Active Matrix Metalloproteinase-8 (aMMP-8) Versus Total MMP-8 in Periodontal and Peri-Implant Disease Point-of-Care Diagnostics.

Active matrix metalloproteinase-8 (aMMP-8) is a promising biomarker candidate for the modern periodontal and peri-implant disease diagnostics utilizing the chairside/point-of-care oral fluid technologies. These rapid biomarker analysis technologies utilize gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), or mouth rinse as the oral fluid matrices that can be collected patient-friendly and non-invasively without causing bacteremia. aMMP-8, but not total or latent proMMP-8, has been shown to be a relevant biomarker to be implemented to the latest 2017 classification system of periodontitis and peri-implantitis. Thus, aMMP-8 point-of-care-testing (POCT)-but not total or latent proMMP-8-can be conveniently used as an adjunctive and preventive diagnostic tool to identify and screen the developing and ongoing periodontal and peri-implant breakdown and disease as well as predict its episodic progression. Similarly, aMMP-8 POCT provides an important tool to monitor the treatment effect of these diseases, but also other diseases such as head and neck cancer, where it can identify and predict the rapid tissue destructive oral side-effects during and after the radiotherapy. Additionally, recent studies support aMMP-8 POCT benefitting the identification of periodontitis and diabetes as the escalating risk diseases for COVID-19 infection. Overall, aMMP-8 POCT has launched a new clinical field in oral medicine and dentistry, i.e., oral clinical chemistry.

Association of chronic periodontitis with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Chronic periodontitis (CP) is a multifactorial, chronic inflammatory disease of microbial etiology that manifests as a result of the dysfunction of the immune mechanism, culminating in the destruction of the alveolar bone of the jaws. Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system (CNS), leads to demyelination and degeneration of nerve axons and often causes severe physical and/or cognitive impairment. As CP and MS involve inflammatory mechanisms and immune dysfunction, researchers have attempted to study the association between them. AIM: To systematically review the literature on the epidemiological association between CP and MS in adults. METHODS: PRISMA 2020 statement was used in the study protocol. The design was done according to the Cochrane methodology. A comprehensive literature search was performed in PubMed, Scopus and Cochrane databases; a manual search and evaluation of the gray literature was also performed. The meta-analysis was performed by Review Manager (RevMan) 5.4. Odds ratio (OR) with 95% confidence interval (CI) was defined as the effect size of the outcome. Heterogeneity was assessed by Chi-square and I2. The articles evaluated were written in English, without a time limit, concern observational studies (patient-controls) and report the diagnostic criteria of the diseases. Duplicate entries were excluded. To evaluate the reliability of the results of each study, Newcastle-Ottawa Scale (NOS) and GRADE tools were used. Two independent reviewers did all evaluations with a resolution of discrepancies by a third. RESULTS: Meta-analysis included three observation studies examined 3376 people. MS patients are significantly more likely to be diagnosed with CP than healthy controls (OR 1.93, 95% CI 1.54-2.42, p<0.0001). CONCLUSION: A high prevalence of CP was found among MS patients compared with healthy controls. Healthcare professionals should be aware of the association between these pathological entities to provide patients with high-quality care through an effective and holistic diagnostic and therapeutic approach.

Association of Chronic Periodontitis with Helicobacter pylori Infection in Stomach or Mouth: A Systematic Review and Meta-Analysis.

Helicobacter pylori (H. pylori) infection and periodontitis are both inflammatory conditions associated with systemic diseases. Researchers have attempted to investigate the correlation between them. This systematic review and meta-analyses were conducted to investigate the association of H. pylori infection in the stomach and/or in subgingival plaque and gingival crevicular fluid with chronic periodontitis. The protocol was created according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. The study was designed according to the Cochrane criteria. A comprehensive literature search was performed in MEDLINE, Scopus, and CENTRAL, combined with hand-searching and assessment of gray literature. The meta-analysis of the included studies was made by the Review Manager (RevMan) 5.4 software. The effect measure of the outcome was odds ratios with 95% confidence intervals. Heterogeneity was assessed by chi-square and I2. Four observational studies involving 818 subjects were included in this meta-analysis. The odds of oral H. pylori presence were higher in patients with chronic periodontitis, compared to healthy controls, with an odds ratio of 1.87 (95% confidence interval 0.85-4.10; p = 0.12). The odds of the presence of H. pylori in the stomach also were higher in patients with chronic periodontitis, with an odds ratio of 1.80 (95% confidence interval 0.82-3.95; p = 0.15). There is no evidence for an association between chronic periodontitis and the prevalence of H. pylori, detected either in subgingival plaque and gingival crevicular fluid or in the stomach.

aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases.

The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75-85% and specificity in the range of 80-90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.

Is There a Link between COVID-19 and Periodontal Disease? A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic greatly affected human well-being, social behavior, global economy, and healthcare systems. Everyday clinical practice in dentistry has been adjusted to the increased hazards of aerosol production by routine dental procedures. The objective of this study was to assess the existing literature to determine possible mechanisms of a relationship between COVID-19 and periodontitis, as well as describe findings from relevant epidemiological studies.Scarce data exist in the literature that directly addresses the relationship between the two diseases. However, several data describe the role of the oral cavity and periodontal tissues as portals of entry of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and the contribution of cytokines known to be produced in periodontal disease to severe forms of COVID-19. It is also suggested from the current literature that periodontal disease, shown to be associated with systemic diseases such as diabetes mellitus, cardiovascular and respiratory diseases, shares common risk factors with-especially-severe forms of COVID-19.Further clinical studies are required to establish the relationship between these diseases. Oral hygiene performance and intact periodontal tissues can assist in mitigating the pandemic, and it is suggested that dental practitioners can contribute to identifying at-risk patients.

Periodontitis and Helicobacter pylori Infection: Eradication and Periodontal Therapy Combination.

OBJECTIVES: This study was aimed to assess (1) the prevalence of salivary and gastric Helicobacter pylori (HP) infection in patients with and without periodontitis, (2) the prevalence of HP infection in patients with periodontitis according to its clinical classification, (3) the effect of periodontitis treatment in patients with or without gastric HP infection, and (4) if gastric HP eradication in combination with periodontitis treatment influences periodontitis clinical outcome. MATERIALS AND METHODS: Thirty-three adults with periodontitis treated by quadrant scaling and root planning (QSRP). The simplified plaque index (PI), bleeding on probing index (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed pretreatment and 3 months of posttreatment. The patients were tested for oral and gastric HP. Gastric HP (+) patients received eradication therapy. A control group of 32 periodontically healthy volunteers was tested for oral and gastric HP. Saliva samples were evaluated by real-time polymerase chain reaction (rtPCR); gastric HP was detected by urea breath test (UBT). STATISTICAL ANALYSIS: Normality of variables assessed by the Kolmogorov-Smirnov test, while the differences of pre- and post-treatment were analyzed by paired samples t-test. Differences between subgroups were compared by a Student's t-test or a Mann-Whitney U-test. Comparisons of nominal variables were made by Pearson's Chi-square test. RESULTS: No saliva samples were positive for HP. Gastric HP was detected in six patients with periodontitis and seven controls (p > 0.05). HP infection affected patients with higher disease stages and grades. All HP (+) patients underwent successful eradication treatment. All clinical periodontitis indices improved following QSRP. HP (+) patients who received QSRP as adjunctive to eradication treatment showed improvement in BOP (p < 0.001), PI (p < 0.013), and CAL (p < 0.004) compared with HP (-) patients who received QSRP alone. CONCLUSION: Periodontitis was not associated with gastric HP infection. Saliva was not a gastric HP supply reservoir. Gastric HP infection was associated with advanced stages and grades of periodontitis. Although all periodontal clinical markers improved after QSRP, BOP, PI, and CAL, they were further improved when combined with eradication treatment. Periodontal evaluation and treatment combined with HP eradication are recommended in patients with HP gastric infection.

Active matrix metalloproteinase-8: A potential biomarker of oral systemic link.

OBJECTIVES: This mini review aims to address some possible gaps in periodontal diagnosis in clinical studies particularly involving the oral-systemic connection with a view to minimize such gaps, and thus improve patient treatment experiences and outcomes. METHODS: The conventional assessment of periodontitis has traditionally been by clinical and radiographic oral parameters. We reviewed numerous studies published mainly within the past decade, to affirm the oral-systemic link, the contribution of periodontitis to the inflammatory burden in various systemic diseases and conditions, and the potential role of active matrix metalloproteinase-8 (aMMP-8). RESULTS: While it is established that periodontal pathogens in dental plaque biofilm are the primary initiating agents in periodontitis, it has become clear from the appraisal of recent studies that the host inflammation, including biomarkers such as aMMP-8 play a major role, being the driving underlying pathological mechanism in both periodontitis and systemic diseases. CONCLUSIONS: The apparent limitations of conventional diagnostic tools have led researchers to seek alternative methods of evaluation such as the quantification of biomarkers including aMMP-8, which can be a bridge between oral/periodontal and systemic diseases; aMMP-8 can form a mouth-body connection.

Interaction between TCF7L2 rs7903146 Genotype, HbA1c Levels, and the Periodontal Status of Dental Patients.

OBJECTIVE: The aim of the study was to investigate the potential interaction between TCF7L2 rs7903146 genotype, which is implicated for type-2 diabetes mellitus genetic susceptibility, HbA1c levels, and the periodontal status of dental patients. MATERIALS AND METHODS: HbA1c levels, clinical periodontal parameters (probing depth, clinical attachment level, bleeding on probing, and plaque index), and several parameters (such as body mass index [BMI], smoking habits, education level, and age) were recorded in 150 patients who fulfilled the criteria for screening for prediabetes/diabetes of the Centers for Disease Control and Prevention. DNA was extracted and the TCF7L2 single nucleotide polymorphism (SNP) rs7903146 was genotyped in all participants. RESULTS: Thirty-one patients out of 150 tested were found with unknown hyperglycemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between patients displaying HbA1c < 5.7 and ≥ 5.7% (Pearson's Chi-square test, p > 0.05). Regarding periodontal parameters and differences between subgroups (HbA1c levels ≥ 5.7 and HbA1c levels < 5.7), statistically significant differences were observed for probing depth (3.20 ± 0.94 vs. 2.81 ± 0.78 mm), clinical attachment level (3.54 ± 1.20 vs. 3.18 ± 1.06 mm) and bleeding on probing (0.62 ± 0.25 vs. 0.50 ± 0.24%) with hyperglycemic patients exhibiting worse periodontal conditions (Mann-Whitney test p < 0.05). The allelic and genotype frequencies for the transcription factor 7-like 2 (TCF7L2) gene, SNPs 7903146 did not exhibit a significant difference between the HbA1c > 5.7 and HbA1c < 5.7 groups and the periodontitis and nonperiodontitis subgroups respectively (Fisher's exact test >0.05). Statistical Analysis Patient characteristics and their association with prediabetes were tested by Pearson's Chi-square test (asymptotic, two sided). Differences of periodontal parameters between subgroups were tested with the Mann-Whitney U-test. The associations of allele and genotype frequencies in the patient and control groups were analyzed using the Fisher's exact test of independence.The significance level was set at the 0.05 for all tests. CONCLUSION: A statistically significant association between TCF7L2 rs7903146 genotype and periodontal condition or HbA1c levels was not observed in contrast to statistically significant differences of clinical parameters of periodontitis in patients with hyperglycemia.

An aMMP-8 Point-of-Care and Questionnaire Based Real-Time Diagnostic Toolkit for Medical Practitioners.

The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761-0.906), total MMP-8 = 0.800 (0.722-0.878), active MMP-9 = 0.787 (0.704-0.870), total MMP-9 = 0.773 (0.687-0.858) and calprotectin = 0.773 (0.687-0.858) vs. questionnaire = 0.764 (0.676-0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment.

Prediabetes/diabetes screening strategy at the periodontal clinic.

OBJECTIVE: The aim of the study was to propose an efficient chairside clinical strategy for the identification of undiagnosed hyperglycaemia in periodontal clinics. MATERIAL AND METHODS: Α chairside system was used for assessment of glycated hemoglobin 1c (HbA1c) and active Matrix Metalloproteinase-8 levels (aMMP-8) were analyzed by immunotest in patients (n = 150) who fulfilled the criteria for screening of the Centers for Disease Control and Prevention. Full-mouth periodontal parameters were assessed and various data such as Body Mass Index (BMI), smoking and education were recorded. RESULTS: Thirty-one patients out of 150 tested were found with unknown hyperglycaemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between subjects displaying HbA1c < 5.7 and ≥5.7% (Pearson's Chi-square test, p > .05). Subgroups differed regarding BMI (kg/m2 ), tooth count, percentages of 4 and 5 mm pockets (Mann-Whitney and z-test, p < .05). The diagnostic performance for HbA1c ≥5.7 was tested by Receiving Operator Characteristic curves and Areas Under the Curve (AUC) for the following: age ≥ 45 years and BMI (AUC 0.651, p = .010), the above and aMMP-8 (AUC 0.660, p = .006), age ≥ 45 years, BMI and Stage of Periodontitis (AUC 0.711, p < .001) and age ≥ 45 years, BMI, aMMP-8 and stage of periodontitis (AUC 0.713, p < .001). CONCLUSIONS: Findings of the study suggest that the combination of stage of periodontitis, increasing age, BMI and aMMP-8, without chairside HbA1c assessment appears to be a viable screening strategy for referring dental patients for testing for prediabetes/diabetes.

Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era.

Periodontal disease is a chronic multifactorial infectious and inflammatory disease associated with several chronic systemic diseases, such as diabetes, cardiovascular diseases (CVD), chronic obstructive pulmonary disease, hypertension, Alzheimer's disease and so on. These same systemic diseases have been associated with severe COVID-19 infections. Several recent studies have suggested hypotheses for the potential association between periodontal disease and severe COVID-19. Periodontal disease is also one of the most prevalent diseases globally. All this supports the importance of good oral health, also in the COVID-19 era. Thus, new strategies and approaches to identify patients at risk of periodontal disease could be beneficial to enhance secondary prevention, especially if targeted to COVID-19 risk groups. Diagnostic biomarkers for periodontal disease have been researched extensively. Potential biomarkers in oral fluid with currently available rapid non-invasive point-of-care technology, such as aMMP-8, could help to extend screening and identification of patients at risk for periodontal disease also to situations and places where professional dental expertise and equipment are limited or unavailable. i.e., nursing and care homes, and rural and distant places. The oral fluid point-of-care technologies could also be useful in the hands of medical professionals (diabetes, CVD, etc.) to identify patients at risk for undiagnosed periodontal disease and to refer them to a dentist for examination and evaluation. Finally, if there is a causality between periodontal disease and severe COVID-19 infections, these point-of-care oral fluid biomarker technologies could possibly also help in the assessment of the risk of deterioration and complications.

Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification.

The aim of this study was to investigate the utility of incorporating active matrix metalloproteinase-8 (aMMP-8) as a biomarker into the new periodontitis classification system (stage/grade) presented in 2018. This study included 150 Greek adults aged 25-78, of whom 74 were men and 76 women. Participants were tested with an aMMP-8 point-of-care mouthrinse test, after which a full-mouth clinical examination was performed to assess their periodontal and oral health. The aMMP-8 levels in mouthrinse were significantly lower among healthy patients compared with patients in more severe periodontitis stages and grades (Kruskal-Wallis test and Dunn-Bonferroni test for pairwise post-hoc comparisons; p < 0.01 and p < 0.05, respectively). Furthermore, aMMP-8 levels were less correlated with plaque levels than bleeding on probing (BOP) (Spearman's rho = 0.269, p < 0.001; Spearman's rho = 0.586, p < 0.001); respectively). Thus, aMMP-8 was more robust to the confounding effects of oral hygiene than traditional periodontal parameter bleeding on probing. The aMMP-8 point-of-care mouthrinse test can be utilized as an adjunctive and preventive diagnostic tool to identify periodontal disease, classified by stage and grade, and ongoing periodontal breakdown chairside in clinical practice in only 5 min. Overall, integrating aMMP-8 into the new periodontitis classification system seems beneficial.

Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest.

Pre-diabetes and diabetes are strongly associated with periodontal disease (gingivitis and periodontitis), and these conditions are known to upregulate aMMP-8 in inflamed gingiva and oral fluids. Thus, it would be feasible to screen for prediabetes and diabetes at the dental office by chairside tests. Chair-side assessment of HbA1c and a quantitative point-of-care (PoC) active matrix metalloproteinase (aMMP)-8 oral rinse immunotest developed for periodontal diseases, were performed on patients (n = 69) attending a Periodontology University Clinic who fulfilled the criteria for testing according to the screening questionnaire of the Centers for Disease Control and Prevention, USA. Clinical parameters of periodontal disease were also recorded with an automated probe. Twenty seven-point-five percent of the subjects were found with previously unknown hyperglycemia (HbA1c ≥ 5.7%). There was a statistically-significant positive association between the aMMP-8test and prediabetes (p < 0.05, unadjusted and adjusted for BMI and age ≥ 45 years logistic regression models). The dental setting is suitable for opportunistic screening for undiagnosed diabetes and pre-diabetes and point-of-care HbA1c, especially when combined with aMMP-8 assessment by dental professionals, being convenient and effective.

Outcomes of implant therapy in patients with a history of aggressive periodontitis. A systematic review and meta-analysis.

OBJECTIVE: To investigate the outcomes of implant therapy in partially dentate patients treated for aggressive periodontitis (GAgP) in comparison to periodontally healthy (HP) and patients treated for chronic periodontitis (CP) utilizing radiographic and clinical parameters. MATERIAL AND METHODS: An electronic search of databases, supplemented by hand searching, was conducted to identify relevant clinical studies. Sequential screenings at the title, abstract and full-text levels were performed independently and in duplicate. A random effects meta-analysis was conducted and bias corrected bootstrap 95 % confidence intervals were estimated for group comparisons. RESULTS: The search strategy revealed a total of 899 results. After title screening, abstract scanning, and full-text reading, seven articles fulfilled the inclusion criteria. The 3-year survival rate for CP and HP patients was 100 % while in GAgP subjects, the respective value was 97.98 %; this difference being statistically significant. The 3-year mean marginal bone loss (MBL) was 1.07 mm for the GAgP group, 0.47 mm for the CP group, and 0.69 mm for the HP group. A significant difference between the GAgP and CP groups was identified (p < 0.05). The weighted mean differences of MBL concerning the above groups were also calculated and examined for statistical significance in both 1 and 3 years. CONCLUSIONS: The 3-year survival rate and peri-implant marginal bone loss was found statistically significantly lower in GAgP subjects (SR 97.98 % vs 100 %) in comparison to HP and CP individuals. CLINICAL RELEVANCE: The outcome of implant therapy in terms of survival rate and marginal bone loss is considered very important for the clinician in decision making when placing implants in patients with a history of aggressive periodontitis.