Genetic signature reveals new way to classify gum disease

Researchers at Columbia University Medical Center (CUMC) have devised a new system for classifying periodontal disease based on the genetic signature of affected tissue, rather than on clinical signs and symptoms. The new classification system, the first of its kind, may allow for earlier detection and more individualized treatment of severe periodontitis, before loss of teeth and supportive bone occurs. The findings were published recently in the online edition of the Journal of Dental Research.
Currently, periodontal disease is classified as either "chronic" or "aggressive," based on clinical signs and symptoms, such as severity of gum swelling and extent of bone loss. "However, there is much overlap between the two classes," said study leader Panos N. Papapanou, DDS, PhD, professor and chair of oral and diagnostic sciences at the College of Dental Medicine at CUMC. "Many patients with severe symptoms can be effectively treated, while others with seemingly less severe infection may continue to lose support around their teeth even after therapy. Basically, we don't know whether a periodontal infection is truly aggressive until severe, irreversible damage has occurred."

Looking for a better way to classify periodontitis, Dr. Papapanou turned to cancer as a model. In recent years, cancer biologists have found that, in some cancers, clues to a tumor's aggressiveness and responsiveness to treatment can be found in its genetic signature. To determine if similar patterns could be found in periodontal disease, the CUMC team performed genome-wide expression analyses of diseased gingival (gum) tissue taken from 120 patients with either chronic or aggressive periodontitis. The test group included both males and females ranging in age from 11 to 76 years.

The researchers found that, based on their gene expression signatures, the patients fell into two distinct clusters. "The clusters did not align with the currently accepted periodontitis classification," said Dr. Papapanou. However, the two clusters did differ with respect to the extent and severity of periodontitis, with significantly more serious disease in Cluster 2. The study also found higher levels of infection by known oral pathogens, as well as a higher percentage of males, in Cluster 2 than in Cluster 1, in keeping with the well-established observation that severe periodontitis is more common in men than in women.

"Our data suggest that molecular profiling of gingival tissues can indeed form the basis for the development of an alternative, pathobiology-based classification of periodontitis that correlates well with the clinical presentation of the disease," said Dr. Papapanou.

The researchers' next goal is to conduct a prospective study to validate the new classification system's ability to predict disease outcome. The team also hopes to find simple surrogate biomarkers for the two clusters, as it would be impractical to perform genome-wide testing on every patient.

The new system could offer huge advantages for classifying people with different types of periodontitis. "If a patient is found to be highly susceptible to severe periodontitis, we would be justified in using aggressive therapies, even though that person may have subclinical disease," said Dr. Papapanou. "Now, we wait years to make this determination, and by then, significant damage to the tooth-supporting structures may have occurred.

Genetic techniques have role in future of dental care

A visit to the dentist could one day require a detailed look at how genes in a patient's body are being switched on or off, as well as examining their pearly whites, according to researchers at the University of Adelaide.

In a new paper published in the Australian Dental Journal, researchers from the University of Adelaide's School of Dentistry have written about the current and future use of the field of epigenetics as it relates to oral health.

Co-author Associate Professor Toby Hughes says epigenetics has much to offer in the future treatment and prevention of dental disease.

"Our genetic code, or DNA, is like an orchestra - it contains all of the elements we need to function - but the epigenetic code is essentially the conductor, telling which instruments to play or stay silent, or how to respond at any given moment," Associate Professor Hughes says.

"This is important because, in the case of oral health, epigenetic factors may help to orchestrate healthy and unhealthy states in our mouths. They respond to the current local environment, such as the type and level of our oral microbes, regulating which of our genes are active. This means we could use them to determine an individual's state of health, or even influence how their genes behave. We can't change the underlying genetic code, but we may be able to change when genes are switched on and off," he says.

Associate Professor Hughes is part of a team of researchers at the University of Adelaide that has been studying the underlying genetic and environmental influences on dental development and oral health.

He says that since the completion of the Human Genome Project in 2007, epigenetics has had an increasing role in biological and medical research.

"Dentistry can also greatly benefit from new research in this area," he says. "It could open up a range of opportunities for diagnosis, treatment and prevention.

"We know that our genome plays a key role in our dental development, and in a range of oral diseases; we know that the oral microbiota also play a key role in the state of our oral health; we now have the potential to develop an epigenetic profile of a patient, and use all three of these factors to provide a more personalized level of care.

"Other potential oral health targets for the study of epigenetics include the inflammation and immune responses that lead to periodontitis, which can cause tooth loss; and the development and progression of oral cancers.

"What's most exciting is the possibility of screening for many of these potential oral health problems from an early age so that we can prevent them or reduce their impact."

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The full paper can be found at the Australian Dental Journal's website.

Pulling problem teeth before heart surgery to prevent infection may be catch-22

Patients with dental extractions before cardiac surgery still at risk for poor outcomes, study finds

To pull or not to pull? That is a common question when patients have the potentially dangerous combination of abscessed or infected teeth and the need for heart surgery. In such cases, problem teeth often are removed before surgery, to reduce the risk of infections including endocarditis, an infection of the inner lining of the heart that can prove deadly. But Mayo Clinic research suggests it may not be as simple as pulling teeth: The study found that roughly 1 in 10 heart surgery patients who had troublesome teeth extracted before surgery died or had adverse outcomes such as a stroke or kidney failure.

The findings are published in The Annals of Thoracic Surgery.

Prosthetic heart valve-related endocarditis accounts for up to one-fourth of infective endocarditis cases and proves fatal for up to 38 percent of patients who develop it. In light of that high mortality rate, physicians try to address risk factors such as poor dental health before cardiac surgery. Removing diseased teeth at some point before surgery as a preventive measure is common, but research on whether that helps has been limited. Medical guidelines acknowledge a lack of conclusive evidence, the Mayo researchers noted.

The new study shows that the risk for patients who do have teeth removed before heart surgery "may be higher than we thought," says senior author Kendra Grim, M.D., a Mayo Clinic anesthesiologist.

"We are always concerned with improving safety, and pulling infected teeth before heart surgery seemed to be the safer intervention. But we became interested in studying this complex patient group, as many patients that come to the operating room for dental surgery just before heart surgery are quite ill," Dr. Grim says.

The study is believed to be the largest so far evaluating adverse outcomes after pre-cardiac surgery dental extractions. The researchers studied outcomes in 205 adult Mayo patients who had teeth pulled before cardiovascular surgery. The study covered January 1, 2003, through Feb. 28, 2013; 80 percent of the patients were men, the median age at the time of tooth extraction was 62, and the median time lapse between dental extraction and heart surgery was seven days. The research found:

Six patients, or 3 percent, died in the period between their tooth extraction and the planned cardiac procedure.

Another six died after heart surgery, all while still hospitalized.

Ten patients, or roughly 5 percent, had other major adverse outcomes after heart surgery, such as bleeding, stroke, kidney failure requiring dialysis, acute coronary syndrome or stroke-like transient ischemic attacks.

Due to unexpected complications or findings from dental surgery, at least 14 patients, or 7 percent, had to have heart surgery delayed.

More information is needed to understand why patients died or had other major adverse outcomes, the researchers say. In addition to the stress placed on the body by dental extraction and heart surgery themselves, potential factors include the severity of individual patients' heart disease, other serious health problems they may have had, and how they reacted to anesthesia.

The bottom line for patients and physicians, the researchers conclude: Rather than following a rule of thumb, physicians should evaluate each patient individually to weigh the possible benefit of tooth extraction before heart surgery against the risk of death and other major adverse events.

"We hope this study sparks future discussion and research," Dr. Grim says. "In the meantime, we recommend an individualized approach for these patients, to weigh their particular risk and benefit of a dental procedure before cardiac surgery with the information we have currently available."

Two bacteria prevalent in gum disease incite the growth of deadly Kaposi's sarcoma-related (KS) lesions and tumors in the mouth

Researchers from Case Western Reserve University have discovered how byproducts in the form of small fatty acids from two bacteria prevalent in gum disease incite the growth of deadly Kaposi's sarcoma-related (KS) lesions and tumors in the mouth.

The discovery could lead to early saliva testing for the bacteria, which, if found, could be treated and monitored for signs of cancer and before it develops into a malignancy, researchers say.

"These new findings provide one of the first looks at how the periodontal bacteria create a unique microenvironment in the oral cavity that contributes to the replication the Kaposi's sarcoma Herpesvirus (KSHV) and development of KS," said Fengchun Ye, the study's lead investigator from Case Western Reserve School of Dental Medicine's Department of Biological Sciences.

The discovery is described in The Journal of Virology article, "Short Chain Fatty Acids from Periodontal Pathogens Suppress HDACs, EZH2, and SUV39H1 to Promote Kaposi's Sarcoma-Associated Herpesvirus Replication."

The research focuses on how the bacteria, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn), which are associated with gum disease, contribute to cancer formation.

Ye said high levels of these bacteria are found in the saliva of people with periodontal disease, and at lower levels in those with good oral health -- further evidence of the link between oral and overall physical health.

KS impacts a significant number of people with HIV, whose immune systems lack the ability to fight off the herpesvirus and other infections, he said.

"These individual are susceptible to the cancer," Ye said.

KS first appears as lesions on the surface of the mouth that, if not removed, can grow into malignant tumors. Survival rates are higher when detected and treated early in the lesion state than when a malignancy develops.

Also at risk are people with compromised immune systems: people on medications to suppress rejection of transplants, cancer patients on chemotherapies and the elderly population whose immune systems naturally weaken with age.

The researchers wanted to learn why most people never develop this form of cancer and what it is that protects them.

The researchers recruited 21 patients, dividing them into two groups. All participants were given standard gum-disease tests.

The first group of 11 participants had an average age of 50 and had severe chronic gum disease. The second group of 10 participants, whose average age was about 26, had healthy gums, practiced good oral health and showed no signs of bleeding or tooth loss from periodontal disease.

The researchers also studied a saliva sample from each. Part of the saliva sample was separated into its components using a spinning centrifuge. The remaining saliva was used for DNA testing to track and identify bacteria present, and at what levels.

The researchers were interested in Pg's and Fn's byproducts of lipopolysaccharide, fimbriae, proteinases and at least five different short-chain fatty acids (SCFA): butyric acid, isobutryic acid, isovaleric acid, propionic acid and acetic acid.

After initially testing the byproducts, the researchers suspected that the fatty acids were involved in replicating KSHV. The researchers cleansed the fatty acids and then introduced them to cells with quiescent KSHV virus in a petri dish for monitoring the virus' reaction.

After introducing SCFA, the virus began to replicate. But the researchers saw that, while the fatty acids allowed the virus to multiple, the process also set in motion a cascade of actions that also inhibited molecules in the body's immune system from stopping the growth of KSHV.

"The most important thing to come out of this study is that we believe periodontal disease is a risk factor for Kaposi sarcoma tumor in HIV patients," Ye said.

With that knowledge, Ye said those with HIV must be informed about the importance of good oral health and the possible consequences of overlooking that area.

First evidence-based diagnostic criteria published for temporomandibular disorders

The first evidence-based diagnostic criteria have been developed to help health professionals better diagnose temporomandibular disorders (TMD), commonly known as TMJ, a group of often-painful jaw conditions that affect an estimated 10 to 15 percent of Americans. The diagnostic criteria, developed by researchers in North America, Europe and Australia, are professional recommendations on how best to detect a disease or condition.

The new criteria, supported in part by the National Institutes of Health, comprise an improved screening tool to help researchers and health professionals including dentists more readily differentiate the most common forms of TMD and reach accurate diagnoses that are grounded in supportive scientific evidence. Historically, diagnostic criteria for TMD have been based on a consensus of expert opinion and often reflect a shared clinical perspective. None have been rigorously tested by scientists.

“We’ve had diagnostic criteria for years,” said Eric Schiffman, D.D.S., a co-lead author on the article, who studies TMD at the University of Minnesota School of Dentistry, Minneapolis. “What is unique here is instead of a panel of experts empirically deciding best practices, we relied on science as a methodology to test our best assumptions and see if we were actually correct.”

Called DC/TMD, the latest criteria are published today in the winter issue of the Journal of Oral and Facial Pain and Headache. They are available online at the International RDC/TMD Consortium Network website: http://www.rdc-tmdinternational.org/TMDAssessmentDiagnosis/DCTMD.aspx External Web Site Policy

Although TMD is commonly considered a jaw problem, researchers have determined that most people with chronic temporomandibular problems also contend with other ailments. In 1992, the Research Diagnostic Criteria for TMD (RDC/TMD) reflected this awareness. They were the first to integrate biological, psychological, and social factors into two distinct protocols, or axes. Axis I was designed to evaluate the physical diagnoses, while Axis II characterized the nature of a person's pain, distress, and disability. The criteria were translated into 18 languages and become the most widely used diagnostic system among TMD researchers.

But the RDC/TMD dual axes represented a first step with biopsychosocial diagnostic criteria. In the early 2000s, the NIH's National Institute of Dental and Craniofacial Research (NIDCR) assembled a group of experts to lead the first comprehensive assessment of the criteria. The group found Axis I in particular to be less valid than previously thought, leading to a mandate from the TMD clinical and research communities to create the diagnostic equivalent of RDC/TMD 2.0.

All agreed at the outset that the "R" was no longer needed. Research criteria, while useful for scientists in the laboratory and clinic, can leave researchers and health care providers using different diagnostic terms, measures, and tools.

“A common language allows clinicians to communicate more easily to researchers about their daily diagnostic challenges,” said Richard Ohrbach, D.D.S., Ph.D., a co-lead author on the publication who studies TMD at the University at Buffalo School of Dental Medicine in New York. “Conversely, a common language allows research findings to be more easily integrated into a clinical setting and improve patient care.”

The DC/TMD start with a refined version of Axis I, the physical assessment. It begins with an easily administered patient questionnaire that is specially designed to detect pain-related TMD. If TMD is detected, the protocol moves on to newly crafted diagnostic criteria to help practitioners differentiate among the common subtypes. In field tests, the diagnostic criteria for painful TMD were found to have at least 86 percent sensitivity and 97 percent specificity. Sensitivity refers to how well a test identifies a person with a given ailment, while specificity characterizes the ability to identify correctly those who are not affected.

Axis II, the psychosocial assessment, screens patients to assess pain location, pain intensity, pain-related disability, psychological distress, degree of jaw dysfunction, and presence of oral habits (i.e.,e.g. grinding teeth) that may contribute to the dysfunction. If more information is needed, a more comprehensive follow-up questionnaire is available to tap into additional anxiety measures and the possible presence of other pain-causing physical ailments. Both instruments have been scientifically validated.

“By diagnosing the person, beyond only the physical condition, a whole avenue of treatment options opens up,” said Schiffman. “Instead of prescribing mouth guards, exercises, or surgery, practitioners can consider trying bio-behavioral treatments including relaxation techniques and biofeedback to help the patient successfully manage their TMD. In short, you can better customize the treatment to fit the whole person, not just their disorder.”

The National Institute of Dental and Craniofacial Research (NIDCR) is the Nation’s leading funder of research on oral, dental, and craniofacial health. The NIDCR-supported International RDC/TMD Consortium Network provided the investigative framework for researchers from North America, Europe, and Australia to develop an improved diagnostic system and test its validity. Visit the NIDCR website at http://www.nidcr.nih.gov.

Antibacterial Agent Boosts Toothpaste Effectiveness

Source: Health Behavior News Service

Regular use of fluoride toothpaste containing triclosan, an antibacterial agent, and a copolymer, which helps prevent the triclosan from being washed away by saliva, reduces plaque, gingivitis, and bleeding gums and slightly reduces tooth decay compared to fluoride toothpaste without those ingredients, finds a new review in The Cochrane Library.

"We are very confident that adding triclosan and copolymer to a fluoride toothpaste will lead to additional benefits, in terms of less plaque, inflammation, bleeding, and tooth decay," said Philip Riley, a researcher at the University of Manchester in England, and a co-author of the study. But he added, "We don’t know how important the effects are clinically."

Tooth decay and gingivitis are the main causes of tooth loss. Both are caused by plaque, the film of bacteria that builds up on teeth, and if left untreated, can lead to periodontitis, a more serious gum disease that can cause pain and loose teeth. A team from the Cochrane Oral Health Group reviewed 30 published studies of toothpastes containing triclosan and copolymer.

Their analysis of the combined data found a 22 percent reduction in plaque, a 22 percent reduction in gingivitis, a 48 percent reduction in bleeding gums, and a 5 percent reduction in tooth decay (cavities) compared to toothpaste with fluoride alone. However, they did not find significant evidence that triclosan/copolymer toothpaste reduced the incidence of periodontis more than toothpaste without the combination. No adverse reactions to triclosan or the copolymer were reported.

The findings of the review are not surprising, according to Clifford Whall, Ph.D., director of the American Dental Association's (ADA) Seal of Acceptance Program and Product Evaluations. The ADA's Council on Scientific Affairs has independently reviewed data on the safety and effectiveness of triclosan /copolymer for reducing cavities, plaque and gingivitis. The council concluded that there were sufficient clinical studies that showed these toothpastes reduced the incidence of cavities, the presence of plaque and gingivitis.

Most of the studies of toothpastes evaluated in the Cochrane report were directly or indirectly supported by companies that make toothpaste. Only three studies appeared to be independent, according to the reviewers. The independent or government-funded research community and industry should work together to research antibacterial agents in toothpastes, Riley noted. "But we would argue for complete independent control of the research, including study design, conducting the study, and ownership of the data."

Study Examines Treatment Responses in TMD Patients

Tempromandibular pain disorders (TMDs) are characterized by a dysfunction of the TMD joint and cause orofacial pain, masticatory dysfunction or both. A new study published in The Journal of Pain showed that standard treatment approaches yield modest to large improvement in pain, but the addition of cognitive behavioral therapy may be helpful. The Journal of Pain is published by the American Pain Society, www.americanpainsociety.org.

Some 10 to 36 million U.S. adults, primarily women, have TMD pain, making this condition the second most frequent pain disorder following low-back pain. MD pain usually can be managed with conservative treatment with non-steroidal anti-inflammatory pain medications (NSAIDS), supportive patient education, diet modifications and an intraoral splint and/or occlusal therapy. Not all patients benefit, however, and previous research has shown that many TMD patients benefit from cognitive behavioral therapy (CBT). But the reasons behind CBT treatment success or failure are unclear.

Researchers from the University of Connecticut Health Center evaluated 101 TMD patients on a daily basis for three months. Study subjects reported having TMD pain for an average of 6.7 years. They were randomly assigned to one of two treatment groups: standard conservative care and standard care with CBT added, which included coping skills training. The purpose of the study was to determine if specific subtypes of treatment nonresponsive TMD patients could be identified to determine if CBT could be helpful.

The authors hypothesized that certain CBT treatment-related outcomes, such as lower retention in treatment and less adaptive changes in coping, self efficacy and catastrophizing, might be predictive of treatment non-response.

Results showed that nonresponders scored higher on depression scores, exhibited lower self efficacy and coping ability, and catastrophized more than more adaptive patients. It was noted that nonresponsive patients did not show more joint pathology than patients who responded well to treatment. Despite lack of joint pathology, the nonresponsive subjects were more likely to report being disabled by their TMD pain.

The study concluded it is important to recognize the importance of the heterogeneous nature of TMD pain, and that treating TMD patients as a homogeneous group is likely to result in suboptimal therapy for many patients. Even though no treatment is successful for all TMD patients, certain psychosocial factors can make some patients unresponsive to CBT.