Steven Offenbacher

• University of North Carolina at Chapel Hill

Background and objectives Plakophilin-2 (PKP2) is an intracellular desmosomal anchoring protein that has been implicated in a genome-wide association study, in which genetic variants of PKP2 are associated with Porphyromonas gingivalis (P.gingivalis) -dominant periodontal dysbiosis. In this study, we compared the ex vivo PKP2 expression in periodon...

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study met...

Periodontitis is one of the most prevalent chronic inflammatory diseases and is induced by the interaction between oral microorganisms and the host immune system. Plasma cells are of special interest in chronic periodontitis (CP), as they represent ~50% of infiltrated immune cells in periodontal lesions. Plasma cells constitute the only known cell...

Objectives The long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular m...

Epigenetic factors are heritable genome modifications that potentially impact gene transcription, contributing to disease states. Epigenetic marks play an important role in chronic inflammatory conditions, as observed in periodontal diseases, by allowing microbial persistence or by permitting microbial insult to play a role in the so-called ‘hit-an...

Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with in...

Objective: NAFLD prevalence is greater among Hispanics/Latinos than other racial/ethnic groups and is reported to vary among Hispanic/Latino groups. Experimental animal and human studies demonstrate associations between periodontitis and non-alcoholic fatty liver disease (NAFLD), not yet reported among Hispanics/Latinos. This study examined period...

The purpose of this study was to evaluate the associations between interdental cleaning behavior and the prevalence of caries and periodontal disease and numbers of missing teeth, with data from the National Health and Nutrition Examination Survey (2011 to 2012 and 2013 to 2014). Analysis included the following parameters: interproximal clinical at...

Background: This paper focuses on Periodontal Profile Class (PPC), a component of the Periodontal Profile Phenotype (P3) System that may be more representative of the periodontitis phenotype than current case definitions of periodontitis. Data illustrate the unique aspects of the PPC compared with other commonly used periodontal classification ind...

Background: This paper focuses on the Periodontal Profile Class (PPC) System that may be more informative and representative of periodontitis phenotypes than current case definitions of periodontitis. This study illustrates the unique aspects of the PPC compared with other periodontal indices for studying associations between periodontal disease a...

Background and purpose: Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. Methods: In the ARIC (Atherosclerosis Risk in Communities) study, pattern...

Background: While evidence is increasingly consistent with a positive association between periodontitis and cancer risk, most studies have relied on self-reported periodontitis. In this study, we prospectively evaluated the association of periodontal disease severity with cancer risk in black and white older adults in a cohort study that included...

Periodontitis is one of the most common inflammatory human diseases with a strong genetic component. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWASs) of chronic periodontitis (CP) have largely been unsuccessful in identifying common susceptibility facto...

Background: Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of adults with risk factors like obesity and insulin resistance putatively acting through chronic low-grade inflammation. Because periodontitis elicits low-grade inflammation, we hypothesized that it could contribute to NAFLD occurrence. Objective To investigate epidemiologic ass...

Aim: Several papers have considered the potential relationship between periodontitis and lipid parameters. The present systematic review, meta-analysis and meta-regression study focused on investigating whether serum lipid parameter levels were elevated in patients with periodontal disease (PD) (without altered systemic conditions) in comparison w...

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodo...

Objective: To investigate racial differences in the associations between periodontitis and 10-year self-reported incident tooth loss in a biracial, community-based cohort of US late middle-aged and older adults. Methods: Subjects were 3,466 dentate men and women aged 53-74 who underwent dental examinations from 1996 to1998. In 2012-2013, telepho...

Aim: The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP. Material and methods: The association of PLG candidate rs4252120 was tested in a...

Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWAS) of chronic periodontitis (CP) have been unsuccessful in discovering susceptibility factors. A strategy that c...

Background Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic...

Background: We investigated the single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus and examined its association with microbial, biological and periodontal disease clinical parameters. Methods: We annotated a 200Kb-spanning region of 1q12 previously highlighted in a genome-wide association scan...

Introduction: Gum, or periodontal disease (PD) is a risk factor for cardiovascular disease. We assessed the graded association of PD levels with incident ischemic stroke as well as the etiological stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: PD was assessed by full-mouth periodontal measurements from 6 sites per...

Introduction: Prior epidemiological studies have shown that periodontal disease (PD), also referred to as gum disease, is an independent risk factor for ischemic stroke. We assessed the hypothesis that users of regular dental care may have a lower risk for incident ischemic stroke and specific stroke subtype when compared with users of episodic den...

Introduction: Epidemiological studies have shown that serum inflammatory markers are independently associated with ischemic stroke. We assessed the hypothesis that specific inflammatory mediator is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: In the ARIC study, serum inflammator...

Purpose: The purpose of this study was to compare the prevalence of third molars from the US National Health and Nutrition Examination Survey (NHANES) and the Swedish survey. Materials and methods: This cross-sectional study involved the comparison of the only published data on third molar prevalence. The number of visible third molars in the NH...

Introduction: Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects minorities and the poor, despite intense efforts targeting traditional risk factors. Periodontal diseases are common bacterial plaque-induced inflammatory conditions that can respond to treatment and have been implicated as a CKD ri...

Background: Our goal was to use bioinformatics tools to explore the identification and definition of distinct periodontal profile and tooth profile classes (PPC/TPC) among a cohort of individuals using detailed clinical measures at the tooth-level, including both periodontal measurements and tooth loss. Materials and methods: Full-mouth clinical...

Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean inte...

An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4,077 European American adults, participants in the Dental Atherosclerosis Ris...

Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of 8 periodontal pathogens) and local inflammatory response [gingival crevicular fluid (GCF...

In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in perio...

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the US with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWAS) for dental...

Background: This study determines the microbial composition changes during biofilm overgrowth and subsequent removal among subjects with various states of periodontal disease. Methods: Prospective cohort study. The 175 participants with various periodontal states [five biofilm-gingival interface (BGI) groups] abstained from oral hygiene by using...

Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction bet...

The purpose of this report was to describe the management of an eight-year-old Bulgarian male with Down syndrome presenting with periodontitis as a manifestation of systemic disease in the early mixed dentition. Treatment involved full-mouth mechanical debridement and extraction of hopeless teeth under general anesthesia followed by systemic antibi...

In a previous report, we demonstrated the inverse association of high serum 8-isoprostane levels, a marker for oxidative stress, with decreased serum IgG antibodies to oral bacteria. The association between increased serum IgG with increased plaque and periodontitis (increased probing depths) was attenuated by high systemic oxidative stress. Other...

Purpose To determine the prevalence of third molars in the US population and to report the differences in prevalence of visible third molars in the most recent National Health and Nutrition Examination Survey (NHANES) population of 2011 through 2012 by participant, jaw, and demographics. Materials and Methods The number of visible third molars in...

The purpose of this study was to evaluate the microbial community (MC) composition as it relates to salivary metabolites and periodontal clinical parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled equally into 5 categories of periodontal status per the biofilm-gingival interface classification. Microbial species within...

To assess whether partial mouth protocols (PRPs) result in biased estimates of the associations between smoking, alcohol, obesity, and diabetes with periodontitis. Using a sample (n=6,129) of the 1996-1998 Atherosclerosis Risk in Communities study, we used measures of probing pocket depth and clinical attachment level to identify moderate-severe pe...

Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS)...

Population studies consistently support associations between poor oral (periodontal) health and systemic diseases such as cardiovascular disease (CVD) and diabetes. The aim of this study was to assess the knowledge of dentists and document their opinions regarding the evidence on oral-systemic disease relationships. A survey consisting of 39 items...

Bacterial infections are known to alter glucose metabolism within tissues via mechanisms of inflammation. We conducted this study to examine whether insulin response genes are differentially expressed in gingival tissues, comparing samples from experimental gingivitis and periodontitis subjects to those from healthy individuals. Total RNA was extra...

AimThe aim of this cross-sectional study is to explore if periodontitis is associated with alterations of the retinal microcirculation, a predictive marker of cardiovascular events.Material and Methods457 subjects aged 52 years and more from the ARIC cohort were included. Retinal vascular diameters were measured and summarized as central retinal ar...

Background: Periodontal disease (PD) is independently associated with recurrent vascular events in Stroke/TIA. Aortic arch atheroma (AA) is an independent risk factor for stroke. The association between PD and AA has not been described. Objective: To test the association between: 1) significant AA and recurrent vascular event in stroke/TIA 2) PD an...

To assess changes at 2-year intervals in the periodontal status of the third molar region in participants enrolled with asymptomatic third molars and no clinical evidence of third molar region periodontal pathology. The included participants who presented with a healthy periodontal status (all probing depths [PDs], <4 mm) in the third molar region,...

There has been an increase in awareness of the link between oral health and systemic health in recent years. While questions exist about the relationship of oral disease to cardiovascular conditions, no published study to date has addressed cardiologists' knowledge and opinions about this area of science. This study examined North Carolina cardiolo...

Observational studies consistently support a relationship between poor oral health and systemic diseases like cardiovascular disease and diabetes mellitus. The purpose of this study was to identify current practices and perceived barriers among North Carolina dentists regarding the incorporation of oral-systemic evidence into the delivery of patien...

The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. Engebretson SP, Hyman LG, Michalowicz BS, Schoenfeld ER, Gelato MC, Hou W, et al (16 authors). JAMA 2013;310(23):2523-32.

Current treatments for periodontitis (e.g., scaling/root planing and chlorhexidine) have limited efficacy since they fail to suppress microbial biofilms satisfactorily over time, and the use of adjunctive antimicrobials can promote the emergence of antibiotic-resistant organisms. Herein, we report the novel application of nitric oxide (NO)-releasin...

Background: The purpose of this study is to determine whether baseline salivary inflammatory biomarkers could discriminate between different clinical levels of disease and/or detect clinical changes over a 3-week stent-induced biofilm overgrowth (SIBO) period. Methods: A total of 168 participants were enrolled in a 21-day experimental gingivitis...

Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer rich data sources for the investigation of candidate genes, functional elements, and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen colonization (n = 1,020) from a cohort of adult Americans of European descent participating in the Atheroscleros...

Objective: Dental caries and chronic periodontitis (CP), the most common oral diseases, are the major causes of tooth morbidity and edentulism. Both diseases are associated with pathogenic shifts of the oral microbiome and their pathogenesis entails complex interactions of highly organized intra-oral biofilms with host immunity and protective facto...

Denture stomatitis, inflammation and redness beneath a denture, affects nearly half of all denture wearers. Candidal organisms, the presence of a denture, saliva, and host immunity are the key etiological factors for the condition. The role of salivary proteins in denture stomatitis is not clear. In this study 30 edentulous subjects wearing a maxil...

Objective: We evaluated whether first-trimester high-sensitivity C-reactive protein (hsCRP), a suggested marker of pregnancy-associated hyperglycemia, predicts third-trimester impaired glucose tolerance (IGT) in a secondary analysis of a prospective cohort of nondiabetic singletons enrolled at <26 weeks gestation. Study design: We measured the a...

Background and objective: Genetic markers associated with disease are often non-functional and generally tag one or more functional "causative" variants in linkage disequilibrium. Markers may not show tight linkage to the causative variants across multiple ethnicities due to evolutionary divergence, and therefore may not be informative across diff...

Tooth loss is a clinically-meaningful outcome of untreated caries and periodontitis. It also represents an outcome from an accumulation of adverse social, behavioral, and biological events occurring over the life course. Objectives: To describe 10-year incidence and risk factors of tooth loss in a well-characterized population-based biracial coho...

Objective: Interleukin-37 has been recently discovered as a novel anti-inflammatory cytokine. This study is aimed to compare the transcriptional levels of IL37, IL1B, and IL6 in gingival biopsies collected from chronic periodontitis patients with samples of periodontal health and to study cellular expression patterns of IL37 in gingival tissues and...

Objective: The presence and accumulation of advanced glycation end products (AGEs) in gingiva is associated with chronic periodontitis and is even more elevated patients with diabetes. We conducted this study to examine whether AGEs modified the transcriptional expression of key genes which regulate gingival wound healing and migration activity of...

Objective: The aim of this study was to conduct metabolomic analysis of saliva during a 3-week induction and 4-week resolution of stent-induced, biofilm overgrowth (SIBO) in humans to elucidate an association between changes in clinical disease and the salivary metabolome. Method: Five disease classifications were developed using probing depths (...

Objective: In periodontal diseases changes of host DNA methylation status appear to be an early molecular event, and such epigenetic modifications, which may be mitotically heritable, occur locally in gingival tissues at the biofilm gingival interface. In this study we examined the potential alteration in the methylation status of selected gene pan...

Objectives: Previous GWA (genome-wide association) studies seeking to identify susceptibility genes associated with periodontal disease defined by clinical criteria have not revealed statistically significant risk loci. We hypothesized that supplementing clinical data with microbial composition findings and gingival crevicular fluid (GCF) levels of...

Objective: A previous genome-wide association study (GWAS) was conducted using a phenotype that was based upon a combination of clinical parameters and the levels of 8 disease-related bacteria and gingival crevicular fluid (GCF) IL-1beta. The focus of this investigation was to examine the fine-mapping associated with a major risk locus that encodes...

Epigenetics as a modifiable risk factor in periodontal diseases has been investigated in light of the current knowledge of how chronic infection and inflammation can affect gene-specific epigenetic reprogramming in periodontal tissues. Epigenomic programming might be particularly sensitive to environmental influences, and a combination of physiolog...

Investigate short-term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states. Overall, 175 subjects representing each of five biofilm-gingival interface (BGI) periodontal groups were enrolled in a single-blind, randomized study. After stent-induced biofilm overgrowth for 21 days subjects rece...

Effective monitoring of glucose levels is necessary for patients to achieve greater control over their diabetes. However, only about a quarter of subjects with diabetes who requires close serum glucose monitoring, regularly check their serum glucose daily. One of the potential barriers to patient compliance is the blood sampling requirement. Saliva...

In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities. Analyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD. Cases were id...

Periodontal disease (PD) has been shown to be associated with incident stroke. We investigated whether PD is independently associated with recurrent vascular events and certain inflammatory markers in stroke/transient ischemic attack (TIA) patients. In this prospective, longitudinal, hospital-based cohort study, PD was assessed in stroke/TIA patien...

To assess the impact of third molar removal on the periodontal status of adjacent second molars and teeth more anterior in the mouth in patients with mild symptoms of pericoronitis. Healthy patients with mild symptoms of pericoronitis affecting at least 1 mandibular third molar were recruited for a study approved by the institutional review board....

Aim: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). Material & methods: Human, experimental and in vitro studies were evaluated. Results: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circula...

Background Porous tantalum trabecular metal has recently been incorporated in titanium dental implants as a new form of implant surface enhancement. However, there is little information on the applications of this material in implant dentistry. PurposeThe purpose of this article is to summarize the contemporary concept on the applications of porous...

Objective: To determine the association between the plaque microbial and salivary metabolomic composition as biomarkers for categorizing the clinical response to biofilm overgrowth among moderate and severe periodontitis subjects Method: 97 healthy adults aged 18-75 years completed a single-blind, randomized treatment study assessing microbiome a...

Objective: To determine the effects of using a powered toothbrush (Sonicare FlexCare) vs manual brushing on the microbiome composition following experimental induction and resolution of biofilm overgrowth in subjects with gingivitis or periodontitis. Method: 97 healthy adults, aged 18-75 years, completed a single-blind, randomized study assessing...

Objective: Current tools in monitoring for serum glucose require blood sampling. Many serum proteins related to diabetes are present in saliva. Method: 150 subjects with type 1 or 2 diabetes were recruited. For each type of diabetes, label-free multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) proteomics was used to de...

Objective: Denture stomatitis affects 1/3 to 1/2 of denture wearers. Candida organism, denture, and saliva are the key etiological factors. The role of salivary proteins in denture stomatitis is not clear. Method: 30 edentulous subjects wearing a maxillary complete denture were recruited. Unstimulated whole saliva from each subject was collected...

Objective: We conducted a pilot study to examine whether insulin regulated genes are differentially expressed in gingival biopsy samples comparing gingivitis and periodontitis to health, and whether obesity modified this expression pattern. Method: Total RNA was extracted from gingival biopsy samples collected from 21 patients: 7 periodontal healt...

Objectives: To characterise clinical, microbial and host-response effects following an oral hygiene intervention and subsequent professional prophylaxis in subjects with gingivitis. Methods: 31 subjects with gingivitis (Löe and Silness Gingival index > 2 at 20 sites) completed an 8-week longitudinal study comprising two interventions: Hygiene pha...

Purpose: To assess the relationship between the presence or absence of visible third molars and outcomes for periodontal inflammatory disease. Methods: Obstetric subjects, at enrollment in an institutional review board-approved, multisite study, Maternal Oral Therapy to Reduce Obstetric Risk (N = 1,798), were divided into 2 groups, those with no...

Objective: We previously reported results of genome-wide association studies (GWAS) of periodontal disease using phenotypes based upon either clinical parameters, including categorical or continuous definitions of disease, or plaque composition, which did not identify any genome-wide significant loci. We sought to improve our candidate-gene discove...

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (A...

Background: Tumor necrosis factor-α (TNF-α) plays a central role in the molecular pathogenesis of periodontal disease. However, the epigenetic regulation attributable to microbial and inflammatory signals at the biofilm-gingival interface are poorly understood. In this study, the DNA methylation alteration within the TNFA promoter in human gingiva...

PURPOSE: To assess the impact of mechanical debridement of subgingival biofilm on periodontal outcomes in adolescents and young adults with asymptomatic third molars. METHODS: Healthy participants with 4 asymptomatic third molars were enrolled in an institutional review board-approved longitudinal study. Clinical data were collected at enrollment a...

Background: Periodontitis is a novel risk factor for inflammation and cardiovascular disease in the dialysis population. Limited information exists about the impact of periodontal therapy in patients receiving dialysis. Study design: Randomized controlled trial to assess feasibility and gather preliminary data. Setting & participants: Dialysis...

We aimed to evaluate the microbial and inflamma-tory characteristics associated with Denture Stomati-tis (DS) analyzing: l) Levels of salivary cytokines and cultivable C. albicans; 2) DNA-DNA checkerboard on biofilm associated with mucosal tissue-bearing den-ture surfaces, 3) Serum C-reactive protein (CRP) lev-els. Thirty-two subjects were enrolled...

Periodontitis is a primarily bacterial infection that is common in dentate individuals, while denture stomatitis is a predominantly fungal infection that is common among denture wearers. Both infections may increase a patient's risk for chronic systemic infection dissemination, and may in turn increase the risk of chronic, inflammatory-based system...

Objectives We examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the Dental Atherosclerosis Risk in Communities Study. Design Cross-sectional. Setting Community dwelling subjects from four US communities. Participants an...