Publications by authors named "Bruno G Loos"

117 Publications

Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans.

J Clin Periodontol 2021 Aug 18. Epub 2021 Aug 18.

Department of Periodontology, Oral Medicine and Oral Surgery, Charité - University Medicine Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Berlin, Germany.

Aims: Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity.

Materials And Methods: Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population.

Results: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13).

Conclusions: Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.
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http://dx.doi.org/10.1111/jcpe.13538DOI Listing
August 2021

Risk factors, diagnosis and treatment of peri-implantitis: A cross-cultural comparison of U.S. and European periodontists' considerations.

J Periodontol 2021 Aug 14. Epub 2021 Aug 14.

Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI.

Background: Peri-implantitis (PI) is a growing concern in the dental community worldwide. The study aimed to compare U.S. vs. European periodontists' considerations of risk factors, diagnostic criteria, and management of PI.

Materials And Methods: 393 periodontists from the U.S. and 100 periodontists from Europe (Germany, Greece, Netherlands) responded to anonymous surveys electronically or by mail.

Results: Compared to U.S. periodontists, European respondents were younger, more likely to be female and placed fewer implants per month (9.12 vs. 13.90;p = 0.003). Poor oral hygiene, history of periodontitis, and smoking were considered as very important risk factors by both groups (rated >4 on 5-point scale). European periodontists rated poor oral hygiene (4.64 vs. 4.45;p = 0.005) and history of periodontitis (4.36 vs. 4.10;p = 0.006) as more important and implant surface (2.91 vs. 3.18;p = 0.023), occlusion (2.80 vs. 3.75;p<0.001) and presence of keratinized tissue (3.27 vs. 3.77;p<0.001) as less important than did U.S. periodontists. Both groups rated clinical probing, radiographic bone loss, and presence of bleeding and suppuration as rather important diagnostic criteria. They rated implant exposure/mucosal recession as relatively less important with U.S. periodontists giving higher importance ratings than European periodontists (3.99 vs. 3.54;p = 0.001). Both groups nearly always used patient education, plaque control and mechanical debridement when treating PI. U.S. periodontists were more likely to use antibiotics (3.88 vs. 3.07;p<0.001), lasers (2.11 vs. 1.68;p = 0.005), allograft (3.39 vs. 2.14;p<0.001) and regenerative approaches (3.57 vs. 2.56;p<0.001), but less likely to use resective surgery (3.09 vs. 3.53;p<0.001) than European periodontists.

Conclusions: U.S. and European periodontists' considerations concerning risk factors, diagnosis and management of PI were evidence-based. Identified differences between the two groups can inform future educational efforts. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/JPER.21-0010DOI Listing
August 2021

Oral health-related quality of life in patients with early rheumatoid arthritis is associated with periodontal inflammation and painful temporomandibular disorders: a cross-sectional study.

Clin Oral Investig 2021 Jul 19. Epub 2021 Jul 19.

Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry of Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.

Objectives: To evaluate oral health-related quality of life (OHRQoL) in early rheumatoid arthritis (ERA) patients and individuals at risk of rheumatoid arthritis (RA) compared to healthy controls, and to explore possible associated factors.

Materials And Methods: Fifty ERA patients, 50 at-risk individuals, and 50 age and gender matched healthy controls were recruited. OHRQoL (Oral Health Impact Profile-14 (OHIP-14)); number of decayed, missing, and filled teeth (DMFT); denture use; periodontal inflamed surface area (PISA); xerostomia (xerostomia inventory (XI)); and possible TMD (-pain) diagnoses were recorded. The groups were compared on these variables. Subsequently, backward multiple regression analyses were performed for the ERA and at-risk groups, with OHRQoL as the dependent variable and gender, age, DMFT, denture use, PISA, XI, non-painful TMD, and TMD pain as independent variables.

Results: At-risk individuals had higher XI scores (U = 789.5, z = -3.181, p = 0.001, r = -0.32) and higher prevalence of TMD pain (p = 0.046, OR = 4.57; 95% CI 0.92-22.73) than healthy controls and higher OHIP-14 scores than the ERA group (U = 894.5, z = -2.418, p = 0.016, r = -0.24), while no difference in OHIP-14 was found between the control group and both other groups. For ERA patients, OHRQoL was associated with PISA and TMD pain (R = 0.498, p < 0.001). For at-risk individuals, OHRQoL was associated with XI score (R = 0.410, p < 0.001).

Conclusions: Alertness of health professionals to TMD pain and periodontal inflammation in ERA patients and to xerostomia and TMD pain in at-risk individuals is recommended.

Clinical Relevance: The results of this study address orofacial aspects that require attention of health professionals in the timeframe around RA onset.

Trial Registration: Dutch National Trial Register (NTR, NTR6362).
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http://dx.doi.org/10.1007/s00784-021-04034-zDOI Listing
July 2021

Implementation of an Oral Care Protocol for Primary Diabetes Care: A Pilot Cluster-Randomized Controlled Trial.

Ann Fam Med 2021 May-Jun;19(3):197-206. Epub 2021 May 10.

Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.

Purpose: Although diabetes care guidelines recommend paying attention to oral health, the effect on daily practice has been limited, and patients with diabetes have yet to benefit. We investigated whether implementation of an oral care protocol for general practitioners (GPs [family physicians]) can improve patient-centered outcomes for patients with type 2 diabetes.

Methods: Twenty-four GP offices were randomly assigned to the experimental or control group (12 offices each). In the experimental group, GPs and nurse practitioners implemented an oral care protocol. No extra attention was given to oral health in the control group. The primary outcome parameter was oral health-related quality of life (QoL) assessed with the 14-item Oral Health Impact Profile at baseline and 1 year later. Other outcomes were self-reported oral health complaints and general health-related QoL (36-item Short Form Health Survey).

Results: Of 764 patients with type 2 diabetes, 543 (71.1%) completed the 1-year follow-up. More patients reported improved oral health-related QoL in the experimental group (35.2%) compared to the control group (25.9%) ( = .046; = .049). In a secondary post hoc analysis including GP offices with ≥60% patient follow-up (n = 18), improvement was 38.3% and 24.9%, respectively ( and = .011). Improvement of self-reported oral health complaints did not differ between groups. The intervention had no effect on general health-related QoL, with the exception of the concept scale score for changes in health over time ( = .033).

Conclusions: Implementation of an oral care protocol in primary diabetes care improved oral health-related QoL in patients with type 2 diabetes.
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http://dx.doi.org/10.1370/afm.2645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118494PMC
May 2021

Submucosal microbiome of peri-implant sites: A cross-sectional study.

J Clin Periodontol 2021 Sep 14;48(9):1228-1239. Epub 2021 Jul 14.

Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU Amsterdam, Amsterdam, The Netherlands.

Aim: To study the peri-implant submucosal microbiome in relation to implant disease status, dentition status, smoking habit, gender, implant location, implant system, time of functional loading, probing pocket depth (PPD), and presence of bleeding on probing.

Materials And Methods: Biofilm samples were collected from the deepest peri-implant site of 41 patients with paper points, and analysed using 16S rRNA gene pyrosequencing.

Results: We observed differences in microbial profiles by PPD, implant disease status, and dentition status. Microbiota in deep pockets included higher proportions of the genera Fusobacterium, Prevotella, and Anaeroglobus compared with shallow pockets that harboured more Rothia, Neisseria, Haemophilus, and Streptococcus. Peri-implantitis (PI) sites were dominated by Fusobacterium and Treponema compared with healthy implants and peri-implant mucositis, which were mostly colonized by Rothia and Streptococcus. Partially edentulous (PE) individuals presented more Fusobacterium, Prevotella, and Rothia, whereas fully edentulous individuals presented more Veillonella and Streptococcus.

Conclusions: PPD, implant disease status, and dentition status may affect the submucosal ecology leading to variation in composition of the microbiome. Deep pockets, PI, and PE individuals were dominated by Gram-negative anaerobic taxa.
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http://dx.doi.org/10.1111/jcpe.13502DOI Listing
September 2021

Lower Number of Teeth Is Related to Higher Risks for ACVD and Death-Systematic Review and Meta-Analyses of Survival Data.

Front Cardiovasc Med 2021 7;8:621626. Epub 2021 May 7.

Academic Centre for Dentistry Amsterdam, Department of Social Dentistry, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Tooth loss reflects the endpoint of two major dental diseases: dental caries and periodontitis. These comprise 2% of the global burden of human diseases. A lower number of teeth has been associated with various systemic diseases, in particular, atherosclerotic cardiovascular diseases (ACVD). The aim was to summarize the evidence of tooth loss related to the risk for ACVD or death. Cohort studies with prospective follow-up data were retrieved from Medline-PubMed and EMBASE. Following the PRISMA guidelines, two reviewers independently selected articles, assessed the risk of bias, and extracted data on the number of teeth (tooth loss; exposure) and ACVD-related events and all-cause mortality (ACM) (outcome). A total of 75 articles were included of which 44 were qualified for meta-analysis. A lower number of teeth was related to a higher outcome risk; the pooled risk ratio (RR) for the cumulative incidence of ACVD ranged from 1.69 to 2.93, and for the cumulative incidence of ACM, the RR ranged from 1.76 to 2.27. The pooled multiple adjusted hazard ratio (HR) for the incidence density of ACVD ranged from 1.02 to 1.21, and for the incidence density of ACM, the HR ranged from 1.02 to 1.30. This systematic review and meta-analyses of survival data show that a lower number of teeth is a risk factor for both ACVD and death. Health care professionals should use this information to inform their patients and increase awareness on the importance of good dental health and increase efforts to prevent tooth loss.
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http://dx.doi.org/10.3389/fcvm.2021.621626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138430PMC
May 2021

Comparing periodontitis biomarkers in saliva, oral rinse and gingival crevicular fluid: A pilot study.

J Clin Periodontol 2021 Sep 20;48(9):1250-1259. Epub 2021 Jun 20.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Aim: To explore the feasibility of screening for periodontitis by measuring biomarkers, namely total proteolytic activity (TPA), matrix metalloproteinase (MMP)-8, chitinase, lysozyme or their combination, in saliva, oral rinse and gingival crevicular fluid (GCF).

Material And Methods: Subjects were recruited among healthy/gingivitis individuals and untreated periodontitis patients in Academic Centre for Dentistry Amsterdam (ACTA). All participants donated samples of unstimulated whole saliva, oral rinse and GCF. The protein concentrations and MMP-8 levels were determined by ELISA. Enzymatic activities were measured using appropriate fluorogenic substrates.

Results: In oral rinse samples, periodontitis patients (n = 19) exhibited significantly higher concentrations of MMP-8 and TPA than controls (n = 20). MMP-8 in combination with chitinase explained 88% of the variance and assigned a subject to control or periodontitis group, with best accuracy (87.2%) in oral rinse.

Conclusions: The combination of MMP-8 and chitinase in the current oral rinse procedure has the potential to discriminate periodontitis from periodontal health/gingivitis.
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http://dx.doi.org/10.1111/jcpe.13479DOI Listing
September 2021

The oral microbiome in early rheumatoid arthritis patients and individuals at risk differs from healthy controls.

Arthritis Rheumatol 2021 May 4. Epub 2021 May 4.

Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry of Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objective: It has been suggested that rheumatoid arthritis (RA) may originate at the oral mucosa. Our aim was to assess the oral microbiome and the periodontal condition in patients with early rheumatoid arthritis (ERA) and individuals at risk of RA.

Methods: Three groups were recruited (50 participants each): (1) ERA patients (2010 ACR/EULAR criteria), (2) at-risk individuals (arthralgia and autoantibodies), and (3) healthy controls. A periodontal examination resulted in scores for bleeding on probing (BOP), pocket probing depth (PPD), and periodontal inflamed surface area (PISA). The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S rDNA amplicon sequencing, and compared between groups with permutational multivariate analyses of variance (PERMANOVA).

Results: There was no difference between the groups on the periodontal variables (BOP p=0.70; PPD p=0.30; PISA p=0.56). PERMANOVA showed a difference between the groups in the microbial composition of saliva (F=2.08, p<0.001) and tongue coating (F=2.04, p=0.008), but not plaque (p=0.51). Post-hoc tests showed no difference between the ERA group and at-risk group (saliva F=1.12, p=0.28; tongue coating F=0.834, p=0.59). Discriminative zero-radius operational taxonomic units (zOTUs) were identified: in ERA patients and at-risk individuals, Prevotella in saliva and Veillonella in saliva and tongue coating were at higher relative abundance compared to healthy controls.

Conclusion: The results show similarities in the oral microbiome between ERA patients and at-risk individuals, both presenting with increased relative abundance of potentially pro-inflammatory species compared to healthy controls, suggesting a possible association between the oral microbiome and RA onset.
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http://dx.doi.org/10.1002/art.41780DOI Listing
May 2021

Surgical treatment of peri-implantitis defects with two different xenograft granules: A randomized clinical pilot study.

Clin Oral Implants Res 2020 Nov 9;31(11):1047-1060. Epub 2020 Sep 9.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.

Objectives: To investigate whether xenograft EB (EndoBon) is non-inferior to xenograft BO (Bio-Oss) when used in reconstructive surgery of peri-implant osseous defects.

Materials And Methods: Dental patients with one implant each demonstrating peri-implantitis were randomized to receive surgical debridement and defect fill with either BO or EB. Changes in bone level (BL) and intrabony defect depth (IDD) evaluated radiographically were the primary outcomes. The secondary outcomes included changes in probing pocket depth (PPD), bleeding on probing (BoP), and suppuration on probing (SoP). All outcomes were recorded before treatment and at 6 and 12 months post-treatment.

Results: Twenty-four patients (n = 11 BO, n = 13 EB) completed the study. Both groups demonstrated significant within-group improvements in all clinical and radiographic parameters at 6 and 12 months (p ≤ .001). At 12 months, both groups presented with IDD reductions of 2.5-3.0 mm on average. The inter-group differences were not statistically significant at all time points and for all the examined parameters (p > .05). While the radiographic defect fill in both groups exceeded > 1 mm and can be considered treatment success, successful treatment outcomes as defined by Consensus Reporting (no further bone loss, PPD ≤ 5 mm, no BOP, and no SoP) were identified in 2/11 (18%) BO and 0/13 (0%) EB individuals (Fisher's exact test, p = .199).

Conclusions: Within the limitations of this pilot study, the application of xenograft EB showed to be non-inferior to xenograft BO when used in reconstructive surgery of peri-implant osseous defects.
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http://dx.doi.org/10.1111/clr.13651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693249PMC
November 2020

Three periodontitis phenotypes: Bone loss patterns, antibiotic-surgical treatment and the new classification.

J Clin Periodontol 2020 11 14;47(11):1371-1378. Epub 2020 Sep 14.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Aim: To compare three periodontitis clusters (A, B and C) for alveolar bone loss (ABL) patterns, antibiotic prescriptions and surgeries and to relate them to the new classification of periodontitis.

Materials And Methods: ABL patterns, prescription of systemic antibiotics and the number of surgeries were retrieved for all patients (n = 353) in the clusters. Comparisons and possible predictors for antibiotics were assessed, and results also evaluated in relation to the new classification.

Results: Cluster A is characterized by angular defects often affecting the first molars and localized stage III/IV grade C periodontitis. Cluster B contains mainly localized or generalized stage III/IV, grade C patients. Cluster C contains mainly patients with generalized stage III/IV grade C periodontitis. Patients in cluster A received significantly more antibiotics compared to B and C (78% vs. 23% and 17%); the predictors for antibiotic prescription were young age and localized ABL. No differences in numbers of periodontal surgeries were observed between clusters (A = 1.0 ± 1.4, B = 1.3 ± 1.4 and C = 1.3 ± 1.5).

Conclusions: Within stage III/IV grade C periodontitis, we could detect three clusters of patients. The distinct localized ABL pattern and younger age in cluster A presumably prompted clinicians to prescribe antibiotics.
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http://dx.doi.org/10.1111/jcpe.13356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693056PMC
November 2020

Dentistry and OMICS: Transcriptome Dynamics of an Oral Ecosystem as Measured by Changes in Oral Polymorphonuclear Neutrophils in Experimental Gingivitis.

OMICS 2020 09 19;24(9):531-540. Epub 2020 Jun 19.

Department of Periodontology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam (UVA) and Vrije Universiteit Amsterdam (VU), Amsterdam, The Netherlands.

Oral health and dentistry are essential components of systems medicine, which has received lesser attention in comparison to other medical fields, such as cancer biology. In this context, oral polymorphonuclear neutrophils (oPMNs) play an important role in the maintenance of oral health. To the best of our knowledge, this is the first study to report original observations on the transcriptional responses of oPMNs during experimentally induced gingivitis, by temporarily refraining from regular oral care. Oral rinses were prospectively collected at four different time points for oPMNs isolation from healthy volunteers: day 1 (start of the experimental gingivitis challenge), day 9 (during challenge), day 14 (end of the challenge), and day 21 (postchallenge). Transcriptome of oPMNs was determined by RNA sequencing. Differentially expressed genes (DEGs) were selected at  < 0.01 level, and evaluated for pathway regulation using Ingenuity Pathway Analysis suite. We found four major clusters of DEGs, consisting of 256 initial response DEGs (day 9 only), 221 late response DEGs (day 14 only), 53 persistent responsive DEGs (consistent at day 9 and 14), and 524 DEGs showing responses only in the postchallenge phase (day 21 only). Pathway analysis of the initial and late response DEGs showed involvement in many immune regulatory pathways and PMN function, whereas DEGs at day 21 were associated with epithelial adherence signaling and other miscellaneous related signaling pathways. The results from this pilot study showed that oPMNs mediate oral inflammatory processes, suggesting their immunomodulatory role in oral equilibrium.
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http://dx.doi.org/10.1089/omi.2020.0034DOI Listing
September 2020

Development and validation of a screening model for diabetes mellitus in patients with periodontitis in dental settings.

Clin Oral Investig 2020 Nov 15;24(11):4089-4100. Epub 2020 Jun 15.

Department of Social Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Objectives: To identify predictors in patient profiles and to develop, internally validate, and calibrate a screening model for diabetes mellitus (DM) in patients with periodontitis in dental settings MATERIALS AND METHODS: The study included 204 adult patients with periodontitis. Patients' socio-demographic characteristics, general health status, and periodontal status were recorded as potential predictors. The diabetic status was considered the outcome, classified into no DM, prediabetes (pre-DM), or DM. Multinomial logistic regression analysis was used to develop the model. The performance and clinical values of the model were determined.

Results: Seventeen percent and 47% of patients were diagnosed with DM and pre-DM, respectively. Patients' age, BMI, European background, cholesterol levels, previous periodontal treatment, percentage of the number of teeth with mobility, and with gingival recession were significantly associated with the diabetic status of the patients. The model showed a reasonable calibration and moderate to good discrimination with area under the curve (AUC) values of 0.67 to 0.80. The added predictive values for ruling in the risk of DM and pre-DM were 0.42 and 0.11, respectively, and those for ruling it out were 0.05 and 0.17, respectively.

Conclusions: Predictors in patient profiles for screening of DM and pre-DM in patients with periodontitis were identified. The calibration, discrimination, and clinical values of the model were acceptable.

Clinical Relevance: The model may well assist clinicians in screening of diabetic status of patients with periodontitis. The model can be used as a reliable screening tool for DM and pre-DM in patients with periodontitis in dental settings.
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http://dx.doi.org/10.1007/s00784-020-03281-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544748PMC
November 2020

The role of inflammation and genetics in periodontal disease.

Periodontol 2000 2020 06;83(1):26-39

Center for Clinical and Translational Research, Forsyth Institute, Cambridge, Massachusetts, USA.

Periodontitis is a complex disease: (a) various causative factors play a role simultaneously and interact with each other; and (b) the disease is episodic in nature, and bursts of disease activity can be recognized, ie, the disease develops and cycles in a nonlinear fashion. We recognize that various causative factors determine the immune blueprint and, consequently, the immune fitness of a subject. Normally, the host lives in a state of homeostasis or symbiosis with the oral microbiome; however, disturbances in homeostatic balance can occur, because of an aberrant host response (inherited and/or acquired during life). This imbalance results from hyper- or hyporesponsiveness and/or lack of sufficient resolution of inflammation, which in turn is responsible for much of the disease destruction seen in periodontitis. The control of this destruction by anti-inflammatory processes and proresolution processes limits the destruction to the tissues surrounding the teeth. The local inflammatory processes can also become systemic, which in turn affect organs such as the heart. Gingival inflammation also elicits changes in the ecology of the subgingival environment providing optimal conditions for the outgrowth of gram-negative, anaerobic species, which become pathobionts and can propagate periodontal inflammation and can further negatively impact immune fitness. The factors that determine immune fitness are often the same factors that determine the response to the resident biofilm, and are clustered as follows: (a) genetic and epigenetic factors; (b) lifestyle factors, such as smoking, diet, and psychosocial conditions; (c) comorbidities, such as diabetes; and (d) local and dental factors, as well as randomly determined factors (stochasticity). Of critical importance are the pathobionts in a dysbiotic biofilm that drive the viscious cycle. Focusing on genetic factors, currently variants in at least 65 genes have been suggested as being associated with periodontitis based on genome-wide association studies and candidate gene case control studies. These studies have found pleiotropy between periodontitis and cardiovascular diseases. Most of these studies point to potential pathways in the pathogenesis of periodontal disease. Also, most contribute to a small portion of the total risk profile of periodontitis, often limited to specific racial and ethnic groups. To date, 4 genetic loci are shared between atherosclerotic cardiovascular diseases and periodontitis, ie, CDKN2B-AS1(ANRIL), a conserved noncoding element within CAMTA1 upstream of VAMP3, PLG, and a haplotype block at the VAMP8 locus. The shared genes suggest that periodontitis is not causally related to atherosclerotic diseases, but rather both conditions are sequelae of similar (the same?) aberrant inflammatory pathways. In addition to variations in genomic sequences, epigenetic modifications of DNA can affect the genetic blueprint of the host responses. This emerging field will yield new valuable information about susceptibility to periodontitis and subsequent persisting inflammatory reactions in periodontitis. Further studies are required to verify and expand our knowledge base before final cause and effect conclusions about the role of inflammation and genetic factors in periodontitis can be made.
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http://dx.doi.org/10.1111/prd.12297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319430PMC
June 2020

Effect of diode laser application as an adjunct to nonsurgical periodontal therapy on the reduction of red complex microorganisms in type 2 diabetics with chronic periodontitis.

Lasers Med Sci 2020 Aug 19;35(6):1403-1410. Epub 2020 Mar 19.

Department of Periodontology, Faculty of Dentistry, Selcuk University, Konya, Turkey.

Bactericidal and detoxification effects of diode laser (DL) have been reported in periodontal treatment. The objective of this study was investigating the additional effect of DL with nonsurgical periodontal treatment on the red complex bacteria in type 2 diabetes mellitus (DM) patients with chronic periodontitis (CP). Sixty type 2 DM patients with chronic periodontitis (CP) were randomly assigned in two parallel groups to receive scaling root planning (SRP, n = 30) or SRP followed by DL periodontal pocket irradiation (SRP + DL, n = 30). Recording of clinical parameters and subgingival plaque sampling were performed at baseline, and post therapy (1 and 3 months after treatment). Amounts of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia were evaluated with quantitative RT-PCR. Significant reductions for numbers of all three bacterial species were observed at 1 and 3 months compared with baseline for both treatments (p < 0.001), but no significant differences were found between two groups regarding bacterial reductions at these follow-up time points. No additional benefit of DL as an adjunct to nonsurgical periodontal therapy was recognized in the reduction of P. gingivalis, T. denticola, and T. forsythia for type 2 DM patients with CP. Further studies are required to clarify the effects of diode laser on the other periodontopathogens.
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http://dx.doi.org/10.1007/s10103-020-02997-1DOI Listing
August 2020

Translation of mouse model to human gives insights into periodontitis etiology.

Sci Rep 2020 03 17;10(1):4892. Epub 2020 Mar 17.

Department of Clinical. Microbiology and Immunology, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10) and RNASE2 (rs2771342, P = 2.84×10) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10) and HLA-DPA1 (rs17214512, P = 5.14×10). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.
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http://dx.doi.org/10.1038/s41598-020-61819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078197PMC
March 2020

Occlusal Migration of Teeth Adjacent to Implant Prostheses in Adults: A Long-Term Study.

Int J Oral Maxillofac Implants 2020 Mar/Apr;35(2):342-349

Purpose: To evaluate the effect of continuous tooth eruption on the outcomes of single-implant-supported restorations in the anterior maxilla of adults.

Materials And Methods: Seventy-six patients (age: 21 to 78 years) treated with single-implant-supported restorations in the esthetic zone were included. Radiographs obtained at crown placement and follow-up examinations from 1 to 15 years postloading were analyzed with regard to vertical incisal plane changes of the implant-supported crown relative to adjacent teeth.

Results: Infraocclusion increased over time by 0.08 ± 0.02 mm/year. Infraocclusion was more pronounced (P = .04) for delayed (0.09 mm/year) versus immediate implant placement (0.06 mm/year) and for younger versus older adults (0.0013 mm/year per additional year of age; P = .014). No statistically significant association between infraocclusion and sex, ethnicity, implant site, timing of implant temporization, surgical protocol, and type of restoration was found.

Conclusion: Infraocclusion of single-implant-supported maxillary anterior restorations may result in esthetic concerns over time. Greater infraocclusion occurs in delayed implant placement and in younger individuals.
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http://dx.doi.org/10.11607/jomi.7784DOI Listing
August 2020

A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility.

Sci Rep 2020 02 20;10(1):3008. Epub 2020 Feb 20.

TI Food and Nutrition, Nieuwe Kanaal 9-A, 6709 PA, Wageningen, The Netherlands.

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.
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http://dx.doi.org/10.1038/s41598-020-59988-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033112PMC
February 2020

Endpoints of active periodontal therapy.

J Clin Periodontol 2020 07;47 Suppl 22:61-71

Unit of Periodontology, University College London Eastman Dental Institute, London, UK.

Aim: Position paper on endpoints of active periodontal therapy for designing treatment guidelines. The question was as follows: How are, for an individual patient, commonly applied periodontal probing measures-recorded after active periodontal therapy-related to (a) stability of clinical attachment level, (b) tooth survival, (c) need for re-treatment or (d) oral health-related quality of life.

Methods: A literature search was conducted in Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily <1946 to 07 June 2019>.

Results: A total of 94 papers were retrieved. From the literature search, it was found that periodontitis patients with a low proportion of deep residual pockets after active periodontal therapy are more likely to have stability of clinical attachment level over a follow-up time of ≥1 year. Other supporting literature confirms this finding and additionally reports, at the patient level, that probing pocket depths ≥6 mm and bleeding on probing scores ≥30% are risks for tooth loss. There is lack of evidence that periodontal probing measures after completion of active periodontal treatment are tangible to the patient.

Conclusions: Based on literature and biological plausibility, it is reasonable to state that periodontitis patients with a low proportion of residual periodontal pockets and little inflammation are more likely to have stability of clinical attachment levels and less tooth loss over time. Guidelines for periodontal therapy should take into consideration (a) long-term tangible patient outcomes, (b) that shallow pockets (≤4 mm) without bleeding on probing in patients with <30% bleeding sites are the best guarantee for the patient for stability of his/her periodontal attachment, (c) patient heterogeneity and patient changes in immune response over time, and (d) that treatment strategies include lifestyle changes of the patient. Long-term large population-based and practice-based studies on the efficacy of periodontal therapies including both clinical and patient-reported outcomes (PROs) need to be initiated, which include the understanding that periodontitis is a complex disease with variation of inflammatory responses due to environment, (epi)genetics, lifestyle and ageing. Involving people living with periodontitis as co-researchers in the design of these studies would also help to improve their relevance.
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http://dx.doi.org/10.1111/jcpe.13253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670400PMC
July 2020

T Cell Proliferation Is Induced by Chronically TLR2-Stimulated Gingival Fibroblasts or Monocytes.

Int J Mol Sci 2019 Dec 5;20(24). Epub 2019 Dec 5.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit, 1081 LA Amsterdam, The Netherlands.

During inflammation of the gums, resident cells of the periodontium, gingival fibroblasts (GFs), interact with heterogeneous cell populations of the innate and adaptive immune system that play a crucial role in protecting the host from pathogenic infectious agents. We investigated the effects of chronic inflammation, by exposing peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocyte (PBL) cultures, and GF-PBMC cocultures to Toll-like receptor 2 (TLR2) and TLR4 activators for 21 days and assessed whether this influenced leukocyte retention, survival, and proliferation. Chronic stimulation of PBMC-GF cocultures with TLR2 and TLR4 agonists induced a reduction of NK (CD56+CD3-), T (CD3+), and B (CD19+) cells, whereas the number of TLR-expressing monocytes were unaffected. TLR2 agonists doubled the T cell proliferation, likely of a selective population, given the net decrease of T cells. Subsequent chronic exposure experiments without GF, using PBMC and PBL cultures, showed a significantly ( < 0.0001) increased proinflammatory cytokine production of TNF-α and IL-1β up to 21 days only in TLR2-activated PBMC with concomitant T cell proliferation, suggesting a role for monocytes. In conclusion, chronic TLR activation mediates the shift in cell populations during infection. Particularly, TLR2 activators play an important role in T cell proliferation and proinflammatory cytokine production by monocytes, suggesting that TLR2 activation represents a bridge between innate and adaptive immunity.
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http://dx.doi.org/10.3390/ijms20246134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940768PMC
December 2019

Effects of L-PRF and A-PRF+ on periodontal fibroblasts in in vitro wound healing experiments.

J Periodontal Res 2020 Apr 28;55(2):287-295. Epub 2019 Nov 28.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objective: To determine whether leukocyte-platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF+) differ in their in vitro capacity to induce proliferation and migration of periodontal fibroblasts.

Background: L-PRF and A-PRF + are autologous materials used in periodontal regenerative surgery. They derive from blood from patients, but have different characteristics. The literature is controversial regarding the effects of the two PRF preparations on periodontal tissue fibroblasts.

Materials And Methods: L-PRF and A-PRF + membranes were prepared from eight patients and incubated in 3 mL of culture medium for 2 days. Gingival fibroblasts (G-F) and periodontal ligament fibroblast (PDL-F) primary cells were retrieved from 7 donors. These cells were pre-cultured for 1 day in wound healing experiment plates leaving a gap of 500 ± 50 µm in a concentration of 3.3 x 10 cells/mL. 70 µL of the cell suspension was placed in each half of the well. Thereafter, the pre-cultured L-PRF and A-PRF + supernatants were added to the experimental plates, and the fibroblasts were incubated for another 24 h. Medium alone (NEG) and fibroblast growth factor II (FGF) were used as controls. Subsequently, cell migration was registered for 24 h with live cell imaging in a time frame microscope at 5% CO in air at 37°C. Images were analyzed using ImageJ. Cell proliferation and cell viability were measured.

Results: L-PRF and A-PRF + induced higher cell proliferation than FGF and NEG. Both A-PRF + and L-PRF induced significant faster artificial wound closure than controls. Both PRF conditioned media induced faster cell migration in the initial phase (P < .01), but in the stoppage phase, the induced migration was higher for the A-PRF+, compared with L-PRF (P < .01).

Conclusion: L-PRF and A-PRF + have a stimulatory effect on migration and proliferation of periodontal fibroblasts, and artificial wound closure was longer sustained by A-PRF + than L-PRF.
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http://dx.doi.org/10.1111/jre.12714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154757PMC
April 2020

Periodontal therapy increases neutrophil extracellular trap degradation.

Innate Immun 2020 07 22;26(5):331-340. Epub 2019 Nov 22.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, The Netherlands.

In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.
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http://dx.doi.org/10.1177/1753425919889392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903525PMC
July 2020

Hidden noise in immunologic parameters might explain rapid progression in early-onset periodontitis.

PLoS One 2019 1;14(11):e0224615. Epub 2019 Nov 1.

Department of Periodontology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

To investigate in datasets of immunologic parameters from early-onset and late-onset periodontitis patients (EOP and LOP), the existence of hidden random fluctuations (anomalies or noise), which may be the source for increased frequencies and longer periods of exacerbation, resulting in rapid progression in EOP. Principal component analysis (PCA) was applied on a dataset of 28 immunologic parameters and serum IgG titers against periodontal pathogens derived from 68 EOP and 43 LOP patients. After excluding the PCA parameters that explain the majority of variance in the datasets, i.e. the overall aberrant immune function, the remaining parameters of the residual subspace were analyzed by computing their sample entropy to detect possible anomalies. The performance of entropy anomaly detection was tested by using unsupervised clustering based on a log-likelihood distance yielding parameters with anomalies. An aggregate local outlier factor score (LOF) was used for a supervised classification of EOP and LOP. Entropy values on data for neutrophil chemotaxis, CD4, CD8, CD20 counts and serum IgG titer against Aggregatibacter actinomycetemcomitans indicated the existence of possible anomalies. Unsupervised clustering confirmed that the above parameters are possible sources of anomalies. LOF presented 94% sensitivity and 83% specificity in identifying EOP (87% sensitivity and 83% specificity in 10-fold cross-validation). Any generalization of the result should be performed with caution due to a relatively high false positive rate (17%). Random fluctuations in immunologic parameters from a sample of EOP and LOP patients were detected, suggesting that their existence may cause more frequently periods of disease activity, where the aberrant immune response in EOP patients result in the phenotype "rapid progression".
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824576PMC
March 2020

The Possible Role of Neutrophils in the Induction of Osteoclastogenesis.

J Immunol Res 2019 15;2019:8672604. Epub 2019 Sep 15.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

The ligand of the receptor activator of NF-B (RANKL) is a key molecule in the formation of osteoclasts, the key cells that cause the disease-associated alveolar bone resorption in periodontitis. We hypothesized that polymorphonuclear leukocytes (PMNs), found as the most prominent cells of inflamed periodontal tissues, could play an important role in providing signals to trigger osteoclastogenesis and thus activating pathological bone resorption in periodontitis. RANKL expression was investigated on circulatory PMNs (cPMNs) and oral PMNs (oPMNs) taken from both controls and periodontitis patients. On average, 2.3% and 2.4% RANKL expression was detected on the cPMNs and oPMNs from periodontitis patients, which did not differ significantly from healthy controls. Since cPMNs may acquire a more osteoclastogenesis-facilitating phenotype while migrating into the inflamed periodontium, we next investigated whether stimulated (with LPS, TNF-, or IL-6) cPMNs have the capacity to contribute to osteoclastogenesis. Enduring surface expression of RANKL for short-lived cells as cPMNs was achieved by fixating stimulated cPMNs. RANKL expression on stimulated cPMNs, as assessed by flow cytometry and immunohistochemistry, was limited (6.48 ± 0.72%, mean expression ± SEM) after 24 and 48 hours of stimulation with LPS. Likewise, stimulation with TNF- and IL-6 resulted in limited RANKL expression levels. These limited levels of expression did not induce osteoclastogenesis when cocultured with preosteoclasts for 10 days. We report that, under the aforementioned experimental conditions, neither cPMNs nor oPMNs directly induced osteoclastogenesis. Further elucidation of the key cellular players and immune mediators that stimulate alveolar bone resorption in periodontitis will help to unravel its pathogenesis.
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http://dx.doi.org/10.1155/2019/8672604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766092PMC
February 2020

The link between periodontitis and erectile dysfunction: a review.

Br Dent J 2019 Oct;227(7):599-603

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, 1081LA, Amsterdam, The Netherlands.

Introduction Consistent evidence has shown that periodontitis can be considered a risk factor for the development of vascular complications such as myocardial infarction and cerebrovascular accident. The majority of cases of erectile dysfunction (ED) are considered to result from the complication of vascular impairments. Therefore, it is conceivable to hypothesise that periodontitis can also be associated with ED.Aims To determine whether a possible link between periodontitis and ED exists by reviewing and presenting the current available evidence.Methods Current, up to June 2018, case-control studies, randomised controlled trials (RCT) and meta-analyses were reviewed.Results Nine case-control studies and three meta-analyses found significant positive associations between these two conditions, with odds ratios ranging from 1.53 to 5.94. Furthermore, one RCT found a significant improvement in subjective measurements of ED in patients treated for periodontitis.Conclusions The current associations must be interpreted with caution because of the considerable heterogeneity of the cross-sectional investigations and the short-term character of the only RCT included. Nevertheless, the preliminary results can be taken into consideration for the general physician or the specialist in the motivation of the male patient to visit dental professionals and, if indicated, treated for periodontitis, which may help in managing the vasculogenic form of impotence.
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http://dx.doi.org/10.1038/s41415-019-0724-6DOI Listing
October 2019

Resistance and resilience to experimental gingivitis: a systematic scoping review.

BMC Oral Health 2019 09 11;19(1):212. Epub 2019 Sep 11.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: This systematic scoping review aimed to identify changes in biomarkers of microbiological, immunological and biochemical origin during experimental gingivitis (EG) studies that might indicate resistance and resilience.

Methods: The term 'experimental gingivitis' was run in PubMed from inception to April 11th, 2018. From the 411 studies retrieved, 22 studies were included for this review.

Results: Studies reporting data on biomarker changes during and after full mouth EG trial were included. Two studies reported findings on changes in biomarkers of microbiological, 12 on immunological and eight on biochemical origin. Changes were reported in the induction phase, and occasionally in the resolution phase. The microbiological composition of both supragingival and subgingival dental plaque changed over the course of EG to a more pathogenic direction, but showed a shift back to a more normal composition. This indicates resilience of the oral microbiome. For immunological biomarkers, it was challenging to retrieve a robust pattern of changes across multiple studies. IL-1β and IL-6 in saliva and in gingival crevicular fluid increased during induction phase and returned in the resolution phase below baseline values. The biochemical parameters cystatin-SN, cystatin-S and lactoferrin in saliva were increased at the end of induction phase, however also here no clear pattern emerged based on all available studies.

Conclusions: More research is needed to investigate which microbiological, immunological, and biochemical biomarkers can be useful for future investigations into the resistance and resilience of the oral cavity to experimental gingivitis.
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http://dx.doi.org/10.1186/s12903-019-0889-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737651PMC
September 2019

Self-reported oral health and quality of life in patients with type 2 diabetes mellitus in primary care: a multi-center cross-sectional study.

Diabetes Metab Syndr Obes 2019 18;12:883-899. Epub 2019 Jun 18.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.

Guidelines for primary diabetes care recommend to pay attention to oral health in patients with diabetes mellitus type 2 (T2DM). However, research about dental care utilization and the extent of problems regarding oral health in these patients is limited. To assess self-reported oral health, general health-related quality of life (QoL) and oral health-related QoL in patients with T2DM who regularly attend a family physician office. Family physician offices were recruited in the area of Amsterdam, the Netherlands, as part of a cluster-randomized controlled trial. At these offices, patients with T2DM were included by family physicians and/or nurse practitioners. Patient data on general characteristics, self-reported oral health (including periodontitis), general health-related QoL (SF-36) and oral health-related QoL (OHIP-NL14) were collected. Twenty-four family physician offices participated, who enrolled 764 patients with T2DM (mean age: 65.9±10.7 years, 56% male, 16% smoker). Almost 11% of the patients were metabolically poorly controlled (HbA1c >63 mmol/mol), 39% were obese (body mass index≥30 kg/m), 37% had hypertension (systolic blood pressure ≥140 mmHg) and 44% had dyslipidemia (LDL-cholesterol >2.5 mmol/L). About a quarter (24%) reported not to visit a dentist regularly and 30% did not have dental insurance coverage. Furthermore, 16% of the patients were edentulous and having full dental prostheses, while 29% had a partial dental prosthesis. Pain in the mouth, dry mouth and bad breath were reported by 15%, 37% and 12% of the patients, respectively. Almost 70% suffered from periodontitis. Oral health-related QoL was impaired in 19% of the patients, and those subjects also had worse general health-related QoL. Almost a quarter of patients with T2DM at Dutch family physician offices does not visit the dentist regularly. The estimated prevalence of periodontitis is particularly high, but other oral health complaints and impaired oral health-related QoL are also relatively common.
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http://dx.doi.org/10.2147/DMSO.S207087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590843PMC
June 2019

A rapid, non-invasive tool for periodontitis screening in a medical care setting.

BMC Oral Health 2019 05 23;19(1):87. Epub 2019 May 23.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081, LA, Amsterdam, the Netherlands.

Background: Since periodontitis is bi-directionally associated with several systemic diseases, such as diabetes mellitus and cardiovascular diseases, it is important for medical professionals in a non-dental setting to be able examine their patients for symptoms of periodontitis, and urge them to visit a dentist if necessary. However, they often lack the time, knowledge and resources to do so. We aim to develop and assess "quick and easy" screening tools for periodontitis, based on self-reported oral health (SROH), demographics and/or salivary biomarkers, intended for use by medical professionals in a non-dental setting.

Methods: Consecutive, new patients from our outpatient clinic were recruited. A SROH questionnaire (8 questions) was conducted, followed by a 30 s oral rinse sampling protocol. A complete clinical periodontal examination provided the golden standard periodontitis classification: no/mild, moderate or severe periodontitis. Total periodontitis was defined as having either moderate or severe. Albumin and matrix metalloproteinase-8 concentrations, and chitinase and protease activities were measured in the oral rinses. Binary logistic regression analyses with backward elimination were used to create prediction models for both total and severe periodontitis. Model 1 included SROH, demographics and biomarkers. The biomarkers were omitted in the analysis for model 2, while model 3 only included the SROH questionnaire. The area under the receiver operating characteristic curves (AUROCC) provided the accuracy of each model. The regression equations were used to create scoring algorithms, composed of the remaining predictors, each with its own weight.

Results: Of the 156 patients participating in this study, 67% were classified with total periodontitis and 33% had severe periodontitis. The models for total periodontitis achieved an AUROCC of 0.91 for model 1, 0.88 for model 2 and 0.81 for model 3. For severe periodontitis, this was 0.89 for model 1, 0.82 for model 2 and 0.78 for model 3. The algorithm for total periodontitis (model 2), which we consider valid for the Dutch population, was applied to create a freely accessible, web-based screening tool.

Conclusions: The prediction models for total and severe periodontitis proved to be feasible and accurate, resulting in easily applicable screening tools, intended for a non-dental setting.
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http://dx.doi.org/10.1186/s12903-019-0784-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533660PMC
May 2019

Oral Neutrophils Characterized: Chemotactic, Phagocytic, and Neutrophil Extracellular Trap (NET) Formation Properties.

Front Immunol 2019 29;10:635. Epub 2019 Mar 29.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Maintenance of oral health is in part managed by the immune-surveillance and antimicrobial functions of polymorphonuclear leukocytes (PMNs), which migrate from the circulatory system through the oral mucosal tissues as oral PMNs (oPMNs). In any microorganism-rich ecosystem, such as the oral cavity, PMNs migrate toward various exogenous chemoattractants, phagocytose bacteria, and produce neutrophil extracellular traps (NETs) to immobilize and eliminate pathogens. PMNs obtained from the circulation through venipuncture (hereafter called cPMNs) have been widely studied using various functional assays. We aimed to study the potential of oPMNs in maintaining oral health and therefore compared their chemotactic and antimicrobial functions with cPMNs. To establish chemotactic, phagocytic, and NET forming capacities, oPMNs and cPMNs were isolated from healthy subjects without obvious oral inflammation. Directional chemotaxis toward the chemoattractant fMLP was analyzed using an Insall chamber and video microscopy. fMLP expression was assessed by flow cytometry. Phagocytosis was analyzed by flow cytometry, following PMN incubation with heat-inactivated FITC-labeled micro-organisms. Furthermore, agar plate-based killing assays were performed with (). NET formation by oPMNs and cPMNs was quantified fluorimetrically using SYTOX™ Green, following stimulation with either PMA or RPMI medium (unstimulated control). In contrast to cPMNs, the chemotactic responses of oPMNs to fMLP did not differ from controls (mean velocity ± SEM of cPMNs: 0.79 ± 0.24; of oPMNs; 0.10 ± 0.07 micrometer/min). The impaired directional movement toward fMLP by oPMNs was explained by significantly lower fMLP receptor expression. Increased adhesion and internalization of various micro-organisms by oPMNs was observed. oPMNs formed 13 times more NETs than stimulated cPMNs, in both unstimulated and stimulated conditions. Compared to cPMNs, oPMNs showed a limited ability for intracellular killing of . In conclusion, oPMNs showed exhausted capacity for efficient chemotaxis toward fMLP which may be the result of migration through the oral tissues into the oral cavity, being a highly "hostile" ecosystem. Overall, oPMNs' behavior is consistent with hyperactivity and frustrated killing. Nevertheless, oPMNs most likely contribute to maintaining a balanced oral ecosystem, as their ability to internalize microbes in conjunction with their abundant NET production remains after entering the oral cavity.
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http://dx.doi.org/10.3389/fimmu.2019.00635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449731PMC
August 2020

Evaluating All Potential Oral Complications of Diabetes Mellitus.

Front Endocrinol (Lausanne) 2019 18;10:56. Epub 2019 Feb 18.

Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, Netherlands.

Diabetes mellitus (DM) is associated with several microvascular and macrovascular complications, such as retinopathy, nephropathy, neuropathy, and cardiovascular diseases. The pathogenesis of these complications is complex, and involves metabolic and hemodynamic disturbances, including hyperglycemia, insulin resistance, dyslipidemia, hypertension, and immune dysfunction. These disturbances initiate several damaging processes, such as increased reactive oxygen species (ROS) production, inflammation, and ischemia. These processes mainly exert their damaging effect on endothelial and nerve cells, hence the susceptibility of densely vascularized and innervated sites, such as the eyes, kidneys, and nerves. Since the oral cavity is also highly vascularized and innervated, oral complications can be expected as well. The relationship between DM and oral diseases has received considerable attention in the past few decades. However, most studies only focus on periodontitis, and still approach DM from the limited perspective of elevated blood glucose levels only. In this review, we will assess other potential oral complications as well, including: dental caries, dry mouth, oral mucosal lesions, oral cancer, taste disturbances, temporomandibular disorders, burning mouth syndrome, apical periodontitis, and peri-implant diseases. Each oral complication will be briefly introduced, followed by an assessment of the literature studying epidemiological associations with DM. We will also elaborate on pathogenic mechanisms that might explain associations between DM and oral complications. To do so, we aim to expand our perspective of DM by not only considering elevated blood glucose levels, but also including literature about the other important pathogenic mechanisms, such as insulin resistance, dyslipidemia, hypertension, and immune dysfunction.
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http://dx.doi.org/10.3389/fendo.2019.00056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439528PMC
February 2019

Qualitative and quantitative differences in the subgingival microbiome of the restored and unrestored teeth.

J Periodontal Res 2019 Aug 8;54(4):405-412. Epub 2019 Feb 8.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.

Background And Objective: Metal-based dental restorations with a subgingival outline may enhance plaque accumulation and bacterial colonization. This study aimed to investigate whether metal-based restorations influence the composition of subgingival microbiome.

Material And Methods: Per subject one site with a metal-based restoration and one contra-lateral site without a restoration were selected on basis of radiographic bone loss ≤2 mm, restoration outline at sulcus level/subgingivally, pocket depth ≤4 mm, and no root canal treatments. Subgingival samples were collected with sterile paper-points, and microbial profiles were obtained by 16S rRNA gene amplicon sequencing. Restorations were sampled with an Arkansas-stone and the metal composition was determined using energy-dispersive X-ray spectroscopy.

Results: A total of 22 sites from 11 subjects were included. No significant differences for the clinical parameters were found between the restored and unrestored sites. The average age of the restorations was 14.9 ± 7.1 years. Firmicutes was the most prevalent phylum at the restored sites (32% vs 20% of the reads of the unrestored sites, P = 0.016), and Actinobacteria at the unrestored sites (33% vs 18% of the reads of the restored sites, P = 0.01). Overall, sequences clustered into 573 operational taxonomic units (OTUs). Species richness of the restored sites was significantly higher than species richness of the unrestored sites (117 ± 32 and 96 ± 20 OTUs, respectively, P = 0.013). No associations between the metal composition and bacterial profiles were found.

Conclusion: This study shows that metal-based restorations may enhance colonization of Firmicutes and the neighboring pocket may harbor more diverse microbial communities.
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http://dx.doi.org/10.1111/jre.12642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766957PMC
August 2019
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