Warum aMMP-8-Speicheldiagnostik?

Mehr als 30 Jahre Forschung machen aMMP-8 zum oralen Biomarker der Wahl: dentognostics‘ patentierte Technologie misst die aktivierte Form des Enzyms Matrix-Metalloproteinase-8, daher aMMP-8 genannt, um den Abbau von oralem Kollagengewebe auf zellulärer Ebene zu bestimmen.

Bei oralem Kollagenabbau gehen 90-95 % der kollagenolytischen Aktivität in der Gingivakrevikularflüssigkeit auf das Enzym Matrix-Metalloproteinase-8 zurück². Wissenschaftler der Sapienza Universität Rom zeigen, dass 6 Monate alte Implantate mit erhöhtem aMMP-8 nach 2 Jahren signifikant mehr Knochenverlust aufweisen als Implantate mit niedrigen Werten³ und belegen die Prädiktivität von aMMP-8 in einer weiteren Studie für den Zeitraum von 5 Jahren⁴. aMMP-8 wurde als Biomarker zur Bestimmung des Progressionsgrades im Rahmen der AAP-Klassifizierung von Parodontalerkrankungen nach stage und grade vorgeschlagen⁵⁺⁶, wobei hohe Konzentrationen von aMMP-8 auf einen hohen Grad der Krankheitsprogression hinweisen⁵. aMMP-8 ist nachweislich besser geeignet, um Parodontitis in einem subklinischen Stadium (stage) zu erkennen, als Blutungen beim Sondieren (Bleeding on Probing)⁷.

Wenn die orale Immunbarriere durch das Fortschreiten der Parodontalerkrankung geschwächt wird⁸⁺⁹, kann dies über den Blutkreislauf zu systemischen Entzündungen führen¹⁰⁻¹². Hohe aMMP-8 Werte sind mit systemischen Gesundheitsrisiken verbunden, z. B. mit Diabetes¹³⁻¹⁵, Herz-Kreislauf-Erkrankungen¹⁶⁻¹⁷ und Unfruchtbarkeit¹⁸⁻²⁰. Dieser Zusammenhang zwischen oraler und systemischer Gesundheit wird als oral systemic link bezeichnet und aMMP-8 als ein wichtiger Biomarker dafür vorgeschlagen ²¹.

Wie dient Speicheldiagnostik als Patientenmanagement-Tool?

Personalisiertes Biofeedback kann Patienten dazu motivieren, ihr gewöhnliches Mundgesundheitsverhalten zu ändern²².  aMMP-8-Biomarker-Feedback wurde erfolgreich eingesetzt, um individuelle Recall-Intervalle für Prophylaxe zu erstellen und bessere Präventionsergebnisse zu erzielen²³⁺²⁴.  Das Monitoring von aMMP-8-Werten ist für Patienten motivierend²³, denn es gibt ihnen ein klares Ziel vor: in den grünen Wertebereich zu kommen²³. Intrinsisch motivierte Patienten gehen regelmäßiger zum Zahnarzt und haben eine bessere Mundgesundheit²⁵. Die aMMP-8-Testergebnisse sind einfach zu kommunizieren und stehen nach 5 Minuten am Point-of-Care zur Verfügung²³.

Literaturverzeichnis:

1. Al-Majid, A. et al. Matrix Metalloproteinase-8 as an Inflammatory and Prevention Biomarker in Periodontal and Peri-Implant Diseases. Int. J. Dent. 2018, 1–27 (2018).
2. Sorsa, T. et al. Analysis of matrix metalloproteinases, especially MMP‐8, in gingival crevicular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontol. 2000 70, 142–163 (2016).
3. Guarnieri, R. et al. Correlation between peri-implant marginal bone loss progression and peri-implant sulcular fluid levels of metalloproteinase-8. J. Pers. Med. 12, 58 (2022).
4. Guarnieri, R. et al. Can Peri-Implant Marginal Bone Loss Progression and a-MMP-8 Be Considered Indicators of the Subsequent Onset of Peri-Implantitis? A 5-Year Study. Diagnostics 12, 2599 (2022).
5. Sorsa, T. et al. Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification. Diagnostics 10, 61 (2020).
6. Tonetti, M. S., Greenwell, H. & Kornman, K. S. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J. Periodontol. 89, (2018).
7. Räisänen, I. et al. Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents. Diagnostics 9, 34 (2019).
8. Bosshardt, D. D. The periodontal pocket: pathogenesis, histopathology and consequences. Periodontol. 2000 76, 43–50 (2018).
9. Kinane, D. F., Stathopoulou, P. G. & Papapanou, P. N. Periodontal diseases. Nat. Rev. Dis. Primer 3, 17038 (2017).
10. Botelho, J. et al. Periodontitis and circulating blood cell profiles: a systematic review and meta-analysis. Exp. Hematol. 93, 1–13 (2021).
11. Bui, F. Q. et al. Association between periodontal pathogens and systemic disease. Biomed. J. 42, 27–35 (2019).
12. Vitkov, L. et al. Connection between periodontitis-induced low-grade endotoxemia and systemic diseases: neutrophils as protagonists and targets. Int. J. Mol. Sci. 22, 4647 (2021).
13. Grigoriadis, A. et al. Prediabetes/diabetes screening strategy at the periodontal clinic. Clin. Exp. Dent. Res. 7, 85–92 (2021).
14. Grigoriadis, A. et al. Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest. Diagnostics 9, 151 (2019).
15. Umeizudike, K. A. et al. Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues. Eur. J. Dent. s-0044-1788797 (2024) doi:10.1055/s-0044-1788797.
16. Sorsa, T. et al. Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines. Pharmacol. Res. 63, 108–113 (2011).
17. Tuomainen, A. M. et al. Serum Matrix Metalloproteinase-8 Concentrations Are Associated With Cardiovascular Outcome in Men. Arterioscler. Thromb. Vasc. Biol. 27, 2722–2728 (2007).
18. Nwhator, S. et al. Could periodontitis affect time to conception? Ann. Med. Health Sci. Res. 4, 817 (2014).
19. Nwhator, S. O. Association between aMMP-8 Chairside Test for Chronic Periodontitis and Selected Reproductive Health Parameters. (2018).
20. Nwhator, S. O. et al. Another Reason for Impeccable Oral Hygiene: Oral Hygiene-Sperm Count Link. J. Contemp. Dent. Pract. 15, 352–358 (2014).
21. Umeizudike, K. et al. Active matrix metalloproteinase‐8: A potential biomarker of oral systemic link. Clin. Exp. Dent. Res. 8, 359–365 (2022).
22. Chapple, I. L. & Hill, K. Getting the message across to periodontitis patients: the role of personalised biofeedback. Int. Dent. J. 58, 294–306 (2008).
23. Neefs, D. Een aMMP-8 use-case – Voorspellende biomarkers in de moleculaire tandheelkunde [An aMMP-8 use case – Predictive biomarkers in molecular dentistry]. ConsulTand vol. 17 14–17 (2024).
24. Raivisto, T. et al. Active Matrix Metalloproteinase-8 Chair Side Mouth Rinse Test, Health Behaviour and Oral Health in Finnish Adolescent Cohort. J. Clin. Diagn. Res. (2020) doi:10.7860/JCDR/2020/43031.13467.
25. Münster Halvari, A. E., Halvari, H., Bjørnebekk, G. & Deci, E. L. Motivation and anxiety for dental treatment: Testing a self-determination theory model of oral self-care behaviour and dental clinic attendance. Motiv. Emot. 34, 15–33 (2010).

Die 7 wichtigsten Studien zu aMMP-8

1. Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification

Sorsa, T., Alassiri, S., Grigoriadis, A., Räisänen, I. T., Pärnänen, P., Nwhator, S. O., Gieselmann, D.-R., & Sakellari, D. (2020). Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification. Diagnostics (Basel, Switzerland). https://doi.org/10.3390/diagnostics10020061

Abstract:

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.

2. Can Peri-Implant Marginal Bone Loss Progression and a-MMP-8 Be Considered Indicators of the Subsequent Onset of Peri-Implantitis? A 5-Year Study.

Guarnieri, R., Reda, R., Zanza, A., Miccoli, G., Nardo, D. D., & Testarelli, L. (2022). Can Peri-Implant Marginal Bone Loss Progression and a-MMP-8 Be Considered Indicators of the Subsequent Onset of Peri-Implantitis? A 5-Year Study. Diagnostics (Basel, Switzerland), 12(11), Article 11. https://doi.org/10.3390/diagnostics12112599

Abstract:

The aim of this retrospective study was to investigate the relationship between the amount of early bone remodeling, the marginal bone loss (MBL) progression, and the peri-implant sulcular fluid concentration of active metalloproteinase-8 (a-MMP-8) and the incidence of peri-implantitis (P) over 5 years of implant function. It has been documented that dental implants with a high degree of early marginal bone loss (MBL) are likely to achieve additional increased MBL during function. Moreover, it has been speculated that early increased MBL might be a predictive factor for the subsequent onset of peri-implant inflammatory diseases. Clinical and radiographic data at implant placement (T0) and restoration delivery (TR) at 6 months (T1), 2 years (T2), and 5 years (T5) post-loading were retrospectively collected. MBL levels/rates (MBLr) and peri-implant sulcular fluid levels/rates of a-MMP-8 were assessed at TR, T1, T2, and T5. Implants were divided into two groups: group 1 with peri-implantitis (P+) and group 2 without peri-implantitis (P−). A multi-level simple binary logistic regression, using generalized estimation equations (GEEs), was implemented to assess the association between each independent variable and P+. A receiver operating characteristics (ROC) curve was used to evaluate an optimal cutoff point for T1 MBL degree and a-MMP-8 level to discriminate between P+ and P− implants. A total of 80 patients who had received 80 implants between them (39 implants with a laser-microtextured collar surface (LMS) and 41 implants with a machined collar surface (MS)) were included. Periapical radiographs and a software package were used to measure MBL rates. Peri-implant sulcular implant fluid samples were analyzed by a chairside mouth-rinse test (ImplantSafe^®) in combination with a digital reader (ORALyzer®). Twenty-four implants (six with an LMS and eighteen with an MS) were classified as P+. No statistically significant association was found between the amount of early bone remodeling, MBL progression, and MBLr and the incidence of peri-implantitis. Implants with a-MMP-8 levels >15.3 ng/mL at T1 presented a significantly higher probability of P+. The amount of early marginal bone remodeling cannot be considered as an indicator of the subsequent onset of P, whereas high a-MMP-8 levels 6 months after loading could have a distinct ability to predict P.

3. Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents.

Räisänen, I. T., Sorsa, T., van der Schoor, G.-J., Tervahartiala, T., van der Schoor, P., Gieselmann, D.-R., & Heikkinen, A. M. (2019). Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents. Diagnostics (Basel, Switzerland), 9 (1), Article 1. https://doi.org/10.3390/diagnostics9010034

Abstract:
This cross-sectional study compares the effectiveness of an active MMP-8 (aMMP-8) point-of-care (PoC)/chairside mouthrinse test to the conventional bleeding on probing (BOP) (cutoff 20%) test in detecting subclinical periodontitis/pre-periodontitis in Finnish adolescents. The study was carried out at the Kotka Health Center, Finland. A total of 47 adolescents (30 boys/17 girls) aged 15–17 were first tested with the aMMP-8 PoC test, followed by a full-mouth evaluation of clinical parameters of oral health including periodontal, oral mucosal, and caries assessment. A periodontist performed these clinical examinations. The aMMP-8 PoC test result had much stronger association with subclinical periodontitis than the BOP 20% test (2.8–5.3 times stronger in terms of odds ratio). The aMMP-8 PoC test had ≥2 times higher sensitivity than the BOP 20% test with, generally, the same specificity. Further, the aMMP-8 PoC test had generally better accuracy and lower false negative percentages. The aMMP-8 PoC test seemed to be more effective than the conventional BOP test in detecting subclinical periodontitis/pre-periodontitis in adolescents reducing the risk of their undertreatment. However, the sample size may be a limiting factor, and more studies are needed to confirm our results for both adolescents and adults.

4. The Ability of Quantitative, Specific, and Sensitive Point-of-Care/Chair-Side Oral Fluid Immunotests for aMMP-8 to Detect Periodontal and Peri-Implant Diseases.

Alassiri, S., Parnanen, P., Rathnayake, N., Johannsen, G., Heikkinen, A.-M., Lazzara, R., Schoor, P. van der, Schoor, J. G. van der, Tervahartiala, T., Gieselmann, D., & Sorsa, T. (2018). The Ability of Quantitative, Specific, and Sensitive Point-of-Care/Chair-Side Oral Fluid Immunotests for aMMP-8 to Detect Periodontal and Peri-Implant Diseases. Disease Markers. https://doi.org/10.1155/2018/1306396

Abstract:

The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth rinse, gingival crevicular fluid (GCF), and peri-implantitis fluid (PISF)) is demanding. Several hosts and microbial factors may influence their expression, release, and levels. The type of saliva/oral fluids utilized for the diagnostics affects the analysis. High sensitivity and specificities together with sophisticated methods and techniques are essential for valuable outcome. We describe here recently developed practical, convenient, inexpensive, noninvasive, and quantitative mouth rinse and PISF/GCF/chair-side/point-of-care (PoC) lateral-flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer®) to detect, predict, and monitor successfully the course, treatment, and prevention of periodontitis and peri-implantitis, respectively. The tests have been independently and successfully validated to differentiate periodontal and peri-implant health and disease in Finland, Germany, Netherland, Sweden, Turkey, Nigeria, Malawi, and USA. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires additional studies utilizing these noninvasive screening, diagnostic, and preventive aMMP-8 PoC/chair-side technologies.

5. Active MMP-8 point-of-care (PoC)/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis.

Lähteenmäki, H., Tervahartiala, T., Räisänen, I. T., Pärnänen, P., Mauramo, M., Gupta, S., Sampson, V., Rathnayake, N., Heikkinen, A.-M., Alassiri, S., Gieselmann, D.-R., Frankenberger, R., & Sorsa, T. (2022). Active MMP-8 point-of-care (PoC)/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis. Clinical and Experimental Dental Research. https://doi.org/10.1002/cre2.537

Abstract:

Objective
The aim of this study was to investigate the utility of the active matrix metalloproteinase (aMMP-8)-point-of-care (PoC) test as a quantitative real-time chair-side diagnostic tool for peri-implant diagnosis, as well as assess the potentially developing and ongoing risk relative to the traditional clinical methods.

Background
Current peri-implant and periodontal disease diagnoses rely on clinical and radiological examinations. This case-control study investigated the applicability of aMMP-8-PoC immunotest for quantitative real-time diagnosis and monitoring of dental implants in health and disease.

Methods
Sixty-eight patients visiting a specialist clinic for maintenance following dental implant placement underwent assessment of their peri-implant health. aMMP-8-PoC peri-implant sulcular fluid (PISF) lateral-flow immunotests were performed using ImplantSafe® technology quantitated by ORALyzer®. In addition, the PISF samples were analyzed for total MMP-8, calprotectin, and interleukin (IL)-6 by enzyme-linked immunosorbent assays (ELISA), aMMP-8 by western immunoblot, and MMP-2 and MMP-9 by gelatin zymography.

Results
The aMMP-8-PoC test promptly recorded and reflected peri-implant disease, differentiating it clearly from health. X-ray findings (bone loss > 2 mm), peri-implant pocket depth ≥ 3 mm, and bleeding on probing were significantly more prevalent among implants positive for the aMMP-8-PoC test. aMMP-8/ORALyzer® analysis was more precise in recording disease than total MMP-8, calprotectin, IL-6, MMP-2, and MMP-9.

Conclusions
The aMMP-8-PoC test can be conveniently implemented to alert for and detect active collagenolysis affecting peri-implant tissues, both in the early and advanced stages of the disease. Active and fragmented MMP-8 exhibits a strong and significant association with peri-implantitis as compared to total MMP-8 and other biomarkers and can be utilized as the POC/chairside biomarker of choice in the new classification of peri-implantitis.

6. Prediabetes/Diabetes Screening at the Periodontal Clinic.

Grigoriadis, A., Räisänen, I. T., Pärnänen, P., Tervahartiala, T., Sorsa, T., & Sakellari, D. (2021). Prediabetes/diabetes screening strategy at the periodontal clinic. Clinical and Experimental Dental Research, 7(1), 85–92. https://doi.org/10.1002/cre2.338

Abstract:

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.

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

Umeizudike, K., Räisänen, I., Gupta, S., Nwhator, S., Grigoriadis, A., Sakellari, D., & Sorsa, T. (2022). Active matrix metalloproteinase‐8: A potential biomarker of oral systemic link. Clinical and Experimental Dental Research, 8(1), 359–365. https://doi.org/10.1002/cre2.516

Abstract:

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.

Keywords:
aMMP-8; biomarkers; clinical studies; diseases; health; matrix metalloproteinases; oral; periodontitis; systemic.

Die 100 neusten Publikationen zu aMMP-8

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