Exploration of Medicine

Table 3. aMMP-8 PISF mean values and clinical parameters of implant sites for the different groups, before and after treatment

Variable	Time-point	Healthy (H)	Peri-implant mucositis (PIM)	Peri-implantitis (P)	Multiple comparisons
aMMP-8 (ng/mL)	T0 T3	11.44 ± 6.60 9.83 ± 3.10	13.69 ± 4.70 11.98 ± 4.90	24.60 ± 3.20 20.85 ± 5.40	H vs. PIM H vs. P* PIM vs. P*
sGI	T0 T3	0.54 ± 0.05 0.42 ± 0.05	2.18 ± 0.27 1.53 ± 0.35 (T0 vs. T3*)	2.82 ± 0.50 2.11 ± 0.62	H vs. PIM* H vs. P* PIM vs. P*
mPI	T0 T3	1.20 ± 0.05 0.32 ± 0.23 (T0 vs. T3*)	1.88 ± 0.61 1.33 ± 0.76 (T0 vs. T3*)	2.29 ± 0.54 1.93 ± 0.21 (T0 vs. T3*)	H vs. PIM* H vs. P* PIM vs. P
mBOPI	T0 T3	0.11 ± 0.32 0.08 ± 0.09	1.74 ± 0.40 1.17 ± 0.28 (T0 vs. T3*)	2.22 ± 0.27 1.53 ± 0.68	H vs. PIM* H vs. P* PIM vs. P
PD (mm)	T0 T3	1.93 ± 0.27 1.88 ± 0.35	2.70 ± 0.46 2.47 ± 0.78	5.06 ± 1.12 4.78 ± 0.74	H vs. PIM H vs. P* PIM vs. P*
rMBL (mm)	T0 T3	2.20 ± 0.40 2.10 ± 0.70	3.30 ± 0.50 3.10 ± 0.40	6.40 ± 1.20 6.10 ± 0.90	H vs. PIM H vs. P* PIM vs. P*

Return to article view

Values are presented as mean ± SD. *: P ≤ 0.05

Declarations

Author contributions

RG: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. RR: Conceptualization, Data curation, Investigation, Writing—original draft. AZ: Supervision, Methodology, Formal analysis. EX: Conceptualization, Writing—review & editing. SP: Visualization, Formal analysis, Writing—review & editing. DDN: Validation, Investigation, Writing—review & editing. LT: Supervision, Project administration. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Ethics Committee of Università Campus Bio-Medico di Roma [protocol code: PAR 30.21 (OSS) ComEt CBM-30/03/2021].

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The datasets for this manuscript are not publicly available because they expose sensitive data from included patients. Requests for accessing the datasets should be directed to Dr. Guarnieri and Dr. Reda.

Funding

Not applicable.

Copyright

References

Löe H, Silness J. Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand. 1963;21:533–51. [DOI] [PubMed]

Löe H. The Gingival Index, the Plaque Index and the Retention Index systems. J Periodontol. 1967;38:610–6. [DOI] [PubMed]

Ravidà A, Galli M, Siqueira R, Saleh MHA, Galindo-Moreno P, Wang HL. Diagnosis of peri-implant status after peri-implantitis surgical treatment: proposal of a new classification. J Periodontol. 2020;91:1553–61. [DOI] [PubMed]

Karbach J, Callaway A, Kwon YD, d’Hoedt B, Al-Nawas B. Comparison of five parameters as risk factors for peri-mucositis. Int J Oral Maxillofac Implants. 2009;24:491–6. [PubMed]

Heitz-Mayfield LJ. Peri-implant diseases: diagnosis and risk indicators. J Clin Periodontol. 2008;35:292–304. [DOI] [PubMed]

Hashim D, Cionca N, Combescure C, Mombelli A. The diagnosis of peri-implantitis: a systematic review on the predictive value of bleeding on probing. Clin Oral Implants Res. 2018;29:276–93. [DOI] [PubMed]

Alassy H, Parachuru P, Wolff L. Peri-implantitis diagnosis and prognosis using biomarkers in peri-implant crevicular fluid: a narrative review. Diagnostics (Basel). 2019;9:214. [DOI] [PubMed] [PMC]

Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, et al. Peri-implant diseases and conditions: consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018;45:S286–91. [DOI] [PubMed]

Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol. 2018;89:S159–72. [DOI] [PubMed]

10.

Kinney JS, Morelli T, Oh M, Braun TM, Ramseier CA, Sugai JV, et al. Crevicular fluid biomarkers and periodontal disease progression. J Clin Periodontol. 2014;41:113–20. [DOI] [PubMed] [PMC]

11.

Dursun E, Tözüm TF. Peri-implant crevicular fluid analysis, enzymes and biomarkers: a systemetic review. J Oral Maxillofac Res. 2016;7:e9. [DOI] [PubMed] [PMC]

12.

Buduneli N. Biomarkers for periodontal diseases. In: Biomarkers in periodontal health and disease. Cham: Springer; 2020. pp. 41–58.

13.

Gul SS, Abdulkareem AA, Sha AM, Rawlinson A. Diagnostic accuracy of oral fluids biomarker profile to determine the current and future status of periodontal and peri-implant diseases. Diagnostics (Basel). 2020;10:838. [DOI] [PubMed] [PMC]

14.

Sorsa T, Tjäderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38:306–21. [DOI] [PubMed]

15.

Honibald EN, Mathew S, Padmanaban J, Sundaram E, Ramamoorthy RD. Perioceutics: matrix metalloproteinase inhibitors as an adjunctive therapy for inflammatory periodontal disease. J Pharm Bioallied Sci. 2012;4:S417–21. [DOI] [PubMed] [PMC]

16.

Alassiri S, Parnanen P, Rathnayake N, Johannsen G, Heikkinen AM, Lazzara R, et al. 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. Dis Markers. 2018;2018:1306396. [DOI] [PubMed] [PMC]

17.

Räisänen IT, Heikkinen AM, Nwhator SO, Umeizudike KA, Tervahartiala T, Sorsa T. On the diagnostic discrimination ability of mouthrinse and salivary aMMP-8 point-of-care testing regarding periodontal health and disease. Diagn Microbiol Infect Dis. 2019;95:114871. [DOI] [PubMed]

18.

Sorsa T, Gieselmann D, Arweiler NB, Hernández M. A quantitative point-of-care test for periodontal and dental peri-implant diseases. Nat Rev Dis Primers. 2017;3:17069. [DOI] [PubMed]

19.

Golub LM, Räisänen IT, Sorsa T, Preshaw PM. An unexplored pharmacologic/diagnostic strategy for peri-implantitis: a protocol proposal. Diagnostics (Basel). 2020;10:1050. [DOI] [PubMed] [PMC]

20.

Ma J, Kitti U, Teronen O, Sorsa T, Husa V, Laine P, et al. Collagenases in different categories of peri-implant vertical bone loss. J Dent Res. 2000;79:1870–3. [DOI] [PubMed]

21.

Nomura T, Ishii A, Shimizu H, Taguchi N, Yoshie H, Kusakari H, et al. Tissue inhibitor of metalloproteinases-1, matrix metalloproteinases-1 and -8, and collagenase activity levels in peri-implant crevicular fluid after implantation. Clin Oral Implants Res. 2000;11:430–40. [DOI] [PubMed]

22.

Basegmez C, Yalcin S, Yalcin F, Ersanli S, Mijiritsky E. Evaluation of periimplant crevicular fluid prostaglandin E2 and matrix metalloproteinase-8 levels from health to periimplant disease status: a prospective study. Implant Dent. 2012;21:306–10. [DOI] [PubMed]

23.

Melguizo-Rodríguez L, Costela-Ruiz VJ, Manzano-Moreno FJ, Ruiz C, Illescas-Montes R. Salivary biomarkers and their application in the diagnosis and monitoring of the most common oral pathologies. Int J Mol Sci. 2020;21:5173. [DOI] [PubMed] [PMC]

24.

Guarnieri R, Reda R, Di Nardo D, Pagnoni F, Zanza A, Testarelli L. Effects of maintenance implant therapy with and without periodic removal and decontamination of prosthetic components on inflammatory peri-implant parameters. Int J Periodontics Restorative Dent. 2023:s118–28. [DOI] [PubMed]

25.

Lähteenmäki H, Umeizudike KA, Heikkinen AM, Räisänen IT, Rathnayake N, Johannsen G, et al. aMMP-8 point-of-care/chairside oral fluid technology as a rapid, non-invasive tool for periodontitis and peri-implantitis screening in a medical care setting. Diagnostics (Basel). 2020;10:562. [DOI] [PubMed] [PMC]

26.

Reda R, Zanza A, Cicconetti A, Bhandi S, Guarnieri R, Testarelli L, et al. A systematic review of cementation techniques to minimize cement excess in cement-retained implant restorations. Methods Protoc. 2022;5:9. [DOI] [PubMed] [PMC]

27.

Guarnieri R, Reda R, Zanza A, Miccoli G, Nardo DD, Testarelli L. 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). 2022;12:2599. [DOI] [PubMed] [PMC]

28.

Mombelli A, van Oosten MA, Schurch E Jr, Land NP. The microbiota associated with successful or failing osseointegrated titanium implants. Oral Microbiol Immunol. 1987;2:145–51. [DOI]

29.

Apse P, Zarb GA, Schmitt A, Lewis DW. The longitudinal effectiveness of osseointegrated dental implants. The Toronto Study: peri-implant mucosal response. Int J Periodontics Restorative Dent. 1991;11:94–111. [PubMed]

30.

Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem. 1997;378:151–60.

31.

Kiili M, Cox SW, Chen HY, Wahlgren J, Maisi P, Eley BM, et al. Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol. 2002;29:224–32. [DOI] [PubMed]

32.

Lee W, Aitken S, Sodek J, McCulloch CA. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis. J Periodontal Res. 1995;30:23–33. [DOI] [PubMed]

33.

Salvi GE, Aglietta M, Eick S, Sculean A, Lang NP, Ramseier CA. Reversibility of experimental peri-implant mucositis compared with experimental gingivitis in humans. Clin Oral Implants Res. 2012;23:182–90. [DOI] [PubMed]

34.

Xu L, Yu Z, Lee HM, Wolff MS, Golub LM, Sorsa T, et al. Characteristics of collagenase-2 from gingival crevicular fluid and peri-implant sulcular fluid in periodontitis and peri-implantitis patients: pilot study. Acta Odontol Scand. 2008;66:219–24. [DOI] [PubMed]

35.

Lazaridou T, Doufexi AE, Menexes G, Tsalikis L. Expression of metalloproteinase-8 in gingival crevicular fluid, peri-implant sulcular fluid and saliva in healthy and diseased periodontal and peri-implant tissue. Mod Approaches Dent Oral Health Care. 2021;4:407–15. [DOI]

36.

Konopka L, Pietrzak A, Brzezińska-Błaszczyk E. Effect of scaling and root planing on interleukin-1β, interleukin-8 and MMP-8 levels in gingival crevicular fluid from chronic periodontitis patients. J Periodontal Res. 2012;47:681–8. [DOI] [PubMed]

37.

Zhang L, Li X, Yan H, Huang L. Salivary matrix metalloproteinase (MMP)-8 as a biomarker for periodontitis: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2018;97:e9642. [DOI] [PubMed] [PMC]

38.

Kinane DF, Darby IB, Said S, Luoto H, Sorsa T, Tikanoja S, et al. Changes in gingival crevicular fluid matrix metalloproteinase-8 levels during periodontal treatment and maintenance. J Periodontal Res. 2003;38:400–4. [DOI] [PubMed]

39.

Renvert S, Widén C, Persson RG. Cytokine and microbial profiles in relation to the clinical outcome following treatment of peri-implantitis. Clin Oral Implants Res. 2017;28:1127–32. [DOI] [PubMed]

40.

Hentenaar DFM, De Waal YCM, Vissink A, Van Winkelhoff AJ, Meijer HJA, Liefers SC, et al. Biomarker levels in peri-implant crevicular fluid of healthy implants, untreated and non-surgically treated implants with peri-implantitis. J Clin Periodontol. 2021;48:590–601. [DOI] [PubMed]

41.

Schmidt KE, Auschill TM, Sculean A, Arweiler NB. Clinical evaluation of non-surgical cleaning modalities on titanium dental implants during maintenance care: a 1-year follow-up on prosthodontic superstructures. Clin Oral Investig. 2019;23:1921–30. [DOI] [PubMed]

42.

Bassetti M, Schär D, Wicki B, Eick S, Ramseier CA, Arweiler NB, et al. Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or photodynamic therapy: 12-month outcomes of a randomized controlled clinical trial. Clin Oral Implants Res. 2014;25:279–87. [DOI] [PubMed]

43.

Listgarten MA, Lang NP, Schroeder HE, Schroeder A. Periodontal tissues and their counterparts around endosseous implants. Clin Oral Implants Res. 1991;2:1–19. [DOI] [PubMed]

44.

Chaytor DV, Zarb GA, Schmitt A, Lewis DW. The longitudinal effectiveness of osseointegrated dental implants. The Toronto Study: bone level changes. Int J Periodontics Restorative Dent. 1991;11:112–25. [PubMed]

45.

Mombelli A, Graf H. Depth-force-patterns in periodontal probing. J Clin Periodontol. 1986;13:126–30. [DOI] [PubMed]

46.

Hermann JS, Buser D, Schenk RK, Schoolfield JD, Cochran DL. Biologic Width around one- and two-piece titanium implants. Clin Oral Implants Res. 2001;12:559–71. [DOI] [PubMed]

47.

Caram SJ, Huynh-Ba G, Schoolfield JD, Jones AA, Cochran DL, Belser UC. Biologic width around different implant-abutment interface configurations. A radiographic evaluation of the effect of horizontal offset and concave abutment profile in the canine mandible. Int J Oral Maxillofac Implants. 2014;29:1114–22. [DOI] [PubMed]

48.

Gerber JA, Tan WC, Balmer TE, Salvi GE, Lang NP. Bleeding on probing and pocket probing depth in relation to probing pressure and mucosal health around oral implants. Clin Oral Implants Res. 2009;20:75–8. [DOI] [PubMed]

49.

Abrahamsson I, Berglundh T, Wennström J, Lindhe J. The peri-implant hard and soft tissues at different implant systems. A comparative study in the dog. Clin Oral Implants Res. 1996;7:212–9. [DOI] [PubMed]

50.

Cionca N, Hashim D, Cancela J, Giannopoulou C, Mombelli A. Pro-inflammatory cytokines at zirconia implants and teeth. A cross-sectional assessment. Clin Oral Investig. 2016;20:2285–91. [DOI] [PubMed] [PMC]

51.

Jepsen S, Berglundh T, Genco R, Aass AM, Demirel K, Derks J, et al. Primary prevention of peri-implantitis: managing peri-implant mucositis. J Clin Periodontol. 2015;42:S152–7. [DOI] [PubMed]

52.

Jepsen S, Rühling A, Jepsen K, Ohlenbusch B, Albers HK. Progressive peri-implantitis. Incidence and prediction of peri-implant attachment loss. Clin Oral Implants Res. 1996;7:133–42. [DOI] [PubMed]

53.

Luterbacher S, Mayfield L, Brägger U, Lang NP. Diagnostic characteristics of clinical and microbiological tests for monitoring periodontal and peri-implant mucosal tissue conditions during supportive periodontal therapy (SPT). Clin Oral Implants Res. 2000;11:521–9. [DOI] [PubMed]

54.

Verstappen J, Von den Hoff JW. Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease. J Dent Res. 2006;85:1074–84. [DOI] [PubMed]

55.

Botero JE, Yepes FL, Roldán N, Castrillón CA, Hincapie JP, Ochoa SP, et al. Tooth and periodontal clinical attachment loss are associated with hyperglycemia in patients with diabetes. J Periodontol. 2012;83:1245–50. [DOI] [PubMed]

56.

Emecen-Huja P, Eubank TD, Shapiro V, Yildiz V, Tatakis DN, Leblebicioglu B. Peri-implant versus periodontal wound healing. J Clin Periodontol. 2013;40:816–24. [DOI] [PubMed] [PMC]

57.

Nowzari H, Botero JE, DeGiacomo M, Villacres MC, Rich SK. Microbiology and cytokine levels around healthy dental implants and teeth. Clin Implant Dent Relat Res. 2008;10:166–73. [DOI] [PubMed]

58.

Ertugrul AS, Sahin H, Dikilitas A, Alpaslan N, Bozoglan A. Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. J Periodontal Res. 2013;48:44–51. [DOI] [PubMed]

59.

Larsson C, Thomsen P, Aronsson BO, Rodahl M, Lausmaa J, Kasemo B, et al. Bone response to surface-modified titanium implants: studies on the early tissue response to machined and electropolished implants with different oxide thicknesses. Biomaterials. 1996;17:605–16. [DOI] [PubMed]

60.

Puleo DA, Nanci A. Understanding and controlling the bone-implant interface. Biomaterials. 1999;20:2311–21. [DOI] [PubMed]

61.

Sollazzo V, Pezzetti F, Massari L, Palmieri A, Brunelli G, Zollino I, et al. Evaluation of gene expression in MG63 human osteoblastlike cells exposed to tantalum powder by microarray technology. Int J Periodontics Restorative Dent. 2011;31:e17–28. [PubMed]