidemiology, biospecimen processing, and microbial assessments. More than 30 posters were presented and 10 travel grants awarded for junior faculty and residents who presented outstanding posters.
These events were interwoven with an outstanding lecture series by international leaders, who presented at the UNC Friday Center in live video streaming viewed in the United States and internationally. There were 21 talks in six sessions, with panel moderators for each session and an open question/dialogue format. Alumni events and receptions were hosted at the Friday Center, The George Watts Alumni Center, and the School of Dentistry to round out the social events.
Much has changed since the last Sunstar oral-systemic disease symposium held 20 years ago. The Kaneda family at the helm of the Sunstar enterprise has long appreciated how oral health is important for overall well-being. Research coming from the UNC Dental ARIC study (James Beck, PhD, principle investigator) and other studies began to provide compelling data linking periodontal disease to systemic conditions, including incident stroke and atherosclerosis, confirming some of the pioneering studies conducted in Finland. And the links of periodontal disease with pregnancy problems, such as preterm birth, had just been identified at UNC in work that included research in animals and humans. Twenty years ago, the dean of the UNC School of Dentistry, John Stamm, arranged with the Kaneda family to host the oral-systemic disease symposium, which was widely attended and became a landmark evidence-based symposium that boldly reasserted the fact that the mouth is indeed connected to the body. In 1997, models were presented regarding the possible biologic plausibility of such a connection, and it is in this arena that much has been confirmed and detailed over the last two decades. It is now clear that periodontal disease can serve as a source of infection, sepsis, and inflammation that can disseminate and exacerbate problems with many chronic diseases that have inflammation as a component of pathogenesis, including diabetes, renal disease, and cancer.
The field of periodontology and periodontal medicine (the effects of periodontal disease on systemic health) has been transformed by molecular epidemiology, panomics (genetic sequencing, epigenetic analyses, microbiome sequencing, transcriptomics, infectomics, and inflammatory signatures), and the merging of large clinical datasets. These advancements often have involved what are called multidimensional data (eg, 2 million genes, 300 microbes), merging with clinical data to create biologically informed phenotypes. The first speaker for the 2017 symposium, Gary Armitage, DDS, MS, suggested that what is known as periodontal disease may represent up to 300 different conditions. If you think about that for a moment, it is no wonder that some patients don’t respond well to some treatments. And when we speak of evidence-based dentistry, which is designed to provide guidance to the dentist for treatment choices for the “average” patient with an “average” response, some caution and questions must arise as to how well your patient “maps” to that average person. As a practicing dentist, one worries first about the patient in the chair, that “n of one,” and appreciates that there are many “hidden” attributes that make the patient “above average,” as they all are in Lake Wobegon. Some of the key nuggets from the symposium that represent important information for clinicians to help guide the future of periodontology and periodontal medicine are highlighted as articles in this issue. In the narrative to follow, we recap new areas of investigation presented during the UNC Perio 2017 Expo.
• We now appreciate the mobility of the oral microbiome in that it can be found translocating to many extraoral sites. Microbiome sequencing studies presented by Flavia Teles, DDS, MS, DMSc; and Krystal Reyes-Viruet, DMD, demonstrated the presence of periodontal organisms in the placenta and in the umbilical cord with different colonization patterns among preterm deliveries compared with term deliveries.
• New periodontal disease classifications based on over 16,000 individuals are revealing new patterns of disease. Beck, Morelli, and colleagues demonstrated the application of new computer models that incorporate missing teeth into definitions of disease and provide stronger models for prediction of tooth loss, disease progression, systemic inflammation, and systemic disease. Di Wu, PhD, a faculty member at UNC in the new program of health and bioinformatics, demonstrated the application of these new classifications to dental school records. This approach was very sensitive for comparing clinical outcomes with different therapies.
• The clinical importance of periodontal disease as an inflammatory signal that worsens diabetes was discussed by Phoebus Madianos, DDS, PhD; while Evie Lalla, DDS, MS, provided current concepts for clinical management of periodontal disease among patients with diabetes.
• Kenneth Kornman, DDS, PhD, provided a blueprint for optimizing care using precision periodontal medicine. In this context, biomarkers, genetics, and behavioral exposures (smoking, nutrition, obesity) can be used to identify a patient at high risk and enable personalized treatment options. Panos Papapanou, DDS, PhD, described how gene expression profiles can be used as possible biomarkers, while Ricardo Teles, DDS, DMSc, demonstrated how inflammatory markers can be used to predict risk for disease progression. The presentation by Kimon Divaris, DDS, PhD, provided overall insight for clinicians defining precision medicine and describing how precision dentistry will improve care.
• Sessions providing insight into preventing implant diseases (Mariano Sanz, MD, DDS, DrMed, DrHC), computer-aided digital implant placement (Thiago Morelli, DDS, MS), the unique microbiome of peri-implantitis (Flavia Teles, DDS, MS, DMSc), and the management of peri-implantitis using erbium water lasers (Atsuhiko Yamamoto, DDS, PhD) provided a glimpse for clinicians into the future of implantology.
• Maurizio Tonetti, DMD, PhD, MMSc, provided a video-rich presentation that elegantly summarized our current knowledge of surgical approaches to tissue regeneration. His lecture combined with the stellar graphics illustrations provided by Mariano Sanz, MD, DDS, DrMed, DrHC on implants provided an exceptional educational enrichment for all participants.
• Thomas Van Dyke, DDS, PhD, showed that resolvins (a class of lipids) not only actively reduce inflammation and promote regeneration in periodontal disease, but also demonstrate systemic benefits in certain conditions, such as atherosclerosis in animal models. New inflammatory pathways in gingivitis were demonstrated by Shaoping Zhang, DDS, PhD, MS, which point to new neural genes that control inflammation in the gingiva. Both talks involved new therapeutic drug opportunities as treatments for periodontal disease.
• Epigenetics includes changes to the DNA structure that occur in response to environmental exposures. These changes can accumulate over time, and cells with epigenetic marks can persist. Using a genome-wide analysis, Silvana Barros, DDS, PhD, demonstrated the effect of smoking on DNA structure. She provided evidence that epigenetic changes may be an underlying mechanism whereby smoking worsens periodontal disease.
• Periodontal disease has been recognized as a potential risk factor for stroke, a major cause of disability and mortality. Two physicians emphasized the importance of oral health as it relates to stroke. Souvik Sen, MD, MS, FAHA, presented new findings that severe periodontal disease is a precursor of new stroke events and some specific subtypes of stroke. He also presented evidence that regular dental healthcare resulted in fewer cases of stroke. Jukka Meurman, MD, PhD, DOdont, made a global case for integrating oral health as part of a stroke prevention program.
• Julie Marchesan, DDS, PhD, presented new data on the benefits of flossing, one form of inter-dental cleaning, an area of recently renewed interest with the public. Her findings, using longitudinal data, showed that regular flossing reduced new attachment loss over time, decreased tooth loss, lowered the incidence of caries, and showed fewer new cardiovascular events, even adjusting for other risk factors.
• Michael Alfano, DMD, PhD, was the final speaker, summarizing the field by presenting compelling findings from insurance companies and analyses from healthcare think-tank organizations on the medical cost savings that can be attained by providing periodontal care for periodontal disease patients with diabetes, heart, pulmonary, and kidney diseases.
Twenty years ago at the first Sunstar conference, there was only a working hypothesis on how periodontal infections may relate to systemic conditions. Many of those elements, including common genetic risk factors, mechanisms of dissemination of organisms, and systemic inflammation, have now become better characterized pathways of pathogenesis. Scientific advancements have strengthened the current concept of periodontal medicine, which is now more widely accepted among dentists and physicians. Although randomized clinical trials have either not been attempted or are inconclusive with regard to efficacy of periodontal care in reducing chronic systemic conditions, insurance companies, using their own effectiveness data, are now paying for periodontal care to reduce medical morbidity and consequently reduce medical costs.