[Temporomandibular dysfunction and bruxism in patients with early rheumatoid arthritis and at-risk patients: a cross-sectional study]. / Temporomandibulaire disfunctie en bruxisme bij patiënten met vroege reumatoïde artritis en risicopatiënten: een cross-sectioneel onderzoek.

What is the prevalence of temporomandibular dysfunction in patients with early rheumatoid arthritis and individuals at risk of rheumatoid arthritis? 3 groups (of 50 participants each) were examined for a possible TMD diagnosis: 1. patients with early rheumatoid arthritis, 2. at-risk individuals, and 3. healthy controls. A possible association with bruxism, determined on the basis of self-reporting and clinical features, was also examined. At-risk patients had a higher prevalence of TMD pain diagnoses compared to healthy controls (p = 0.046). Within the early rheumatoid arthritis group, seronegative patients had a higher prevalence of TMD pain diagnoses than seropositive patients (p = 0.048). No further differences in the prevalence of TMD diagnoses were found between the groups. Participants with a TMD pain diagnosis were more often diagnosed with probable sleep bruxism than those without a TMD pain diagnosis. The prevalence of TMD pain is increased in individuals at risk of rheumatoid arthritis and seronegative early rheumatoid arthritis patients, and is associated with signs of bruxism.

[Non-surgical peri-implantitis treatment with or without systemic antibiotics]. / Initiële behandeling van peri-implantitis met of zonder systemische antibiotica.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

External validation of a rapid, non-invasive tool for periodontitis screening in a medical care setting.

OBJECTIVES: Medical professionals should advise their patients to visit a dentist if necessary. Due to the lack of time and knowledge, screening for periodontitis is often not done. To alleviate this problem, a screening model for total (own teeth/gum health, gum treatment, loose teeth, mouthwash use, and age)/severe periodontitis (gum treatment, loose teeth, tooth appearance, mouthwash use, age, and sex) in a medical care setting was developed in the Academic Center of Dentistry Amsterdam (ACTA) [1]. The purpose of the present study was to externally validate this tool in an outpatient medical setting. MATERIALS AND METHODS: Patients were requited in an outpatient medical setting as the validation cohort. The self-reported oral health questionnaire was conducted, demographic data were collected, and periodontal examination was performed. Algorithm discrimination was expressed as the area under the receiver operating characteristic curve (AUROCC). Sensitivity, specificity, and positive and negative predictive values were calculated. Calibration plots were made. RESULTS: For predicting total periodontitis, the AUROCC was 0.59 with a sensitivity of 49% and specificity of 68%. The PPV was 57% and the NPV scored 55%. For predicting severe periodontitis, the AUROCC was 0.73 with a sensitivity of 71% and specificity of 63%. The PPV was 39% and the NPV 87%. CONCLUSIONS: The performance of the algorithm for severe periodontitis is found to be sufficient in the current medical study population. Further external validation of periodontitis algorithms in non-dental school populations is recommended. CLINICAL RELEVANCE: Because general physicians are obligated to screen patients for periodontitis, it is our general goal that they can use a prediction model in medical settings without an oral examination.

Gingival epithelium attachment to well- or partially cured resin composites.

Ideal restoration material for caries would allow attachment of gingival epithelia. The attachment of epithelial cells to specimens of the 4 most commercially used well- or partially-cured resin composites, with and without TEGDMA, was assessed. Effects of resin composite on the Ca9-22 gingival epithelial cell-line were assessed by measuring the cytotoxicity, viability and gene expression for attachment, apoptosis, ROS-production, pro-inflammatory cytokines, and matrix metalloproteinases. As controls, cells on tissue culture plastic or bovine tooth enamel specimens were used. Significantly less cell attachment was measured on freshly made resin-composite specimens. Concomitantly, significantly higher cytotoxicity was measured in the presence of freshly made resin-composite specimens. However, after 8 d of leakage, the cell attachment to and cytotoxicity of the resin composite was comparable to bovine tooth enamel. Significantly higher expressions of IL6, MMP2, BCL6 and ITGA4 were measured in cells attached to resin-composite surfaces than controls. There were no significant differences between the results using different conditions of resin composite, with or without TEGDMA and well or partially cured. Less cell attachment and presence of more inflammatory markers were observed on all freshly-made resin-composite surfaces. However, after a leakage period attachment of cells to the resin composite improved to the level of natural tooth materials such as enamel. This indicated that the negative effects of resin composites on epithelial cells might be transient.

[Stress and periodontitis]. / Stress en parodontitis.

Gingivitis and periodontitis can worsen with reduced immune fitness. Various causes can reduce immune fitness in a host, as a result of which the balance between the host and the microbiome is disturbed. Among others, lifestyle factors, such as stress and smoking, can have a negative influence on immune fitness. An association has been demonstrated between stress and periodontitis and also acute necrotising ulcerative gingivitis or periodontitis. There are indications that neurons are able to secrete pro-inflammatory cytokines and chemokines that worsen chronic inflammatory reactions in the periodontium and compromise immune fitness. In vitro studies show high cortisol levels may contribute to the increased growth of P. gingivalis. Stress as a risk factor for periodontitis and the role of stress as a negative influence on the results of periodontal treatment are difficult to estimate clinically. Nevertheless, attention to and awareness of stress as an aspect of the comprehensive set of risk factors for periodontitis can diminish its negative impact on immune fitness.

Family history of periodontal disease and prevalence of smoking status among adult periodontitis patients: a cross-sectional study.

OBJECTIVES: What is the family history of periodontal disease and the prevalence of smoking status among patients with professionally diagnosed periodontitis? Are these factors related to extent and severity of periodontitis? METHODS: Over a 10-year period, referred patients from a clinic for periodontology in the Netherlands were examined in a cross-sectional study. Patients received at the intake appointment a full-mouth periodontal examination. Data regarding family history of periodontitis and smoking status were recorded. RESULTS: A total of 5375 adult periodontitis patients were included in this study sample with a mean age of 50 years. The prevalence of smoking was 34% and 37% of the subjects had at least one parent or sibling with periodontitis. The chance to have severe periodontitis was higher if the patient was male, smoker or had a brother with periodontitis. Being male, smoker and having a parent with periodontitis were significantly associated with a larger extent of periodontitis. CONCLUSIONS: Within the investigated population familial aggregation, smoking status, age and gender are factors that were related to extent and severity of adult periodontitis.

Implementation process of all periodontal competences and assessments as proposed in the 2010 European consensus meeting into the existing local undergraduate curriculum.

AIM: To report on our implementation process within the existing local curriculum of all periodontal competences and assessments as proposed in the 2010 European consensus meeting. MATERIAL AND METHOD: In 2011, a workshop for all teaching staff at the Department of Periodontology, ACTA, an education and assessment blueprint, was developed to test for missing education and assessment of European competences, divided into seven domains. This was repeated in 2013. An oral evaluation of the staff followed both meetings. RESULTS: It appeared that eight of 58 (14%) European competences were not taught, and 21 (35%) competences were not assessed. After evaluation of the results on the actual curriculum and the assessment programme, shared decisions were made about how to teach and assess the missing competences within the local periodontal educational programme. The second workshop in 2013 revealed still 8 (14%) competences were not taught and 8 (14%) competences were not assessed. Staff appreciated the used method of validation; it gave insight and an overview of the curriculum. The existence of the European consensus report for undergraduate periodontal education, based on seven domains, has been instrumental and essential. CONCLUSION: The development of a blueprint from the education programme and concomitant assessment methods in periodontology by participating teaching staff gives a validation and appreciation of the curriculum and will improve the quality of education and assessment. It is advised that for quality control of the curriculum, dental schools could do this exercise for all their specialties if European consensus reports exist.

[Periodontitis and systemic diseases: from science to clinical practice]. / Parodontitis en systemische ziekten - van wetenschap naar praktijk.

The evidence for an association between systemic diseases and periodontitis is strongest with diabetes mellitus type 2 and cardiovascular disease. There is a moderate association of periodontitis with adverse pregnancy outcomes and rheumatoid arthritis. Periodontal treatment has, on average, a positive effect on reducing systemic infection and improving the condition of the vascular system. For diabetes patients, periodontal treatment can also have a positive effect on metabolic regulation. There is insufficient evidence that periodontal treatment prevents adverse pregnancy outcomes and rheumatoid arthritis.

Moving into a new era of periodontal genetic studies: relevance of large case-control samples using severe phenotypes for genome-wide association studies.

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial 'hypothesis-dependent' candidate-gene polymorphism studies did not report valid genetic risk loci. Following a large-scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of 'hypothesis-free' genome-wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published - one reported genome-wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well-designed genetic study with large and sufficiently powered case-control samples of severe phenotypes, are also discussed.

Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer.

Interrelationships between periodontal infection and systemic conditions such as cardiovascular disease, adverse pregnancy outcomes, and head-and-neck cancer have become increasingly appreciated in recent years. Periodontitis is associated with cardiovascular disease (CVD) and, experimentally, with measures of atherosclerosis and endothelial dysfunction. Periodontal therapy may reduce atherosclerotic changes and improve endothelial function. Preliminary findings suggest a role for the genetic locus ANRIL in the pathobiology of both CVD and periodontitis. Periodontal pathogens induce anticardiolipin in periodontitis patients by molecular mimicry of the serum protein ß-2 glycoprotein I. These antibodies have biological and pathological activities consistent with those reported for other infection-induced antiphospholipid antibodies. Anticardiolipin may explain some of the observed associations between periodontitis and systemic conditions such as CVD and adverse pregnancy outcomes. The oral commensal Fusobacterium nucleatum (Fn) becomes pathogenic on migration to extra-oral sites. Fn infection of the fetal-placental unit has been linked to pregnancy complications, including preterm birth, stillbirth, and early-onset neonatal sepsis. Reagents aimed at inhibiting or resolving inflammatory responses may be used to treat or prevent pregnancy complications due to bacterial infection. Chronic periodontitis may be independently associated with head-and-neck squamous cell carcinoma (HNSCC) through direct toxic effects of bacteria and their products, and/or through indirect effects of inflammation. Additionally, chronic periodontitis may facilitate the acquisition and persistence of oral HPV infection, a recently emerged risk factor for HNSCC.

[Treatment of periodontitis in cases of diabetes mellitus is always worthwhile!]. / Behandeling van parodontitis bij diabetes mellitus heeft altijd zin!

In the May edition of The Nederlands Tijdschrift voor Tandheelkunde the editorial commentary was devoted to the question to what extent the treatment of periodontitis in patients with diabetes mellitus is worthwhile. B.G. Loos, W.J. Teeuw, V. Gerdes and F. Abbas offer a response to this commentary and argue that the treatment of periodontitis in patients with diabetes mellitus is always worthwhile.

Cytokine and matrix metalloproteinase expression in fibroblasts from peri-implantitis lesions in response to viable Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: To assess inflammatory reactions of fibroblasts in the pathophysiology of peri-implantitis, we compared the pro-inflammatory and matrix-degrading responses of gingival and granulation tissue fibroblasts from periodontally healthy controls, peri-implantitis, and periodontitis lesions to an in vitro challenge with Porphyromonas gingivalis. METHODS: Fibroblasts from periodontally healthy, peri-implantitis and periodontitis donors were challenged with viable P. gingivalis. The inflammatory reactions of fibroblasts were analyzed before and after 6 h P. gingivalis challenge, and 2.5 and 18 h after removal of the challenge. Gene expression and induction of pro-inflammatory mediators, and matrix metalloproteinases (MMPs) were assessed by real-time polymerase chain reaction. Protein expression was measured by enzyme-linked immunosorbent assay. RESULTS: Non-challenged fibroblasts from peri-implantitis and periodontitis lesions expressed higher levels of interleukin (IL)-1ß, IL-8, and monocyte chemotactic protein (MCP)-1 than fibroblasts from periodontally healthy individuals. The P. gingivalis challenge induced expression of IL-1ß, IL-8, IL-6, MCP-1, and MMP-1 in periodontitis and peri-implantitis fibroblasts, but not in fibroblasts from periodontally healthy individuals. MMP-8 expression was higher in non-challenged peri-implantitis fibroblasts than in fibroblasts from periodontally healthy individuals. However, the P. gingivalis challenge downregulated MMP-8 gene expression in peri-implantitis fibroblasts. After removal of the P. gingivalis challenge, peri-implantitis fibroblasts sustained higher induction of IL-1ß, MCP-1, and MMP-1 compared to periodontitis fibroblasts. CONCLUSIONS: Fibroblasts from peri-implantitis and periodontitis lesions gave a more pronounced inflammatory response to the P. gingivalis challenge than fibroblasts from healthy donors. They may therefore be involved in the development of inflammation in peri-implantitis and periodontitis. Moreover, the sustained upregulation of inflammatory mediators and MMP-1 in peri-implantitis fibroblasts may play a role in the pathogenesis of peri-implantitis.

Comparing culture, real-time PCR and fluorescence resonance energy transfer technology for detection of Porphyromonas gingivalis in patients with or without peri-implant infections.

BACKGROUND AND OBJECTIVE: The aim of the study was to compare the detection of Porphyromonas gingivalis using a fluorescence resonance energy transfer (FRET) technology with commonly used diagnostic methods in salivary and subgingival plaque samples from subjects with dental implants. P. gingivalis was considered as a marker for a pathogenic microbiota. MATERIAL AND METHODS: Ninety-seven adult subjects were recruited, including periodontally healthy controls with no dental implants, implant controls with no peri-implant disease and patients with peri-implant disease. Saliva and subgingival/submucosal plaque samples were collected from all subjects and were analyzed using culture, real-time PCR and FRET technology employing P. gingivalis-specific substrates. RESULTS: It was found that the P. gingivalis-specific substrates were highly suitable for detecting the presence of P. gingivalis in saliva and in subgingival plaque samples, showing comparable specificity to culture and real-time PCR. CONCLUSION: We applied the FRET technology to detect P. gingivalis in implant patients with or without an implant condition and in controls without implants. The technique seems suitable for detection of P. gingivalis in both plaque and saliva samples. However, with all three techniques, P. gingivalis was not very specific for peri-implantitis cases. Future work includes fine-tuning the FRET technology and also includes the development of a chair-side application.

The Effect of Periodontal Treatment on the Reactive Hyperemia Index. A 1-Year Follow-Up Pilot Study.

Background: Periodontitis is a chronic multifactorial inflammatory disease of the supportive tissues of the teeth. In more recent years, remarkable epidemiological and pathophysiological associations between periodontitis and cardiovascular disease (CVD) have been presented. Whether or not treatment of periodontitis is valuable for primary or secondary prevention of cardiovascular disease, has not yet been fully established. In this practice-based pilot study we focused on primary prevention of cardiovascular disease, by investigating the effect of periodontal treatment on the earliest detectable stage of CVD; endothelial dysfunction. Methods: Otherwise healthy periodontitis and non-periodontitis participants 45-70 years of age were included in the study. One year after completing periodontal (non-surgical and surgical) treatment of the periodontitis patients and 1 year after inclusion of the controls, all baseline measurements were repeated. Full-mouth examinations were performed by a periodontist to determine their Periodontal Inflamed Surface Area (PISA) score and other dental parameters. To assess the cardiovascular conditions, endothelial function through the reactive hyperemia index (RHI) assessed by the EndoPAT™, and several physical and biochemical parameters were measured. Results: 21 patients with diagnosed, untreated periodontitis and 21 participants without periodontitis were included in this follow-up study. After periodontal therapy in the periodontitis patients, the PISA reduced significantly. The RHI did not show a significant improvement after treatment of the periodontitis patients (-0.1 ± 0.8, p = 0.524). Similarly, other secondary cardiovascular outcome measurements, hsCRP, total cholesterol, HDL cholesterol, triglycerides, HbA1c, and systolic blood pressure did not improve significantly after periodontal treatment. Controls did not show any significant changes in the RHI, in other CVD parameters and in the PISA after 1-year follow-up. Conclusion: In this practice-based pilot study, periodontal treatment did not improve the endothelial function in otherwise healthy adults with periodontitis. Future studies are needed to be of larger size and could focus on periodontitis patients with co-morbidities to investigate whether periodontal treatment has secondary preventive effect on endothelial function and other CVD parameters. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ISRCTN55656827].

[Periodontal disease and quality of life]. / Parodontitis en levenskwaliteit.

In order to gain insight into the degree to which periodontal disease is related to quality of life, research was carried out among 85 patients with moderate or severe periodontal disease in which they were asked to complete the Oral Health Impact Profile-NL49. Their scores on this questionnaire were compared with the scores of 85 control subjects of comparable age and gender. The patients with periodontal disease demonstrated significantly worse scores compared to the control group and patients with severe periodontal disease had scores which were statistically significantly worse than patients with moderate periodontal disease. The results of this study suggest a causal negative association of periodontal disease with quality of life.

The association between periodontitis and cardiovascular risks in asymptomatic healthy patients.

BACKGROUND: Periodontitis is a chronic multifactorial inflammatory disease of the supportive tissues of the teeth. Pathophysiological evidence suggests a possible common inflammatory background between periodontitis and cardiovascular diseases (CVD). Pathological and epidemiological associations between these two diseases have been presented, but are still debated. This study aimed to investigate the association between the inflammatory burden of periodontitis and the presence and extent of coronary calcification. Secondary aims were to study other cardiovascular parameters and cardiovascular risk predictors in relation to periodontitis and dental health. METHODS: Healthy periodontitis or non-periodontitis patients 45-70 years of age were included in a prospective cross-sectional study. Full-mouth examinations were performed by a periodontist to determine their Periodontal Inflamed Surface Area (PISA) score and other dental parameters. To assess the cardiovascular conditions, Coronary Artery Calcium (CAC) scores, endothelial function assessments by the EndoPAT ™, and several physical and biochemical examinations were performed. RESULTS: Seventy-one patients were included. Elevated CAC scores and endothelial dysfunction were not significantly related to PISA or dental health. PISA was significantly related to the Framingham and Reynolds CVD risk predictors, but were no longer significant after correction for confounders. The same applied to the significant relations between tooth loss, dental plaque and bleeding scores and the CVD risk predictors. CONCLUSIONS: Periodontitis is associated with increased CVD risk, but is not an independent risk factor. This link is still important to make to bridge the gap between dentistry and general medicine and to identify patients at risk for CVD in an earlier stage.

A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis.

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

Elevated Coronary Artery Calcium scores are associated with tooth loss.

AIM: This study explores the association between Coronary Artery Calcium (CAC) scores and dental pathology such as missing teeth, the (peri-apical) health status and restoration grade of the teeth, and the grade of alveolar bone loss seen on a dental panoramic radiograph (Orthopantomograph-OPG). MATERIALS AND METHODS: In this retrospective cross-sectional study, data was collected from three hospitals spread in the Netherlands. Patients were included when a CAC score and an OPG were available, both recorded within a maximum period of 365 days from 2009-2017. The CAC score was measured on a CT scan, using the Agatston method. To assess dental pathology, the number of missing teeth, the number of dental implants, alveolar bone loss, caries, endodontic treatments, peri-apical radiolucencies, bone loss at implants, impacted teeth and dental cysts, were determined on the OPG. All observers were calibrated. The electronic health records provided information about: gender, age, smoking, Diabetes Mellitus, hypercholesterolemia, hypertension and Body Mass Index (BMI). RESULTS: 212 patients were included. We found a statistically significant association between the number of missing teeth and the CAC score. When modeling age, sex, and other well-known risk factors for cardiovascular disease, the significant correlation was no longer present after multivariate correction. Furthermore, the results showed a trend for more teeth with peri-apical lesions and a higher percentage of mean alveolar bone loss in the group with the highest CAC scores. CONCLUSION: This study showed that being edentulous or missing teeth is correlated to higher CAC scores however failed to be an independent predictor of atherosclerotic cardiovascular diseases. The number of (missing) teeth is an easily accessible marker and could be used as a marker for atherosclerotic cardiovascular disease (ACVD) risk by almost any healthcare worker. The current study needs to be considered as an explorative pilot study and could contribute to the design of further (prospective) studies on the relationship between dental pathology and coronary artery calcification by adding clinical information and extra cardiovascular biomarkers.

Temporomandibular joint function, periodontal health, and oral microbiome in early rheumatoid arthritis and at-risk individuals: a prospective cohort study protocol.

OBJECTIVES/AIMS: Rheumatoid arthritis (RA) is an autoimmune disease affecting the joints, including the temporomandibular joint (TMJ). Early diagnosis and treatment can alleviate symptoms and prevent progression. Predictors for disease outcome in individuals at risk for RA are therefore valuable. While limited information is available on the prevalence of TMJ involvement in early RA, previous studies suggest that RA, periodontitis and the oral microbiome are interrelated. Predictive factors for RA development may thus be present in the oral cavity. Our two aims are: (1) to assess the prevalence of TMJ involvement in early RA, and (2) to investigate the predictive value of oral factors in RA development. MATERIALS AND METHODS: We will include 150 individuals in this multi-center, prospective cohort study: 50 patients with early RA, 50 at-risk individuals, and 50 healthy controls. At baseline, the TMJ, periodontal health, and the oral microbiome will be examined. The general health will be followed over time, on four occasions up to 3 years. DISCUSSION: Our results will provide insight into the prevalence and clinical characterization of TMJ involvement in early RA. For at-risk individuals, oral factors can be studied as possible predictors for the development of RA.