Benjamin Ehmke

University Hospital Münster

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Thomas Kocher

Universitätsmedizin Greifswald

Sebastian‐Edgar Baumeister

University of Münster

Birte Holtfreter

Universitätsmedizin Greifswald

Daniel S. Thoma

University of Zurich

Michael Nolde

University of Münster

Hansjörg Baurecht

University of Regensburg

Ulrich Schlagenhauf

Universitätsklinikum Würzburg

Stefan Lars Reckelkamm

University of Münster

Peter Eickholz

Goethe University Frankfurt

Joerg Meyle

University of Giessen

Cooperative Institutions

University of Münster

University Hospital Münster

University of Würzburg

Poliklinik für Zahnerhaltung und Parodontologie

Guarulhos University

Charité - Universitätsmedizin Berlin

Ludwig-Maximilians-Universität München

Heinrich Heine University Düsseldorf

Institute of Medical Microbiology and Hygiene

Universitätsmedizin Greifswald

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Cirugía ósea resectiva en periodoncia: un tipo de tratamiento de eficacia comprobada

Martin M. Sachs Benjamin Ehmke

La cirugia osea resectiva como parte del tratamiento periodontal constituye un metodo seguro y de eficacia comprobada para la eliminacion de las bolsas a largo plazo. En estos caso, deben sopesarse las posibilidades y alternativas relacionadas con los resultados del examen y con el paciente. El objetivo es conseguir una anatomia osea positiva en el periodonto enfermo aplicando medidas resectivas y asi restablecer un periodonto sano en un diente con soporte reducido. Debido a la variabilidad de los defectos oseos, resulta complicado determinar estrictamente las pautas a seguir en cuanto a la forma de realizar la cirugia osea resectiva. Esto requiere una categorizacion morfologica de los defectos oseos, la cual debe considerarse ademas en relacion con el hueso alveolar y la superficie radicular. Unicamente de este modo pueden elaborarse indicaciones y contraindicaciones claras. Debido al aplanamiento del recorrido gingival concomitante a la reseccion, han de respetarse escrupulosamente las indicaciones y la tecnica quirurgica. Traduccion del articulo original publicado en la revista Quintessenz Paradontologie 2013;24(1).49-1

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A Concept for Clinical Research Triggered by Suggestions from Systematic Reviews About Adjunctive Antibiotics

Applied Clinical Research Clinical Trials and Regulatory Affairs (2014)

Inga Harks Dag Harmsen Martina Gravemeier Karola Prior Raphael Koch

Aim: Adjunctive systemic antibiotics may improve the outcome of mechanical periodontitis therapy. Systematic reviews revealed the lack of sufficient data and well-designed clinical trials about the efficacy of this adjunct to periodontal therapy. This protocol was designed to address demands and suggestions for further clinical trials made by recent EFP reviews. Materials and Methods: Investigation's design was a double-blind, placebo-controlled, multi-center randomized controlled trial over a 38-month period. We hypothesized that adjunctive antibiotic therapy significantly reduces (Δ50%) the occurrence of further attachment loss compared to subgingival debridement alone. The primary objective efficacy variable was the percentage of sites with a loss of clinical attachment ≥ 1.3 mm over the 24-month follow-up period. Key secondary variables were additional periodontal, microbiological and psychological parameters. Results: For eligibility 3261 patients were screened, 542 patients were recruited, and finally 406 patients completed the trial in December 2011 (power calculation revealed 350 completed cases). Conclusions: The experiences from this trial, considering demands and suggestions for clinical research from systematic reviews, showed that realization is possible. Those study designs are highly labor- and cost-intensive. Public funding will be even more important in the future to answer clinical questions on a generalizable population level. Keywords: Amoxicillin, metronidazole, RCT, periodontitis, trial design, scaling, clinically significant additional effect, multicenter study, placebo-controlled clinical study, oral health-related quality of life.

Clinical study design

Adjunctive treatment

10.2174/2213476x01666140327211914

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Protective effect of serum antibodies against a 110‐kilodalton protein of Actinobacillus actinomycetemcomitans following periodontal therapy

Oral Microbiology and Immunology (1999)

Thomas Beikler Helge Karch Benjamin Ehmke B Klaiber Daniel S. Thoma

Thirty-four adult patients with untreated periodontitis were randomly assigned to receive full mouth scaling alone or scaling with an adjunctive antimicrobial therapy, both followed by supportive periodontal therapy. At 24 months, specific serum immunoglobulin A (IgA), IgG and IgG subclass antibody reactivities against a 110-kDa protein of Actinobacillus actinomycetemcomitans were assessed by Western blot. In patients harboring A. actinomycetemcomitans intraorally, the IgG4 antibody reactivity against the 110-kDa protein of A. actinomycetemcomitans was associated with significantly increased survival rates of teeth and of sites not exhibiting 2 mm or more of probing attachment loss. The same trend was found for IgG3 and IgG2 antibody reactivities, but it was statistically insignificant. No association with clinical treatment outcome was observed for IgA, IgG and IgG1 antibody reactivities. The results indicated that systemic IgG4 antibody reactivity against the 110-kDa protein of A. actinomycetemcomitans may have a protective effect against periodontal disease progression in patients harboring A. actinomycetemcomitans and receiving periodontal therapy.

Actinobacillus

Subclass

Aggressive periodontitis

Periodontal pathogen

10.1034/j.1399-302x.1999.140503.x

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Administration of systemic antibiotics during non-surgical periodontal therapy—a consensus report

Clinical Oral Investigations (2018)

Bernadette Pretzl Sonja Sälzer Benjamin Ehmke Ulrich Schlagenhauf Bettina Dannewitz

Systemic antibiotics

Antibiotic Therapy

10.1007/s00784-018-2727-0

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The role of the oral microbiota in the causal effect of adjunctive antibiotics on clinical outcomes in stage III–IV periodontitis patients

Microbiome (2024)

Sven Kleine Bardenhorst Daniel Hagenfeld Johannes Matern Karola Prior Inga Harks

Abstract Background Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota’s composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy’s efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment. Methods Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes. Results We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14–1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00–1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes. Conclusions The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles.

Medical microbiology

10.1186/s40168-024-01945-3

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Significant Short-Term Shifts in the Microbiomes of Smokers With Periodontitis After Periodontal Therapy With Amoxicillin & Metronidazole as Revealed by 16S rDNA Amplicon Next Generation Sequencing

Frontiers in Cellular and Infection Microbiology (2020)

Daniel Hagenfeld Johannes Matern Karola Prior Inga Harks Peter Eickholz

The aim of this follow-up study was, to compare the effects of mechanical periodontal therapy with or without adjunctive amoxicillin and metronidazole on the subgingival microbiome of smokers with periodontitis using 16S rDNA amplicon next generation sequencing. Fifty-four periodontitis patients that smoke received either non-surgical periodontal therapy with adjunctive amoxicillin and metronidazole (n = 27) or with placebos (n = 27). Subgingival plaque samples were taken before and two months after therapy. Bacterial genomic DNA was isolated and the V4 hypervariable region of the bacterial 16S rRNA genes was amplified. Up to 96 libraries were normalized and pooled for Illumina MiSeq paired-end sequencing with almost fully overlapping 250 base pairs reads. Exact ribosomal sequence variants (RSVs) were inferred with DADA2. Microbial diversity and changes on the genus and RSV level were analyzed with non-parametric tests and a negative binomial regression model, respectively. Before therapy, the demographic, clinical, and microbial parameters were not significantly different between the placebo and antibiotic groups. Two months after the therapy, clinical parameters improved and there was a significantly increased dissimilarity of microbiomes between the two groups. In the antibiotic group, there was a significant reduction of genera classified as Porphyromonas, Tannerella, and Treponema, and 22 other genera also decreased significantly, while Selenomonas, Capnocytophaga, Actinomycetes, and five other genera significantly increased. In the placebo group, however, there was not a significant decrease in periodontal pathogens after therapy and only five other genera decreased, while Veillonella and nine other genera increased. We conclude that in periodontitis patients who smoke, microbial shifts occurred two months after periodontal therapy with either antibiotics or placebo, but genera including periodontal pathogens decreased significantly only with adjunctive antibiotics.

Veillonella

Aggressive periodontitis

10.3389/fcimb.2020.00167

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Association between bone turnover markers and periodontitis: A population‐based cross‐sectional study

Journal Of Clinical Periodontology (2022)

Stefan Lars Reckelkamm Anke Hannemann Thomas Kocher Matthias Nauck Henry Völzke

To examine the associations between bone turnover markers and periodontitis in two cross-sectional population-based studies.We used data from two independent adult samples (N = 4993), collected within the Study of Health in Pomerania project, to analyse cross-sectional associations of N-procollagen type 1 amino-terminal propeptide (P1NP), C-terminal cross-linking telopeptide, osteocalcin, bone-specific alkaline phosphatase (BAP), fibroblast growth factor 23, wingless-type mouse mammary tumour virus integration site family member 5a (WNT5A), and sclerostin values with periodontitis. Confounder-adjusted gamma and fractional response regression models were applied.Positive associations were found for P1NP with mean pocket probing depth (PPD; eβ=1.008 ; 95% confidence interval [CI]: 1.001-1.015), mean clinical attachment loss (mean CAL; eβ=1.027 ; 95% CI: 1.011-1.044), and proportion of sites with bleeding on probing (%BOP; eβ=1.055 ; 95% CI: 1.005-1.109). Similar associations were seen for BAP with %BOP ( eβ=1.121 ; 95% CI: 1.042-1.205), proportion of sites with PPD ≥4 mm (%PPD4) ( eβ=1.080 ; 95% CI: 1.005-1.161), and sclerostin with %BOP ( eβ=1.308 ; 95% CI: 1.005-1.704). WNT5A was inversely associated with mean PPD ( eβ=0.956 ; 95% CI: 0.920-0.993) and %PPD4 ( eβ=0.794 ; 95% CI: 0.642-0.982).This study revealed scattered associations of P1NP, BAP, WNT5A, and sclerostin with periodontitis, but the results are contradictory in the overall context. Associations reported in previous studies could not be confirmed.

Cross-sectional study

Bone remodeling

Association (psychology)

10.1111/jcpe.13649

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Guided tissue regeneration using a polylactic acid barrier

Journal Of Clinical Periodontology (2003)

Benjamin Ehmke Stefan G. Rüdiger A. Hommens Helge Karch Daniel S. Thoma

Abstract Objectives: The purpose of this study was to determine the relative impact of various predictors responsible for the variability in treatment outcome after guided tissue regeneration (GTR) in intraosseous periodontal defects. Patients and methods: 30 patients with chronic periodontitis and at least one intraosseous periodontal lesion (≥4 mm) were enrolled. Following full‐mouth scaling, GTR using polylactic acid membranes was performed at one site in each patient. Main periodontal pathogens, defect morphology, membrane exposure and smoking habit were assessed as predictor variables. Alveolar bone level change served as the primary outcome variable in a multiple regression analysis. Results: After 12 months, the 29 patients completing the study showed alveolar bone changes ranging from 4 mm bone gain to 1 mm bone loss (mean: 1.6±0.4 mm gain). Active smoking (β‐weight:‐0.49, P =0.003) and persistence of subgingival infection with P. gingivalis (P.g.) (β‐weight:‐0.25, P =0.11) were associated with poor treatment outcome. Deep initial intraosseous defects (β‐weight: 0.32, P =0.045) were associated with favorable treatment outcome, and membrane exposure had no impact on bone gain. Conclusion: Active smoking was the strongest predictor variable negatively affecting alveolar bone gain following GTR in the treatment of periodontal defects. It was followed by a positive influence of a deeper intraosseous defect and by a negative effect by persistent subgingival infection of P. gingivalis . The relative impact of these factors may be useful in assessing the prosgnosis of GTR in intraosseous periodontal defects.

10.1034/j.1600-051x.2003.00312.x

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Clonal Infection with Actinobacillus actinomycetemcomitans Following Periodontal Therapy

Journal of Dental Research (1999)

Benjamin Ehmke Herbert Schmidt Thomas Beikler Chirag Rajkumar Kopp Helge Karch

Mechanical debridement results in a shift of the bacterial composition in the periodontal pocket on the species level. It is unknown, however, whether a clonal change within a species could lead to the emergence of strains with different levels of virulence. Therefore, in the present study, the genetic variability of Actinobacillus actinomycetemcomitans was assessed and strains identified which were associated with periodontal disease progression following periodontal therapy, i.e., refractory periodontitis. Twenty adult patients with untreated periodontitis and subgingival colonization of A. actinomycetemcomitans were randomly assigned to receive full-mouth scaling alone or scaling with an adjunctive antimicrobial therapy. Both groups received supportive periodontal therapy at 3, 6, 9, 12, 18, and 24 months. Subgingival plaque samples were taken at every visit; venous blood was obtained at 24 months only. A. actinomycetemcomitans isolates were typed by the RAPD method, and antibody reactivity against outer membrane proteins was assessed by immunoblot analysis. Eleven distinct RAPD patterns were found in 18 patients completing the study. All patients harbored only one A. actinomycetemcomitans genotype, and within each patient this genotype persisted throughout the 24-month observation period. No differences in the expression of antibody reactivity against outer membrane proteins were found between strains isolated at baseline and at 24 months. Three genotypes were associated with reduced survival rates of teeth without probing attachment loss of 2 mm or more. The results indicated that (i) most patients harbored only one A. actinomycetemcomitans genotype; (ii) the genotype persisted following therapy; and (iii) only some genotypes were associated with refractory periodontitis.

Actinobacillus

Aggressive periodontitis

Prevotella intermedia

Clinical attachment loss

10.1177/00220345990780090601

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Citations (19)

A Mendelian randomization study on the effect of 25‐hydroxyvitamin D levels on periodontitis

Journal of Periodontology (2021)

Sebastian‐Edgar Baumeister Stefan Lars Reckelkamm Hansjörg Baurecht Michael Nolde Thomas Kocher

Twenty five-hydroxy vitamin D (25OHD) levels have been proposed to protect against periodontitis based on in vitro and observational studies but evidence from long-term randomized controlled trials (RCTs) is lacking. This study tested whether genetically proxied 25OHD is associated with periodontitis using Mendelian randomization (MR).Genetic variants strongly associated with 25OHD in a genome-wide association study (GWAS) of 417,580 participants of European ancestry were used as instrumental variables, and linked to GWAS summary data of 17,353 periodontitis cases and 28,210 controls. In addition to the main analysis using an inverse variance weighted (IVW) model, we applied additional robust methods to control for pleiotropy. We also undertook sensitivity analyses excluding single nucleotide polymorphisms (SNPs) used as instruments with potential pleiotropic effects and used a second 25OHD GWAS for replication. We identified 288 SNPs to be genome-wide significant for 25OHD, explaining 7.0% of the variance of 25OHD levels and providing ≥90% power to detect an odds ratio (OR) of ≤ 0.97.MR analysis suggested that a 1 standard deviation increase in natural log-transformed 25OHD was not associated with periodontitis risk (IVW OR = 1.04; 95% confidence interval (CI): 0.97-1.12; P-value = 0.297). The robust models, replication, and sensitivity analyses were coherent with the primary analysis.Collectively, our findings suggest that 25OHD levels are unlikely to have a substantial effect on the risk of periodontitis, but large long-term RCTs are needed to derive definitive evidence on the causal role of 25OHD in periodontitis.

Mendelian Randomization

Genome-wide Association Study

Pleiotropy

Genetic Association

10.1002/jper.21-0463

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Citations (10)