Fluoride toothpastes for preventing dental caries in children and adolescents

104 Pages·2010·0.84 MB·English

Fluoride toothpastes for preventing dental caries in children
and adolescents (Review)
Marinho VCC, HigginsJPT, Logan S, Sheiham A
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2009,Issue1
http://www.thecochranelibrary.com
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review)
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Analysis1.3.Comparison1Fluoridetoothpasteversusplacebo,Outcome3D(M)FSincrement(SMD)-nearestto3years
(70trials). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Analysis1.4.Comparison1Fluoridetoothpasteversusplacebo,Outcome4D(M)FTincrement(SMD)-nearestto3years
(53trials). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Analysis1.5.Comparison1Fluoridetoothpasteversusplacebo,Outcome5Developingoneormorenewcaries(6trials). 99
Analysis1.6.Comparison1Fluoridetoothpasteversusplacebo,Outcome6Acquiringextrinsictoothstaining(5trials). 100
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) i
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Fluoride toothpastes for preventing dental caries in children
and adolescents
ValeriaCCMarinho1,JulianPTHiggins2,StuartLogan3,AubreySheiham4
1Clinical andDiagnostic OralSciences,Institute ofDentistry, BartsandTheLondon SchoolofMedicine andDentistry,London,
UK.2MRCBiostatisticsUnit,Cambridge,UK.3InstituteofHealthandSocialCareResearch,PeninsulaMedicalSchool,Universities
ofExeter&Plymouth,Exeter,UK.4DepartmentofEpidemiologyandPublicHealth,UniversityCollegeLondonMedicalSchool,
London,UK
Contact address: Valeria CC Marinho, Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London
School of Medicine and Dentistry, Queen Mary, University of London, Turner Street, Whitechapel, London, E1 2AD, UK.
[email protected]@qmul.ac.uk.
Editorialgroup:CochraneOralHealthGroup.
Publicationstatusanddate:Edited(nochangetoconclusions),publishedinIssue1,2009.
Reviewcontentassessedasup-to-date: 12September2002.
Citation: Marinho VCC, Higgins JPT, Logan S, Sheiham A. Fluoride toothpastes for preventing dental caries in children and
adolescents.CochraneDatabaseofSystematicReviews2003,Issue1.Art.No.:CD002278.DOI:10.1002/14651858.CD002278.
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Fluoridetoothpasteshavebeenwidelyusedforover3decadesandremainabenchmarkinterventionforthepreventionofdentalcaries.
Objectives
Todeterminetheeffectivenessandsafetyoffluoridetoothpastesinthepreventionofcariesinchildrenandtoexaminefactorspotentially
modifyingtheireffect.
Searchstrategy
We searched the Cochrane Oral Health Group’s Trials Register (May 2000), the Cochrane Central Register of Controlled Trials
(CENTRAL)(TheCochraneLibrary2000,Issue2),MEDLINE(1966toJanuary2000),plusseveralotherdatabases.Wehandsearched
journals,referencelistsofarticlesandcontactedselectedauthorsandmanufacturers.
Selectioncriteria
Randomised or quasi-randomised controlled trials with blind outcome assessment, comparing fluoride toothpaste with placebo in
childrenupto16yearsduringatleast1year.Themainoutcomewascariesincrementmeasuredbythechangeindecayed,missing
andfilledtoothsurfaces(D(M)FS).
Datacollectionandanalysis
Inclusiondecisions,qualityassessmentanddataextractionwereduplicatedinarandomsampleofonethirdofstudies,andconsensus
achievedbydiscussionorathirdparty.Authorswerecontactedformissingdata.Theprimarymeasureofeffectwasthepreventedfraction
(PF)thatisthedifferenceincariesincrementsbetweenthetreatmentandcontrolgroupsexpressedasapercentageoftheincrementin
thecontrolgroup.Random-effectsmeta-analyseswereperformedwheredatacouldbepooled.Potentialsourcesofheterogeneitywere
examinedinrandom-effectsmetaregressionanalyses.
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 1
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Seventy-fourstudieswereincluded.Forthe70thatcontributeddataformeta-analysis(involving42,300children)theD(M)FSpooled
PFwas24% (95% confidence interval (CI), 21to28%; P<0.0001). This meansthat1.6childrenneedtobrushwith afluoride
toothpaste(ratherthananon-fluoridetoothpaste)topreventoneD(M)FSinpopulationswithcariesincrementof2.6D(M)FSper
year.Inpopulationswithcariesincrementof1.1D(M)FSperyear,3.7childrenwillneedtouseafluoridetoothpastetoavoidone
D(M)FS.Therewasclearheterogeneity,confirmedstatistically(P<0.0001).Theeffectoffluoridetoothpasteincreasedwithhigher
baselinelevelsofD(M)FS,higherfluorideconcentration,higherfrequencyofuse,andsupervisedbrushing,butwasnotinfluencedby
exposuretowaterfluoridation.Thereislittleinformationconcerningthedeciduousdentitionoradverseeffects(fluorosis).
Authors’conclusions
Supportedbymorethanhalfacenturyofresearch,thebenefitsoffluoridetoothpastesarefirmlyestablished.Takentogether,thetrials
areofrelativelyhighquality,andprovideclearevidencethatfluoridetoothpastesareefficaciousinpreventingcaries.
PLAIN LANGUAGE SUMMARY
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents
Childrenwhobrushtheirteethatleastonceadaywithatoothpastethatcontainsfluoridewillhavelesstoothdecay.
Tooth decay (dental caries)is painful, expensive to treatand can sometimes leadto serious damage toteeth.Fluoride isa mineral
thatpreventstoothdecay.Thereviewoftrialsfoundthatchildrenaged5to16yearswhousedafluoridatedtoothpaste hadfewer
decayed,missingandfilledpermanentteethafterthreeyears(regardlessofwhethertheirdrinkingwaterwasfluoridated).Twiceaday
useincreasesthebenefit.Noconclusioncouldbereachedabouttheriskthatusingfluoridetoothpastescouldmottleteeth(fluorosis),
aneffectofchronicingestionofexcessiveamountsoffluoridewhenchildrenareyoung.
BACKGROUND
hasincreasedoverrecentdecades.Bydefinition,theterm’topically
Thepreventionofdentalcariesinchildrenandadolescentsisgen-
appliedfluoride’isusedtodescribethosedeliverysystemswhich
erallyregardedasapriorityfordentalservicesandconsideredmore
providefluoridetoexposedsurfacesofthedentition,atelevated
cost-effectivethanitstreatment(Burt1998).Fluoridetherapyhas
concentrations,foralocalprotectiveeffect,andarethereforenot
beenthecentrepieceofcaries-preventivestrategiessincetheintro-
intendedforingestion. Themostimportantanti-carieseffectof
ductionofwaterfluoridationschemesover5decadesago(Murray
fluorideisconsideredtoresultfromitsactiononthetooth/plaque
1991).Thesewereintroduced whencarieswashighlyprevalent
interface,throughpromotionofremineralizationofearlycariesle-
andsevere,andwhenevenmodestpreventionactivitiesledtocon-
sionsandbyreducingtoothenamelsolubility(Featherstone1988).
siderablereductionsindiseaselevels.Inthelast20years,withthe
Fluoride-containing toothpastes (dentifrices), mouthrinses, gels
substantial decline in dental cariesratesin many westerncoun-
andvarnishesarethemodalitiesmostcommonlyusedatpresent,
tries,anincreaseindentalfluorosislevelsinsomecountries,and
either alone or in combination. Various products are marketed
intensive researchonthemechanismofaction offluoride high-
indifferentcountriesandavarietyofcariespreventiveprograms
lighting theprimary importance of its topical effect,greater at-
based on these have been implemented. Toothpastes are by far
tention has been paid to the appropriate use of other fluoride-
themostwidespreadformoffluorideusage(Murray1991a;Ripa
basedinterventions(Glass1982;Featherstone1988;Ripa1991;
1991)andalthoughthereasonsforthedeclineintheprevalence
O’Mullane1994;Marthaler1996;Featherstone1999).
ofdentalcariesinchildrenfromdifferentcountriescontinuesto
Theuseoftopicallyappliedfluorideproductsinparticular,which bedebated(Nadanovsky1995;Krasse1996;Marthaler1996;de
aremuchmoreconcentratedthanthefluorideindrinkingwater, Liefde 1998), it has been mainly attributed to the gradual in-
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 2
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
creasein, andregular homeuse of fluoride intoothpaste (Glass as it is convenient and culturally approved, widespread, and it
1982;Ripa1991;Rolla1991;Marthaler1994;O’Mullane1994; iscommonly linkedtothedecline incariesprevalenceinmany
Bratthall1996). countries.Thereisanargumentthattheeffectoffluoridetooth-
pastesareunderestimatedin’shortterm’clinicaltrialsoftwoto
Atthesametime, thelowercariesprevalencenow prevailingin
threeyearsduration, as theseare used throughout life.In addi-
manycountries andthewidespreadavailability offluoride from
tion,itisarguedthattheuseoffluoridetoothpasteinfluoridated
multiplesourceshaveraisedthequestionofwhethertopicallyap-
areasoffersmoreprotectionthaneitheralone.However,concern
pliedfluoridesarestilleffectiveinreducingcaries,andsafe,mainly
hasbeenexpressedthatdentalfluorosis,enameldefectscausedby
intermsofthepotentialriskoffluorosis(mottledenamel).This
youngchildrenchronicallyingestingexcessiveamountsoffluoride
isparticularlyimportantasnearlyallchildpopulationsindevel-
duringtheperiodoftoothformation(uptotheageof6years),is
opedcountriesareexposedtosomesourceoffluoride(notablyin
increasinginbothfluoridatedandnon-fluoridatedcommunities,
toothpaste),andadverseeffectsmayberare(suchasacutefluoride
andtheearlyuseoffluoridetoothpastesbyyoungchildrenmaybe
toxicity)ormoresubtle(suchasmilddentalfluorosis).
animportantriskfactor(Horowitz1992;Stookey1994;Ellwood
Theevidenceontheeffectoftopicalfluoridesonthepreventionof 1995).
dentalcariesinchildrenhasbeenextensivelyreviewedinanumber Theusualconcentrationoffluorideintoothpastesis1000/1100
oftraditionalnarrativereviews.Asmallnumberofreviewsfocusing partspermillion(ppmF);toothpasteswithhigher(1500ppmF)
ontheevaluationofspecifictopicalfluorideactiveagentswithin andlowerthanconventionalfluoridelevels(around500ppmF)
specificdeliverysystemshaveusedaquantitativemeta-analytical areavailableinmanycountries.Whiletheevidenceoftheeffec-
approachtosynthesisestudiesresults(Clark1985;Johnson1993; tivenessoflowfluoride-containing toothpastesinreducingden-
Helfenstein1994;Stamm1995;vanRijkom1998).However,a talcariesappearstobeconflicting,toothpastescontaininghigher
systematicquantitativeevaluationoftheavailableevidenceonthe concentrationsoffluorideconfergreaterprotectionagainstcaries
effectofthemainmodalitiesoftopicalfluorideshasneverbeen (Stephen1988;O’Mullane1997),butincreasetheriskoffluoro-
undertaken. sis, whichisrelatedtoboth,theamount ingested andthefluo-
rideconcentration.Chronicingestionoffluoridefromtoothpaste
Thisreviewisoneinaseriesofsystematicreviewsoftopicalfluo-
inchildreniscommon(Bentley1999;Rojas-Sanchez1999)and
rideinterventionsandassessestheeffectivenessoffluoridetooth-
despitethelargevariationintheamountswallowed,theyounger
pastesinthepreventionofdentalcariesinchildren.
childrenare,themorelikelytheyaretoswallowlargeramounts,
whichoftenrepresentasubstantialpartofthetotaldailyfluoride
intake and can be enough to cause fluorosis (Levy 1994; Lewis
Fluoridetoothpastes(dentifrices) 1996).Althoughtheamountoffluorideingestedbeyondwhich
fluorosismayoccurisnotknownaccurately,athresholdof0.05
Toothbrushing withfluoridetoothpasteisbyfarthemostcom-
to 0.07 mgF/kg body weight has been suggested (Burt 1992).
mon formof caries control in use today. The intensive promo-
A child-sized toothbrush covered with a full strip of toothpaste
tion of fluoride toothpastes by the oral healthcare industry has
holdsapproximately0.75to1.0goftoothpaste,andeachgram
beenamajorfactorintheirincreaseduse,and,inthedeveloped
offluoridetoothpaste,containsapproximately1.0mgoffluoride;
world, since the1980s, nearly allcommercially available tooth-
childrenaged lessthan6 yearsmay swallow an estimated 0.3 g
pasteformulationscontainfluoride.Variousfluoridecompounds
oftoothpasteperbrushing(0.3mgoffluoride)andcaninadver-
havebeen usedalone or combined in theformulations, includ-
tently swallow as much as 0.8 g (Levy 1994). As a result, it is
ingsodiumfluoride,sodiummonofluorophosphate,aminefluo-
generallyrecommendedthatchildrenunder6yearsofageshould
rideandstannousfluoride,and,accordingtoeachmanufacturer’s
besupervisedwhenbrushingtheirteeth,andthatnomorethan
specificationsthesemustbecompatiblewithotherbasicingredi-
apea-sizedamount, approximately 5mm, shouldbe used. The
ents,especiallyabrasivesystems(whichaccountforalmosthalfof
frequencyoftoothpasteuseandtherinsingmethodaftertooth-
theentiretoothpasteformulation).Fluoridetoothpastesmustbe
brushing wouldbe otherfactorsinfluencing theeffectivenessof
differentiatedfromfluorideprophylacticpastes,sincetheirfluo-
fluoridetoothpastes(andalsotheirsafety).Brushingtwiceaday
rideconcentrations,methodsandfrequenciesofapplicationdif-
or more, or rinsing less thoroughly, or not rinsing at all would
fer,aswellasamountsofabrasivesintheirformulation(abrasives
confergreatercariesreductionsthanbrushingonceadayorless,or
accountforalmosttheentirecontentofaprophylacticpaste).In
rinsingwithlargervolumesofwateraftertoothbrushing(Chesters
addition,althoughsometoothpastesareavailableinthetranslu-
1992;O’Mullane1997;Chestnutt1998;Ashley1999).Aformal
centformofgel,theyaredifferentfromfluoridegels,whichhave
investigation of these aspects should helpto clarify the optimal
higherfluoridelevels,noabrasivesandareappliedmuchlessfre-
level of fluoride toothpaste needed to achieve caries prevention
quently,usuallybyaprofessional.
whilelimitingobjectionableenamelfluorosis.
Consensusamongresearchersandpublichealthauthoritiesplaces
Althoughacutetoxicityisextremelyrare,youngchildrenarepar-
fluoridetoothpasteasthemethodofchoiceforpreventingcaries,
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 3
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ticularlyatrisk of ingesting toxic dosesof fluoride fromastan- orreportedfluoridesourcesotherthanthestudyoption.
dardtoothpastetubeof125g,generallycontaining1100ppmF
(4)Toexaminewhethertheeffectoffluoridetoothpasteisinflu-
(1.1mgF/gpaste).Astheprobabletoxicdose(PTD)isaround5
encedby fluoride concentration or application features, such as
mgF/kgbodyweight(Whitford1992),theaccidentalswallowing
frequencyofuse.
ofone-thirdofatoothpastetube(45g)ortwo-thirdsofit(90g)
ispotentiallylife-threateningfora1-year-old(10kg)or fora5
to6-year-old(20kg)respectively(Ellwood1998).Forthisreason
itisrecommendedthatafluoridetoothpastetubeshouldbekept METHODS
outofthereachofyoungchildren.
Morethan100clinicaltrialsconductedinmanyareasoftheworld
sincethe1940s,andsummarisedinseveralnarrativereviewssince
Criteriaforconsideringstudiesforthisreview
the1950s,haveinvestigatedthecaries-reducingeffectoffluoride
toothpastesinchildren.Inthelate1970s,theacceptanceofflu-
oridetoothpastesaseffectivecariesinhibitingagentshadbecome
sowellestablishedthatclinicaltrialsinmanydevelopedcountries
Typesofstudies
hadtobebenchmarkedagainststandardfluoridetoothpastes,as
Randomisedorquasi-randomisedcontrolledtrials(RCTs)usingor
itwasconsideredunethicaltowithdrawtheirbenefitfromastudy
indicatingblindoutcomeassessment,inwhichfluoridetoothpaste
group. Thus,theeffectivenessofnew formsand concentrations
iscomparedconcurrentlytoplacebotoothpasteduringatleast1
offluoridetoothpasteshasnotbeensoextensivelyinvestigatedin
year/schoolyear.
placebo-controlledtrialsinchildrenwiththelowerlevelsofdental
RCTs with open outcome assessment or no indication of blind
cariesprevalenceprevailinginmanycountries.
assessment, or lastinglessthan1year/schoolyear,orcontrolled
Inthelast20years,guidelinesforcariesclinicaltrialshavechanged
trials where random or quasi-random allocation is not used or
(FDI1982;CDT-ADA1988;ICW-CCT2002)inrecognition
indicatedwereexcluded.
ofthefactthatwiththedeclineincariesprevalenceandtheneed,
forethicalreasons,touseapositivecontrolinsteadofaplacebo
influoride toothpaste trials, differencesbetweentreatmentshad
Typesofparticipants
becomesmallerinbothabsoluteandpercentageterms.Inorder
to overcome this problemof small group differences, study de- Childrenoradolescentsaged16orlessatthestartofthestudy
signapproacheshavebeenmodified.Themostimportantgeneral (irrespectiveofinitiallevelofdentalcaries,backgroundexposure
strategieshavefocused onincreasing samplesize andpower,re- tofluorides,dentaltreatmentlevel,nationality,settingwherein-
ducingmeasurementerrorandconductingstudieswithhighrisk terventionisreceivedortimewhenitstarted).
subjects,mainlydefinedonthebasisofinitialcariesscores. Studies where participants were selected on the basis of special
Todate,therearetwopublishedmeta-analysesinvestigating the (generalororal)healthconditionswereexcluded.
comparative efficacy of the two commercially available fluoride
toothpastecompoundsusedmostcommonlynowadays:sodium
fluoride (NaF) and sodium monofluorophosphate (SMFP) ( Typesofinterventions
Johnson1993;Stamm1995),aquestionthatisnotaddressedin
Topicalfluorideintheformoftoothpastesonly,usinganyofthe
thepresentreview.Thereis,however,nosystematicquantitative
following fluoride agents combined or not in the formulation:
investigationassessingtheoveralleffectivenessandsafetyoffluo-
sodium fluoride (NaF), sodium monofluorophosphate (SMFP),
ridetoothpastesincomparisontoplaceboandexaminingformally
stannous fluoride (SnF2), acidulated phosphate fluoride (APF),
themainfactorsthatmayinfluencetheireffectiveness.
aminefluoride(AmF).Thesemaybeformulatedwithanycom-
patibleabrasivesystemandareconsideredatanyfluorideconcen-
tration(ppmF),frequencyofuse,amountordurationofapplica-
tion,andwithanytechniqueoftoothbrushingorpost-brushing
OBJECTIVES
procedure.Thecontrolgroupisplacebo(non-fluoridetoothpaste)
(1)Todeterminetheeffectivenessandsafetyoffluoridetoothpaste whichmakesthefollowingastherelevantcomparison: Fluoride
inpreventingdentalcariesinthechild/adolescentpopulation. toothpastecomparedwithplacebotoothpaste.
Studies where the intervention consisted of any other active
(2)Toexaminewhethertheeffectoffluoridetoothpasteisinflu-
agent(s)orcariespreventivemeasure(s)(e.g.chlorhexidineagent,
encedbytheinitiallevelofcariesseverity.
otherfluoride-basedprocedures,oralhygieneprocedures,sealants,
(3)Toexaminewhethertheeffectoffluoridetoothpasteisinflu- xylitolchewinggums,glassionomers)usedinadditiontofluoride
encedbythebackgroundexposuretofluorideinwater(orsalt), toothpastewereexcluded.
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 4
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Typesofoutcomemeasures 1997),andareavailableonrequest.Thesewereusedforthede-
velopment of a register of topical fluoride clinical trials for the
Theprimaryoutcomemeasureinthisreviewiscariesincrement,
systematic reviews, as the Cochrane Oral Health Group’s Trials
as measured by change from baseline in the decayed, (missing)
Registerwasnotyetdevelopedin1997/98.
andfilledsurface(D(M)FS)index,inallpermanentteetherupted
TheCochraneCentralRegisterofControlledTrials(CENTRAL)
atstartanderupting overthecourse of thestudy.Dental caries
(TheCochraneLibrary1997,Issue1),theCommunityofScience
is definedhere as being clinically and radiographically recorded
database(1998),whichincludedongoingtrialsfundedbytheNa-
at thedentine levelof diagnosis. (See Methods for the different
tionalInstituteofDentalResearch(NIDR),theSystemforInfor-
waysofreportingthedecayed,(missing)andfilledteethorsurfaces
mationonGreyLiteratureinEurope(SIGLE)database(1980to
(D(M)FT/S)scoresinclinicaltrialsofcariespreventives).
1997),andOLDMEDLINE(1963to1965)weresearchedusing
Thefollowingoutcomeswereconsideredrelevant:coronaldental
theterms’fluor’and’carie’truncated.(Greyliteraturesearchhad
cariesanddental fillings,inboththepermanentandthedecid-
alsobeencarriedoutbysearchingtheIndextoScientificandTech-
uousdentitions;toothloss;dentalpain/discomfort;specificside
nicalProceedings(ISTP)andDISSERTATIONABSTRACTS.)
effects(fluorosis,toothstaining/discolouration,oralallergicreac-
tions,adversesymptomssuchasnausea,vomiting);useofhealth
serviceresources(suchasvisitstodentalcareunits,lengthofden-
taltreatmenttime). From1999to2001
Studiesreportingonlyonplaque/gingivitis,calculus,dentinehy- ThestrategyincludedinAppendix2wasusedtosearchLILACS/
persensitivity or fluoride physiological outcome measures (fluo- BBOin1999(1982to1998),wherefree-textsubjectsearchterms
ride uptake by enamel or dentine, salivary secretion levels, etc) werecombinedwithamethodologicalfilterforRCTs.
wereexcluded. Asupplementaryandmorespecificsubjectsearchphrase(includ-
ing ’free-text’ and ’controlled vocabulary’ terms), refined exclu-
sively for this review, formulated around three concepts: tooth-
Searchmethodsforidentificationofstudies paste,fluorideandcaries,wasusedtosearchSilverplatterMED-
LINE (up to January 2000) without methodological filters (
Withacomprehensivesearch,weattemptedtoidentifyallrelevant
Appendix3).Thisstrategy wasadaptedtosearchtheCochrane
studiesirrespectiveoflanguage,from1965onwards.
OralHealthGroup’s TrialsRegister (uptoMay 2000), and has
alsobeenrunonCENTRAL(TheCochraneLibrary2000,Issue
2)todouble-check.
Electronicsearching
The metaRegister of Controlled Trials was searchedin October
2001forongoingRCTsusingtheterms’fluoride’and’caries’.
Upto1998
Relevant studies were identified (for the series of topical fluo- Referencesearching
ride reviews) by searching several databases from date of incep-
All eligible trials retrieved fromthe searches, meta-analyses and
tion: MEDLINE (1966 to 1997), EMBASE (1980 to 1997),
reviewarticleswerescannedforrelevantreferences.Reviewshad
SCISEARCH (1981 to 1997), SSCISEARCH (1981 to 1997),
beenidentifiedmainlybyaMEDLINEsearchstrategyspecifically
ISTP(1982to1997),BIOSIS(1982to1997),CINAHL(1982
carriedouttoprovideinformationonavailablesystematicreviews
to1997),ERIC(1966to1996),DISSERTATIONABSTRACTS
ormeta-analysesandonthescopeoftheliteratureonthetopic,
(1981to1997)andLILACS/BBO(1982to1997).
whentheCochraneDatabaseofSystematicReviews(CDSR),and
Two overlapping but complementary subject search phrases (
theDatabaseofAbstractsofReviewsofEffects(DARE)andNHS
Appendix 1)with very lowspecificity (buthigh sensitivity), us-
EconomicEvaluationDatabase(NHSEED),werealsosearched.
ing’free-text’and’controlledvocabulary’,wereformulatedwithin
Referencelistsofrelevantchaptersfrompreventivedentistrytext-
SilverplatterMEDLINEaroundtwomainconcepts,fluorideand
books ontopicallyappliedfluoride interventionswerealsocon-
caries,andcombinedwithallthreelevelsoftheCochraneOptimal
sulted.
SearchStrategyforRandomisedControlledTrials(RCTs).These
subject search phrases were customised for searching EMBASE
andtheotherdatabases.
Full-textsearching
RCT filters were also adapted to search EMBASE, BIOSIS,
SCISEARCH, DISSERTATION ABSTRACTS, and LILACS/ Prospectivehandsearchingofthosejournals(seven)identifiedas
BBO. All the strategies (subject search and methodological fil- havingthehighestyieldofeligibleRCTs/controlledclinicaltrials
ters)developedtosearcheachdatabasearefullydescribedinare- (CCTs)werecarriedout,fromJanuary1999untilJanuary2000:
portproducedfortheSystematicReviewsTrainingUnit(Marinho BritishDentalJournal,CariesResearch,CommunityDentistryand
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 5
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
OralEpidemiology,JournaloftheAmericanDentalAssociation,Jour- this was available in English or in languages known by the re-
nalofDentalResearch,JournalofPublicHealthDentistryandEuro- viewer)and/orkeywordsbyonereviewer,ValeriaMarinho(VM).
peanJournalofOralSciences.ThehandsearchofCommunityDen- Obviouslyirrelevantrecordswerediscardedandthefulltextofall
tistryandOralEpidemiologywasundertaken(1990toDecember remainingwereobtained.Recordswereconsideredirrelevantac-
1999), as this was the journal with the highest yield of eligible cordingtostudydesign/duration, participants,orinterventions/
reports. comparisons(ifitcouldbedeterminedthatthearticlewasnota
reportofarandomised/quasi-randomisedcontrolledtrial;orthe
trialwasoflessthan6to8monthsduration;orthetrialwasexclu-
Personalcontact sivelyinadults;orthetrialdidnotaddressafluoridetoothpaste
intervention;orthetrialcomparedfluoridetoothpasteexclusively
Searchingforunpublishedstudies(or’grey’literaturesuchastech-
tonotreatment,insteadoffluoride-freetoothpaste).
nicalreportsanddissertations,orstudiespublishedinlanguages
All potentially relevant reports identified when searching other
other than English which may not have been indexed to major
sources(referencelistsofrelevantstudies,reviewarticlesandbook
databases)startedbycontactingexpertsinthefieldofpreventive
chapters,journalhandsearch,personalcontact)werealsoobtained.
dentistry.Aletterwassenttotheauthor(s)ofeachincludedstudy
(Reportsthatmightbeidentifiedbycontactingmanufacturerswill
published during the last two decades in order to obtain infor-
beobtainedtofeatureinupdatesofthisreview.)
mationonpossibleunpublishedstudieseligibleforinclusion.All
Itwasconsideredessentialtoidentifyandcheckallreportsrelated
theauthorsofstudieswhohadbeencontactedinordertoclarify
tothesamestudy;incaseofanydiscrepancy,authorswerecon-
reportedinformationtoenableassessmentofeligibilityorobtain
tacted.
missingdatawerealsoaskedforunpublishedstudies.
Basedoninformation extractedmainlyfromincludedstudies,a
list of manufacturers of fluoride toothpastes was created for lo-
Selectionofstudies
catingunpublishedtrials.Letterstomanufacturersweresentout
bytheCochraneOralHealthGroup,inthehopethatcompanies With the inclusion criteria form previously prepared and pilot
mightbemoreresponsivetocontactfromtheeditorialbasethan tested,onereviewer(VM)assessedallstudiesforinclusioninthe
fromindividualreviewers.Ninefluoridetoothpastemanufacturers review,andasecondreviewer,JulianHiggins(JH),independently
werecontacted(October2000)andinformationonanyunpub- duplicatedtheprocessforasampleofthose(approximately30%).
lishedtrialsrequested:Colgate-Palmolive,Unilever/Gibbs,Gaba Inaddition,anystudythatcouldnotbeclassifiedbythefirstre-
AG,SmithklineBeecham,ProcterandGamble,Oral-B,Bristol- viewerwasindependentlyassessedbythesecond.Athirdreviewer
MyersCo,Warner-Lambert,Synthelabo. wasconsulted,StuartLogan(SL)orAubreySheiham(AS),tore-
solveanydisagreement.Itwasdecidedinadvancetoexcludeany
trialwhereagreementcouldnotbereached(butthisdidnotoc-
cur).Trialreportsthoughttobepotentiallyrelevantinlanguages
Datacollectionandanalysis
notknownbythereviewersweretranslatedandthereviewer(VM)
completedtheinclusionformwithreferencetothetranslator.At-
temptsweremadetocontactauthorsoftrialsthatcouldnotbe
Identificationofreportsproducedbythesearches classifiedinordertoascertainwhetherinclusioncriteriaweremet.
Becausemultipledatabasesweresearched,thedownloadedsetof
records from each database, starting with MEDLINE, was im-
Dataextraction
portedtothebibliographicsoftwarepackageReferenceManager
and mergedinto one core database to removeduplicate records Data from all included studies were extracted by one reviewer
andtofacilitateretrievalofrelevantarticles.Therecordsyielded (VM)usingapilottesteddataextractionform.Asecondreviewer
fromLILACS, BBO,CENTRAL, SIGLE and NIDRdatabases (JH)extracteddatafromarandomsampleofapproximatelyone
werenotimportedtoReferenceManagerandwerescannedwith- thirdofincludedstudies.However,infutureupdatesallreports
outthebenefitofeliminating duplicates.Therecordsproduced will be data extracted and quality assessed in duplicate. Check-
byOLDMEDLINE andbythespecificMEDLINE searchper- ingofinterobserverreliabilitywaslimitedtovalidityassessments.
formed without methodological filter were imported to Refer- Again,datathatcouldnotbecodedbythefirstreviewerwerein-
enceManagerforinspection,inadatabaseseparatefromthecore dependentlycodedbythesecond,anydisagreementwasdiscussed
database.TherecordsproducedbysearchingtheCochraneOral andathirdreviewerconsultedtoachieveconsensuswhereneces-
HealthGroup’sTrialsRegisterandthemetaRegisterofControlled sary.Provisionwasmadetoexcludedatawhereagreementcould
TrialswerealsocheckedoutsideReferenceManager. notbe reachedbutthissituation didnotoccur. Datapresented
Allrecordselectronicallyidentifiedbythesearcheswereprinted onlyingraphsandfigureswereextractedwheneverpossible,but
offandscannedonthebasisoftitlefirst,thenbyabstract(when wereincludedonlyiftworeviewersindependentlyhadthesame
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 6
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
result.Attemptsweremadetocontactauthorsthroughanopen- non-cavitatedlesions;netcariesincrementdatawouldbechosen
endedrequestinordertoobtainmissinginformationorforclari- overcrude(observed)incrementdata;andfollowupnearestto3
ficationwhenevernecessary. years(oftentheoneattheendofthetreatmentperiod)wouldbe
Additional informationrelatedtostudymethodology orquality chosenoverallotherlengthsoffollowup,unlessotherwisestated.
thatwasextractedincluded:studyduration(yearsoffollowup); Whennospecificationwasprovidedwithregardtothemethodsof
comparability of baseline characteristics: methods used pre-ran- examinationadopted,diagnosticthresholdsused,groupsofteeth
domisation in sizing/balancing (stratification based on relevant andtypesoftootheruptionrecorded,andapproachesforreversals
variables)or usedpost-randomisation inanalysing/adjusting for adopted,theprimarychoicesdescribedabovewereassumed.
possibledifferencesinprognosticfactorsbetweengroups;objectiv- TheCharacteristicsofincludedstudiestableprovidesadescription
ity/reliabilityofprimaryoutcomemeasurement(diagnosticmeth- ofallthemainoutcomedatareportedfromeachstudywiththe
odsandthresholds/definitionsusedandincluded,andmonitor- primary measure chosenfeaturing atthe top. Allother relevant
ingofdiagnosticerrors);anyco-interventionand/orcontamina- outcomesassessed/reportedinthetrialsarealsolistedinthistable.
tion. Information onsponsoring institutions andmanufacturers
involvedwasalsorecorded.
Characteristicsrelatedtoparticipantsthatwereextractedincluded: Qualityassessment
age(range)atstart,cariesseverityatstart(averageDMFS,DFS,or
Themethodologicalqualityoftheincludedstudieswasassessed
othermeasure),backgroundexposuretootherfluoridesources(in
accordingtothecriteriaforconcealmentoftreatmentallocation
water,topicalapplications,etc),yearstudybegan,locationwhere
describedintheCochraneReviewers’Handbook(Clarke2000)used
study was conducted (country), setting where participants were
intheCochraneReviewManagersoftware(RevMan).Allocation
recruited,anddentaltreatmentlevel(F/DMF).Characteristicsof
concealmentforeachtrialwasratedasbelongingtooneofthree
theintervention thatwere extractedincluded: mode of applica-
categories.
tion (howtheintervention was delivered),methods(technique/
A.Adequatelyconcealed(anadequatemethodtoconcealalloca-
device)of application, prior- and post-application (rinsing with
tionisdescribed).
water),fluorideactiveagentsandconcentrationsused,frequency
B.Concealmentunclear(’random’allocationstated/indicatedbut
anddurationofapplication,andamountapplied.
theactualallocationconcealmentmethodisnotdescribedoran
Differentwaysofassessing/reportingcariesincrementinthetri-
apparentlyadequateconcealmentschemeisreportedbutthereis
als(changefrombaselineasmeasuredbytheDMFindex)were
uncertaintyaboutwhetherallocationisadequatelyconcealed).
recorded separately and/or combined according to the compo-
C. Inadequately concealed(an inadequate methodof allocation
nentsoftheindexchosenandunitsofmeasurement(DMFT/S,
concealmentisdescribed).
orDFT/S,orDT/S,orFT/S),typesoftooth/surfaceconsidered
Excluded:random(orquasi-random)allocationclearlynotused
(permanent/deciduous teeth/surfaces, first molar teeth, approx-
in the trial, or ’random’ allocation not stated and not implied/
imal surfaces, etc), state of tooth eruption considered (erupted
possible.
and/oreruptingteethorsurface),diagnosticthresholdsused(cav-
Blinding of main outcome assessment was also rated according
itated/dentine lesions, non-cavitated incipient lesions), methods
tothefollowingthreecategoriesdefinedforthetopical fluoride
ofexaminationadopted(clinicaland/orradiolographical),andap-
reviews.
proachestoaccountornotforreversalsincariesincrementadopted
A.Double-blind (blindoutcome assessment and use ofplacebo
(inanetorobserved/crudecariesincrementrespectively).Inaddi-
described).
tion,cariesincrementshavebeenrecordedwhenevertheauthors
B.Single-blind(blindoutcomeassessmentstatedandnoplacebo
reportedthem(variousfollowups).
used).
Aswewereawarethatcariesincrementcouldbereporteddiffer-
C.Blindingindicated(blindoutcomeassessmentnotstatedbut
entlyindifferenttrialswedevelopedasetofapriorirulestochoose
likelyin any element/phaseof outcome assessment, e.g. clinical
theprimaryoutcomedataforanalysisfromeachstudy:dataon
and/or radiographic examinations performed independently of
permanentteethwouldbechosenoverdataondeciduousteeth;
previous results, or radiographic examinations performed inde-
dataonsurfacelevelwouldbechosenoverdataontoothlevel;DFS
pendentlyofclinicalexaminationswithresultsreportedseparately/
datawouldbechosenoverDMFSdata,andthiswouldbecho-
addedlater,orexaminersclearlynotinvolvedingivingtreatment,
senoverDSorFS;datafor’allsurfacetypescombined’wouldbe
oruseofplacebodescribed)orreportedbutunclear(blindout-
chosenoverdatafor’specifictypes’only;datafor’alleruptedand
comeassessmentreportedbutthereisinformation thatleadsto
eruptingteethcombined’wouldbechosenoverdatafor’erupted’
suspicion/uncertaintyaboutwhethertheexaminationwasblind).
only,andthisoverdatafor’erupting’only;datafrom’clinicaland
Excluded:clearlyopenoutcomeassessmentusedorblindoutcome
radiological examinationscombined’wouldbechosenoverdata
assessmentnotreportedandunlikely(nodescriptionofanexami-
from’clinical’only,andthisover’radiological’only;datafordenti-
nationperformedindependentlyofpreviousresults,ofx-raysreg-
nal/cavitatedcarieslesionswouldbechosenoverdataforenamel/
isteredindependentlyofclinicalexamination,ofuseofaplacebo,
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 7
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
andofexaminersclearlynotinvolvedingivingtreatment). appropriatethanthemeandifferenceorstandardisedmeandiffer-
Onereviewer(VM)assessedthequalityofallincludedstudies.A ence,sinceitallowscombinationofdifferentwaysofmeasuring
secondreviewer (JH)duplicatedtheprocessforarandomsam- cariesincrementandameaningfulinvestigationofheterogeneity
ple of approximately one third of those. Any disagreement was between trials. It is also simple to interpret. The meta-analyses
discussedandwherenecessaryathirdreviewerwasconsultedto wereconductedasinversevarianceweightedaverages.Variances
achieve consensus. Where uncertainty could not be resolvedan wereestimatedusingtheformulapresentedinDubey1965which
effortwasmadetocontactauthorsdirectlytoclarifythemethod wasmoresuitableforuseinaweightedaverage,andforlargesam-
usedtoconcealallocationorwhetherassessmentofthemainout- plesizestheapproximationshouldbereasonable.Random-effects
comehadbeencarriedoutblind. meta-analyseswereperformedthroughout.
Other methodological characteristics of the trials such as com- Withtheuseofpreventedfraction,itwasnotpossibletoperform
pletenessoffollowup(proportionexcluded)andhandlingofex- themainoutcomeanalysesinRevMan/MetaView.However,the
clusions (extent to which reasons for attrition are explicitly re- rawresultsofthestudies(mean/SD/n)wereenteredinRevMan
ported,orlossesareindependentoftreatmentallocated)werenot and mean differences were presented without meta-analyses. If
usedasthresholdsforinclusion.However,allassessmentsofstudy meta-analysesusingstandardisedmeandifferencesyieldedmate-
quality are described in the table of included studies, and were riallysimilarresultstothoseusingpreventedfractions,wewould
codedforpossibleuseinmetaregression/sensitivityanalyses. also presentthese within MetaView. Deciduous and permanent
teethwouldbeanalysedseparatelythroughout.
Forillustrativepurposestheresultswerealsopresentedasthenum-
Dataanalyses berofchildrenneededtotreat(NNT)topreventonecariousteeth/
surface.Thesewerecalculatedbycombiningtheoverallprevented
fraction with an estimate of the caries incrementin the control
Handlingofmissingmainoutcomedata groupsoftheindividualstudies.
Itwasdecidedthatmissing standard deviations for cariesincre-
mentsthatwerenotrevealedbycontactingtheoriginalresearchers
wouldbeimputedthroughlinearregressionoflog(standarddevia- Assessmentofheterogeneityandinvestigationofreasonsfor
tion)sonlog(meancaries)increments.Thisisasuitableapproach heterogeneity
forcariespreventionstudiessince,astheyfollowanapproximate Heterogeneity was assessed by inspection of a graphical display
Poissondistribution,cariesincrementsarecloselyrelatedtotheir oftheestimatedtreatmenteffectsfromthetrialsalongwiththeir
standarddeviations(vanRijkom1998). 95%confidenceintervalsandbyformaltestsofhomogeneityun-
dertakenpriortoeachmeta-analysis(Thompson1999).
In addition to aspects of study quality, three potential sources
Handlingofresultsofstudies(mainoutcome)withmore
ofheterogeneitywerespecifiedaprioriasinvestigationsofthese
thanonetreatmentarm
formedpartoftheprimaryobjectivesofthereview.Wehypoth-
Inthestudieswithmorethanonerelevantinterventiongroupand esisedthat:(1)theeffectoffluoridetoothpastesdiffersaccording
acommoncontrolgroup,suchasthosecomparingdifferentac- tothe baseline levelsof caries severity;(2)the effectof fluoride
tivefluorideagentsorconcentrationsoffluorideionstoaplacebo toothpastesdiffersaccordingtoexposuretootherfluoridesources
group,rawresults(thenumbers,meancariesincrementsandstan- (in water, etc); and (3) the effectof fluoride toothpastes differs
darddeviations)fromallrelevantexperimentalgroupswerecom- according toconcentration of fluoride. The association of these
binedinordertoobtainameasureoftreatmenteffect.Thisenables factors with estimated effects(D(M)FS PFs) were examined by
theinclusionofallrelevantdataintheprimarymeta-analysis,al- performingrandomeffectsmeta-regressionanalysesinStataver-
thoughmayslightlycompromisethesecondaryinvestigationsof sion6.0(StataCorporation,USA)usingtheprogramMetareg(
doseresponse. Sharp1998).
Toallowsuchinvestigation,relevantdataweredealtwithasfol-
lows: data on ’baseline levelsof caries’ werecalculatedfromthe
Choiceofmeasureofeffectandmeta-analysesofmain studysampleanalysed(finalsample)andinconnectionwiththe
outcome cariesincrementindexchosenunlessotherwisestated,andwere
Thechosenmeasureof treatmenteffectwas thepreventedfrac- averagedamongallrelevantstudygroups.Dataon’background
tion (PF), thatis (mean increment in thecontrols minus mean exposure to other fluoride sources’ combined reported data on
incrementinthetreatedgroup)dividedbymeanincrementinthe the use (outside the trial) of topical fluorides/fluoride rinses or
controls.Foranoutcomesuchascariesincrement(wherediscrete evenfluoride toothpastes(instudieswheretheinterventionwas
countsareconsideredtoapproximatetoacontinuousscaleandare testedundersupervisionatschoolandnosupplyofanytoothpaste
treatedascontinuousoutcome)thismeasurewasconsideredmore hadbeenprovidedforhomeuse)andtheconsumption offluo-
Fluoridetoothpastesforpreventingdentalcariesinchildrenandadolescents(Review) 8
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.