Advances in precision oral health.

The concept of precision dentistry as it relates to precision medicine is relatively new to the field of oral health. Precision dentistry is a contemporary, multifaceted, data-driven approach to oral health care that uses individual characteristics to stratify similar patients into phenotypic groups. The objective is to provide clinicians with the information that will allow them to improve treatment planning and a patient's response to treatment. Providers that use a precision oral health approach would move away from using an "average treatment" for all patients with a particular diagnosis and move toward more specific treatments for patients within each diagnostic subgroup. Precision dentistry requires a method or a model that places each individual in a subgroup where each member is the same as every other member in relation to the disease of interest. Precision dentistry is a paradigm shift that requires a new way of thinking about diagnostic categories. This approach uses patients' risk factor data (including, but not limited to, genetic, environmental, and health behavioral), rather than expert opinion or clinical presentation alone, to redefine traditional categories of health and disease. We review aspects of current efforts to allow precision dentistry to be realized and focus on one of the major innovations that may help precision dentistry to be practiced by periodontists, the World Workshop Model. Another approach is the Periodontal Profile Class system. These two approaches represent examples of supervised and unsupervised learning systems, respectively. This review compares and contrasts these two learning systems for their ability to classify patients into homogeneous disease and risk groups, as well as their feasibility at achieving the objective of enabling precision dentistry. We conclude that: (a) the World Workshop Model concept of stages and grades works as expected, in that periodontal status appears to be more serious in each successive stage. In addition, the seriousness and the complexity of the disease are greater as the grade increases within each stage. Stages and grades are important for precision dentistry because they consider the risk of future disease and the prognosis, and enable practitioners to use more signs, symptoms, and other associated factors when placing a patient in a diagnostic category; (b) the assignment of stages and grades using unsupervised learning systems is superior to using supervised learning systems for the prediction of 10-year tooth loss and 3-year attachment loss progression. In addition, the unsupervised learning approach (Periodontal Profile Class stages) results in stronger associations between the periodontal phenotypes and systemic diseases and conditions (prevalent diabetes, C-reactive protein, and incident stroke). This probably occurs because an unsupervised learning model produces more data-driven, mutually exclusive, homogeneous groups than a supervised learning model.

Biologically Defined or Biologically Informed Traits Are More Heritable Than Clinically Defined Ones: The Case of Oral and Dental Phenotypes.

The genetic basis of oral health has long been theorized, but little information exists on the heritable variance in common oral and dental disease traits explained by the human genome. We sought to add to the evidence base of heritability of oral and dental traits using high-density genotype data in a well-characterized community-based cohort of middle-age adults. We used genome-wide association (GWAS) data combined with clinical and biomarker information in the Dental Atherosclerosis Risk In Communities (ARIC) cohort. Genotypes comprised SNPs directly typed on the Affymetrix Genome-Wide Human SNP Array 6.0 chip with minor allele frequency of >5% (n = 656,292) or were imputed using HapMap II-CEU (n = 2,104,905). We investigated 30 traits including "global" [e.g., number of natural teeth (NT) and incident tooth loss], clinically defined (e.g., dental caries via the DMFS index, periodontitis via the CDC/AAP and WW17 classifications), and biologically informed (e.g., subgingival pathogen colonization and "complex" traits). Heritability (i.e., variance explained; h2) was calculated using Visscher's Genome-wide Complex Trait Analysis (GCTA), using a random-effects mixed linear model and restricted maximum likelihood (REML) regression adjusting for ancestry (10 principal components), age, and sex. Heritability estimates were modest for clinical traits-NT = 0.11 (se = 0.07), severe chronic periodontitis (CDC/AAP) = 0.22 (se = 0.19), WW17 Stage 4 vs. 1/2 = 0.15 (se = 0.11). "High gingival index" and "high red complex colonization" had h2 > 0.50, while a periodontal complex trait defined by high IL-1ß GCF expression and Aggregatibacter actinomycetemcomitans subgingival colonization had the highest h2 = 0.72 (se = 0.32). Our results indicate that all GWAS SNPs explain modest levels of the observed variance in clinical oral and dental measures. Subgingival bacterial colonization and complex phenotypes encompassing both bacterial colonization and local inflammatory response had the highest heritability, suggesting that these biologically informed traits capture aspects of the disease process and are promising targets for genomics investigations, according to the notion of precision oral health.

Antepartum periodontitis treatment and risk of offspring screening positive for autism spectrum disorder.

BACKGROUND: To evaluate if treating maternal periodontal disease, a pro-inflammatory condition, during pregnancy (intervention) compared to after pregnancy (control) reduces the likelihood of offspring screening positive for autism spectrum disorder (ASD). METHODS: In a follow-up study to the MOTOR randomized trial, we compared rates of positive screens on the Modified Checklist for Autism in Toddlers (M-CHAT) among n = 306 two-year-old toddlers and correlated findings to maternal and cord blood pro-inflammatory interleukin-6 (IL-6). RESULTS: Toddlers in the intervention group had decreased risk of a positive M-CHAT screen (adjusted RR = 0.53, 95% CI 0.29-0.99). Toddlers screening positive compared to negative had higher mean IL-6 in cord blood (1.58 ± 1.14 vs. 1.09 ± 0.72 p = 0.001) and maternal IL-6 change from baseline (1.30 ± 0.61 vs 0.96 ± 0.62 p = 0.03). CONCLUSIONS: Treating periodontal disease during pregnancy reduced risk of a positive ASD screen. M-CHAT positivity was associated with increased IL-6 in maternal and cord blood. CLINICAL TRIAL: Trial Registration numbers: Clinicaltrials.gov NCT03423836.

Periodontal disease, undiagnosed diabetes, and body mass index: Implications for diabetes screening by dentists.

BACKGROUND: Periodontal disease and diabetes are widespread comorbid conditions that are detrimental to oral and overall health. Dentists' performing chairside screenings for undiagnosed diabetes mellitus (UDM) can be beneficial to both patients and providers. The authors determined UDM rates in a population-based study and whether UDM and periodontal disease were independently associated. METHODS: Data from 7,343 participants in the Atherosclerosis Risk in Communities study visit 4 were used to determine rates of UDM by periodontal status, edentulism, and body mass index. The authors used a χ2 test or analysis of variance, along with a 2-stage logistic regression model, to determine relationships with UDM. UDM was defined as no self-reported diabetes and blood glucose levels (fasting glucose ≥ 126 milligrams/deciliter or nonfasting glucose > 200 mg/dL). Periodontal disease was defined using the Periodontal Profile Classes system adapted to stages and the Centers for Disease Control and Prevention and American Academy of Periodontology index. RESULTS: UDM rates overall were 5.6%. The highest rates occurred in patients who were obese and edentulous (12.6%) and obese and had severe periodontal disease (12.2%). Significant associations were found for UDM and severe periodontal disease (Periodontal Profile Classes system stage IV) (odds ratio, 1.78; 95% confidence interval, 1.10 to 2.88). Edentulism was significantly associated with UDM in the Periodontal Profile Classes system model (odds ratio, 1.87; 95% confidence interval, 1.27 to 2.75) and Centers for Disease Control and Prevention and American Academy of Periodontology index (odds ratio, 1.70; 95% confidence interval, 1.08 to 2.67). Hyperglycemia was found in participants of all body mass index categories. CONCLUSIONS: UDM is significantly associated with obesity, edentulism, and periodontitis. These characteristics could help dentists identify patients at higher risk of developing DM. Patients without these characteristics still have UDM, so dentists performing chairside diabetes screening for all patients would yield additional benefit. PRACTICAL IMPLICATIONS: Dental offices are a major point of contact within the US health care system. Diabetes screening in this setting can provide important health information with direct relevance to patient care.

Periodontitis and Risk of Diabetes in the Atherosclerosis Risk In Communities (ARIC) Study: A BMI-Modified Association.

PURPOSE: To determine whether periodontal disease is positively associated with incident diabetes across the continuum of body mass levels (BMI) and test the hypothesis that the periodontal risk for incident diabetes is modified by BMI. METHODS: We included 5569 diabetes-free participants from Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities study and followed them until 2018. Periodontal disease status was classified by periodontal profile class (PPC)-Stages , and incident diabetes was based on participant report of physician diagnosis. We estimated the hazard ratios (HR) for diabetes using a competing risk model for each PPC-Stage. We assessed multiplicative interactions between periodontal disease and BMI (as a continuous variable) on risk of diabetes. RESULTS: During a median time of 19.4 years of follow-up, 1348 incident diabetes cases and 1529 deaths occurred. Compared to the "Health/Incidental Disease" stage, participants with PPC "Severe Periodontal Disease" or "Severe Tooth Loss" stage and lower BMI had elevated risk for diabetes adjusting for demographic, smoking, education, and biological variables when accounting for death as a competing risk with HRs of 1.76 (95% CI 1.10-2.80) and 2.11 (95% CI 1.46-3.04), respectively. The interaction between PPC-Stages and BMI was significant (P = 0.01). No significant associations of PPC-Stages with incident diabetes were present when BMI was above 31 kg/m2. CONCLUSION: Periodontal disease was associated with incident diabetes, especially in nonobese participants. Dentists should be aware that periodontal disease is associated with incident diabetes but the association may be modified for patient's at higher BMI levels.

Periodontal disease classifications and incident coronary heart disease in the Atherosclerosis Risk in Communities study.

BACKGROUND: Periodontal disease has been linked to coronary heart disease (CHD), but studies have been inconclusive. This study investigates the link between periodontal disease and incident CHD. METHODS: Baseline periodontal data from a full-mouth periodontal exam (N = 6,300) and CHD outcomes through 2017 were obtained from the Atherosclerosis Risk in Communities Study. Periodontitis was defined by the Periodontal Profile Class System adapted to Stages (PPC stages) and the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) index. Competing risk models were used to determine hazard ratios (HR) for incident CHD, congestive heart failure (CHF), and other causes of death. Secondary analysis included myocardial infarction (MI) and fatal CHD. RESULTS: Females comprised 56% of participants and males 44% with a combined mean age of 62.3 years (range: 52 to 74). Participants were followed for an average of 16.7 (SD: 5.5) years. In a fully adjusted model, PPC stage VII (Severe Tooth Loss) was moderately significantly related to incident CHD, (HR 1.51 [1.11 to 2.09]). PPC stage V (Mild Tooth Loss/High Gingival Inflammation) was significant for fatal CHD (HR, 5.27 [1.80 to 15.4]) and PPC stage VII was significant for incident MI (HR, 1.59 [1.13 to 2.23]). The CDC/AAP definition was not significantly associated with incident CHD. CONCLUSIONS: Incident CHD was moderately significantly associated with a specific stage of periodontal disease characterized by severe tooth loss, while none of the categories of the CDC/AAP were significantly associated. Thus, while periodontal therapy may improve oral health, it may be effective at impacting CHD incidence in only certain groups of people.