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J Clin Periodontol. 2019;1–17. wileyonlinelibrary.com/journal/jcpe | 1© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Received:5June2018 | Revised:7January2019 | Accepted:9January2019DOI: 10.1111/jcpe.13070
S U P P L E M E N T A R T I C L E
Efficacy of reconstructive surgical therapy at peri- implantitis- related bone defects. A systematic review and meta- analysis
Cristiano Tomasi1 | Erik Regidor2 | Alberto Ortiz-Vigón2,3 | Jan Derks1
1DepartmentofPeriodontology,InstituteofOdontology,TheSahlgrenskaAcademyatUniversityofGothenburg,Gothenburg,Sweden2ClínicaOrtiz-Vigón,PerioCentrum,Bilbao,Spain3ETEPResearchGroup,FacultyofOdontology,UniversityComplutenseofMadrid,Madrid,Spain
CorrespondenceJanDerks,DepartmentofPeriodontology,InstituteofOdontology,TheSahlgrenskaAcademyatUniversityofGothenburg,Gothenburg,Sweden.Email:jan.derks@odontologi.gu.se
Funding informationThisConsensusMeetingwassupportedbytheOsteologyFoundationandbytheEuropeanFederationofPeriodontology.
AbstractObjectives: The present systematic review aimed at evaluating the efficacy ofreconstructivesurgicaltherapyatperi-implantitis-relatedbonedefects.Methods: Studiesreportingonoutcomesofreconstructivesurgeryatperi-implantitis-related bone defects at 12months were identified through an electronic search.Following data extraction, two different sets of meta-analyses were performed.Primarily, controlled studies were used to evaluate the potential benefit ofreconstructive surgical therapy over controls. Secondly, overall outcome ofreconstructive surgical therapy was assessed by comparing baseline values withoutcomes at 12months. Results were expressed as weighted mean differences(WMD)orriskratios(RR).HeterogeneitywasdescribedbyI2andpredictionintervals.Results: Thepotentialbenefitofreconstructivetechniquesovercontrolprocedureswasevaluatedinthreestudies,representingatotalof116implants.Altogether,16studies reported on the outcome of reconstructive measures at 12months aftersurgery.Themeta-analysesidentifiedalargerimprovementinmarginalbonelevels(MBL, WMD=1.7mm) and in defect fill (WMD=57%) for test procedures, butfound no differences for clinical measures (reduction of probing depth (PD) andbleedingonprobing(BOP).Changesofclinicalattachmentandsofttissuelevelswerenot considered. In terms of overall outcome, therapy resulted in improved MBL(WMD=2.0mm) and CAL (WMD=1.8mm), in recession (WMD=0.7mm), inreduced PD (WMD=2.8mm) and in reduced BOP (Implants: RR=0.4/Sites:RR=0.2). None of the included studies addressed patient-reported outcomemeasures.Conclusions: Theavailable evidenceon reconstructive therapyatperi-implantitis-relateddefectsislimitedby(a)thelownumberofcontrolledstudies,(b)thelackofcontrolled studies for commonly used procedures, (c) the heterogeneity betweenstudies and (d) the choice of outcomemeasures. A high variability for predictedoutcomesat12monthswasnoted.The interpretationof thedemonstrated largerMBLgainfortestproceduresisdifficultasgraftmaterialmaynotbedistinguishablefrom newly formed bone. Potential aesthetic and patient-reported advantagesremaintobedemonstrated.
K E Y WO RD S
boneregeneration,dentalimplant,peri-implantitis,reconstructivetherapy
2 | TOMASI eT Al.
1 | INTRODUCTION
Peri-implantitis is a pathological condition occurring in tissuesaround dental implants. It is characterized by inflammation in theperi-implant connective tissue and progressive loss of supportingbone (Schwarz,Derks,Monje,&Wang, 2018). In a systematic re-view,aweightedmeanpatientprevalenceofperi-implantitisof22%wasreported(Derks&Tomasi,2015).Theprevalencerangedfrom1%to47%indifferentreports,mainlyduetothevariationofcasedefinitionsamongstudies(Tomasi&Derks,2012).Itwassuggestedthatperi-implantitis-associatedbone losswastime-dependentandacceleratedovertime(Derksetal.,2016;Franssonetal.,2010).
The goal of peri-implantitis treatment is resolution of softtissue inflammation and, subsequently, the prevention of fur-ther marginal bone loss. Non-surgical treatment modalities arefrequently insufficient to achieve this objective (Faggion, Listl,Frühauf,Chang,&Tu,2014;John,Becker,Schmucker,&Schwarz,2017),whilesurgicalproceduresareconsideredmoreefficaciousinthetreatmentofperi-implantitis(Faggion,Chambrone,Listl,&Tu,2013;Lindhe&Meyle,2008).Thefeasibilityofasurgicalap-proachhasbeenextensivelydemonstratedinpre-clinicalresearch(Albouy, Abrahamsson, Persson, & Berglundh, 2011; Carcuac,Abrahamsson, Charalampakis, & Berglundh, 2015; Persson,Araújo, Berglundh, Gröndahl, & Lindhe, 1999), and clinical ef-ficacy has been documented in studieswith substantial periodsof follow-up (Berglundh,Wennström,&Lindhe,2018;Roccuzzo,Pittoni, Roccuzzo, Charrier, & Dalmasso, 2017; Schwarz, John,Schmucker,Sahm,&Becker,2017).
Outcomesofsurgicaltherapyofperi-implantitisarereportedtobeinfluencedbyimplantsurfacecharacteristics(Carcuacetal.,2017;Roccuzzoetal.,2017)andbytheconfigurationoftheperi-implantbonedefect (Schwarz, Sahm, Schwarz,&Becker, 2010).Bonede-fectsassociatedwithperi-implantitiscommonly involve thewholecircumferenceoftheaffected implantandhaveanangularoutlineonthemesialanddistalaspects(Schwarzetal.,2007).Angularbonedefectsatteethmayhaveanoveralldifferentmorphology,andstud-ieshaveindicatedthatreconstructivetechniquesaresuccessful intermsofclinicalattachmentgainandpreventionofsofttissuereces-sion(Reynoldsetal.,2015).Whilethedocumentationofreconstruc-tivesurgeryintheperiodontalliteratureisextensive,evidenceonitsuseatperi-implantitissitesisonlyemerging.Theaimofthepresentsystematic review was to evaluate the efficacy of reconstructivesurgicaltherapyatperi-implantitis-relatedbonedefects.
2 | MATERIALS AND METHODS
2.1 | Protocol and eligibility
Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)guidelineswereconsidered (Moher,Liberati,Tetzlaff, & Altman, 2009), and the protocol was registered atProspero (CRD42018089236). The focused question of this
systematicreviewwas:Whatisthebenefitofusingareconstruc-tivetechniqueasadjuncttosurgicaltherapyofperi-implantitis?
2.2 | Inclusion criteria (PICOS)
2.2.1 | Population
Patientsingoodgeneralhealthrequiringtreatmentofperi-implantitis.
2.2.2 | Intervention
Reconstructive technique as adjunction to surgical therapy ofperi-implantitis.
2.2.3 | Comparison
Surgicaltherapyofperi-implantitisalone(open-flapdebridement).
2.2.4 | Outcomes
Changes of radiographic marginal bone level, clinical attachmentlevel and soft tissue level. Reduction of probing depth and peri-implant bleeding on probing. Implant survival (in studies with afollow-upof≥5years).
2.2.5 | Study design
Randomized clinical trials (RCT), controlled clinical trials orprospectivecaseserieswithatleast12monthsoffollow-upwithaminimumof10patients(5pergroupincontrolledstudies).
2.3 | Exclusion criteria
• Pre-clinicalstudies.• Surgicaltherapyofperi-implantitisapplyingpocketelimination.• ArticlespublishedinlanguagesotherthanEnglish.
Clinical Relevance
Scientific rationale for review:Peri-implantitis isacommoncomplicationinpatientsprovidedwithimplant-supportedrestorativetherapy,andtreatmentcommonlyrequiressur-gicalaccess.Principal findings:Evidenceonreconstructivetherapyatperi-implantitis-relatedbonedefectsislimited.Abenefitforreconstructivetechniquesovercontrolpro-cedures was observed for radiographic outcomes only.Practical implications:Cliniciansshouldbeawareofthelackof evidence suggesting improved aesthetic or patient-reported outcomes following reconstructive therapy atperi-implantitis-relatedbonedefects.
| 3TOMASI eT Al.
2.4 | Interventions and comparisons
Studies on reconstructive techniques in the surgical therapy ofperi-implantitis were considered. The following procedures andpossiblecombinationswereaccepted:(a)bonegrafting(autologous,allogeneicorxenogeneic);(b)guidedboneregeneration;and(c)useofbiologicalagents/growthfactors.
Primarily, the outcomes of reconstructive therapywere com-paredtoresultsafteridenticalsurgicalinterventionsomittingthereconstructive technique (control: open-flap debridement). In asecond step, the overall outcome of reconstructive therapywasevaluated by comparing pre-surgical findings with outcomes at12months.
2.5 | Outcome measures
Outcomes at 12months following surgical therapy of peri-implantitiswereextracted.Theprimaryoutcomewas changeofradiographicmarginalbonelevel(MBL)expressedinmm.Wefur-therconsideredfillofthebonedefectexpressedasapercentage.Additional secondary outcomeswere changes of clinical attach-ment level (CAL), changes of soft tissue level (REC), changes ofbleeding on probing (BOP), changes of suppuration on probing(SUP) and changes of probing depth (PD). Combinations of out-comes, that is composite outcomes (absence of additional boneloss,absenceof inflammationandshallowprobing), andpatient-reported outcome measures (PROMs) were also considered.Implant survival was assessed in studies with a follow-up of≥5years.
2.6 | Search strategy
Three electronic databases were searched for relevant articles inFebruary2018usingthefollowingsearchalgorithms.
2.6.1 | MEDLINE via PubMed (2018- 02- 20)
(peri-implantitis OR periimplantitis OR peri implantitis) AND(surgical treatment OR surgery OR surgical OR reconstructiveOR regenerative OR regeneration) NOT (retrospective OR re-viewOR invitroORcase reportORorthopedicORanimalORexperimental)
Filter:English
2.6.2 | Web of science (2018- 02- 20)
((peri-implantitis OR periimplantitis OR peri implantitis) AND(surgical treatmentORsurgeryORsurgicalOR reconstructiveORregenerativeORregeneration))
Refined by: WEB OF SCIENCE CATEGORIES:(DENTISTRYORALSURGERYMEDICINE)ANDDOCUMENTTYPES:(ARTICLE)ANDLANGUAGES:(ENGLISH)
2.6.3 | Cochrane central register of controlled trials (2018- 02- 20)
(peri-implantitis OR periimplantitis OR peri implantitis) AND(surgical treatmentORsurgeryORsurgicalOR reconstructiveORregenerativeORregeneration)
In addition, a hand searchwas performed including referencelistsandprevioussystematicreviews.Titlesofallidentifiedarticleswere screened for eligibility.Abstractswere then studied and se-lectedindependentlybytworeviewers(CT&JD).Relevantarticleswereanalysedinfulltextand,again,independentlyselectedforin-clusion.Thelevelofagreementforthetwoselectionswasexpressedby k-scores.Disagreementwasresolvedbydiscussion.
2.7 | Data extraction
Tworeviewers(ER&JD)extracteddatafromincludedarticlesandentered relevant information into pre-defined evidence tables.Studies were sorted according to design (controlled studies vs.studieswithoutcontrols), andoutcomesat12monthswere illus-tratedforallstudyarms.Forcontrolledstudies,potentialbenefitsoftestprocedureswerehighlighted.Wespecificallyfocusedonin-clusionandexclusioncriteriaforeachofthestudysamplesinorderto evaluate potential heterogeneity among the sampled popula-tions.Incaseofmissingdata/information,authorswerecontacted.
2.8 | Quality assessment
Onereviewer(AOV)assessedtheriskofbiasfor includedstudies.Forrandomizedtrials,criteriadescribedintheCochraneHandbook(Higgins etal., 2011) were used. In six categories (sequencegeneration, allocation concealment, detection bias, attrition bias,selectivereportingbiasandotherpotentialriskofbias),aratingoflow,unclearorhighriskofbiaswasperformed.
Forstudieslackingcontrols,thatisobservationalstudies,riskofbiaswasassessedusingamodifiedversionoftheNewcastle-OttawaScale for cohort studies (Wells etal., 2014).Thus, five items (rep-resentativenessofcohort, ascertainmentofexposure,outcomeatstartofstudy,comparabilityofcohortsandassessmentofoutcome)werescoredaspresent,notpresentornotapplicable.
2.9 | Risk of bias across studies
The publication bias was evaluated using funnel plots for theoutcomes: (a) changes ofMBL and (b) PD reduction. A sensitivityanalysisofthemeta-analysisresultswasalsoperformed,ifplausible,byselectivelyexcludingstudiesfromthedifferentanalyses.
2.10 | Data analysis
Forcontinuousoutcomesat12months(changesofMBL,defectfill,CAL,RECandPD),meanvaluesandstandarddeviationswerepooled
4 | TOMASI eT Al.
andanalysedwithweightedmeandifferences(WMD)and95%con-fidence intervals (CIs). Fordichotomousdata (BOP), theestimatesoftheeffectwereexpressedasriskratios(RR)and95%CIs.Study-specific estimateswere pooledwith both the fixed- and random-effectsmodels(DerSimonian&Laird,1986),andtherandom-effectsmodelresultswerepresented.
We performed two different sets of analyses. Primarily, con-trolledstudieswereusedtoevaluatethepotentialbenefitofrecon-structivesurgicaltherapy.Forthisanalysis,nodistinctionwasmadebetweenthedifferentsurgicaltechniques.Open-flapdebridementwasconsideredascontrol.Secondly,theoutcomeofreconstructive
surgical therapy was assessed by comparing baseline values withoutcomes at 12months. In this analysis, controlled studies andstudieswithout controlswere included. For studieswithmultiplearms,each reconstructive interventionwasconsidered separately.Further, sensitivity analysiswasperformedby considering studieswithandwithoutcontrolsseparately.
StatisticalheterogeneityamongstudieswasexploredbytheI2 index(Higgins,Thompson,Deeks,&Altman,2003)andCochrane'sQ statistic (p < 0.1). Forest plotswere used to illustrate the out-comesoftheanalyses.Resultswerecombinedwithrandom-effectsmeta-analysis, reporting tau-squared (between studies variance
F IGURE 1 PRISMAflowdiagramdepictingtheselectionprocess
| 5TOMASI eT Al.
TABLE 1 Includedstudies:Outcomesreportedincontrolledstudies(n=4articles,n=3studies)
Study
Arm
s
Number of
obse
rvat
ions
at
12
mon
ths
Outcomes
at
12
mon
ths
Bene
fit o
f tes
t pro
cedu
re
at 1
2 m
onth
sCo
mm
ents
Isehedetal.(2016)
Open-flap
debridement
13patients
13implants
ΔMBL:−0.2±1.1mm
ΔPD:−4.0±2.9mm
ΔBOP%(implants):−20
ΔSUP%(implants):−36
ΔMBL:0.5mm
ΔPD:1.5mm(infavourofcontrol
group)
ΔBOP%(implants):0
ΔSUP%(implants):17
Mea
n ΔMBLandΔPDkindlyprovidedbytheauthors.
BOP/SUPpositiveifpresentatanysiteofimplant.
RECandPROMsnotreported.
Nosystemicantibioticsprescribed.
Enamelmatrix
derivative
12patients
12implants
ΔMBL:−0.7±1.1mm
ΔPD:−2.5±2.0mm
ΔBOP%(implants):−20
ΔSUP%(implants):−53
Jepsenetal.(2016)
Open-flap
debridement
26patients
26implants
ΔMBL:−1.0±1.4mm(mesial),
−0.8±1.1mm(distal)
%Defectfill:23.1±46.3
(mesial),21.9±30.2(distal)
ΔPD:−2.6±1.4mm
ΔBOP%(sites):−44.9±38.2
ΔBOP%(implants):−30.8
ΔSUP%(implants):−25.6±32.7
ΔMBL:2.6mm(mesial),
2.7mm(distal)
%Defectfill:55.9(mesial),52.3
(distal)
ΔPD:0.2mm
ΔBOP%(sites):11.2
ΔBOP%(implants):0
ΔSUP%(implants):2.4(infavour
ofcontrolgroup)
Compositeoutcome(BOP-,PD<5mmandabsence
ofadditionalboneloss)
Control:23.0%ofimplants
Test:30.3%ofimplants
BOP%basedon6sites/implant.
BOP/SUPpositiveifpresentatanysiteofimplant.
RECandPROMsnotreported.
Systemicantibioticsprescribed
Poroustitanium
granules
33patients
33implants
ΔMBL:−3.6±2.1mm(mesial),
−3.5±2.2mm(distal)
%Defectfill:79.0±29.9(mesial),
74.2±36.3(distal)
ΔPD:−2.8±1.3mm
ΔBOP%(sites):−56.1±30.5
ΔBOP%(implants):−30.3
ΔSUP%(implants):−23.2±32.8
Wohlfahrtetal.(2012)
12
mon
ths
alsoreportedin:
Andersenetal.(2017)
7
year
s
Open-flap
debridement
16patients
16implants
ΔMBL:−0.1±1.9mm
%Defectfill:−14.8±83.4
ΔPD:−2.0±2.3mm
ΔBOP(sites):−0.56±2.9
ΔMBL:1.9mm
%Defectfill:71.8
ΔPD:0.3mm(infavourofcontrol
group)
ΔBOP(sites):0.18(infavourof
controlgroup)
BOPexpressedasmeannumberofpositivesites(out
of6)perimplant.
SUP,RECandPROMsnotreported.
Systemicantibioticsprescribed.
Submergedhealingfor6monthsfollowingsurgery.
17/32patientsattendedthe7-yearexamination:3
implantsin3patients(allinthetestgroup)werelost
duringfollow-up.
Poroustitanium
granules
16patients
16implants
ΔMBL:−2.0±1.7mm
%Defectfill:57.0±45.1
ΔPD:−1.7±1.7mm
ΔBOP(sites):−0.38±2.1
Not
e.BOP:bleedingonprobing;MBL:marginalbonelevel;PD:probingdepth;REC:softtissuelevel;PROMs:patient-reportedoutcomemeasures;SUP:suppurationonprobing.
6 | TOMASI eT Al.
TABLE 2 Includedstudies:Outcomesreportedinstudieswithoutcontrols(n=21articles,n=13studies)
Study
Gro
ups
Number of observations
at
12
mon
ths
Outcomes
at
12
mon
ths
Com
men
ts
Aghazadehetal.(2012)
Group1:
Autologousbonegraft
(particulate),resorbablemembrane
22patients
36implants
ΔMBL:−0.2mm(S
E: 0
.3)
ΔPD:−2.0mm(S
E: 0
.2)
ΔBOP%(sites):−44.8(S
E:6.3)
ΔSUP%(sites):−11.5(S
E: 5
.2)
Compositeoutcome1(BOP-,PD<5mmandabsence
ofadditionalboneloss)
Group1:11.1%ofimplants
Group2:20.5%ofimplants
Compositeoutcome2(BOP+at≤1site,PD<5mm
andabsenceofadditionalboneloss)
Group1:13.9%ofimplants
Group2:38.5%ofimplants
BOP/SUP%basedon4sites/implant.
RECandPROMsnotreported.
Systemicantibioticsprescribed
Group2:
Bovinebonemineral(particles),
resorbablemembrane
23patients
39implants
ΔMBL:−1.1mm(S
E: 0
.3)
ΔPD:−3.1mm(S
E: 0
.2)
ΔBOP%(sites):−50.4(S
E: 5
.3)
ΔSUP%(sites):−25.2(S
E:4.2)
Behnekeetal.(2000)
Autologousbonegraft(blockor
particulate),supportingscrewsor
fibringlue
Numberofpatientsnot
reported
18implants
ΔMBL:−3.9mm
ΔPD:−2.7mm
ΔCAL:−2.2mm
SE o
r SDofmeanchangesnotreported.
BOP,SUP,RECandPROMsnotreported.
ΔRECcalculated:0.5mm
Outcomesat12monthsreportedforsubsample.
Systemicantibioticsprescribed.
KhouryandBuchmann
(200
1)Group1:
Autologousbonegraft(blockand
particulate)
7patients
12implants
ΔMBL:−2.4mm
ΔPD:−5.4mm
ΔProbingbonelevel:−2.4mm
SE o
r SDofmeanchangesnotreported.
BOP,SUP,RECandPROMsnotreported.
Systemicantibioticsprescribed
Group2:
Autologousbonegraft(blockand
particulate),ePTFEmembrane
11patients
20implants
ΔMBL:−3.3mm
ΔPD:−4.8mm
ΔProbingbonelevel:−3.7mm
Group3:
Autologousbonegraft(blockand
particulate),collagenmembrane
7patients
9implants
ΔMBL:−2.5mm
ΔPD:−3.3mm
ΔProbingbonelevel:−2.5mm
Matarassoetal.(2014)
Bovinebonemineral(particles),
collagenmembrane
11patients
11implants
ΔMBL:−2.8mm
%Defectfill:93.3±13.0
ΔREC:−1.3mm
ΔPD:−4.1mm
ΔCAL:−3.0mm
ΔBOP%(sites):−13.6
SE o
r SDofmeanchangesnotreported.
BOP%basedon6sites/implant.
6of11implantsfreeofBOPpriortosurgery.
SUPandPROMsnotreported.
Systemicantibioticsprescribed
Nartetal.(2017)
Allograft(impregnatedwith
vancomycinandtobramycine),
collagenmembrane
13patients
17implants
ΔMBL:−3.6mm
%Defectfill:87.0±18.2
ΔREC:−1.3±0.5mm
ΔPD:−4.2±1.5mm
ΔBOP%(sites):−70.6
ΔSUP%(sites):−100.0
SE o
r SDofmeanchangesnotreportedforall
outcomes.
BOP/SUP%basedon6sites/implant.
PROMsnotreported.
Nosystemicantibioticsprescribed
(Continued)
| 7TOMASI eT Al.
Study
Gro
ups
Number of observations
at
12
mon
ths
Outcomes
at
12
mon
ths
Com
men
ts
Roccuzzoetal.(2011)
12
mon
ths
alsoreportedin:
Roccuzzoetal.(2017)
7
year
s
Group1:TPSimplants
Bovinebonemineral(block)
14patients
14implants
ΔMBL:−1.6±0.7mm
ΔPD:−2.1±1.2mm
ΔBOP%(sites):−33.9
ΔSUP%(implants):−60.0
BOP%basedon4sites/implant.
SUPexpressedas%ofimplantsdemonstrating
suppuration.
RECandPROMsnotreported.
Systemicantibioticsprescribed.
24/26patientsattendedthe7-yearexamination:4
implantsin4patients(2ineachgroup)werelost
duringfollow-up
Group2:SLAimplants
Bovinebonemineral(block)
12patients
12implants
ΔMBL:−1.9±1.3mm
ΔPD:−3.4±1.7mm
ΔBOP%(sites):−60.4
ΔSUP%(implants):−100.0
Roccuzzoetal.(2016)
Bovinebonemineral(block)
71patients
71implants
ΔPD:−2.9±1.7mm
ΔBOP%(sites):−53.2
ΔSUP%(implants):−35.5
Compositeoutcome1(BOP-andPD≤5mm)
49.3%ofimplants
Compositeoutcome2(BOP-andPD≤6mm)
56.0%ofimplants
BOP%basedon4sites/implants.
SUPexpressedas%ofimplantsdemonstrating
suppuration.
MBL,RECandPROMsnotreported.
ΔRECfordifferentdefectcategoriesvariedfrom
0.5mmto0.9mm.Estimatedmean:0.69±0.76mm.
Systemicantibioticsprescribed
Roos-Jansåkeretal.(2007a)
Hydroxyapatite,resorbable
mem
bran
e12patients
16implants
ΔMBL:−2.3±1.2mm
ΔREC:−2.8±1.4mm
ΔPD:−4.2±1.5mm
ΔCAL:−1.4±1.7mm
ΔBOP%(implants):−62.5
BOPexpressedas%ofbleedingatdeepestsiteof
implant.
SUPandPROMsnotreported.
Systemicantibioticsprescribed.
Submergedhealingfor6monthsfollowingsurgery.
Roos-Jansåkeretal.(2007b)
12 m
onth
salsoreportedin:
Roos-Jansåker,Lindahl,
Persson,andRenvert(2011)
3
year
sRoos-Jansåkeretal.(2014)
5
year
s
Group1:Hydroxyapatite,
resorbablemembrane
17patients
29implants
ΔMBL:−1.5±1.2mm
ΔREC:−1.3±1.5mm
ΔPD:−2.9±2.0mm
ΔCAL:−1.6±2.0mm
ΔBOP%(sites):−57.7
BOP%basedon4sites/implant.
SUPandPROMsnotreported.
Systemicantibioticsprescribed.
25/38patientsattendedthe5-yearexamination:no
implantswerelostduringfollow-up
Group2:Hydroxyapatite
19patients
36implants
ΔMBL:−1.4±1.3mm
ΔREC:−1.6±1.6mm
ΔPD:−3.4±1.6mm
ΔCAL:−1.8±1.4mm
ΔBOP%(sites):−67.9
TABLE 2 (Continued)
(Continued)
8 | TOMASI eT Al.
Study
Gro
ups
Number of observations
at
12
mon
ths
Outcomes
at
12
mon
ths
Com
men
ts
Schwarzetal.(2008)
2
year
salsoreportedin:
Schwarz,Bieling,Latz,
Nuesry,andBecker(2006)
6 m
onth
sSchwarz,Sahm,Bieling,and
Becker(2009)
4
year
s
Group1:Hydroxyapatite
9patients
9implants
ΔREC:−0.4±0.2mm
ΔPD:−2.0±0.5mm
ΔCAL:−1.6±0.3mm
ΔBOP%(sites):−44
BOP%basedon6sites/implant.
MBL,SUPandPROMsnotreported.
Nosystemicantibioticsprescribed
Group2:Bovinebonemineral
(particles),collagenmembrane
11patients
11implants
ΔREC:−0.3±0.4mm
ΔPD:−2.7±0.6mm
ΔCAL:−2.4±0.7mm
ΔBOP%(sites):−49
Schwarzetal.(2010)
Bovinebonemineral(particles),
collagenmembrane
27patients
27implants
DefectClassIb(n=9)
ΔREC:−0.4±0.7mm
ΔPD:−1.6±0.9mm
ΔCAL:−1.2±1.1mm
ΔBOP%(sites):−39.9±16.6
DefectClassIc(n=9)
ΔREC:−0.5±0.5mm
ΔPD:−1.6±0.7mm
ΔCAL:−1.1±0.9mm
ΔBOP%(sites):−25.9±14.7
DefectClassIe(n=9)
ΔREC:−0.3±0.6mm
ΔPD:−2.7±0.7mm
ΔCAL:−2.4±1.0mm
ΔBOP%(sites):−61.1±16.7
BOP%basedon6sites/implant.
MBL,SUPandPROMsnotreported.
Nosystemicantibioticsprescribed
Schwarzetal.(2012)
2
year
salsoreportedin:
Schwarz,Sahm,Iglhaut,and
Becker(2011)
6
mon
ths
Schwarz,Hegewald,John,
Sahm,andBecker(2013)
4 ye
ars
Schwarzetal.(2017)
7
year
s
Group1:Implantsurfacedecon-
taminationwithplasticcurettes,
cottonpelletsandsterilesaline
Bovinebonemineral(particles),
collagenmembrane
14patients
ΔREC:−0.5±0.4mm
ΔPD:−2.0±1.6mm
ΔCAL:−1.5±1.6mm
ΔBOP%(sites):−60.1±26.6
BOP%basedon6sites/implant.
MBL,SUPandPROMsnotreported.
Nosystemicantibioticsprescribed.
15/32patientsattendedthe7-yearexamination:4
patientswereexcludedbetweenyears2and3dueto
severere-infection.Noinformationonimplantloss
Group2:Implantsurfacedecon-
taminationwithEr:YAGlaser
Bovinebonemineral(particles),
collagenmembrane
10patients
ΔREC:−0.4±0.2mm
ΔPD:−1.7±1.2mm
ΔCAL:−1.3±1.2mm
ΔBOP%(sites):−55.0±28.4
Wiltfangetal.(2012)
Autologousbonegraft(particulate),
xenogeneicbonegraft
22patients
36implants
ΔDefectdepth:−3.5mm(95%CI:
−4.3/−2.7)
ΔREC:−1.3mm
ΔPD:−4.0mm(95%CI:−4.6/−3.3)
ΔBOP%(implants):−36
ΔSUP%(implants):−72
SE,S
DorCIofmeanchangesnotreportedforall
outcomes.
BOP/SUPpositiveifpresentatanysiteofimplant.
39%implantsfreeofBOPpriortosurgery.
MBLandPROMsnotreported.
Systemicantibioticsprescribed.
Not
e.BOP:bleedingonprobing;CAL:clinicalattachmentlevel;CI:confidenceinterval;MBL:marginalbonelevel;PD:probingdepth;PROMs:patient-reportedoutcomemeasures;REC:softtissuelevel;
SUP:suppurationonprobing;S
E:standarderror;
SD:standarddeviation.
TABLE 2 (Continued)
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includedintheanalysis),whichwasusedtocalculatepredictionin-tervals(Borenstein,Higgins,Hedges,&Rothstein,2017).Statisticalsignificancewassettop < 0.05.AllanalyseswereperformedwithReviewManager (RevMan version 5.3. Copenhagen: The NordicCochraneCentre,TheCochraneCollaboration,2014).
3 | RESULTS
3.1 | Search
ResultsofthesearchareillustratedinFigure1.Theelectronicsearchyielded754titles.Oneadditionalarticle (Hamzacebi,Oduncuoglu,& Alaaddinoglu, 2015) was identified through the hand search,renderinganinitialselectionof755records.Followingscreeningoftitlesandabstracts,35articleswereselectedfor full-textanalysis(kappa=0.86).Anadditional10articleswereexcluded,resultingina finalselectionof25articlesdescribing16differentstudies.ThereasonsforexclusionaregiveninTableA-1.Theagreementonthefinalselectionwaskappa=0.87.
3.2 | Description of selected studies
3.2.1 | Design
TheincludedstudiesaredescribedinTables1and2.Outofthe16relevantstudies,threeincludedcontrolsandweredesignedasrandomizedcontrolledtrials(Isehedetal.,2016;Jepsenetal.,2016;Wohlfahrtetal.,2012).Eachstudyincludedonesingleexperimen-talgroup,andopen-flapdebridementwasprovidedtocontrols.
Of the 13 studies without controls, three were designed asrandomizedtrials (Aghazadeh,Persson,&Renvert,2012;Schwarz,John,Mainusch,Sahm,&Becker,2012;Schwarzetal.,2008),whiletheremainingwereobservationalstudies.Atotaloffourstudiesin-cludedmultipleinterventionalarms(Aghazadehetal.,2012;Khoury& Buchmann, 2001; Roos-Jansåker, Renvert, Lindahl, & Renvert,2007b; Schwarz etal., 2008), comparing different reconstructivetechniqueswitheachother.Oneadditionalstudycomparedtheout-comesofonereconstructivetechniqueattwodifferenttypesofim-plants(Roccuzzo,Bonino,Bonino,&Dalmasso,2011),whileanothertworeportedoutcomesoftreatmentatdifferentdefectconfigura-tions(Roccuzzo,Gaudioso,Lungo,&Dalmasso,2016;Schwarzetal.,2010).Schwarzetal.(2012)assessedtwomethodsofsurfacedecon-taminationpriortoonereconstructiveapproach.Theremainingfivestudiesdidnotincludeanycomparativeanalyses(Behneke,Behneke,&d'Hoedt,2000;Matarasso,IorioSiciliano,Aglietta,Andreuccetti,&Salvi,2014;Nart,deTapia,Pujol,Pascual,&Valles,2017;Roos-Jansåker,Renvert,Lindahl,&Renvert,2007a;Wiltfangetal.,2012)
3.2.2 | Study samples
Sample sizes varied from 29 to 63 patients for the controlledstudiesandfrom11to75patientsforthestudieslackingcontrols.Roughly, every second study included selectedparticipants,while
the remaining studies described consecutive patient enrolment.In 10 studies, patientswithmedical conditions (e.g., uncontrolleddiabetes)wereexcluded.Heavysmokingwasanexclusioncriterionin5studies.
All studies were based exclusively on samples from Europeanpopulations.Fourstudiesreportedonpatientstreatedinaprivatepracticesetting,whiletheothersreportedonpatientstreatedinaspecialist or university setting.One study (Jepsenetal., 2016) in-cluded multiple centres, while the remaining investigations wereperformedatsingleclinicalcentres.Aformalpowercalculationwasdescribedinsix(Aghazadehetal.,2012;Isehedetal.,2016;Jepsenetal., 2016; Schwarz etal., 2010, 2012;Wohlfahrt etal., 2012) ofthe16includedstudies.
Meanageofincludedpatientsrangedfrom48to71years,andtheratiobetweenmalesandfemalesincludedvariedfrom0.9to0.1.Theproportionofsmokersrangedfrom15%to70%. In5studies,onlyonesingletypeofimplantwasincluded,while2to11differentimplantbrandsweretreatedintheremainingstudies.Prerequisitesfor theperi-implantdefects tobe treatedvaried considerablybe-tweenstudies.Eightstudies,forinstance,didnotspecifythepres-enceof signs of inflammation (e.g., BOP) for inclusion.All studiesbuttwo(Roos-Jansåkeretal.,2007a,b),however,requiredthepres-enceofanangularbonedefect.Requirementsintermsofdepthofthebonedefectrangedfromaminimumof3to4mm.Twostudies(Jepsen etal., 2016; Nart etal., 2017) further specified the peri-implantdefectsintermsofconfiguration(fordetails,seeTableA-2).
3.2.3 | Interventions
Intwoofthethreecontrolledstudies,poroustitaniumgranuleswereusedintheinterventiongroups(Jepsenetal.,2016;Wohlfahrtetal.,2012), while the third evaluated the potential benefit of enamelmatrixderivate(Isehedetal.,2016).
Allofthestudieswithoutcontrolsusedbonereplacementgrafts,either alone (Behneke etal., 2000; Khoury & Buchmann, 2001;Roccuzzo etal., 2011, 2016; Roos-Jansåker etal., 2007b; Schwarzetal.,2008;Wiltfangetal.,2012)orincombinationwithmembranes(Aghazadeh etal., 2012; Khoury & Buchmann, 2001; Matarassoetal.,2014;Nartetal.,2017;Roos-Jansåkeretal.,2007a,b;Schwarzetal., 2008, 2010, 2012). The most commonly used graft mate-rialwas bovinebonemineral as particles (Aghazadeh etal., 2012;Matarasso etal., 2014; Schwarz etal., 2008, 2010, 2012) or as ablock(Roccuzzoetal.,2011,2016).Hydroxyapatiteandautologousbonegraftswereappliedin3(Roos-Jansåkeretal.,2007a,b;Schwarzetal.,2008)andfour(Aghazadehetal.,2012;Behnekeetal.,2000;Khoury&Buchmann,2001;Wiltfangetal.,2012)studies, respec-tively.Onestudydescribedtheuseofanallograft(Nartetal.,2017).
3.3 | Risk of bias in individual studies
Theassessmentof riskofbias in the included randomized trials isillustrated inTableA-3.A low riskofbiaswasnoted inonestudyonly (Isehedetal.,2016),basedontheapparentdifficultytoblind
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theexaminerduringradiologicalassessmentsinthestudiesevaluat-ingbonereplacementgrafts(detectionbias).Inaddition,asubstan-tialpatientdropoutwasnotedforthelong-termfollow-up(7years)fortwostudies(Andersen,Aass,&Wohlfahrt,2017;Schwarzetal.,2017).This,however,wasnotrelevantforoutcomesat12months.
Thequalityofreportingintheselectedobservationalstudiesisdepicted inTableA-4.Threeof thestudies (Roccuzzoetal.,2016;
Schwarz etal., 2010;Wiltfang etal., 2012) met all of the qualitycategories.
3.4 | Risk of bias across studies
NosignificantpublicationbiaswasobservedforthethreecontrolledstudiesintermsofchangeofMBLandPDreduction(FigureA-1aand
F IGURE 2 (a)Forestplot.PotentialbenefitintermsofchangeofMBL(studieswithcontrols).Unitofanalysis:implant.AdditionaldatakindlyprovidedbyIsehedetal.(2016).ForJepsenetal.(2016):averageofmesialanddistal.(b)Forestplot.Potentialbenefitintermsofdefectreduction/defectfill[%](studieswithcontrols).Unitofanalysis:implant.ForJepsenetal.(2016):averageofmesialanddistal.(c)Forestplot.PotentialbenefitintermsofPDreduction(studieswithcontrols).Unitofanalysis:implant.AdditionaldatakindlyprovidedbyIsehedetal.(2016).ForJepsenetal.(2016):averageofmesialanddistal.(d)Forestplot.PotentialbenefitintermsofBOPreductionatimplants(studieswithcontrols).Unitofanalysis:implant.Numberofeventsestimatedbasedonreportedpercentages.(e).Forestplot.PotentialbenefitintermsofBOPreductionatimplantsites(studieswithcontrols).Unitofanalysis:implantsite.Numberofeventsestimatedbasedonreportedpercentagesornumbers
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b). Considering only reconstructive interventions from controlledanduncontrolled studies, the funnelplots indicatedno significantpublicationbiasforchangeofMBLbut indicatedasignificantbiasforPDreduction(FigureA-2aandb).
3.5 | Potential benefit of reconstructive surgical therapy
Theanalysisincludedatotalof116implantsfortheprimaryoutcome.Forthesecondaryoutcomes,thenumberofincludedimplantsvariedfrom84to116.HeterogeneityamongstudiesexpressedasI2 varied from0%to88%,dependingontheoutcomemeasure.
3.5.1 | Primary outcome: change of radiographic marginal bone level
Figure2a illustrates the results of the meta-analysis for changesof MBL. All three studies with controls reported on the primaryoutcome. A statistically significant benefit (WMD=1.7mm; 95%CI: 0.3/3.1; p=0.02)wasobserved infavourofthereconstructiveinterventions.
3.5.2 | Secondary outcomes
Defect fill was reported in two of the studies with controls(Figure2b), indicating a statistically significant greater fill at testsites (WMD=56.5%; 95% CI: 39.3/73.8; p < 0.001). The analysisfailed to identify a significant benefit in terms of PD reduction,based on data from all three studies (Figure2c). Similar findingsweremadeforBOPreduction.TheRRforBOPreductionwas1.0(95% CI: 0.8/1.3; p = 0.97) and 0.9 (95% CI: 0.6/1.4; p = 0.70) forimplants and implant sites, respectively (Figures2d and e). Noneof the studieswith controls reported on changes of CAL, REC orPROMs.Implantsurvivaloveratleast5yearswasdescribedinoneoftheinterventionalstudies(Andersenetal.,2017).Overa7-yearfollow-up,3of17implantswerelostinthreepatients,allbelongingtothetestgroup(poroustitaniumgranules).
3.6 | Outcome of reconstructive surgical therapy
The analysis included a total of 433 implants for the primaryoutcome. For the secondary outcomes, the number of includedimplants varied from 147 to 821. Heterogeneity among studies,namelythepercentageofvariationduetoatruevariationbetweentreatmenteffectsinrelationtothevariationduetosamplingerror,variedfrom51%to95%.
3.6.1 | Primary outcome: change of radiographic marginal bone level
Figure3aillustratesthereductionofMBLfrombaselineto12monthspostsurgery.Basedon11armsinsevenstudies,theWMDamountedto2.0mm(95%CI:1.3/2.7;p < 0.001).Thepredictioninterval,that
istheexpectedrangeoftheoutcomeoftreatmentappliedtoaran-dom subject of the overall studied population, was −0.4/4.4mm.Estimateswereconsistent,regardlessofstudydesign.
3.6.2 | Secondary outcomes
ACALgainof1.8mm(95%CI:1.3/2.2;p < 0.001)withapredictionintervalof0.6/3.0(Figure3b)wasobservedbasedonfindingsfromfour studies.ChangeofRECwasassessed in six studies (10arms)andamountedto−0.7mm(95%CI:−1.0/−0.3;p < 0.001)(Figure3c).Theprediction intervalwas−1.7/0.4.PDreduction is illustrated inFigure3d.Theweightedmeaneffectwas2.8mm(95%CI:2.3/3.4;p < 0.001) at 12months, based on 21 arms in 13 studies. Theprediction intervalwas estimated to be0.4/5.3mm.Reduction ofinflammationat12monthswasstatisticallysignificant.TheRRforBOPwas0.4(95%CI:0.2/0.8;p = 0.004)and0.2(95%CI:0.2/0.4;p < 0.001) for implants and implant sites, respectively (Figure3eandf).Therespectivepredictionintervalswere0.1/2.3and0.0/1.7.ResultsofthesensitivityanalysisrevealedthattheRRforBOPforimplantswasconsiderablylowerinstudieswithcontrols(0.07;95%CI:0.0/0.5)thanwithout(0.51;95%CI:0.3/0.8).
NoneofthestudieswithoutcontrolsreportedondefectfillorPROMs,whileimplantsurvivaloveratleast5yearswasdescribedintwo.Resultsrangedfrom83%(Roccuzzoetal.,2017)to100%(Roos-Jansåker,Persson,Lindahl,&Renvert,2014)ontheimplantlevel.
4 | DISCUSSION
Thepresentsystematic reviewaimedatevaluatingtheefficacyofreconstructive surgical therapy at peri-implantitis-related bonedefects. The potential benefit of reconstructive techniques overcontrol procedures was evaluated in three studies, representinga total of 116 implants. Altogether, 16 studies reported on theoutcomeofreconstructivemeasuresat12monthsaftersurgery.Themeta-analyses identified a statistically significant largerMBL gain(WMD=1.7mm)anddefectfill(WMD=57%)fortestprocedures,butfoundnodifferencesforclinicalmeasures(PDreduction,BOPreduction). Changes of clinical attachment and soft tissue levelswerenotconsidered.
In terms of overall outcome, therapy resulted in improvedMBL (WMD=2.0mm) and CAL (WMD=1.8mm), in recession(WMD=0.7mm), in reducedPD (WMD=2.8mm)and in reducedBOP(Implants:RR=0.4/Sites:RR=0.2).Noneoftheincludedstud-iesaddressedpatient-reportedoutcomemeasures.
Resultsofthepresentmeta-analysesareinlinewithcalculationspresented in previously published systematic reviews on the topic(Chan, Lin, Suárez, MacEachern, & Wang, 2014; Khoshkam etal.,2013,2016;Sahrmann,Attin,&Schmidlin,2011).Thepresentanal-ysis suggests that reconstructive therapy at peri-implantitis-relateddefectsisafeasibleconcept,butitisalsoobviousthattheavailableevidence is limited.Themajorityofstudies identified in thepresentreviewwasobservationalandhad thecharacteristicsofcaseseries.
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Onlythreeoftheincludedstudieswererandomizedcontrolledtrialsaddressingthescientificquestionofthepresentreview,thatisthepo-tentialbenefitofreconstructivemeasuresoveropen-flapdebridementalone.Noneoftheincludedstudysamplesoriginatedfromoutsideof
Europe,which represents a limitation in termsofgeneralizability. Inaddition,moststudieswereconductedatspecialistoruniversityclin-ics.Thesignificantheterogeneitywithinandbetweensamplesmayinpartbeattributedtothedifferenttechniquesandmaterialsusedand
F IGURE 3 (continued)
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to inconsistent inclusion/exclusion criteria.The gender ratio amongselectedstudypopulationsvariedconsiderably,asdidtheproportionof smokers and patients with systemic conditions. There was alsoa noteworthy discrepancy in terms of selection of graftingmaterialamongtheincludedarticles.Themostcommonlyusedmaterialintheuncontrolled, observational studieswas bovine bonemineral,whilenoneofthecontrolledstudiesevaluatedthisspecificproduct.
The variation of outcomes between study samples was ex-plored by I2, illustrating the proportion of variance exceeding thesamplingerror(truevariance)(Higgins&Thompson,2002;Higginsetal.,2003).Thepredictionintervalsobservedinthepresentmeta-analysesshowedawiderangeofexpectedeffects,also indicatinga significant variability between the included studies (Borensteinetal., 2017; IntHout, Ioannidis, Rovers, & Goeman, 2016). For
F IGURE 3 (a)Forestplot.ReductionofMBL(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implant.AdditionaldatakindlyprovidedbyIsehedetal.(2016).Notconsidered:Baselineand/or12-monthbonelevels(mean)notreported:Roccuzzoetal.(2016),Roos-Jansåkeretal.(2007a,b),Schwarzetal.(2008,2010,2012),Wiltfangetal.(2012),Wohlfahrtetal.(2012).SE or SDofmeanvaluesnotreported:Behnekeetal.(2000).(b)Forestplot.CALgain(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implant.Notconsidered:Baselineand/or12-monthclinicalattachmentlevels(mean)notreported:Aghazadehetal.(2012),Isehedetal.(2016),Jepsenetal.(2016),KhouryandBuchmann(2001),Nartetal.(2017),Roccuzzoetal.(2011,2016),Roos-Jansåkeretal.(2007a,b),Wiltfangetal.(2012),Wohlfahrtetal.(2012).SE or SDofmeanvaluesnotreported:Behnekeetal.(2000).(c)Forestplot.Changeofsofttissuelevel(REC)(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implant.Notconsidered:Softtissuelevels(mean)atbaselineand/or12monthsnotreported:Aghazadehetal.(2012),Behnekeetal.(2000),Isehedetal.(2016),Jepsenetal.(2016),KhouryandBuchmann(2001),Roccuzzoetal.(2011,2016),Roos-Jansåkeretal.(2007a,b),Wohlfahrtetal.(2012).(d)Forestplot.PDreduction(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implant.AdditionaldatakindlyprovidedbyIsehedetal.(2016).Notconsidered:Baselineand/or12-monthPD(mean)notreported:Roos-Jansåkeretal.(2007a,b).SE or SDofmeanvaluesnotreported:Behnekeetal.(2000).(e)Forestplot.RiskforBOPatimplants(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implant.Notconsidered:BOP%(implants)atbaselineand/or12monthsnotreported:Aghazadehetal.(2012),Behnekeetal.(2000),KhouryandBuchmann(2001),Nartetal.(2017),Roccuzzoetal.(2011,2016),Roos-Jansåkeretal.(2007b),Schwarzetal.(2008,2010,2012),Wohlfahrtetal.(2012).(f)Forestplot.RiskforBOPatimplantsites(reconstructiveinterventionsfromcontrolledanduncontrolledstudies).Unitofanalysis:implantsite.Notconsidered:BOP%(sites)atbaselineand/or12monthsnotreported:Behnekeetal.(2000),Isehedetal.(2016),KhouryandBuchmann(2001),Roos-Jansåkeretal.(2007a),Wiltfangetal.(2012)
14 | TOMASI eT Al.
example, in termsofMBLchanges, theexpectedoutcome rangedfromnoeffectatall(0isincluded)orbonelosstoimprovementofmarginal bone level of4.4mm. It shouldbekept inmind that the95%CIoftheestimatesimplyreflectstheprecisionoftheestima-tionofthemeanvalue.Thepredictioninterval,however,isanindexofdispersion,indicatinghowwidelytheeffectvariesacrossagivenpopulation(Borensteinetal.,2017).
In theconsensus report fromthe8thEuropeanWorkshoponPeriodontology,itwassuggestedtousecompositeoutcomestode-scribe results of peri-implantitis therapy (Sanz&Chapple, 2012).These should ideally include clinical measures of inflammationandradiographicassessmentsofbone-levelalterations.Followingtheserecommendations,studiesapplyingpocketeliminationtech-niques (Carcuac etal., 2016, 2017) or reconstructive techniques(Aghazadehetal.,2012;Jepsenetal.,2016)havereportedresultsaccordingly. An additional goal of reconstructive therapy is themaintenanceofsofttissueheight.Noneofthecontrolledstudies,however, reported data on soft tissue alterations. The recessionobserved in observational studies (WMD=0.7mm) was statisti-cally significant and correspondedwell with findings reported instudiesonperiodontalreconstructivetherapy(Heden,Wennström,&Lindhe,1999;S.Jepsenetal.,2008;Tonettietal.,2004,2002;Trombelli,Simonelli,Minenna,Rasperini,&Farina,2017).Itremainsunclear, however,whether the reconstructive techniques appliedat peri-implant defects resulted in a better aesthetic outcome ascomparedtocontrols.
Studieswithcontrolsindicatedabenefitof1.7mminfavourofreconstructivemeasuresforchangesofmarginalbonelevel.It shouldbekept inmind,however, that twoof the threecon-trolledstudies(Jepsenetal.,2016;Wohlfahrtetal.,2012)usedporoustitaniumgranulesasbonereplacementgraft inthetestgroups.Itisobviousthatblindingoftheexaminerduringradio-graphicassessments in such studieswasnotpossible.Further,itisunclearhowthepresenceofaradiopaquegraftingmaterialaffectedtheassessmentofmarginalbonelevelsasneitherstudyreported measurement errors. Isehed etal. (2016), who usedenamelmatrixderivativeinthetestgroup,reportedamoderatebenefit of 0.5mm. Considering all different reconstructive in-terventionsincludedinthepresentreview,marginalbonelevelswereimprovedby2.0mmonaverage.However,thepredictioninterval was wide and included 0, indicating a high degree ofvariability.
Despite theobservedpotential benefit in radiographic ap-pearance,reconstructivetherapydidnotprovideanybenefitintermsofreductionofPDandBOP.Consideringoverallchangesfrom baseline to 12months, however, peri-implant inflamma-tion was significantly reduced by the surgical treatment. Theanalysis showed that it was more likely to arrest bleeding ata single site (RR=0.2) than to achieve peri-implant health atallaspectsoftheaffectedimplant(RR=0.4).DatareportedbyJepsen etal. (2016) further illustrate this observation. Whilethepercentageofbleedingsiteswasreducedby45%and56%in control and test groups, respectively, the proportion of
implants freeof anybleeding at12monthswas30% forbothgroups. Similar figures have been described in studies apply-ing pocket elimination techniques. Thus,Carcuac etal. (2017)and Heitz-Mayfield etal. (2018) reported 40% of implants tobe completely free of bleeding at 3 and 5years, respectively.Again,ahighvariation intermsofexpectedchangeofBOPatsiteandimplantlevelswastestified,asillustratedbywidepre-dictionintervals.
Thepresentworksuffersfromanumberofshortcomings.Datafrompre-clinical(e.g.,Albouyetal.,2011;Carcuacetal.,2015)andclinicalstudies(e.g.,Berglundhetal.,2018;Roccuzzoetal.,2017)onsurgical therapy of peri-implantitis pointed towards the impact ofimplantsurfacecharacteristicsontreatmentoutcomes.Further,in-clusioncriteriainregardtotheconfigurationofperi-implantdefectsdiffered between studies,whichmay have influenced subsequenthealing(Schwarzetal.,2010).Andfinally,thefrequencyandqualityof maintenance therapy following reconstructive procedures mayalsohavebeenof importanceashasbeendemonstrated forperi-odontitis patients (Cortellini, Pini Prato, & Tonetti, 1994). Neitherof these factors was, however, considered in the present meta-analyses.Inthesecondarycalculationoftheoverallchanges,mea-sures from baseline and 12monthswere handled as independentdatasets.Itmaybearguedthattreatmentoutcomesare,infact,cor-relatedtotheinitialsituation.Inaddition,differenttreatmentarmsoriginatingfromthesamestudywereconsideredtobeindependentofeachother.Thismayhaveaffectedassessmentofheterogeneity.
In conclusion, the available evidence on reconstructive ther-apy at peri-implantitis-related defects is limited by (a) the lownumberofcontrolledstudies, (b) the lackofcontrolledstudies forcommonly used procedures, (c) the heterogeneity between stud-ies and (d) the choiceof outcomemeasures.Ahigh variability forpredictedoutcomesat12monthswasnoted.TheinterpretationofthedemonstratedlargerMBLgainfortestproceduresisdifficultasgraftmaterialmaynotbedistinguishablefromnewlyformedbone.Potential aesthetic and patient-reported advantages remain to bedemonstrated.
ACKNOWLEDGEMENTS
TheauthorsaregratefultoDr.DanielleLaytonforherkindadviceinpreparingthemanuscript.
CONFLICT OF INTEREST
Theauthorsdeclarenoconflictof interestwithrespecttotheau-thorshipand/orpublicationofthisarticle.
ORCID
Cristiano Tomasi https://orcid.org/0000-0002-3610-6574
Alberto Ortiz-Vigón https://orcid.org/0000-0002-1863-5907
Jan Derks https://orcid.org/0000-0002-1133-6074
| 15TOMASI eT Al.
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SUPPORTING INFORMATION
Additional supporting information may be found online in theSupportingInformationsectionattheendofthearticle.
How to cite this article:TomasiC,RegidorE,Ortiz-VigónA,DerksJ.Efficacyofreconstructivesurgicaltherapyatperi-implantitis-relatedbonedefects.Asystematicreviewandmeta-analysis.J Clin Periodontol. 2019;00:1–17. https://doi.org/10.1111/jcpe.13070
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