www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
REVIEW
ARTICLE
Osteonecrosis
of
the
jaws:
a
review
and
update
in
etiology
and
treatment
夽
Guilherme
H.
Ribeiro
a,
Emanuely
S.
Chrun
a,
Kamile
L.
Dutra
a,
Filipe
I.
Daniel
b,
Liliane
J.
Grando
b,∗aUniversidadeFederaldeSantaCatarina(UFSC),ProgramadePós-graduac¸ãoemOdontologia,Florianópolis,SC,Brazil bUniversidadeFederaldeSantaCatarina(UFSC),HospitalUniversitárioPolydoroErnanideSãoThiago,Ambulatóriode
Estomatologia,Florianópolis,SC,Brazil
Received25September2016;accepted31May2017 Availableonline24June2017
KEYWORDS Osteoradionecrosis; Osteonecrosis; Therapy; Review Abstract
Introduction:Osteonecrosis of the jaws can result either from radiation, used in radio-therapy for treatment of malignanttumors, ormedications used for boneremodeling and anti-angiogenesis suchasbisphosphonates.These conditionscanbeassociated with trigger-ingfactorssuchasinfection,traumaanddecreasedvascularity.Themanagementofpatients withosteonecrosisofthejawsrequirescautionsincethereisnospecifictreatmentthatacts iso-latedanddecidedly.However,differenttreatmentmodalitiescanbeemployedinanassociated mannertocontrolandstabilizelesions.
Objective:Toreviewthecurrentknowledgeonetiologyandmanagementofosteonecrosisof thejaws,bothradio-inducedandmedication-related,aimingtoimproveknowledgeof profes-sionalsseekingtoimprovethequalityoflifeoftheirpatients.
Methods:Literaturereview inPubMedaswellasmanual searchfor relevantpublicationsin referencelistofselectedarticles.ArticlesinEnglishrangingfrom1983to2017,whichassessed osteonecrosisofthejawsasmainobjective,wereselectedandanalyzed.
Results:Infections,traumasanddecreasedvascularityhaveatriggeringroleforosteonecrosis ofthe jaws.Prophylactic and/or stabilizing measures canbe employed inassociation with therapeuticmodalitiestoproperlymanageosteonecrosisofthejawspatients.
Conclusion:Selectinganappropriatetherapyforosteonecrosisofthejawsmanagementbased oncurrentliteratureisarationaldecisionthatcanhelpleadtoapropertreatmentplan. © 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
夽 Pleasecitethisarticleas:RibeiroGH,ChrunES,DutraKL,DanielFI,GrandoLJ.Osteonecrosisofthejaws:areviewandupdatein
etiologyandtreatment.BrazJOtorhinolaryngol.2018;84:102---8.
∗Correspondingauthor.
E-mail:lilianejgrando@gmail.com(L.J.Grando).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial. https://doi.org/10.1016/j.bjorl.2017.05.008
1808-8694/©2017Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
PALAVRAS-CHAVE
Osteorradionecrose; Osteonecrose; Terapia; Revisão
Osteonecrosedamandíbula:revisãoeatualizac¸ãoemetiologiaetratamento
Resumo
Introduc¸ão: Aosteonecrosedamandíbulapoderesultardaradiac¸ãoutilizadanaradioterapia paratratamentodetumoresmalignosoumedicamentosutilizadospararemodelac¸ãoósseae antiangiogênese,comoosbifosfonatos.Essascondic¸õespodemserassociadasafatores desen-cadeantes,comoinfecc¸ão,traumaediminuic¸ãodavascularizac¸ão.Otratamentodepacientes comosteonecrosemandibularequercautela,poisnãoexisteumtratamentoespecíficoqueatue demaneiraisoladaedecisiva.Noentanto,diferentesmodalidadesdetratamentopodemser empregadasdeformaassociadaparacontrolareestabilizarlesões.
Objetivo: Revisarosconhecimentosatuaissobreaetiologiaeotratamentodaosteonecroseda mandíbula,tantoinduzidosporradiac¸ãoquantorelacionadosàmedicac¸ão,visandomelhoraro conhecimentodosprofissionaisbuscandoaqualidadedevidadeseuspacientes.
Método: Revisão de literatura na base de dados PubMed, bem como pesquisa manual de publicac¸ões relevantes na lista de referência de artigos selecionados. Foram selecionados e analisados artigos em inglês publicados de 1983 a2017, que avaliaram osteonecrose da mandíbulacomoseuprincipalobjetivo.
Resultados: Infecc¸ões, traumas e diminuic¸ão davascularizac¸ão são fatores desencadeantes daosteonecrosedamandíbula.Medidasprofiláticase/ouestabilizadoraspodemserutilizadas emassociac¸ãocommodalidadesterapêuticasparaotratamentoadequadodepacientescom osteonecrosemandibular.
Conclusão:Selecionarumaterapiaapropriadaparaotratamentodeosteonecrosedamandíbula combasenaliteraturaatualéumadecisãoracionalquepodeajudaraestabeleceraumplano detratamentoadequado.
© 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Osteonecrosiswasfirstdescribedasaconsequenceof ioniz-ingradiation usedinthetreatment ofmalignanttumors.1
Later, osteonecrosis was discovered as a result of the continueduseofsomemedicationsfromtheclassof bisphos-phonates(BPs)1,2andmorerecentlyasaresultoftheuseof
drugsthatactonboneremodelingandanti-angiogenesis.3
Radio-inducedosteonecrosisiscalledosteoradionecrosis (ORN),andisdefinedasexposureofnecroticbonethat per-sistsforover threemonthsinapreviously irradiatedarea receivingionizingradiation above50Gyandis notcaused bytumorrecurrence.4
In turn, medication-related osteonecrosis of the jaws (MRONJ) is alsodefined clinicallyby exposure of necrotic bone, but the following characteristics should also be present:(a)patientshouldbeintreatmentorhave under-gonepriortreatmentwithantiresorptiveorantiangiogenic agents;(b)presenceofexposedbone,orbonethatcanbe probedviaintraandextraoralfistulawhichpersistsformore thaneightweeks;and(c)nohistoryofradiotherapy(RT)or metastaticlesionevidentinjaws.2However,clinical
mani-festationswithoutboneexposure,suchasdeepperiodontal pocket, loose tooth, trismus, hypoesthesia/numbness of lower lip (Vincent’s symptom) and non-odontogenic pain couldbeeitherclassifiedasnon-exposedMRONJ.3
Dentistsshouldbeabletoactinprevention,early diag-nosis and rehabilitation of patients with osteonecrosis of the jaw (ONJ). Therefore, the present article aims to
presentaconcise reviewregardingetiologyandtreatment ofONJ,bothradio-induced aswell asmedication-related, toimproveprofessionalsseekingimprovedqualityoflifeof theirpatientsonthebasisofthecurrentknowledge.
Objective
and
methods
A PubMed search using ‘‘osteoradionecrosis’’, ‘‘osteonecrosis’’, ‘‘therapy’’, ‘‘MRONJ’’, ‘‘jaws’’ as a term was made from May 1983 to April 2017. Additional papers were included based upon the original literature searchandreferencesintheselectedpapers.Papersabout laboratory research, case series, as well as reviews of literaturewerealsoincluded.
Etiopathogenesis
Osteoradionecrosis
DelanianandLefaix(2004)postulatedthationizingradiation possiblyleadstotissueinjurybycreatingalocal inflamma-toryprocess,inadditiontocausingthedeathofosteoblasts andpreventingtherepopulationofcellularcomponentsof bone.Theseeventsresultinafibroticbonewithareduced numberofvascularizedandviablecells.5Thisweakened
tis-sue hasa high potential risk for developing ORN and the occurrence of minimum chemical or physical trauma can trigger a late inflammatory response that leads totissue necrosis.4
Table1 AvailableBP’sclassmedicines.
Generation Composition Medicines 1st Non-nitrogenous Etidronate Clodronate 2nd Nitrogenous Pamidronate Alendronate 3rd Olpadronate Ibandronate 4th Rizendronate Zolendronate Source:Russel(2007).12
However, ORN may occur spontaneously without local traumaorinfection.Thehighradiationrates,whichpatients withheadandneckcanceraresubmittedto,aresufficient for the occurrenceof bone necrosis.1 Thorn etal. (2000)
reported23cases(29%)ofspontaneousORN,mostly asymp-tomatic,withonlyaslightdehiscenceoftheoralmucosa. Thus,theauthorsemphasized theimportanceof identify-ingearly-stage ORN and listed other risk factors such as: traumabyprosthesis,surgeryandextraction,3%,14%and 55%ofcases,respectively.6Moreover,dentalimplantsmust
be considered a potential risk factor for development of ORN, since the irradiated areaundergoes serious cellular andtissuedamage.Theconditionofthehostforreceiving animplantisnotonlyunfavorablebutalsocontraindicates suchinvasiveprocedures.1,7
Medication-relatedosteonecrosisofthejaws
The known drug participants in etiology of ONJ are antiresorptiveandantiangiogenicagentsusedinantitumor therapyand for treatingin variousdiseases.8 These drugs
causeadecreaseinboneremodelingcapability.
Bone remodeling is a physiological process of balance between deposition (osteoblastic activity) and resorption (osteoclasticactivity)ofthistissue.9Apathologicalprocess
setsinwhentheimbalancebetweentheseactivitiesoccur. Clinical signs and symptoms include bone necrosis, pain, dysgeusia,bucosinusal communication,foulodor,lockjaw, extraoralfistula,andothers.2
Antiresorptivemedications
Bisphosphonates
BPsaresyntheticanalogdrugsofinorganicpyrophosphate, a compound naturally present in organisms, serving as a physiologicalregulatorofcalcificationandboneresorption inhibitor.10
Fourgenerations ofBPsareavailable(Table1).11 From
onegenerationtoanotherthepotentialofinhibitingbone resorptionevidently increases. The amine grouping expo-nentially increases the potency of the drug,12 leading to
suppressionofboneregenerationwithantiangiogenic prop-ertiesandactivatorofT-lymphocytes,resultinginadirect tumoricidaleffect.8
These drugs accumulate in the bone matrix and are slowlyreleasedoverprolongedperiodsoftime,witha half-lifeofapproximately10years.13Therefore,theyposerisks
todevelopmentof MRONJ,whichisdose-dependent.Even
afterdiscontinuationofthedrug,riskofdevelopingMRONJ remains.2
InhibitorRANK-L
RANK-Lisoneoftheosteoclastactivatingproteins.Inhibitor RANK-L, in turn,is an antibody preventingthe binding of RANK-Ltoitsnuclearreceptor,therebynotallowing osteo-clastic activity. This inhibition of osteoclast hinders bone regeneration,increasesbone densityandreducesfracture risk.Drugswiththisfunction,likeDenosumab,areusedin the treatment of bone disorderssuch asosteoporosis and bone metastasis of malignant tumors.Nonetheless, these medicinesalsoplayanimportantroleinthepathogenesisof ONJ.14
MRONJ occurs as an adverse effect dependent on the administered dose of Denosumabas well as BP. However, Denosumabactiontimeis shorterthanBPs,makingit fea-sible to treat patients in occurrence of side effects such asONJ.3The mechanismsofaction aredifferentbetween
thedrugs,butitseffectsonbonetissuearesimilarandthe specificcharacteristicsofDenosumabonMRONJarenotyet clear.
Antiangiogenicagents
The cellular receptor of vascular endothelial growth fac-tor (VEGF) playsan important rolein cancer progression, however, it can be controlled by anti-angiogenicdrugs.15
These medications, suchas Bevacisumab,have antiangio-genic properties favorable totumor restraint, but on the otherhand,cancompromisethemicrovesselintegrity.This may lead to injury of bone tissue in addition to preven-tingtheactionofVEGF,whichmayhavedirectdeleterious effectsoncelldifferentiationandbonefunctionandthereby causeafailureintherepairofaphysiologicaltrauma, induc-ingMRONJ.3
FewcasesofONJrelatedtoBevacisumabaredescribedin theliterature;patientswithearlydiagnosisofONJreceived conservativetreatmentorsurgeryandhadarelativelyquick responsetotreatment,butthereisinsufficientinformation toenableacomparisonwithONJrelatedtoBPs.16
Dentalmanagementofpatientwithdevelopingriskof ONJ
The natural history of ONJ can evolve in different ways. Lesionscandevelopspontaneouslyorafteradental proce-dure,isolatedorrecurrentepisodesmayoccur,scarringcan occurinafewmonthsormaynotbeevidencedinaperiod longer thannine months.It is believed thatpatients who spontaneouslydevelopONJaremorelikelytohave recurr-encescomparedtopatientswhodevelopONJafteradental procedure.17
The AAOMS reported rates of 0.5% risk of developing MRONJ afterdentalextractionproceduresinpatientswho were administered oral BPs, and rates of 1.6---14.8% risk in patients whouseintravenous BPs.The risk of develop-ing MRONJ after other dental procedures such as dental implants,endodontictreatmentandperiodontalprocedures iscomparabletotheriskassociatedwithtoothextraction.2
Someauthorsindicatedimplantplacementinpatientswho were administered oral or intravenous BPs as not safe, despitetherelativelylowriskforMRONJ.18
Table2 TreatmentsapproachesofORNusedinthelast10years.
Authors/date n Successfultreatments Follow-up(months)
D’Souzaetal.(2007)24 23 3HBO 30(minimum)
3HBO,S 5S
ColettiandOrd(2008)27 19 5S 18(mean)
Alametal.(2009)23 33 8ATB,HBO,S 1---61
22ATB,S
Leeetal.(2009)28 13 2S 6---361
3HBO,S
Ohetal.(2009)29 114 4ATB,HBO 12---382
7ATB,S 18ATB,NSD 25ATB,HBO,NSD 34ATB,HBO,S
Delanianetal.(2011)30 54 16ATB,PENTOCLO 2---36
Hampsonetal.(2012)31 411 243HBO 96
Mückeetal.(2013)32 94 44ATB,S 12(minimum)
Niewaldetal.(2013)33 11 1HBO 1---147
2NSD 5S
Lyonsetal.(2014)34 85 3ATB,PENTO,DNS 3---60
4ATB,PENTOCLO 14ATB,PENTO 35ATB,PENTO,S
Porcaroetal.(2015)35 01 1ATB,NSD 12
Raguseetal.(2016)36 149 2ATB 27---54
6S 30NSD
ATB,antibiotictherapy;S,surgery;NSD,non-surgicaldebridement;PENTO,pentoxifyllineandtocopherol;PENTOCLO,pentoxifylline, tocoferolandclodronate;HBO,hyperbaricoxygenation.
Placement of implants in patients undergoing treat-mentwithBPslessthanfiveyearsmaybeconsideredsafe for development of MRONJ, however, osseointegration of implants may be affected by therapy with antiresorptive agents.19
Regarding risk of developing ORN after implant place-ment,Tanaka etal.(2013)sought toassessthe impactof irradiation of head and neck rehabilitation therapy with dental implants, stressing that risk factors are potential and multidimensional for the failure of implants in these patients.Thebenefitsofusingimplant-supportedprosthesis ratherthantheuseofconventionaldenturesmustoutweigh therisks,andyettheplanningmustbemeticulous.20
ThevariouspossibilitiesoftheetiologyofONJtaperina mainaggravatingfactorandtheplacementoftheseimplants fitsasanaggravatingfactor.The bestwaystoreduce the risk of ONJ are: (1)professional knowledge about overall healthof theirpatients;(2)strictcriteriafordental eval-uationsin patients eligible for head and neckRT, aswell asinpatientswithantiresorptiveandantiangiogenicagents treatment;(3)eliminatealldentalinfectionsandimprove oralhealthtopreventfutureinvasivetherapies.Forpatients alreadybeingtreatedwiththesemedicationsorwhohave alreadyreceivedionizingradiation inheadand neck,itis suggestedthatbonemanipulationbeavoidedandcombined withcloseclinicalmonitoring.21
TheliteraturecitesdevelopmentofORNwithinthefirst 12monthspost-RT,22 6months23 or immediatelyafterfirst
month of RT. However, later occurrence of ORN is also evidencedafter36monthsofirradiation.24
Risk-patientidentificationisthefirststepinpreventing thisdisease.Themedicalhistorytakenbydentistsdidnot alwayscoverthedataonhistoryofcancersandRT,and pro-fessionalsdidnothaveaspecificmanagementprotocolfor patientswithONJ.25Itisaremindertohealthprofessionals
thatimportantattitudescan providebetterqualityoflife forpatientsandevenpreventthedevelopmentofONJ.
Treatments
Osteoradionecrosis
Treatmentsincludecombinationtherapies,including antibi-otics and corticosteroids, Hiperbaric oxigenation (HBO), bone debridement and surgical resection followed by reconstruction.1,25,26
Anotheralternativeconsistsof tworelateddrugs, pen-toxifylline and tocopherol (PENTO), but, used separately, they are unable to reverse radio-induced fibrosis. This association becomesmorepowerful whenassociated with clodronate(PENTOCLO).26 Differentmanagements of ORN
arelistedinTable2.
Table 3shows in detailpossible approaches and treat-mentsofORNdescribedintheliteratureinlastelevenyears. In this data comparison, it can be seen the vast major-ityof studies include antibiotictherapy (ATB) alone or in
Table3 Drugtherapydescribedby Delanianetal.(2005)associatedwithconservativetreatmentofheadandneckcancer patientspreviouslyirradiated.
Beforestartingtreatmentwith PENTOCLO---from2to4weeks
Afterstartingtreatmentwith PENTOCLO---atleast6months
Ciprofloxacin 1g 1×/day Pentoxifylline 800mg 1×/day
Amoxicillin+clavulanate 2g 1×/day Tocopherol 1.000IU 1×/day
Fluconazole 50mg 1×/day Clodronate 1.600mg 5days/week
Metilprednisolone 16mg 1×/day Ciprofloxacin 1g/day 2days/week Metilprednisolone 16mg/day 2days/week Source:Delanianetal.(2005).37
combinationwithanothertherapeuticmodality,beingmore efficientwhenassociatedwithbonesurgeryordebridement. HBO,whichresultsin anincreasein tissueoxygentension andimprovescollagen synthesis,angiogenesisand epithe-lization,wasevaluatedin9trialsandproducedcontrasting results,with varying success rates between 0% and100%. Oneofthelatesttreatmentoptions,PENTOCLO,isa well-establishedprotocolsince2005andtheresultsareamazing, ascanbeseeninthestudyofDelanianetal.(2011),where all54patientsevaluatedreachedtotal regressionoftheir lesionsinupto36monthsafterdiagnosisofinjury.29The
lat-terseemstobeaverypromisingstepintheORNapproach, breaking new ground in management of the disease and allowingitsremission.
Ohetal.(2009)28 hadnosuccess(0%)inthetreatment
ofORNinpatientstreatedwithsurgeryalone,whileColetti andOrd(2008)37reached18%successandLeeetal.(2009)27
reached67%success.
Lee et al. (2009)27 treated ORN with HBO associated
with surgery, resolving 65% of cases while Alam et al. (2009)22 resolved91%. D’Souzaet al.(2007)23 stated that
HBOassociatedwithsurgerydoesnotshowstatistically dif-ferentresultsfromresultsachievedbyHBOasanisolated therapy.
Oneofthemost modernapproaches inmanagementof ORNincludesPENTO.Curewasachievedin73%ofpatients whousethedrugcombinationforlong-termand69% short-term26 andaftersix years,Delanianetal. (2011)claimed
to have achieved 100% success in treatment of ORN with PENTOCLO.29
Medication-relatedosteonecrosisofthejaws
Treatment regimensshouldincludeeducationandconsent of patient, routine oral hygiene care to reduce the risk of caries and periodontal disease, use of antibiotics and antimicrobials,regularvisitstodentistforreevaluationand
Table4 TreatmentsapproachesofMRONJusedinthelast10years.
Authors/date n Successfultreatments Follow-up(months)
Thumbigere-Mathetal. (2009)38
26 3ATB,HBO,S 6(minimum)
9ATB,S
Curietal.(2011)39 25 20ATB,S,PRP 36(mean)
Ripamontietal.(2011)40 10 10ATB,NSD,O
3 8
Agrilloetal.(2012)41 94 57ATB,NSD,O
3 6.5(mean)
Freibergeretal.(2012)42 25 7ATB,S 24
13ATB,S,HBO
Martinsetal.(2012)43 22 1ATB 6
3ATB,S
12ATB,S,PRP,LLLT
Schubertetal.(2012)44 54 48S 9
Meleaetal.(2014)45 38 1ATB,NSD 6(minimum)
2S 7ATB 16NSD
Vescovietal.(2014)46 192 17NSD 6---50
78S
Ruganietal.(2015)47 38 2ATB,S 12
6ATB 17ATB,NSD
Klingelhöfferetal.(2016)48 76 22ATB,S 6---24
Minamisakoetal.(2016)49 01 1ATB,NSD,LLLT,PDT 12
ATB,antibiotic therapy;S,surgery; NSD, non-surgicaldebridement; O3, ozonated oil;PENTO, pentoxifyllineand tocopherol; HBO,
preservationofclinicalpicturewitheliminationofnegative habits(smokinganddrinking).36
Therearedifferentapproachesdentistscanchoose, con-ducting each case with its own peculiarities in order to stabilizethepathologicalpictureofthepatientifcomplete remissionis notpossible, which aredescribedin detailin
Table4.ATBisconsensusin95%ofreviewedstudiesandis moreeffectivewhencombinedwithothersmeasures, espe-ciallybonedebridementand/orsurgery.
UnlikeORN,protocolwithPENTOassociatedwithATBdid notshowgoodresults(17%)inhealingofMRONJ.Incontrast, platelet-richplasmawasalsoagoodtreatmentalternative, succeeding in over 80% of cases. Low-level laser therapy (LLLT),inturn,waspresentedasamoreefficientapproach whencombinedwithATBandbonedebridement.HBO had contrastingresultswithvaryingsuccessratesbetween25% and90%.
RegardingMRONJ,itisknownthebettertheoral condi-tionofpatienttobesubjectedtotreatmentwithBPs,the morefavorable theprognosis. However,oftenthe patient andattendingphysicianwereunawareofthepossibleoral repercussionsthatthisdrugclasscancause.Andonceinjury isinstalled,dentist shouldmakeuseof themeasures rec-ommendedby AAOMSto trytosolve thedisease, suchas ATB,mouthwash with0.12% chlorhexidinegluconate,pain management, bone debridement when needed and infec-tionprevention,aswellaskeepinguptodate onthenew effectivetreatmentalternativesthatareemerging.2
Surgery is the treatment option more adopted for MRONJ.32,43 Regardless of whether conservative or
extended, it is usually associated with ATB.42,47,50 With
avarying successrateamongcasesreportedin literature, average treatment success withconservative surgery and extensive surgery are 53% and 67%, respectively. Thus, VELscope system is reported as a promising surgical tool which allows identifying the margin between viable and necroticbonethroughbonefluorescence.48
Thumbigere-Mathetal.(2009)50treatedMRONJwithHBO
associated withATB and extensive surgery solving 25% of cases,whereasFreibergeretal.(2012)41solved52%ofcases
associatingHBOexclusivelywithATB.
Therapyperformedwithplatelet-richplasmaassociated withATBhasshowngoodresultsinpatientswhoare under-going surgical procedures, achieving a cure rate higher than 80%.38,42 Unusual buteffective, ozonetherapy had a
60.6% and 100% success rate in solving 57 and 10 cases, respectively.39
Anothertherapythathasbroughtgoodresultsin combat-ingMRONJis LLLT.However,theiraction ismosteffective whencombinedwithothertherapeuticmodalitiesaswellas surgery, platelet-richplasmaand ATB42 or associatedwith
non-surgicaldebridement,ATBandPDT.49
Conclusion
ThedecisionofthebestapproachformanagementofONJ patients,initsdifferentmodalities,shouldalwaysbe per-formedbyamultidisciplinaryteam,consideringthegeneral stateofthepatientandtherisks/benefitsratio.Infections, traumaanddecreasedvascularityhaveatriggeringroleboth forMRONJandORN,whicharechallengingdiseaseswithno specifictreatmentthatactsaloneandresolutely.
Differenttherapeuticmodalitiescanbeemployedinan associatedmanner, suchasprophylacticand/or stabilizing measures.Furthermore,continuousupdatedknowledgeof thedentalprofessionalisessentialforthemanagementof thesepatients.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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