Periodontitis and risk of cancer: Mechanistic evidence.

This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low-grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro-aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non-indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor-associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor-infiltrating T cells) and the increased expression of pro-inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors.

Association of carotid intima-media thickness with periodontitis may depend on glycemic control.

BACKGROUND: There is evidence indicating that atherosclerosis is associated with periodontitis, especially in those with diabetes. The purpose of the present study was to determine whether glycemic control influences such association. METHODS: Cross-sectional data on 214 patients diagnosed with type 2 diabetes mellitus were obtained including results of basic laboratory tests, a periodontal examination, and carotid measurements. The association of periodontal parameters and carotid intima-media thickness (cIMT) or carotid plaque (CP) was evaluated in subgroups. RESULTS: Mean cIMT was significantly correlated with mean PLI, mean BI or number of PD ≥4 mm in the whole sample and the group with poor glycemic control. In the group with good glycemic control, however, only the number of PD ≥4 mm was associated with mean cIMT. A multiple logistic regression analysis also revealed that each 1 increase in mean PLI, mean BI or number of PD ≥4 mm was correlated with an increased cIMT in the whole sample. CONCLUSIONS: In addition to confirming the relationship between periodontitis and atherosclerosis, our study found a stronger association in groups with poor glycemic control compared to those with good glycemic control, suggesting that blood glucose modifies the association between periodontitis and arterial injury.

In Vitro Models, Standards, and Experimental Methods for Tobacco Products.

Traditional tobacco products have well-known systemic and local oral effects, including inflammation, vasoconstriction, delayed wound healing, and increased severity of periodontal disease. Specifically in the oral cavity and the lung, cigarette smoking produces cancer, increased infectivity, acute and chronic inflammation, changes in gene expression in epithelial lining cells, and microbiome changes. In recent years, cigarette smoking has greatly decreased in the United States, but the use of new tobacco products has gained tremendous popularity. Without significant knowledge of the oral sequelae of products such as electronic cigarettes, researchers must evaluate current in vitro and in vivo methods to study these agents, as well as develop new tools to adequately study their effects. Some in vitro testing has been performed for electronic cigarettes, including toxicologic models and assays, but these mostly study the effect on the respiratory tract. Recently, direct exposure of the aerosol to in vitro 3-dimensional tissue constructs has been performed, demonstrating changes in cell viability and inflammatory cytokines. For in vivo studies, a universal e-cigarette testing machine or standard vaping regime is needed. A standard research electronic cigarette has recently been developed by the National Institute of Drug Abuse, and other devices delivering aerosols with different nicotine concentrations are becoming available. One of the biggest challenges in this research is keeping up with the new products and the rapidly changing technologies in the industry.

Cross-sectional association between oral health and retinal microcirculation.

AIM: To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. METHODS: We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR < 0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. RESULTS: Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [ß = -0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [ß = -0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [ß = 3.80 (0.61; 6.98 95%-CI)], mean probing depth [ß = 1.86 (0.23; 3.49 95%-CI)] and mean attachment level [ß = 1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [ß = 0.91 (0.14; 1.69 95%-CI)]. CONCLUSIONS: Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.

Effect of Periodontitis and Periodontal Therapy on Oral and Gut Microbiota.

Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients (n = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects (n = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. ß-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls (P < 0.001). Periodontal therapy was associated with a significant change in gut microbiota (P < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of Bacteroides, Faecalibacterium, Fusobacterium, and Lachnospiraceae was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, Lactobacillus was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut Bacteroides, Lachnoclostridium, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae, to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.

Quantitive Assessment of Gustatory Function and Its Association with Demographics, and Systemic Morbidity.

This study aimed to analyze the associations of gustatory dysfunction as measured by validated taste strips with demographics and co-morbidities. This cross-sectional study retrospectively analyzed records of patients who attended the Orofacial Chemosensory Center of Hadassah Medical Center between 2017 and 2020. Taste strips were used as a validated method to determine taste dysfunction. A total of 272 subjects were included, 137 (50.4%) women and 135 (49.6%) men, with a mean age of 53.5 ± 19.3 years and age range of 18-98 years. The total taste score among the study population was 8.53 ± 4.03 (scale range 0-16). Age had a significant negative correlation with the total taste score (p = 0.001), and men exhibited worse total (p < 0.001), salty (p = 0.003), and bitter (p < 0.001) scores. Major trauma was associated with worse total (p < 0.001) and specialized taste assessments (sweet (p = 0.001), sour (p = 0.002), salty (p = 0.016), and bitter (p < 0.001)). Chemotherapy was associated with reduced total (p < 0.001), salty (p = 0.003), and bitter (p = 0.001) taste scores. Zinc deficiency exhibited worse salty (p = 0.027) and total (p = 0.038) taste scores. Patients with burning mouth syndrome (BMS) showed higher salty scores (p = 0.017). Patients who experienced exposure to toxic chemicals exhibited worse salty scores (p = 0.024). We conclude that gustatory dysfunction is associated with older age, male sex, and co-morbidities of major trauma, current chemotherapy, zinc deficiency, BMS, and exposure to toxins. The study highlights the importance of systemic evaluation and quantitive gustatory dysfunction assessment as part of the diagnostic process of patients with subjective complaints of taste disorders.

Glycemic and Insulin Status in Periodontitis Patients using the Homeostasis Model Assessment (HOMA): A Pilot Study.

PURPOSE: This study aimed to compare insulin status and dysglycemia (prediabetes/diabetes) of patients with chronic (stage III, grade B) or aggressive periodontitis (stage III, grade C) to that of a healthy population. MATERIALS AND METHODS: Patients with chronic (CP, n = 16) or aggressive periodontitis (AP, n = 15) and periodontally healthy controls (n = 32) were recruited. Body mass index was calculated. Glycemia, plasma insulin, glycated hemoglobin, C-reactive protein, and lipid levels were measured in fasting. The Homeostasis Model Assessment was used to calculate the insulin sensitivity (HOMA-%S), the beta-cell function (HOMA-%B), and their hyperbolic product (HOMA-%BxS). RESULTS: The CP group showed statistically significantly insulin resistance with a lower HOMA-%S (p = 0.0003) and a reduced HOMA-%BxS (p = 0.049) despite a higher insulin level (p = 0.01) vs the control group, even after BMI adjustment. There was also a trend to dysglycemia (prediabetes/diabetes) in the chronic group. In patients with AP, no abnormalities in insulin status were observed and glycemic levels were comparable with controls. Additionally, patients in both AP and CP groups presented significantly higher CRP levels compared to those of the control group (p = 0.02). CONCLUSION: Patients with CP showed reduced insulin sensitivity, increased insulin levels but a reduced %BxS product and a trend to dysglycemia. These abnormalities were not observed in AP.

Exploring the relationship between oral health and multiple health conditions: An outcome-wide approach.

PURPOSE: A growing body of evidence suggests that oral health is associated with a wide range of health outcomes; however, opinions tend to vary because of inconsistent findings. This study aimed to simultaneously examine the association between oral health status and multiple health and well-being indicators using outcome-wide epidemiology. METHODS: Data were obtained from the Japan Gerontological Evaluation Study. Oral health status was categorized as: ≥20 teeth, 10-19 teeth with dental prosthesis, 0-9 teeth with prosthesis, 10-19 teeth without prosthesis, and 0-9 teeth without prosthesis. We examined the associations between oral health status in 2013 and 35 health and well-being outcomes in 2019, including physical/cognitive health, psychological distress, subjective health, social well-being, prosocial/altruistic behaviors, and health behaviors, using two databases (n=32,827 and 15,905). RESULTS: Compared to individuals with ≥20 teeth, those with <20 teeth had a 10-33% higher risk of mortality and a 7-10% higher risk of functional disability six years later. Additionally, individuals with fewer than 20 teeth tended to go out less frequently and eat fewer vegetables and fruits. Furthermore, individuals with 0-9 teeth without a prosthesis were more likely to have severe functional disability (risk ratio (RR):1.17, 95% confidence interval (CI):1.05-1.31), engage in fewer intellectual activities (standardized difference: 0.17, 95% CI: 0.10-0.24), and feel more hopeless (RR: 1.21, 95% CI: 1.04-1.41). CONCLUSIONS: The prevention of tooth loss and prosthodontic treatment may be associated with reduced mortality and functional disability, as well as maintenance of intellectual ability, frequency of going out, and improvements in dietary lifestyle.

A Weighted Composite of Endodontic Inflammatory Disease is Linked to a First Myocardial Infarction.

PURPOSE: To explore a weighted composite of endodontic inflammatory disease (EID) as a risk factor for suffering a first myocardial infarction (MI). MATERIALS AND METHODS: Seven tooth-specific conditions related to EID were assessed radiographically in 797 patients suffering a first MI and 796 controls. A weighted composite of EID was calculated as the sum of all teeth, excluding third molars. Using maximum likelihood estimation, each condition was assigned a specific weight. With multivariable conditional regression, EID variables, periodontal disease, and missing teeth were assessed as predictors of a first MI. RESULTS: Periodontal disease (OR 1.38; 95% CI 1.13-1.69, p = 0.0016) and missing teeth (OR 1.03; 95% CI 1.002-1.05, p = 0.034) were related to the risk of a first MI, while none of the EID-related conditions individually were. However, when assessed as an aggregate, a weighted composite of EID (OR 1.97; 95% CI 1.23-3.17, p = 0.0050) and periodontal disease (OR 1.34; 95% CI 1.09-1.63, p = 0.0046) was associated with the risk of MI. Missing teeth did not remain a statistically significant predictor of MI in the final model. CONCLUSIONS: A weighted composite of EID was associated with the risk of MI and strengthens the evidence for a direct connection between oral inflammatory diseases and cardiovascular disorders.

Periodontitis and Metabolic Syndrome: Statistical and Machine Learning Analytics of a Nationwide Study.

This study aimed to analyze the associations between periodontitis and metabolic syndrome (MetS) components and related conditions while controlling for sociodemographics, health behaviors, and caries levels among young and middle-aged adults. We analyzed data from the Dental, Oral, and Medical Epidemiological (DOME) record-based cross-sectional study that combines comprehensive sociodemographic, medical, and dental databases of a nationally representative sample of military personnel. The research consisted of 57,496 records of patients, and the prevalence of periodontitis was 9.79% (5630/57,496). The following parameters retained a significant positive association with subsequent periodontitis multivariate analysis (from the highest to the lowest OR (odds ratio)): brushing teeth (OR = 2.985 (2.739-3.257)), obstructive sleep apnea (OSA) (OR = 2.188 (1.545-3.105)), cariogenic diet consumption (OR = 1.652 (1.536-1.776)), non-alcoholic fatty liver disease (NAFLD) (OR = 1.483 (1.171-1.879)), smoking (OR = 1.176 (1.047-1.322)), and age (OR = 1.040 (1.035-1.046)). The following parameters retained a significant negative association (protective effect) with periodontitis in the multivariate analysis (from the highest to the lowest OR): the mean number of decayed teeth (OR = 0.980 (0.970-0.991)); North America as the birth country compared to native Israelis (OR = 0.775 (0.608-0.988)); urban non-Jewish (OR = 0.442 (0.280-0.698)); and urban Jewish (OR = 0.395 (0.251-0.620)) compared to the rural locality of residence. Feature importance analysis using the eXtreme Gradient Boosting (XGBoost) machine learning algorithm with periodontitis as the target variable ranked obesity, OSA, and NAFLD as the most important systemic conditions in the model. We identified a profile of the "patient vulnerable to periodontitis" characterized by older age, rural residency, smoking, brushing teeth, cariogenic diet, comorbidities of obesity, OSA and NAFLD, and fewer untreated decayed teeth. North American-born individuals had a lower prevalence of periodontitis than native Israelis. This study emphasizes the holistic view of the MetS cluster and explores less-investigated MetS-related conditions in the context of periodontitis. A comprehensive assessment of disease risk factors is crucial to target high-risk populations for periodontitis and MetS.

Periodontitis Salivary Microbiota Worsens Colitis.

Evidence suggests that periodontitis contributes to the pathogenesis of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. However, few studies have examined the role of swallowing and saliva in the pathogenesis of gastrointestinal diseases. Saliva contains an enormous number of oral bacteria and is swallowed directly into the intestine. Here, we explored the influence of periodontitis salivary microbiota on colonic inflammation and possible mechanisms in dextran sulfate sodium (DSS)-induced colitis. The salivary microbiota was collected from healthy individuals and those with periodontitis and gavaged to C57BL/6 mice. Periodontitis colitis was induced by DSS for 5 d and ligature for 1 wk. The degree of colon inflammation was evaluated through hematoxylin and eosin staining, ELISA, and quantitative real-time polymerase chain reaction. Immune parameters were measured with quantitative real-time polymerase chain reaction, flow cytometry, and immunofluorescence. The gut microbiota and metabolome analyses were performed via 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Although no significant colitis-associated phenotypic changes were found under physiologic conditions, periodontitis salivary microbiota exacerbated colitis in a periodontitis colitis model after DSS induction. The immune response more closely resembled the pathology of ulcerative colitis, including aggravated macrophage M2 polarization and Th2 cell induction (T helper 2). Inflammatory bowel disease-associated microbiota, such as Blautia, Helicobacter, and Ruminococcus, were changed in DSS-induced colitis after periodontitis salivary microbiota gavage. Periodontitis salivary microbiota decreased unsaturated fatty acid levels and increased arachidonic acid metabolism in DSS-induced colitis, which was positively correlated with Aerococcus and Ruminococcus, suggesting the key role of these metabolic events and microbes in the exacerbating effect of periodontitis salivary microbiota on experimental colitis. Our study demonstrated that periodontitis contributes to the pathogenesis of colitis through the swallowing of salivary microbiota, confirming the role of periodontitis in systemic disease and providing new insights into the etiology of gastrointestinal inflammatory diseases.

Commentary: The Changing Face of Dentistry.

KNOWLEDGE TRANSFER STATEMENT: This article reviews social, economic, and technological trends affecting the future of dentistry. These trends have important implications for the training of dentists and the organization of dental care with the aim of improving the oral health of the public. Clinical and translational research has an essential role to play in developing the interventions and evidence base for these improvements.

Serum C-Reactive Protein and Periodontitis: A Systematic Review and Meta-Analysis.

Periodontitis has been associated with low-grade inflammation as assessed by C-reactive protein (CRP) levels and its treatment can decrease CRP serum levels. The aim of this systematic review was to critically appraise the evidence comparing CRP serum levels (standard and high-sensitivity [hs]) of otherwise healthy patients suffering from periodontitis when compared to controls. The impact of intensive and non-intensive nonsurgical periodontal treatment (NSPT) on hs-CRP was also investigated. Four electronic databases (Pubmed, The Cochrane Central Register of Controlled Trials [CENTRAL], EMBASE and Web of Science) were searched up to February 2021 and the review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No. CRD42020167454). Observational and intervention studies that: 1) evaluated CRP and hs-CRP serum levels in patients with and without periodontitis, and; 2) hs- CRP levels after NSPT were included. Following risk of bias appraisal, both qualitative and quantitative analyses were performed. Pooled estimates were rendered through ratio of means (RoM) random-effects meta-analyses. After screening 485 studies, 77 case-control studies and 67 intervention trials were included. Chronic and aggressive periodontitis diagnoses were consistently associated with higher levels of CRP and hs-CRP (p<0.001). Patients with aggressive periodontitis exhibited on average more than 50% higher levels of CRP (RoM [95% confidence interval [CI]]: 1.56 [1.15; 2.12], p=0.0039) than patients with chronic periodontitis. Intensive NSPT induced an immediate increase of hs-CRP followed by a progressive decrease whilst non-intensive NSPT consistently decreased hs-CRP after treatment up to 180 days (p<0.001). These findings provide robust evidence that periodontitis is associated with systemic inflammation as measured by serum CRP levels. Periodontitis treatment induces a short-term acute inflammatory increase when performed in an intensive session, whilst a progressive reduction up to 6 months was demonstrated when performed in multiple visits.

The Bacterial Connection between the Oral Cavity and the Gut Diseases.

More than 100 trillion symbiotic microorganisms constitutively colonize throughout the human body, including the oral cavity, the skin, and the gastrointestinal tract. The oral cavity harbors one of the most diverse and abundant microbial communities within the human body, second to the community that resides in the gastrointestinal tract, and is composed of >770 bacterial species. Advances in sequencing technologies help define the precise microbial landscape in our bodies. Environmental and functional differences render the composition of resident microbiota largely distinct between the mouth and the gut and lead to the development of unique microbial ecosystems in the 2 mucosal sites. However, it is apparent that there may be a microbial connection between these 2 mucosal sites in the context of disease pathogenesis. Accumulating evidence indicates that resident oral bacteria can translocate to the gastrointestinal tract through hematogenous and enteral routes. The dissemination of oral microbes to the gut may exacerbate various gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer. However, the precise role that oral microbes play in the extraoral organs, including the gut, remains elusive. Here, we review the recent findings on the dissemination of oral bacteria to the gastrointestinal tract and their possible contribution to the pathogenesis of gastrointestinal diseases. Although little is known about the mechanisms of ectopic colonization of the gut by oral bacteria, we also discuss the potential factors that allow the oral bacteria to colonize the gut.

Inhibition of angiotensin II receptor I prevents inflammation and bone loss in periodontitis.

BACKGROUND: Periodontal disease is characterized by alveolar bone destruction and degenerative lesions of the periodontal ligament (PDL); it is initiated by bacterial infection of the oral cavity, but the clinical effects are secondary to an aberrant host immune response. Primary hypertension (PH), which causes significant morbidity and mortality worldwide, has also been shown to be an inflammatory disease characterized by aberrant immune cell infiltration and activation. Clinical retrospective studies have shown a link between PH and periodontitis with PH exacerbating periodontitis and vice versa, but the pathophysiologic mechanisms responsible for this remain unknown. METHODS: In this study, we investigate the underlying mechanisms behind PH exacerbation of periodontitis by using a bacteria-induced periodontitis model in normotensive and hypertensive (Nos3-/- ) mice treated with or without an Angiotensin II (Ang II) specific receptor 1 (AT1) antagonist, losartan. The histologic analyses including immunohistochemistry, immunofluorescence were carried out. The qRT-PCR and ELISAs were applied for the target gene and protein detection. RESULTS: We find that PH worsens bone resorption and PDL destruction in periodontitis and that treatment with losartan, rescues this. We also show that PH increases dendritic cell (DC) and osteoclast (OC) infiltration in periodontitis, which is also dependent on Ang II. Finally, we show that PH augments the pro-inflammatory state in periodontitis infiltrating DCs in an Ang II-dependent manner and use in vitro studies to show that Ang II directly augments DC Toll-like receptor 4 (TLR4) signaling. CONCLUSION: Our studies show a central role for Ang II as a pro-inflammatory Toll-like receptor mediator in the pathogenesis of PH-exacerbated periodontitis, indicating that Ang II may be a reasonable target in patients with PH and periodontitis comorbidity.

Tooth Development Associated with Mutations in Hereditary Vitamin D-Resistant Rickets.

Hereditary vitamin D-resistant rickets (HVDRR) is a rare genetic disorder caused by mutations at the level of the vitamin D receptor ( VDR) gene. The disease is characterized by refractory hypocalcemia, elevated serum levels of 1,25-dihydroxy-vitamin D, retarded growth, sparse body hair (sometimes alopecia), premature tooth loss, enlarged pulp chambers, thin dentine, and hypoplastic enamel. The aims of this study were 1) to document the dental development of children with HVDRR in association with the mutation type within the VDR and 2) to evaluate the association between dental development and the timing of and response to HVDRR treatment. Genome analysis was performed for 4 affected children (2 y 2 mo to 6 y 8 mo) under treatment with high doses of vitamin D and calcium. Longitudinal records of clinical and radiographic data on their dental development were assessed in relation to genetic profile and response to treatment. Treatment success depended on the position of the mutation within the VDR protein: children with the p.R391S mutation had a favorable outcome but maintained alopecia totalis, while 1 child with the p.H397P mutation and normal hair had no response to very high doses of vitamin D. The primary incisors, formed prenatally and first to emerge, were missing in 3 children and mobile in 1 child; parents reported loss within months posteruption. Posterior teeth were present, having erupted after treatment initiation. Hypoplastic enamel in emerging teeth was associated with late treatment onset. Mutation type in the VDR gene appears to be related to differences in the disease phenotype and response to treatment. Dental development represents an indicator of the disease process, initially protected by maternal blood levels of calcium and later restored by therapeutic supplies that normalize these levels. Knowledge Transfer Statement: Two novel mutations were associated with different HVDRR phenotypes, one of which responded positively to treatment. Early detection of the mutation should help pediatricians forecast treatment protocol and response. The results also highlight the direct relationship between dental development and blood calcium levels, underscoring the importance of early diagnosis and treatment of HVDRR to minimize the loss of primary teeth and reduce structural abnormalities of permanent teeth.

Metacarpal Cortical Bone Area Predicts Tooth Loss in Men.

The relationship between bone mineral density and tooth loss in men is unclear. The aim of this retrospective cohort study was to determine if relative metacarpal bone area (MCA) predicts tooth loss in a cohort of 273 male participants in the Dental Longitudinal Study and Normative Aging Study of the Department of Veterans Affairs. Outer and inner cortical bone widths of the middle metacarpal of the nondominant hand were measured on anteroposterior hand radiographs approximately 11 y apart. Baseline MCA was computed and categorized into quartiles. The men were followed from 1971 to 2015. Incident tooth loss during 2 intervals was examined: concurrent with the MCA measurements and long term over the total follow-up (17 ± 7 y). Radiographic alveolar bone loss (ABL) was measured on periapical radiographs as a percentage of the distance from the cementoenamel junction to root apex, and the number of teeth with ABL >40% was computed. Negative binomial generalized linear regression models estimated the mean number of teeth with ABL >40% and the number lost (concurrent and total), controlling for age, smoking, number of teeth at baseline, percentage teeth with ≥1 decayed/filled surface, and years of follow-up. At baseline, MCA was inversely related to number of teeth with >40% ABL. Men in the lowest MCA quartile (Q1) lost the most teeth, both concurrent with MCA measurements and long term, but the association differed by caries level (≤55% or >55% decayed/filled teeth). At the low caries level, the numbers lost in Q1 were 29% greater than in the highest MCA quartile (Q4). At the high caries level, the numbers lost in Q1 were more than twice those in Q4. Associations were attenuated when further controlled for number of teeth with ABL>40%. These findings suggest that systemic bone status plays a role in tooth loss and that the association may be mediated by alveolar bone loss. Knowledge Transfer Statement: Low relative metacarpal bone area was related to loss of alveolar bone and incident tooth loss in men. This information extends previous research, primarily studies of women, showing that osteoporosis adversely affects oral health. Knowledge of a patient's systemic bone status may be important for managing his or her periodontal disease. Tooth loss in the absence of periodontal inflammation may signify systemic bone loss. Interprofessional communication is central to maintaining optimal oral and bone health.

From Nitrate to Nitric Oxide: The Role of Salivary Glands and Oral Bacteria.

The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.

Metabolic Syndrome and Periodontal Disease Progression in Men.

Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that comprise the metabolic syndrome may play a role in the development or worsening of periodontitis.