Clinical research on peri-implantdiseases: consensus report ofWorking Group 4Sanz M, Chapple IL, on behalf of Working Group 4 of the VIII EuropeanWorkshop on Periodontology. Clinical research on peri-implant diseases: consensusreport of Working Group 4. J Clin Periodontol 2012; 39 (Suppl. 12): 202–206. doi:10.1111/j.1600-051X.2011.01837.x.

Abstract:Background: Two systematic reviews have evaluated the quality of research andreporting of observational studies investigating the prevalence of, the incidence ofand the risk factors for peri-implant diseases and of experimental clinical studiesevaluating the efficacy of preventive and therapeutic interventions.Materials and Methods: For the improvement of the quality of reporting for bothobservational and experimental studies, the STROBE and the ModifiedCONSORT recommendations were encouraged.Results: To improve the quality of research in peri-implant diseases, the followingwere recommended: the use of unequivocal case definitions; the expression of out-comes at the subject rather than the implant level; the implementation of studyvalidation tools; the reporting of potential sources of bias; and the use of appro-priate statistical methods.

Mariano Sanz1,*, Iain L. Chapple2

and on behalf of Working Group 4 of

the VIII European Workshop onPeriodontology*

1University Complutense of Madrid –

Periodontology, Madrid, Spain; 2Periodontal

Research Group, The University of

Birmingham, Birmingham, United Kingdom

Key words: incidence; intervention;

peri-implant diseases; peri-implant health;

peri-implant mucositis; peri-implantitis;

prevalence; prevention; risk factors

Accepted for publication 26 November 2011

Working Group 4:Mariano Sanz,Iain Chapple,Jan Derks,E. Figuero,Filippo Grazianni,Lisa Heitz-Mayfield,David Herrera,Ann-Marie Jansaker,Soren Jepsen,Bjorn Klinge,Bruno Loos,Andrea Mombelli,Panos Papapanou,Ioannis Polyzois,Stefan Renvert,Giovanni Salvi,

Industry representation:Pascal Kunz,Anna-Karin Lundgren,Rene Willi.

Conflict of interest and source of funding statement

The authors declare that they have no conflict of interests. This workshop wasfinancially supported by the European Federation of Periodontology and by unrest-ricted grants from Astra, Nobel Biocare and Straumann.

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J Clin Periodontol 2012; 39 (Suppl. 12): 202–206 doi: 10.1111/j.1600-051X.2011.01837.x

Conclusions: In observational studies, case definitions for peri-implantitis wereagreed. For risk factor determination, the progressive use of cross-sectional andcase–control studies (univariate analyses), to prospective cohorts (multilevel mod-elling for confounding), and ultimately to intervention studies were recommended.For preventive and interventional studies of peri-implant disease management,parallel arm RCTs of at least 6-months were encouraged. For studies of non-surgical and surgical management of peri-implantitis, the use of a compositetherapeutic end point was advocated. The development of standard controltherapies was deemed essential.

Introduction

The remit of this working group wasto provide answers to key aspects ofclinical research into peri-implantdiseases focusing on aspects of studydesign, reporting and outcome mea-surements.

Two reviews had evaluated thequality of research and the qualityof reporting of observational studiesinvestigating the prevalence of, theincidence of and the risk factors forperi-implant diseases (Tomasi &Derks 2012), as well as those experi-mental clinical studies evaluating theefficacy of preventive and therapeuticinterventions (Graziani et al. 2012)in a systematic manner.

Quality of Reporting, CaseDefinitions and Methods to Study

Incidence of, Prevalence of and RiskFactors for Peri-Implant Diseases

The systematic review evaluating thequality of reporting of the observa-tional studies investigating the inci-dence of, prevalence of and riskfactors for peri-implant diseases(Tomasi & Derks 2012) highlightedthat many studies have solelyreported implant-based data analysisor have not provided a clear defini-tion of the peri-implant diseasesbeing studied.

Another important issue empha-sized in the review was the differentcriteria used for defining a “case” instudies investigating the prevalenceof peri-implant diseases. Whilst stud-ies performed since the previousEuropean Workshops have used thedefinitions developed in those con-sensus meetings (Lang & Berglundh2011), there are still differences inthe thresholds employed for radio-graphic bone loss used to defineperi-implantitis and the referencetime point from which this bone losshas occurred.

The selected studies investigatingthe prevalence of peri-implant dis-eases have used cross-sectional studydesigns and convenience samples,mostly of limited size, with clinicaland radiological outcomes as thebasis for defining health, versus peri-implant mucositis and peri-implanti-tis. These convenience samples maynot be representative of the targetpopulation.

When analysing the quality ofreporting in the selected studies, theSTROBE recommendations (Van-denbroucke et al. 2007a, b, c) havebeen utilized. Although most of thestudies lack reporting of the possiblesources of bias and few have evalu-ated aspects of internal validity,approximately 60–70% of the recom-mendations were fulfilled.

From the outset, the groupagreed and acknowledged the strat-egy of the authors to focus on inves-tigations assessing prevalence ofthose peri-implant diseases based atthe subject level. The group consid-ered that the impact of peri-implantdiseases upon individuals was theoutcome of interest, rather than theimpact upon individual implants.

When discussing the different casedefinitions employed in the studiesevaluating prevalence and incidenceof peri-implant diseases, the groupagreed that the definitions estab-lished in the previous EWP consen-sus workshops published in 2008(Lindhe & Meyle 2008) and 2011(Lang & Berglundh 2011) should beadopted. This consensus attempts tofurther clarify some key aspects thatare relevant to the conduct of obser-vational studies to improve themethodological quality and reportingstandards of clinical research in peri-implant diseases.

For defining a case as peri-implan-titis, it was agreed that the compo-nents described in previous consensusreports must be present: “changes in

the level of crestal bone, presence ofbleeding on probing and/or suppura-tion; with or without concomitantdeepening of peri-implant pockets”(Lang & Berglundh 2011). It wasstrongly recommended that for inves-tigations assessing the prevalence andincidence of peri-implant diseases, allstudies must be underpinned by basicquality assurance procedures includ-ing internal validation of examinerreproducibility and the use of mea-surement instruments aimed at reduc-ing their inherent variability. It isrecommended that long-cone parallelradiographic projection techniqueswere utilized to assess the crestal bonechanges. Details of the probing proto-col utilized should also be described.

In this context, the group agreedthat different approaches should beused when dealing with studies ofdisease prevalence and incidence.

Studies on disease prevalence

For disease prevalence, it wasaccepted that individuals presentingwith peri-implant diseases might nothave baseline clinical or radiologicalmeasures available to benchmarkcurrent findings, and therefore morepragmatic case definitions should bedeveloped to serve as the basis fordiagnosis of peri-implantitis and onclinical decision making for thera-peutic purposes . Here, the focus isspecificity of diagnosis rather thansensitivity, accepting the possibilityof false negative diagnoses. In theabsence of previous radiographicrecords, a threshold vertical dis-tance of 2 mm from the expectedmarginal bone level followingremodelling post-implant placementis recommended, provided peri-implant inflammation is evident. Ifprevious radiographs are available,a more sensitive threshold for mea-surable bone loss can be useddepending on the reproducibility of

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the radiological assessment methodemployed.

Studies on peri-implantitis incidence

For prospective studies evaluatingthe incidence and or progression/recurrence of peri-implantitis, base-line clinical measures and radio-graphs are essential. Since thesestudies must be planned thoroughlyand ethical approval must beobtained, baseline clinical and radio-logical data should be establishedonce the remodelling phase post-implant placement has occurred. Inthis manner, in the presence ofinflammation, any detectable boneloss beyond the inherent variabilityof the radiological measurementerror, should be considered as lossof supporting bone and hence, usedin the case definition. Such referencedata permits more sensitive case defi-nitions to be developed, accountingfor measurement errors, but provid-ing higher sensitivity and acceptingthe potential for some false positiveassignments of peri-implant disease.For these incidence studies, a thresh-old of detectable bone loss of 2–3times the SD of the measurementerror is recommended (1.0–1.5 mm).

Studies on risk factors for peri-implant

diseases

Studies addressing risk factors inperi-implant diseases are in theirinfancy. Traditionally, risk factorsare identified on the basis of a multi-step process including:

● Identification of putative risk fac-tors using cross-sectional or case-control studies and univariateanalyses, followed by multi-variateanalyses aimed at identifyingpotential confounding factors

● Studies validating these putativefactors, which employ a prospec-tive cohort design, ideally con-firmed in different populations

● In the case of modifiable true riskfactors, intervention studies dem-onstrating lower incidence of dis-ease following targeted control ofthe respective factors

The currently available literatureprimarily consists of cross-sectionaland case–control studies, which arelimited in their generalizability.

Based upon the approach taken inthis systematic review (Tomasi &Derks 2012), four prospective cohortstudies exist with limited samplesizes, and based upon convenience,samples rather than broader sam-pling of the population exist . Thereis heterogeneity in the risk indicatorsinvestigated across the broad catego-ries of host-derived, lifestyle, envi-ronmental and local factors. Giventhe limited sample sizes investigatedso far, it is not possible to assesswith precision the interactionsbetween the different exposures ofinterest.

Recommendations for future research

Based upon the available evidence,the group recommends that addi-tional and adequately poweredresearch should be conducted to val-idate the most plausible putative riskfactors for the onset and progressionof peri-implant diseases, including:

● History of treated and/or currentperiodontitis

● Oral hygiene● Smoking and other subject-related

factors● Local factors such as malposition-

ing of implants (within the basalbone, inter-implant, implant-tooth), lack of cleansability of thereconstruction, excess cement andimplant surface characteristics

To establish valid and reliable sta-tistics on the prevalence and incidenceof peri-implant diseases, it is recom-mended that national/regional data-bases of patients receiving implanttherapy be established. These shouldinclude both baseline and annual fol-low-up assessments of implant statusand potential exposures.

These registries will facilitate theconduct of future studies of risk fac-tor assessment that are:

• Adequately powered andadjusted

• Representative of the populationat large

• Of sufficient duration

• Inclusive of different settings(University, Specialist Practice,General Practice)

In the absence of such databases,it is recommended that multicentre

studies be conducted to enhance thegeneralizability (size, power) of studyoutcomes.

Study quality will be improvedby:

● Establishing unequivocal case defi-nitions

● Involving calibrated examiners● Careful assessment and reporting

of exposures (e.g. oral hygiene sta-tus, periodontal status and smok-ing history)

● Selection of unbiased samples ofsufficient size

● Provisions to account for loss tofollow-up

● Appropriate statistical analyses

Employing validated tools suchas the STROBE guidelines willattain improvements in the qualityof reporting.

Quality of Reporting OutcomeMeasurements and Methods to Study

the Ecacy of Preventive andTherapeutic Approaches to Peri-

Implant Diseases

The systematic review evaluating theefficacy of preventive and therapeuticapproaches to peri-implant diseases(Graziani et al. 2012) focussed uponthe selection of randomized clinicaltrials (RCTs) and controlled clinicaltrials (CCTs) assessing the efficacy ofpreventive measures to preserveperi-implant health and therapeuticinterventions aimed at treating per-implant mucositis and peri-implanti-tis either non-surgically or surgically.

Preventive studies of peri-implant

diseases

There was a notable paucity of clini-cal trials addressing the efficacy ofpreventive interventions. From 155studies identified as potentially fulfill-ing the review criteria, only sevenwere selected. Studies were not con-sidered either because their experi-mental design was not an RCT or aCCT, or because the study evaluationtime was too short. The selected stud-ies utilized different experimentaldesigns (parallel, cross-over and splitmouth) and usually employed smallsample sizes and short evaluationtimes. The interventions assessedincluded the use of adjunctive anti-microbials or specific preventive

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interventions aimed at plaque controlaround the implant supported resto-rations, compared with the patient’sself-performed plaque control andwith professional supportive therapy.Reported outcomes employed toevaluate the efficacy of the testedinterventions have mainly been theuse of bleeding and plaque indices,although in some studies, additionalclinical (changes in PPD) and micro-biological outcomes were used. Thestudies demonstrated moderateadherence to modified CONSORTrecommendations (<50% of theitems) and lacked reporting of poten-tial sources of bias.

A significant problem was identi-fied with regard to the lack of astandard preventive measure withdemonstrated efficacy to preserveperi-implant health, which could beused as a standard control treatmentin future intervention trials. It is rec-ommended that with respect toexperimental design, the 6-monthparallel arm RCT should beemployed; comparing the testedpreventive interventions with acombination of the patient’s routineself-performed plaque control mea-sures and regular professionallydelivered supportive therapy (oralprophylaxis). The objective oftherapy should be the absence ofmucosal inflammation around thefunctioning dental implants, andhence the primary outcomes shouldbe the evaluation of the changes inmucosal inflammation (e.g. the mod-ified bleeding index) and the absenceof bleeding upon probing.

Treatment of peri-implant mucositis

There were only six parallel armRCTs evaluating the adjunctiveeffect of antimicrobial compounds(Chlorhexidine, Triclosan and Essen-tial Oils) in the treatment of peri-implant mucositis. These studieshave used short evaluation times (3–8 months) and share the problems ofsmall sample sizes, the lack of aclear definition of the problem inves-tigated (peri-implant mucositis) andincomplete registration of periodon-tal status in the studied samples. Asoutcome measures, the reportedstudies evaluated the inflammatorystatus of the peri-implant mucosa(BOP), probing depths and plaqueindices. Three studies assessed

microbiological outcomes and onereported the percentage of lesionsresolved. When analysing the qualityof reporting and performance in theselected studies, there was between17% and 90% adherence to themodified CONSORT recommenda-tions.

The group agreed that the paral-lel arm RCT of at least 6-monthsduration (and including 3-monthexaminations) should be used forevaluating therapies to treat peri-implant mucositis. The endpoint oftherapy should be the resolution ofperi-implant mucosal inflammation(frequency distribution of resolvedlesions) as determined by the absenceof bleeding upon probing. As sec-ondary outcomes, probing pocketdepth reductions and outcomesassessing host–parasite interactions(presence of inflammatory biomar-kers in peri-implant fluid and/ormicrobiological assessment of sub-gingival plaque samples) may beemployed. Information on the sub-ject’s characteristics (e.g. smoking),the impact of the periodontal statusand the status of the reconstruction(access for plaque control, etc.)should also be reported.

Non-surgical treatment of peri-implantitis

Six parallel arm RCTs and one split-mouth study have evaluated the effi-cacy of non-surgical therapies forthe treatment of peri-implantitis.These intervention studies have useddifferent case definitions for peri-im-plantitis and have small sample sizes,along with short evaluation periods(4.5 months; only one 12-monthstudy) and a lack of a clear descrip-tion of the periodontal status of thesample studied. There was nostandard control treatment in thesestudies; however, mechanicaldebridement was included in alltreatment arms. The tested interven-tions were either the adjunctive useof local antibiotics or alternativeimplant surface debridement meth-ods (laser, ultrasonic or air abrasivedevices). The outcomes utilized inthese studies were reductions inPPD, reductions in the sites bleeding(BOP) and reductions in clinicalattachment levels (CAL), and threestudies also evaluated microbiologi-cal and radiological outcomes andone reported suppuration. A com-

mon finding in the reported studieswas reductions in PPDs and BOPfollowing the test and control inter-ventions; however, it remains unclearas to how frequently the end pointof therapy (resolution of inflamma-tion and shallow probing depths)was met, as it was only reported inone study.

The group agreed that the lack ofa standard control mode of non-sur-gical therapy to treat peri-implantitiswas problematic. At the present time,there are no data indicating that peri-implantitis lesion severity can be thebasis for recommending non-surgicalor surgical therapy. As an RCT eval-uating non-surgical therapy versus anuntreated control arm is unethical,case series and prospective cohortstudies may be used to better definethe effect of non-surgical therapyalone. The parallel arm RCT with amechanical treatment control armshould be utilized to evaluate adjunc-tive/alternative therapies. These stud-ies should include both short-term (1–3 months) and longer-term evalua-tion times (6 and 12-months). At 3-,6- and 12-months, probing pocketdepth, bleeding on probing and sup-puration should be assessed. In addi-tion, the maintenance of bone levelsshould be assessed radiologically at12-months. It is recommended that acomposite outcome of disease resolu-tion is included (absence of deepprobing pocket depths with bleedingand suppuration). As secondary out-come measures, inflammatory bio-markers in peri-implant fluid and/ormicrobiological assessment of sub-mucosal plaque samples may be used.Information on the periodontal statusof the remaining dentition and onpatient reported outcomes (smoking,discomfort, aesthetic consequences,etc.) should be reported. Multi-centreapproaches are advocated to achievesufficiently powered studies.

Surgical treatment of peri-implantitis

There are three parallel arm RCTsand three CCTs that have evaluatedthe efficacy of surgical therapies forthe treatment of peri-implantitis.These intervention studies have useddifferent case definitions for peri-im-plantitis, and have in common, smallsample sizes and the lack of a cleardescription of the periodontal andsmoking status of studied sample.

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There was no standard control inter-vention in these studies; however,access flap, including debridement/degranulation of the lesion anddecontamination of the implant sur-face was included in all treatmentarms, with some studies adding sys-temic antibiotics and others addingonly adjunctive antimicrobials(Chlorhexidine). As interventions,some had employed different modesof decontaminating the implant sur-face with laser devices, air abrasivesand re-shaping the titanium surface,whereas other therapies haveattempted to reduce the intra-bonydefect, either by resection or bytreating the defect with biomaterialsand/or membranes. The paucity ofpublished clinical trials, the limitedsample sizes (n = 17–38) and the het-erogeneity of treatments tested pre-vent the drawing of definitiveconclusions on the efficacy of theseinterventions. The evaluation ofreporting according to the modifiedCONSORT recommendationsresulted in <60% adherence in fourof the studies.

It is recommended that a stan-dard mode of surgical therapy isidentified for the treatment of peri-implantitis is identified. This therapyshould include a clear surgicaldesign, a proven method of decon-taminating the implant surface andan appropriate means of infectioncontrol. From the six selected clini-cal trials, only two have usedadjunctive systemic antimicrobials aspart of the surgical therapy regime,whereas the other four have onlyused adjunctive antiseptics. There istherefore a lack of clear scientificevidence whether the adjunctive use

of systemic antimicrobials might berecommended as part of the stan-dard mode of therapy. An RCT test-ing this hypothesis is needed.

There is a consensus that for theevaluation of different surgical thera-pies, the parallel arm RCT should beused, with assessment of the endpoints of the therapy at least at 6and 12 months.

It is recommended that a com-posite outcome of disease resolutionis included (absence of deep probingpocket depths with bleeding andsuppuration and no additional boneloss).

As principal outcome measure-ments, resolution of mucosal inflam-mation, reduction in probing pocketdepths and changes in the bone lev-els should be employed. As second-ary outcomes, levels of inflammatorybiomarkers in peri-implant fluid and/or microbiological assessment ofsub-marginal plaque samples may beused. Information on the periodontalstatus of the studied samples and onpatient reported outcomes (discom-fort, aesthetic consequences, etc.)should be reported.

It is strongly recommended thatauthors adhere to the reportingguidelines, as detailed in the system-atic review (Graziani et al. 2012).Multi-centre approaches are encour-aged to achieve sufficiently poweredstudies and representative popula-tions of diverse defect morphologiesand severities.

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Address:Mariano SanzUniversidad Complutense de MadridFacultad de OdontologiaPlaza Ramon y CajalE-28040 MadridSpainE-mail: marianosanz@odon.ucm.es

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