REVIEWOpenAccessDefinition,etiology,preventionandtreatmentofareviewRal - PDF document

REVIEWOpenAccess Definition,etiology,preventionandtreatmentof peri-implantitis – areview RalfSmeets 1* ,AndersHenningsen 1 ,OleJung 1 ,MaxHeiland 1 ,ChristianHammächer 2 andJamalMStein 3 Abstract Peri-implantinflammationsrepresentseriousdiseasesafterdentalimplanttreatment,whichaffectboththe implantwithoutmultilateralpreventionandtherapyconcepts.Specificcontinuouscheck-upswithevaluationand eliminationofriskfactors(e.g.smoking,systemicdiseasesandperiodontitis)areeffectiveprecautions.Inaddition toaspectsofosseointegration,typeandstructureoftheimplantsurfaceareofimportance.Forthetreatmentof peri-implantdiseasevariousconservativeandsurgicalapproachesareavailable.Mucositisandmoderateformsof peri-implantitiscanobviouslybetreatedeffectivelyusingconservativemethods.Theseincludetheutilizationof differentmanualablations,laser-supportedsystemsaswellasphotodynamictherapy,whichmaybeextendedby localorsystemicantibiotics.Itispossibletoregainosseointegration.Incaseswithadvancedperi-implantitissurgical therapiesaremoreeffectivethanconservativeapproaches.Dependingontheconfigurationofthedefects,resective surgerycanbecarriedoutforeliminationofperi-implantlesions,whereasregenerativetherapiesmaybeapplicable fordefectfilling.Thecumulativeinterceptivesupportivetherapy(CIST)protocolservesasguidanceforthetreatmentof theperi-implantitis.Theaimofthisreviewistoprovideanoverviewaboutcurrentdataandtogiveadvicesregarding Keywords: Peri-implantitis,Peri-implantdisease,Review,Periodontaldisease,Mucositis,Peri-implantitistherapy, Epidemiology,Etiology Introduction Dentalimplantshavebecomeanindispensableestab- lishedtherapyindentistryinordertoreplacemissing teethindifferentclinicalsituations.Successratesof 82,9%after16yearsfollow-uphavebeenreported[1]. Undercareandattentionofindications,anatomicaland intra-individuallimitingfactors,insertionofdentalim- plantsseemstorepresenta “ safe ” treatmentoption. Nevertheless,inthelastdecadesincreasingevidence raisedonthepresenceofperi-implantinflammations representingoneofthemostfrequentcomplicationsaf- fectingboththesurroundingsoftandhardtissueswhich canleadtothelossoftheimplant.Therefore,strategies forpreventionandtreatmentofperi-implantdisease shouldbeintegratedinmodernrehabilitationconceptsin onthepathogenesis,etiology,riskfactorsandprevention ofperi-implantitis,butalsoonactualrecommendationsin treatmentandtherapyoptions. Review Definitionundpathogenesis Inanalogytogingivitisandperiodontitisaffectingthe periodontiumofnaturalteeth,aninflammationandde- structionofsoftandhardtissuessurroundingdentalim- plantsistermedasmucositisandperi-implantitis[2-4]. Thereby,transitionsareoftenfluentandnotclinically clearlyseparable[5]. Mucositisdescribesabacteria-induced,reversiblein- flammatoryprocessoftheperi-implantsofttissuewith reddening,swellingandbleedingonperiodontalprobing (Figure1)[2-6].Thesearetypicalsigns,buttheyare sometimesnotclearlyvisible.Furthermore,bleedingon probing(BOP)mightbeanindicatorforperi-implant disease,butsufficientevidenceaccordingtothepredict- ivevalueofBOPisstilllacking[7]. r.smeets@uke.de 1 DepartmentofOralandMaxillofacialSurgery,UniversityMedicalCenter Hamburg-Eppendorf,Martinistr.52,20246Hamburg,Germany Fulllistofauthorinformationisavailableattheendofthearticle HEAD & FACE MEDICINE ©2014Smeetsetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative CommonsAttributionLicense(http://creativecommons.org/licenses/by/4.0),whichpermitsunrestricteduse,distribution,and reproductioninanymedium,providedtheoriginalworkisproperlycredited.TheCreativeCommonsPublicDomain Dedicationwaiver(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle, unlessotherwisestated. Smeets etal.Head&FaceMedicine 2014, 10 :34 http://www.head-face-med.com/content/10/1/34 Incontrasttomucositis,peri-implantitisisaprogres- siveandirreversiblediseaseofimplant-surroundinghard andsofttissuesandisaccompaniedwithboneresorp- tion,decreasedosseointegration,increasedpocketfor- mationandpurulence[2-6].Bleedingonprobing,bone lossanddeepprobingdepthsmayhaveotherreasons thaninflammation,e.g.toodeepinsertionoftheimplant [8].Moreover,typeandshapeofttheimplant,connec- tiontype,abutmentandsuprastructurematerialandthe typeofprostheticsuprastructureaffecttheperi-implant softandhardtissues[7]. Dependingontheconfigurationofthebonydefect, Schwarzetal. distinguishedbetweenanintraosseous classIdefectandasupra-alveolarclassIIdefectinthe crestalimplantinsertionarea[5]. Spiekermann charac- terizedthetypeofboneresorptionintohorizontal(class I),key-shaped(classII),funnel-andgap-like(classIIIa, b)aswellashorizontal-circular(classIV)forms[9]. However,itisnotpossibletoconcludeprogressionand prognosiscriteriafromtheseclassifications. Onamicroscopicandmolecularlevel,strikingdiffe- rencesbetweenperi-impla nttissueandintactperi- odontiumcanbedetermined(Table1).Duetothe reducedvascularizationandparallelorientationofthe collagenfibres,peri-implanttissuesaremoresusceptible forinflammatorydiseasethanperiodontaltissues.This phenomenoncanbeverifiedimmunohistochemically throughincreasedformationofinflammatoryinfiltrate, nitricoxide1/3,VEGF,lymphocytes,leukocytesandKi- 67[10].Besides,inanalogytoperiodontitisthelevelof matrix-metalloproteinases(MMP),suchasMMP-8,is increasedupto971%inperi-implantlesions.Thelatter canbeusedfordisgnosticpurposes[11-13]. Adifferentiationofperi-implantitistootherinflam- matoryperiodontalprocessescannotbemadeonthe basisofhumansalivabymarkerssuchasosteocalcin, tartrate-resistantacidphosphatase(TRAP),dickkopf- relatedprotein-1(DKK-1),osteoprotegerin(OPG)and cathepsinK(CatK)[9,14]. Etiologyandepidemiology Thereareseveralreportsontheprevalenceofmucositis andperi-implantitisthatdifferbetween5%and63.4%. Thisenormousrangeismainlybasedonvaryingstudy designsandpopulationsizeswithdifferentriskprofiles andstatisticprofiles[5,15-18]. Zitzmannetal. quantifiedtheincidenceofthedevel- opmentofperi-implantitisinpatientswithahistoryof periodontitisalmostsixtimeshigherthaninpatients withnohistoryofperiodontalinflammation[3].After 10years,10%to50%ofthedentalimplantsshowed signsofperi-implantitis[19,20].BasedontheConsensus ReportoftheSixthEuropeanWorkshopinPeriodontol- ogy, Lindhe&Meyle reportedanincidenceofmucositis ofupto80%andofperi-implantitisbetween28%and 56%[21]. However,theprevalenceofperi-implantdiseases,evalu- atedrecentlyby Mombellietal. ,revealedperi-implantitis in20%ofallimplantedpatientsandin10%ofallinserted implants.Althoughthispercentagehastobeinterpreted withcautionbecauseofthevariabilityoftheanalyzed studies[7],itunderlinesthefactthatboneremodeling processesoftenresultinmarginalbonelossduringthe firstweeksafterabutmentconnectionwhichcannotbe regardedasperi-implantitis.Thisledtotherecommenda- tiontotakearadiographafterinsertionofthesuprastruc- tureandtoconsideritasabasisforanyfutureassessment ofperi-implantboneloss. Frequently,aspectrumofpathogenicgermscanbede- tectedsuchas Prevotellaintermedia,Prevotellanigrescens, Streptococcusconstellatus,Aggregatibacteractinomycetem- comitans,Porphyromonasgingivalis,Treponemadenticola and Tannerellaforsythia [3,22]. Ramsetal. revealed71.7% Figure1 Peri-implantitiswithincreasedprobingdepth(12mm). Table1Comparisonofperi-implantmucosawithphysiologicalperiodontium[3,5] Peri-implantmucosaPhysiologicalperiodontium Desmosomesandhemidesmosomesofepitheliumandjunctionalepithelium(biologicalwidth)arelinkedwiththecontactsurface Directbone-to-implantcontactAnchoringsystemofrootcementum,alveolarboneanddesmodonticfibers Subepitheliallymorecollagenfibersandlessfibroblasts/vesselsSubepitheliallymorefibroblastsandvessels ParallelcollagenfibersinrelationtoimplantsurfaceDentogingival,dentoperiostal,circularandtransseptalfiberorientation Smeets etal.Head&FaceMedicine 2014, 10 :34 Page2of13 http://www.head-face-med.com/content/10/1/34 resistancetoatleastoneantimicrobialsubstanceinagroupof120patients[22].Peri-implantitisisapoly-microbialan-aerobicinfection[23].However,incontrasttoperiodontitis,peri-implantitislesionsharborbacteriathatarenotpartofthetypicalperiodontopathicmicrobiota.Inparticular,Staphylococcusaureusappearstoplayapredominantroleforthedevelopmentofaperi-implantitis.ThisbacteriumshowsanhighaffinitytotitaniumandhasaccordingtotheresultsofSalvietal.ahighpositive(80%)andnegative(90%)predictivevalue[24].Asanotherbeneficialcause,smoothimplantsurfacesincomparisontoroughsurfacescanacceleratetheperi-implantinflammation[10,17,25].RiskfactorsandpreventionImplantlossmayoccurasearlyimplantlossuptooneyearafterimplantinsertionanddelayedimplantlosswithatimeperiodofmorethanoneyearafterimplantinsertion[3].Thefollowingfactorsorcircumstanceshavebeenreportedasriskfactorsforthedevelopmentofperi-implantitis[5,6,16,26-33]:SmokingwithadditionalsignificantlyhigherriskofcomplicationsinthepresenceofanpositivecombinedIL-1genotypepolymorphism.Historyofperiodontitis.Lackofcomplianceandlimitedoralhygiene(includingmissingcheckups).Systemicdiseases(e.g.maladjusteddiabetesmellitus,cardiovasculardisease,immunosuppression).Iatrogeniccauses(e.g.cementitisSofttissuedefectsorpoor-qualitysofttissueattheareaofimplantation(e.g.lackofkeratinizedgingiva).Historyofoneormorefailuresofimplants.Studiesindicatesmokingasthegreatestidentifiableandmostoftencitedriskfactorforperi-implantdiseasefollowedbyahistoryofperiodontitis.Botharerelatedtohigherprevalencesofperi-implantitis[7].Thepresenceofperiodontitisorcigarettesmokingincreasedtheriskforperi-implantitisupto4.7-foldasreportedbyWallowyetal.[6].Moreover,smokinghasbeenshowntobeapredictorforimplantfailure[31].Inarecentmeta-analysissmokingincreasedtheannualrateofbonelossby0.16mm/yearandrepresentedthemainsystemicriskfactor[34].Theextentofosseointegrationaswellastheoralhygienearounddentalimplantswasfoundtobereducedamongsmokers[35].Itiscommonlyacceptedthattheoutcomeofalmostallintraoraltherapeuticpa-rametersarenegativelyaffectedbysmokingalthoughnotinallpreviousstudiesapositivecorrelationbetweenperi-implantitisandtobaccosmokingcouldbefound[36,37].Evidenceofpredictorsforimplantsuccesssuchasgenderoragecouldnotbefoundbutforthejawoftreatment(maxillaryversusmandibularimplants).InastudybyVervaekeetal.maxillaryimplantswereatasig-nificantlyhigherriskforperi-implantbonelosscom-paredtomandibularimplants[31].Boneaugmentedareascouldnotbedeterminedasriskfactorsforimplantfailureorincreasedperi-implantdisease[38].Acrossanobservationperiodof10yearsinagroupofpatientswithperiodontitis,thepreviouslyeliminatedbacterialstrainsofAggregatibacteractinomycetemcomi-tansPorphyromonasgingivaliscouldagainbede-tectedintheoralmucosa[3].Prevotellaintermediawas,however,continuouslyevident.Thisindicatesanichesurvivalofbacteriaaftertoothextractionwithrecur-renceofthesamemicrofloraafterashortperiodoftime.Inparticular,attentionshouldbepaidtotheremainingteethwithperiodontitisasapotentialsourceofinfec-tion.Therefore,thetypeofdentition(edentulousversuspartiallyedentulous)mayinfluencethecolonizationofperi-implanttissueswithperiodontalpathogens[38].Theimpactofkeratinizedgingivaarounddentalim-plantshasbeencontroversiallydiscussed,butmoststud-iesemphasizetheimportanceofanadequatezoneofkeratinizedtissuesurroundingimplants[39-41].Thesomayberegardedasthemostimport-antidentifiableiatrogenicriskfactorsinceitsfirstde-scriptionbyWilsonetal.in2009[42].Thelattergrouprevealedthatresidualdentalcementinagroupofpa-tientswithclinicalorradiographicsignsofperi-implantdiseasewaspresentin81%ofthesites.Afteritsremoval,clinicalsignswereabsentin74%oftheaffectedsites.Korschetal.foundthattheremovalofcementremnantsledtoadecreaseoftheinflammatoryresponsebyalmost60%[43].Linkeviziusetal.examinedthemanifestationofperi-implantitisinagroupofpatientswithpresentce-mentremnants.Inthosewhohadahistoryofperiodon-titis,peri-implantitiswasfoundin100%ofthepatients,whereascementremnantsinpatientswithnopreviousperiodontaldiseaseendedupin65%peri-implantitismanifestations[30].Anotherpreventivearrangementre-gardingantibacterialprecautionsareinternalconnec-tionswithinwardlocatedmicrogap,whichshouldbepreferred.[6].Peri-implantprobingisrecommendedtobecarriedoutcarefullywithaminimalprobingforce.However,theso-calledplatformswitch(abutmentislocatedhorizon-tallybetweenimplantandcrown)cancomplicateprob-ingand,thus,hidethetrueextensionofperi-implantitis[3,5,17,26,44].Nevertheless,studieshaveindicatedthatplatformswitchmightbeanimportantprotectivefactoragainstperi-implantdisease[45].Implantlosscanbedifferentiatedonthebasisofthefollowingadditionalfactors[3,5,6,46-49]:Overloadingoftheimplant,Faultsinmaterialandtechniques,etal.Head&FaceMedicinePage3of13http://www.head-face-med.com/content/10/1/34 Poorbonequalityattheimplantarea,Systemicdiseasesanddrugtherapies,whichinhibitbonemodulationsaccordingtoWolffslaw(bonedensityandstrengthincreasewithstress-andviceversa).Thus,implantsofmorethan10mmlengthinsquarethreaddesignshowhighersuccessratesthanshorterimplantlengthsorshapeswithoutthreadorbuttressthread[48,49].Alsoroughimplantsurfacesofmorethan2micronsseemtofeaturebetterosseointegrationthansmooth(microns)ormoderatesurfaces(1microns)[17].Developmentofstrengthsinthetemporomandibularjointofmorethan1300Newtonmayshifttheimplantsinthefirstfewmonthsofhealingupto100micronsbypresenceofsagittalforcesactingfromanaverageof50Newton[46].Theseaveragereferenceforcesevenin-creaseto87Newtonwhenarticulationanglesupto60°inhorizontalaxis.Inadditiontopatienttrainingsessionsforoptimaloralhygiene,preventivestrategiessuchasprofessionaltoothandimplantcleaningaswellasindividuallycontinuousperi-implantexaminations(probingstatus)shouldbeconsideredinordertopreventperi-implantdiseases(Table2)[6].Attentionhastobepaid,inparticular,tothereductionoftheabove-mentionedriskfactorssuchasheavysmokingordiabetesmellitus.Aspartofaholistictherapy,so-calledreferencepa-rameters(hourzero)andclearlydeterminedcontrolprocedureshavetobeassessedwithadequatedocu-mentation.Radiographsshouldbetakenpre-,intra-andpostoperativelyinordertogetinformationabouttheimplantationsiteinwhichperi-implantinflamma-tionwillbedetectableasbrighteningzonesindicatingincreasedboneresorption[6].Preventionofperi-implantdiseasestartswithasuf-ficientandstructuredplanningincludingindividualevaluationandminimizationofriskfactors(smoking,compliance,oralhygiene,periodontaldisease,systemicdiseases),establishmentofoptimalsoftandhardtissueconditions,thechoiceofthecorrectimplantdesignfollowedbyamaximallyatraumaticapproachandregularclinicalexaminationswithaperiodontalprob-ingstatus.TherapyThetreatmentofperi-implantinfectionscomprisescon-servative(non-surgical)andsurgicalapproaches.De-pendingontheseverityoftheperi-implantdisease(mucositis,moderateorsevereperi-implantitis)anon-surgicaltherapyalonemightbesufficientorastep-wiseapproachwithanon-surgicaltherapyfollowedbyasur-gicaltreatmentmaybenecessary.TherapyofmucositisOneofthemainaimsofperi-implanttherapyistode-toxifythecontaminatedimplantsurface.Inthepresenceofperi-implantmucositis,non-surgicalmethodsareap-propriateandsufficientfordetoxification.Theseincludemechanicalimplantcleaningwithtitaniumorplastic-curettes,ultrasonicsorairpolishing.Moreover,photo-dynamictherapyaswellaslocalantisepticmedication(chlorhexidinglukonate,hydrogenperoxide,sodiumper-carbonate,povidone-iodine)maysupporttheantimicro-bialtherapy.IntworandomizedclinicaltrialsHeitz-Mayfieldetal.andHallströmetal.werenotabletoproveanybenefitsinreductionofpocketdepth,plaqueindexorpurulencywhenadjuvantantimicrobialtherapy(chlorhexidineandazithromycine)wasusedinadditiontomechanicalther-apyonly[50,51].Reductionsofthebleedingindexwereexplainedbythegeneralimprovementoforalhygienewithreferencetothepotentialimportanceofguidelinesandtreatmentprotocols[50-52].Theestablishmentofanadequateoralhygieneshould,therefore,beconsid-eredaskeyissueofthepreventionofperi-implantinfec-tions.Besides,amaintenanceprogramwithregularevaluationoftheperi-implantprobingdepths,support-iveprofessionalimplantcleaningandoralhygienetrain-ingshouldbeintegralpartofeverypost-operativecareafterimplantinsertion[2,6].Therapyofperi-implantitisMostofthepublishedstrategiesforperi-implantitistherapyaremainlybasedonthetreatmentsusedforteethwithperiodontitis.Thereasonisthatthewayofbacterialcolonizationofdentalandimplantsurfacesfol-lowsimilarprinciples,anditiscommonlyacceptedthatthemicrobialbiofilmplaysananalogousroleinthede-velopmentofperi-implantinflammation[53].Forthe Table2Numbersofcheck-ups(cu)annuallyfordifferentpatientcollectivescu=1cu=2cu�3OralhygieneandhygienicabilityoftheimplantwellmiddlebadSmokingstatus/inhistoryinpresencePeriodontitis,mucositis(withhistory)//inpresenceOtherriskfactors//e.g.systemicdiseases,historyofannon-successfulimplantinsertionetal.Head&FaceMedicinePage4of13http://www.head-face-med.com/content/10/1/34 treatmentofperi-implantitis,bothconservative(non- surgival)aswellassurgicaltherapiescanbeapplied. Thereby,thesurgicaltreatmentscanbedoneusing resectiveorregenerativeapproaches[54-59]. Conservativetherapy Inadditiontomedicationandmanualtreatment(e.g. withcurettes,ultrasonicandairpolishingsystems)in- novativetechniquessuchaslaser-supportedandphoto- dynamictherapymethodsarerecentlydescribedas conservativetherapyoptions. Manualtreatment Basicmanualtreatmentcanbeprovidedbyteflon-, carbon-,plastic-andtitaniumcurettes(Figure2). Duetothefactthattherapywithconventionalcurettes isabletomodifytheimplantsurfaceandcanroughen thesurface,ithasbeenrecommendedthatthematerial ofthetipshouldbesofterthantitanium[60,61].Itis possibletoreducebleedingonprobingscoresbyclean- ingwithpiezoelectricscalersaswellaswithhandinstru- ments,andnodifferenceshavebeenfoundbetween thesemethodsconcerningreductionofbleedingon probing,plaqueindexandprobingdepthsafteratleast 6months[62,63]. Astotheabove-mentionedmethods,theefficacyof ultrasoniccurettageseemstounderlytheuseofairpol- ishingsystems(Figure3)[5,62,64-68]. Persson etal.and Renvertetal. experiencedsignificantlylowernumbersof bacteriawithpartialreductionofplaqueandbleeding scoresaftermechanicalcurettage,while Schwarzetal. reported30%-40%lessresidualbiofilmareasbyusing ultrasonicmethods[5,63,66].Dependingonthesurface topographyoftheimplants, Louropoulouetal. recom- menddifferenttherapeuticmethods(Table3). Theresultsofairpolishingsystemsaredependingon theusedmediumandaresignificantlybetterinthefol- lowingorder:hydroxylapatite/tricalciumphosphate� hydroxylapatite�glycine�titaniumdioxide�waterand air(controlgroup)�phosphoricacid[64]. Anabrasiveairpolishingmediumcanmodifythesur- faceofimplants.Afterairpowdertreatmentcellattach- mentandcellviabilitystillshowedsufficientlevels,but cellresponsewasdecreasedcomparedwithsterilesur- faces[64,65,67].Theextentofre-osseointegrationofti- taniumimplantsafterairpolishingtherapyhasbeen reportedbetween39%and46%withincreasedclinical implantattachmentandpocketdepthreduction[65]. Theoccurrenceofbleedingonprobing,oneofthequali- tativeparametersinthepresenceofaperi-implantitis, couldbesignificantlyreduced[67]. Drugtherapy Therearenumerousinvitroandinvivostudiesontheap- plicationofmedicamentsaspartofthetreatmentofmu- cositisandperi-implantitis.However,duetodifferencesin thedesignofallstudies,comparisonofthesestudiesisdif- ficult.Thefollowingtherapiescanbedistinguished:
Antisepticrinsesinrelationtodifferentparameters.
Applicationofsystemicandlocallydelivered antibioticsinrelationtopocketdepthordifferent parameters. Inareviewby Javedetal., summarizingninestudies, systemicandlocalantibioticapplications(e.g.tetracycline, doxycycline,amoxicillin,met ronidazole,minoxicycline hydrochloride,ciprofloxaci n,sulfonamides+trimetho- prim)ledtosignificantreductionsofpocketdepthsin aperiodbetweenoneandsixyears[69]. Mouraetal. noticedthesameforresorbabledoxicyclinereleasing nanospheresinlocalappl icationoveraperiodof 15months[70]. Leonhardtetal. noticedanoverall Figure2 Conservativetherapy – exampleoftheuseofa carbonecurette. Figure3 Conservativetherapy – detoxificationusinganair polishingdevicewithglycinpowder. Smeets etal.Head&FaceMedicine 2014, 10 :34 Page5of13 http://www.head-face-med.com/content/10/1/34 successrateof58%whentreatingperi-implantitiswithsurgicaldebridementandtheuseofvariousantibioticsandcombinationsofthem(includingclindamycin,amoxicillin+metronidazole,tetracycline,ciprofloxa-cin)[71].Astasov-Frauenhofferetal.wereabletoprovecompletegrowth-inhibitingeffectsofamoxicillinandmetronidazoleStreptococcussanguinisPorphyromonasgingivalisandFusobacterumnucleatumapartfromeachother,butthecombinationwasfoundtobemoreefficientthanmetro-nidazolealone[72].Comparinglocalantibiotictherapywithphotodynamictherapy,Bassettietal.presentednodifferencesinreductionofpocketdepthsorreductionofthenumberofbacteriaintheperiodontalpockets[73].Grapefruitjuice,knownasantioxidant,hadonlyabac-teriostaticeffectagainstStreptococcusaureus[74].Butishastobeconsideredthatdependingonthetype,bacteriademonstratedifferenthighresistancesagainstantibiotics(Table4).Submucosalbiofilmspecimenswereculturedfrompatientswithperi-implantitisandafterinvitrotestingforsusceptibilityespeciallythecombinationofamoxicillinandmetronidazoleshowedsignificantlowerresistances(6.7%)[22].Applicationofchlorhexidineresultedinthereductionofpocketdepths,ahigherimplantadhesionandgeneralweakeningofinflammationmeasuredbytheleveloftheinflammatorymarkersIL-1beta,VEGFandPGE-2invariousstudies[75-77].Comparedtominocyclinemicrosphereapplicationrepeatedeverythreemonths[78],thetreatmentwith1%chlorhexidinegelresultedinsignificantlylessreducedpocketdepthsafter12months.Concerningtissueengineering,Lanetal.demonstratedacontinuousrelease-kineticofmetronidazolefor30daysusingaPoly--Caprolacton/Alginat-ring[79].Houetal.incorporatedfluorouracilintocylindricalpoly-caprolactone-implantsofdifferentdiameters[80].Localorsystemicantibioticsareanadditionaltherapyoption.Incombinationwithotherconservativeorsurgi-caltreatmentsitresultsinmoreefficientreductionsofclinicalperi-implantitissymptoms[81].Justadministra-tionofantibioticsisnotreatmentoption.LasertherapyBymeansofabactericidemodeofaction,CO,Diode-,Er:YAG-(erbium-doped:yttrium-aluminandEr,Cr:YSGG-(erbium,chromium-doped:yttrium-scandium-gallium-garnet)lasersareusedinthetreatmentofperi-implantdiseaseswithincreasingfrequency.Min-imalabsorptionandreverberationsmustbeensuredwiththepurposetoprotectimplantandtissue.Er:YAGandEr,Cr:YAGwithawavelengthof3micronscanreducebio-filmsupto90%butincontrasttomostmechanicalther-apiesanybiologicalcompatibilitiesandcellstimulatorypropertiescantbere-induced[5,82,83].Treatmentwitha308nmexcimerlaser,however,ledmainlyandeffi-cientlytosatisfactoryresultsinananaerobicbacteriaspectrum[84].Incomparisontomechanicalmethods(plasticcurettes),treatmentswithanEr:YAGlaserledtosignificantlybetterresultsintermsofbleedingatperi-implantitis.However,bothmethodsshowednosignificantdifferencesinchangesofpocketdepths,clinicalattachmentlevel,plaqueindexandgingivalrecessions,althoughinbothgroupstheseparameterswereimproved[85].Perssonetal.examinedtheeffectivenessofEr:YAGla-serscomparedtoanairpolishingsysteminarandom-izedclinicaltrialwith42patientsover6months[86].Exceptfordifferentreducingeffectsonspecificbacteriastrainsafteronemonth(Er:YAG:Fusobacteriumnuclea-tum;airpolishingsystem:PseudomonasaeruginosaStaphylococcusaureusandPeptostreptococcusanaerobiustherewerenolongterm-reducingeffectsshownafter6months.InarecentstudyMailoaetal.showedthatlasertherapyresultedinsimilarreductionsofprobingdepthswhencomparedtootherdecontaminationmethods[87].Althoughthereisonlyfewdataincom-parisontomanualandsurgicaltherapy,lasertherapyas Table3Qualitativeeffectiveness(x:yes/o:no)ofdifferentcleaningmethodsdependingonimplantsurface[68]SmoothsurfaceSandblastedandacid-etchedsurface(SLA)PlasmasprayedsurfaceRubbercapoooMetaliccurette,rotatingtitaniumbrushoxxPlasticcuretteoooUltrasonicsystemswithmetalictipsx(polished)UltrasonicsystemswithplastictipsoxxAirpolishingxxx Table4AntibioticresistanceofPrevotellaintermediaPrevotellanigrescensStreptococcusconstellatus(n=120)[22]AntibioticResistanceClindamycin46,7%Amoxicillin39,2%Doxycycline25%Metronidazole21,7%Amoxicilin&metronidazol6,7%etal.Head&FaceMedicinePage6of13http://www.head-face-med.com/content/10/1/34 atreatmentoptionhastobeconsideredasanadjunct. Furtherstudiesareneededtoevaluatetheprofitoflaser therapyinperi-implantitistreatment. Photodynamictherapy Photodynamictherapygeneratesreactiveoxygenspecies bymultiplicitywithhelpofahigh-energysingle-frequency light(e.g.diodelasers)incombinationwithphotosen- sitizers(e.g.toluidineblue).Inawavelengthrangeof580 to1400nmandtoluidineblue-concentrationsbetween10 and50ug/ml,photodynamictherapygeneratesbactericide effectsagainstaerobicandanaerobicbacteria(suchas Aggregatibacteractinomycetemcomitans,Porphyromonas gingivalis,Prevotellaintermedia,Streptococcusmutans, Enterococcusfaecalis )[5,88,89].Theonlyprospectiveran- domizedclinicaltrailby Bassetietal. covered12months offollow-up.Aftermanualdebridementbytitaniumcu- rettesandglycineairpowdertreatmenthalfofthepatients receivedadjunctivephotodynamictherapyandtheother halfreceivedminocyclinemicrospheresintoimplant pockets.After12months,thenumberofperiopathogenic bacteriaandlevelofIL-1  decreasedsignificantlyinboth groupswithoutsignificantdifferencesbetweenthem[73]. Inastudyby Deppeetal. regardingtotheeffectivenessof phototherapyonamoderateandsevereperi-implantitis, bothclinicalattachmentandbleedingindexweresignifi- cantlyreducedsuggestingthatseverecasesstillresultedin boneresorption[90]. Asarecommendation,photodynamictherapyhastobe consideredasanadditionaltreatmentoption.Duetothe factthatitisarelativelynewapproach,thedataisrare andtherearenolong-term-studiesavailable.Further evaluationsandprospectiveclinicaltrialsareneededfor evaluation. Surgicaltherapy Thesurgicaltherapycombinestheconceptsofthe alreadymentionednon-surgicaltherapywiththoseof resectiveand/orregenerativeprocedures.Theindication fortheappropriatetreatmentstrategyhasbeendemon- stratedinpatientstudiesleadingtothedevelopmentof the “ cumulativeinterceptivesupportivetherapy(CIST) ” concept[91-93].In2004itwasmodifiedandcalled AKUT-conceptby Langetal. (Table5)[93].Thebasis ofthisconceptisaregularrecalloftheimplantedpa- tientandrepeatedassessmentofplaque,bleeding,sup- puration,pocketsandradiologicalevidenceofboneloss. Afurthercommonlyacceptedconceptby Zitzmann etal. isreferredtosystematicperiodontitistherapy.Du- ringtheinitialphaseoralhygienicconditionshavetobe improvedandmechanicalcleaningandlocalantiinfective treatmentsareapplied,ifnecessary.Ifnon-surgicaltreat- mentfails,surgicalinterventionwithopendebridement andresectiveorregenerativetherapyisrecommended[3]. Theconceptof Schmage followstheCIST-protocolbutrec- ommendsalwaysmechanicalandlocaldisinfectivetreat- mentsinstageAandB.Interventionshouldbeperformed ifprobingdepthsexceed5mmorareprogressiveaswellas underoccurrenceoflocali nflammationsigns[94]. Resectivetherapy Inanalogytoperiodontitis,resectivesurgeryhasbeen showntobeeffectiveinreductionofBOP,probingdepths andclinicalsignsofinflammation.Thebasicprinciples includetheeliminationtheperiimplantosseousdefect usingostectomyandosteoplastyaswellasbacterialde- contamination(Figures4and5).Additionally,smooth- eningandpolishingofthesupracrestalimplantsurface (implantoplasty)maybeapplied. Serinoetal. showedthatinpatientswithactiveperi- implantdiseasesurgicalpocketeliminationandbonere- contouringincombinationwithplaquecontrolbefore andaftersurgeryrepresentsaneffectivetreatment.Two yearsafteropenreductionofinflammatedperi-implant softtissueandosseoussurgery48%ofthepatientshad nosignsofperi-implantitisand77%ofthepatientshad Table5AKUT-protocolby Langetal. [93] StageResultTherapy Pocketdepth(PD) 3mm,noplaqueor bleeding Notherapy APD3mm,plaqueand/ orbleedingonprobing Mechanicallycleaning,polishing, oralhygienicinstructions BPD4-5mm,radiologically noboneloss Mechanicallycleaning,polishing, oralhygienicinstructionspluslocal antiinfectivetherapy(e.g.CHX) CPD�5mm,radiologically boneloss2mm Mechanicallycleaning,polishing, microbiologicaltest,localand systemicantiinfectivetherapy DPD�5mm,radiologically boneloss�2mm Resectiveorregenerativesurgery Figure4 Peri-implantitiswithgranulationtissue. Smeets etal.Head&FaceMedicine 2014, 10 :34 Page7of13 http://www.head-face-med.com/content/10/1/34 noimplantswithpocketdepths
6mmwithbleeding and/orsuppuration[56]. Inaradiographicstudywith3yearsfollow-up, Romeo etal. showedthatthemarginalbonelossafterresective surgerywithimplantoplastywassignificantlylower thanafterresectivetherapyonly[55].Thegroupwith additionalimplantoplasty alsohadsignificantlylower probingpocketdepths,probingattachmentlevelsand modifiedbleedingindi cesafter24months[54]. Adjuvantimplantsurfacedecontaminationwithanti- microbialsubstancesledtoaninitiallylessanaerobic bacteriacontamination,butdidnotimprovetheclinical outcome[75]. Resectivesurgicaltherapyforperi-implantitisisarec- ommendabletherapyoption.Ostectomyandosteoplasty combinedwithimplantoplastyrepresentaneffective therapytoreduceorevenstopperi-implantitisprogres- sion.Nevertheless,duetotheincreasedpostoperative recessions,thisprocedureisnotsuitableforeverysitu- ation,especiallyinhighlyestheticsensitiveareas. Regenerativeapproaches Resectivesurgicaltherapymayre sultinre-osseointegration inonlyminorsuperficialdefects.Fromfunctional,esthetic andlong-time-survivalpointofviews,fullregenerationand re-osseointegrationisaspired.Inanimalmodelsitwaspos- sibletoregenerateexperimentallyinduceddefectsusing variousgraftmaterialsand/orresorbablemembranesfol- lowingtheprinciplesofguidedboneregeneration(GBR) (Figures6,7,8,9and10). Inastudyby Hürzeleretal. in1997indogs,there wasnosignificantdifferencebetweentheapplication ofmembranesonlyversusmembranesincombination Figure5 Peri-implantation1weekafterresectivetherapy. Figure6 Regenerativetherapie – defectafterdegranulation. Figure7 Regenerativetherapie – defectfillwithaxenograft material(BioOss®,Geistlich,Switzerland). Figure8 Regenerativetherapie – membraneapplication (BioGide®,Geistlich,Switzerland). Smeets etal.Head&FaceMedicine 2014, 10 :34 Page8of13 http://www.head-face-med.com/content/10/1/34 withbonegrafts(caninedemineralizedfreeze-dried boneorhydroxyapatite)intermsofboneregeneration. However,thecombinationresultedinagreateramountof re-osseointegration[95].Nostatisticaldifferencesinre- osseointegrationcouldbedemonstratedaftertreatment withGBRusingae-PTFEreinforcedmembranecom- paredtositeswithoutthismembrane[96].Thetreat- mentresultedin60 – 80%bonefillofthebonydefect, buttheabsoluteamountofre-osseointegrationwas small(between0.1-0.6mm). Incontrasttodebridementwithsurfacedecontamin- ation,inmostofallanimalstudiesregenerativemethods werereportedasmoreefficient.Ingeneral,GBRalone andbonefillalonehavebeenshowntobemoreeffective thandebridementaloneregardingtoboneregeneration andre-osseointegration.Theresultsofstudiesusinga combinationofmembranesandbonegraftmaterials weresuperiortothoseusingmembranesorbonegrafts aloneandtendtogivethebestresults,However,thereis ahighvariabilityintheamountofbonefillduetodiffer- entinvestigationprotocolsandmeasurements[97-99] andnotinallstudiestherewasabenefitforthesetreat- mentscomparedtodebridementalone[100-102].The roleofsubmergedhealinginperi-implantitishasnotbeen solvedclearly.Although Singhetal. demonstratedin1993 greaterboneregenerationandre-osseointegrationdu- ringsubmergedhealing, Grunderetal. foundnodiffe- rencesbetweeneitherhealingmethod[103,104]. Additionally,therearenumerousstudiesregardingthe treatmentofperi-implantitisinhumansunderregenera- tiveaspects.Inaretrospectivestudyof Lagervalletal. with150patients(382implants)themostwidelyused operativeinterventionwastheperiodontalflapwithos- teoplasty(47%),followedbytheuseofbonereplacement materials(20%).Acumulativesuccessrateof69%was recordedforbothprocedures,whichwassignificantly lowerinpatientswithriskfactorssuchassmoking,peri- odontaldiseaseandpoororalhygiene[29].Regardingto a “ regenerative ” approach,autologous,allogenicandxeno- genicbonereplacementmaterialsareoftenusedforaug- mentationinbonedefectsusedwithorwithoutcollagen membrane.Allogenicandxenogenicgraftsmaybealmost equivalenttoautogenousmaterial[105-107]. Schwarz etal. treated22patientsrandomlywithaccessflapsurgery andtheapplicationofnanocrystallinehydroxyapatitein contrasttoxenogenicbonematerialwithcollagen membrane.Nosignificantdifferencesweredetermined betweenthegroups,but6monthsaftersurgeryboth treatmentsresultedinclinicallyrelevantreductionsin probingdepthsandgainsofclinicalattachmentlevel [108]. Roos-Jansåkeretal. cametosimilarresultsusing acorallinexenograft[19].Inanotherstudybovine- derivedxenogenicmaterialwascomparedwithau- togenousboneasfillingmaterialforinfracrestaldefects. Thexenograftprovidedradiologicallymorebonefill anddecreasesinpocketdepths,whilebleedingonprob- ingandsuppurationwereobservedatbothprocedures [109].Inaprospectivestudy,36casesofperi-implant bonelossweretreatedafterlocaldisinfectionandre- movalofgranulationtissuewitha1:1mixtureofautolo- gousboneandaxenogenicbonegraft.Theresultwasa meanradiologicallyreductionof3.5mmfrom5.1mm oneyearaftertreatmentwithanaveragereductionof probingdepthsof4mm[59].Inarecentprospectivecase seriesacombinedresectiveandregenerativeapproachin- cludingabovinebonemineralandacollagenmembrane infracrestallyandimplantoplastysupracrestallyshoweda significantperi-implantprobingdepthreductionandan increasedradiographicdefectfillafter12monthsoffollow- up[110].Inanotherstudyof Schwarzetal. defectcleaning witheitherEr:YAGlaserorplasticcurettes/cottonpellets withsalinewascombinedwithr egenerativesurgicalproce- dures(xenogenicbonesubstituteandcollagenmembrane). Figure9 Preoperativeradiographoftheperi-implantdefect. Figure10 Postoperativeradiograph12monthsafter regenerativetherapy. Smeets etal.Head&FaceMedicine 2014, 10 :34 Page9of13 http://www.head-face-med.com/content/10/1/34 Thereby,theclinicaloutcomedidnotdifferaccordingtothechosenmethodofsurfacedebridement[111].Inpurposeofboneregenerationvariousapproacheshavebeendescribedwithvarioussuccessrates.Thereisatendencythatxenograftmaterialsincombinationwitharesorbablemembranesmighthaveadvantagesintermsofre-osseointegration.Nevertheless,becauseofthelackofprospectiverandomizedclinicalstudiesthereisnoevidentdataconcerningthelong-timestabilityofsuchdefectfillingsDuetothelackofprospectiverandomizedlong-termfollow-upstudieslotsofapproachesbutnoidealperi-implantitistherapyhavebeendescribed.Therearemanystudieswithdifferentstudydesignsindifferentpopulationswithdifferentmaterialsused,butthesam-plesizesareoftentoosmallandthefollow-upistooshort.Therefore,preventionisthemostimportantin-strumentbasedonappropriatetreatmentplanning,anatraumaticapproachforimplantinsertionandcontinu-ouscheck-upintervalswithprofessionalteethandim-plantcleaning.Aboveall,attentionshouldbepaidtoriskfactorssuchassmokingandactiveorpreviousperi-odontitis.Innon-surgicaltherapy,combinationsofmechanicalcleaningwithcurettesandairpolishingsys-temsarerecommendable.Adjuvantantisepticrinsesandlocalorsystemicantibioticsareeffectiveforshort-termbacteriaeradication;laserandphotodynamictherapyareadditionaltreatmentoptions.However,resultsforlong-termbenefitsforthesemethodsaremissing.Surgicaltherapywithresectiveandaugmentativepro-cedurescompletesthetreatmentoptions.Resectivesur-gerycanbeusedinordertoeliminateperi-implantdefects,tore-establishhygienicabilitiesandtoreduceorevenstopperi-implantitisprogression.Regenerativeap-proaches,e.g.withxenograftmaterialsincombinationwitharesorbablemembranes,arepromising.Theresultsofbonereplacementmaterialsandautologousbonegraftsmightbeconsideredasnearlyequivalentalthoughlong-termstudiesarestillmissingandonlyfewstudieswithautologousbonematerialexist.AgradedsystematictreatmentplanningaccordingtotheCISTprotocolcanberecommended.Theperi-implantitistherapy,actually,isasumofap-proachesleadingtoanindividualtherapyregimecon-cerningmultifactorialetiology,treatmentoptionsandstudyresults.ConsentWritteninformedconsentwasobtainedfromthepa-tientsforthepublicationofthisreportandanyaccom-panyingimages.CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.TheresearchhasbeencarriedoutequallybyRS,AHandOJ.JMSandMHsupervisedandcorrectedthemanuscript.CHprovidedandeditedthephotographs.Allauthorsreadandapprovedthefinalmanuscript.AuthordetailsDepartmentofOralandMaxillofacialSurgery,UniversityMedicalCenterHamburg-Eppendorf,Martinistr.52,20246Hamburg,Germany.Practice,Schumacherstrasse14,52062Aachen,Germany.DepartmentofConservativeDentistry,PeriodontologyandPreventiveDentistry,UniversityHospitalAachen,Pauwelsstr.30,52074Aachen,Germany.Received:9June2014Accepted:15August2014Published:3September20141.SimonisP,DufourT,TenenbaumH:Long-termimplantsurvivalandsuccess:a10-16-yearfollow-upofnon-submergeddentalimplants.ClinOralImplantsRes2.KhammissaRAG,FellerL,MeyerovR,LemmerJ:Peri-implantmucositisandperi-implantitis:clinicalandhistopathologicalcharacteristicsandtreat-3.ZitzmannNU,WalterC,BerglundhT:Ätiologie,DiagnostikundTherapiederPeriimplantitiseineÜbersicht.DeutscheZahnärztlicheZeitschrift4.WilsonV:Aninsightintoperi-implantitis:asystematicliteraturereview.PrimDentJ5.SchwarzF,SahmN,BeckerJ:AktuelleAspektezurTherapieperiimplantärerEntzündungen.PeriimplantäreEntzündungen.Entzündungen.fachgebiete/oralchirurgie/problemmanagement/periimplantaere-7.MombelliA,MullerN,CioncaN:Theepidemiologyofperi-implantitis.ClinOralImplantsRes(Suppl6):678.HammerleCH,BraggerU,BurginW,LangNP:TheeffectofsubcrestalplacementofthepolishedsurfaceofITIimplantsonmarginalsoftandhardtissues.ClinOralImplantsRes9.SpiekermannH:Stuttgart:Thieme;1984.10.DegidiM,ArteseL,PiattelliA,ScaranoA,ShibliJA,PiccirilliM,PerrottiV,IezziG:Histologicalandimmunohistochemicalevaluationoftheperi-implantsofttissuesaroundmachinedandacid-etchedtitaniumhealingabutments:aprospectiverandomisedstudy.ClinOralInvestig11.XuL,YuZ,LeeH-M,WolffMS,GolubLM,SorsaT,KuulaH:ofcollagenase-2fromgingivalcrevicularfluidandperi-implantsulcularfluidinperiodontitisandperi-implantitispatients:pilotstudy.OdontolScand12.SorsaT,TervahartialaT,LeppilahtiJ,HernandezM,GamonalJ,TuomainenAM,LauhioA,PussinenPJ,MäntyläP:Collagenase-2(MMP-8)asapoint-of-carebiomarkerinperiodontitisandcardiovasculardiseases.Therapeuticresponsetonon-antimicrobialpropertiesoftetracyclines.PharmacolRes13.SorsaT,HernándezM,LeppilahtiJ,MunjalS,NetuschilL,MäntyläP:DetectionofgingivalcrevicularfluidMMP-8levelswithdifferentlaboratoryandchair-sidemethods.OralDis14.HallJ,BritseAO,JemtT,FribergB:Acontrolledclinicalexploratorystudyongeneticmarkersforperi-implantitis.EurJOralImplantol2011,371382.15.AtiehMA,AlsabeehaNHM,FaggionCM,DuncanWJ:Thefrequencyofperi-implantdiseases:asystematicreviewandmeta-analysis.JPeriodontol16.CharyevaO,AltynbekovK,ZhartybaevR,SabdanalievA:Long-termdentalimplantsuccessandsurvivalaclinicalstudyafteranobservationperiodupto6years.SwedDentJImplantatoberflächen-StandderTechnik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