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Peri-implantitis: treatment and effects of enamel matrix derivative
Umeå University, Faculty of Medicine, Department of Odontology. Folktandvården Gävleborg AB, Region Gävleborg. (Avd för Molekylär Parodontologi)ORCID iD: 0000-0002-5327-8028
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological complications affecting osseointegrated dental implants are a growing treatment problem in clinical practice. Since the number of implant carriers has increased in recent decades, this is an urgent topic in dentistry. Peri-implantitis, inflammatory degradation of the implant-supporting jawbone, affects approximately 20% of all implant carriers and approximately 10% of all implants.

Implant surfaces are colonised by microbes that may cause an inflammatory process in the soft tissue around the implant. In some sensitive individuals, the inflammatory response leads to disturbed jawbone remodelling, with increased recruitment and activity of bone-resorbing osteoclasts, which could ultimately lead to implant loss. The corresponding degradation of the bone supporting the teeth is denoted as periodontitis. The current view is that factors such as proinflammatory cytokines and prostaglandins, produced by leukocytes and cells of mesenchymal origin in the inflamed connective tissue, are responsible for local osteoclast recruitment and activation. Pro-inflammatory factors and tissue degradation products will leak into the exudate in the peri-implant sulci and the gingival pockets around the teeth. Analysis of the exudate could be of use for predicting and monitoring peri-implantitis, as well as identifying new targets for treatment.

The standard treatment for peri-implantitis is surgery in combination with mechanical cleaning of the implant surface and optimisation of oral hygiene, with the goal of achieving infection control and pocket reduction. This treatment has a moderate effect on healing of the peri-implantitis lesion around the dental implant. The use of adjunctive bone grafts, membranes and antimicrobials has thus far not been shown to achieve a more successful outcome. Adjunctive treatment with enamel matrix derivative (EMD) during regenerative periodontal surgery contributes to wound healing and increased tissue support, but the adjunctive effect of EMD during surgical treatment of peri-implantitis remains unknown.

The overall aim of this thesis was to investigate the outcome of a regenerative surgical treatment approach with and without adjunctive EMD treatment from the short- and long-term perspectives and to increase our knowledge of microbial flora and biomarkers in the peri-implant sulci before and after treatment. Furthermore, an additional aim of this work was to investigate whether EMD could directly affect osteoclast formation and activity.

We performed a randomised controlled clinical trial of a surgical intervention for peri-implantitis with and without EMD. In multivariate modelling, an increased marginal bone level at the implant site 12 months after surgery was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a gram-positive/aerobic microbial flora, whereas a reduced bone level was associated with a gram-negative/anaerobic microbial flora and the presence of bleeding and pus, with a cross-validated predictive capacity (Q2) of 36.4%. Similar trends were observed for bone level, pocket depth, plaque, pus and bleeding, but these associations were statistically non-significant in the univariate analysis. Five years after treatment, no significant differences in bone level changes were observed between groups, but fewer implants were lost to follow-up due to reinfections in the EMD-treated group.

We used mass spectrometry to analyse the protein content in peri-implant crevicular fluid (PICF) before and up to 12 months after treatment. The total protein amount and diversity displayed decreasing trends 3, 6 and 12 months after treatment. Multivariate analysis of the PICF protein content revealed two major groups, cluster 2 and cluster 3, of which cluster 2 was associated with an increased risk of implant loss. EMD treatment was associated with cluster 3, which was in turn associated with increased implant survival.

To test whether EMD affects osteoclast formation or bone resorption, we added purified EMD to RANKL-stimulated mouse bone marrow macrophage cultures in plastic dishes and counted the number of osteoclasts. We also cultured the cells on bone slices and measured the secretion of TRAP5b and the release of CTX-1 into the culture medium as biomarkers of osteoclast numbers and bone resorption, respectively, but no effect of EMD was observed.

In conclusion, adjunctive EMD during surgical treatment of peri-implantitis changed the microbial flora to a less pathogenic microbiota, and similar changes in the inflammatory protein profile of PICF were observed; these effects were associated with implant survival. However, the trend toward a positive healing response after EMD treatment was not associated with a significant radiographic bone gain in this study and needs to be further explored. In addition, our finding that EMD did not affect osteoclast formation or bone resorption in vitro indicates that the effect of EMD on bone regeneration, as seen in periodontitis treatment, does not seem to depend on a direct inhibitory effect on osteoclast formation or bone resorption.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2018. , p. 72
Series
Umeå University odontological dissertations, ISSN 0345-7532 ; 140
Keywords [en]
implant, peri-implantitis, bone regeneration, enamel matrix derivative, surgical treatment, proteome, bone marrow macrophages, osteoclast formation, bone resorption
National Category
Dentistry
Research subject
Odontology
Identifiers
URN: urn:nbn:se:umu:diva-153092ISBN: 978-91-7601-945-0 (print)OAI: oai:DiVA.org:umu-153092DiVA, id: diva2:1261223
Public defence
2018-12-07, Sal D, byggnad 1D, Tandläkarhögskolan, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-11-09 Created: 2018-11-06 Last updated: 2018-11-08Bibliographically approved
List of papers
1. Effectiveness of enamel matrix derivative on the clinical and microbiological outcomes following surgical regenerative treatment of peri-implantitis: A randomized controlled trial
Open this publication in new window or tab >>Effectiveness of enamel matrix derivative on the clinical and microbiological outcomes following surgical regenerative treatment of peri-implantitis: A randomized controlled trial
Show others...
2016 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 43, no 10, p. 863-873Article in journal (Refereed) Published
Abstract [en]

Objective: This randomized clinical trial aimed at comparing radiological, clinical and microbial effects of surgical treatment of peri-implantitis alone or in combination with enamel matrix derivative (EMD).

Methods: Twenty-six subjects were treated with open flap debridement and decontamination of the implant surfaces with gauze and saline preceding adjunctive EMD or no EMD. Bone level (BL) change was primary outcome and secondary outcomes were changes in pocket depth (PD), plaque, pus, bleeding and the microbiota of the peri-implant biofilm analyzed by the Human Oral Microbe Identification Microarray over a time period of 12 months.

Results: In multivariate modelling, increased marginal BL at implant site was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a Gram+/aerobic microbial flora, whereas reduced BL was associated with a Gram-/anaerobic microbial flora and presence of bleeding and pus, with a cross-validated predictive capacity (Q(2)) of 36.4%. Similar, but statistically non-significant, trends were seen for BL, PD, plaque, pus and bleeding in univariate analysis.

Conclusion: Adjunctive EMD to surgical treatment of peri-implantitis was associated with prevalence of Gram+/aerobic bacteria during the follow-up period and increased marginal BL 12 months after treatment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
bone level, EMD treatment, microbiota, peri-implantitis
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-128974 (URN)10.1111/jcpe.12583 (DOI)000388357000008 ()27418458 (PubMedID)
Available from: 2016-12-28 Created: 2016-12-20 Last updated: 2018-11-07Bibliographically approved
2. Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT: 3-and 5-year follow-up
Open this publication in new window or tab >>Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT: 3-and 5-year follow-up
2018 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 45, no 6, p. 744-753Article in journal (Refereed) Published
Abstract [en]

Objective: To assess the clinical and radiographic outcomes 3 and 5years after the surgical treatment of peri-implantitis per se or in combination with an enamel matrix derivative (EMD).

Materials and Methods: At baseline, 29 patients were randomized to surgical treatment with adjunctive EMD or no EMD. One year after the surgical treatment of peri-implantitis, 25 patients remained eligible for survival analyses at the 3- and 5-year follow-up. The primary outcomes were implant loss and bone level (BL) change measured on radiographs, and the secondary outcomes, bleeding on probing, pus and plaque at each implant were analysed in 18 and 14 patients at the 3- and 5-year follow-up, respectively.

Results: After exclusion of four patients who discontinued the study, at the 3-year follow-up, 13 (100%) implants survived in the EMD group, and 10 of 12 (83%) in the non-EMD group. At the 5-year follow-up, 11 of 13 (85%) implants in the EMD group and nine of 12 (75%) in the non-EMD group survived. In multivariate modelling, BL changes and EMD treatment were positively associated with implant survival. Similarly, the same trend was seen in univariate analysis.

Conclusions: An exploratory analysis suggests that adjunctive EMD is positively associated with implant survival up to 5 years, but larger studies are needed.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
bone regeneration, enamel matrix derivative, long-term outcome, peri-implantitis, surgical treatment
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-150885 (URN)10.1111/jcpe.12894 (DOI)000434128500011 ()29574866 (PubMedID)2-s2.0-85045944566 (Scopus ID)
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-11-06Bibliographically approved
3. PICF proteome before and after adjunctive EMD treatment of peri-implantitis
Open this publication in new window or tab >>PICF proteome before and after adjunctive EMD treatment of peri-implantitis
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim: The aim of this study was to explore which peri-implant crevicular fluid (PICF) protein patter that are associated with the active peri-implantitis process.

Materials and methods: PICF from 25 peri-implantitis sites were subjected to proteomic analysis using liquid chromatography-tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between protein expression and implant loss, radiographic bone level change, bleeding on probing, pocket depth, and enamel matrix derivative (EMD) treatment. 

Results: Clustering of subjects based on their 3 to 12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 was differentiated from cluster 3 by 52 proteins (R2=90%, Q2=80%) and belonging to cluster 2 had an odds ratio for implant loss of 7.9 (95% confidence interval 1.8 to 35.9). Cluster 3 was related to implant survival (p=0.007) after 5 years and associated with EMD treatment (p=0.044). Furthermore, cluster 2 was associated with radiographic bone loss (p<0.0001) and bleeding on probing (p=0.001). 

Conclusion: EMD treatment was associated with the PICF proteomic profile related to implant survival. EMD reduced number of proteins, dominated by proteins associated with implant loss. However, whether these effects are direct or indirect requires further exploration.

Keywords
implant, peri-implantitis, proteome, enamel matrix derivative, bone level change
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-153072 (URN)
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2018-11-06
4. Enamel matrix derivative does not affect osteoclast formation or bone resorption in mouse bone marrow macrophage cultures
Open this publication in new window or tab >>Enamel matrix derivative does not affect osteoclast formation or bone resorption in mouse bone marrow macrophage cultures
(English)Manuscript (preprint) (Other academic)
Keywords
Enamel matrix derivative, Emdogain, bone marrow macrophages, osteoclast formation, bone resorption
National Category
Dentistry
Research subject
Odontology; Odontology
Identifiers
urn:nbn:se:umu:diva-153081 (URN)
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2018-11-06

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