REVIEW ANALYSIS & EVALUATION

ARTICLE TITLE ANDBIBLIOGRAPHICINFORMATION

Effects of low and standard fluoridetoothpastes on caries and fluorosis:systematic reviewandmeta-analysis.

Santos APP, Oliveira BH, Nadanovsky P.

Caries Res 2013;47(5):382-90.

REVIEWERS

Mar�ılia Afonso Rabelo Buzalaf, PhD,Cristiane de Almeida BaldiniCardoso, PhD, Ana CarolinaMagalh~aes, PhD

PURPOSE/QUESTION

The authors attempt to study theeffect of low-dose and standardfluoride toothpastes on caries andfluorosis development

SOURCE OF FUNDING

Santos received a PhD scholarshipfrom the Research SupportFoundation of the State of Rio deJaneiro (FAPERJ) (E-26/101.250/2008); B.H. Oliveira receivesfinancial support fromFAPERJ (E-26/102.248/2009) and P. Nadanovskyreceives financial support from theBrazilian National Research Council(CNPq) (grant No. 310807/2009-3)

TYPE OF STUDY/DESIGN

Systematic reviewwithmeta-analysisof data

LEVEL OF EVIDENCE

Level 2: Limited-quality,patient-oriented evidence

STRENGTH OFRECOMMENDATION GRADE

Grade B: Inconsistent or limited-quality patient-oriented evidenceJ Evid Base Dent Pract 2013;13:148-1501532-3382/$36.00� 2013 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.jebdp.2013.10.003

Low-fluoride Toothpastes May Not Leadto Dental Fluorosis But May Not ControlCaries Development. Standard FluorideToothpastes Can Control CariesDevelopment But May Lead to DentalFluorosis

SUMMARY

Selection CriteriaThe databases consulted from date of online availability to January 2010were the following: The Cochrane Central Register of Controlled Trials(CENTRAL/CCTR), MEDLINE via PubMed, EMBASE, Web of Science,LILACS, and BBO (Brazilian Library of Dentistry). The electronic searchwas updated by one of the authors (A.P.P. Santos) in March 2012 and noadditional studies were found. Additional sources included a Brazilian da-tabase of theses and dissertations (Banco de Teses CAPES), a Brazilian reg-istry of ethically approved projects involving human beings (SISNEP), andtwo international registries of ongoing trials (Current Controlled Trialsand ClinicalTrials.gov). The search strategy included controlled vocabu-lary and free terms. It was developed for MEDLINE (online suppl. appen-dix 1; for all online suppl. material, see www. karger.com, http://dx.doi.org/10.1159.000348492), without idiom restraints, and adapted for theother databases. Meeting abstracts of the International Association forDental Research (2001–2012) and the European Organisation for CariesResearch (1998–2012) were also searched. Sixteen dental journals thatare also in the Cochrane Master List of Journals Being Searched (Bickleyand Glenny, 2003) were hand searched. Two independent examinershand searched these 16 dental journals from the last date of the CochraneCollaboration’s hand search until June 2010. References of eligible trialsand systematic and narrative reviews on fluoride were checked to detectpotential studies. Finally, specialists in the field were contacted by e-mail.The studies involved the systematic review of individual or clusterrandomized/quasi-randomized clinical trials with a follow-up period ofat least 1 year.

Key Study FactorReview of studies comparing the anti-caries effect of low-concentration(less than 600 ppm F) and standard (1000-1500 ppm F) fluoride tooth-pastes and their effect on the development of dental fluorosis. All studieshad to include the intervention in primary dentition and the observationof moderate to severe fluorosis in the permanent dentition. Childrenhad to be not older than 7 years when the outcome caries was assessed,and there was no age limit for the assessment of fluorosis.

Main Outcome MeasureThe main outcome was the prevention of enamel and dentin caries in theprimary dentition and the prevention of moderate to severe fluorosis in thepermanent dentition.

JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE

Main ResultsOne hundred fifty-nine full-text articles were assessed foreligibility. Five studies were included in the review and139 were excluded. The number of excluded studiesdoes not add up to 154 because the results of some studieswere published in several articles. Pooled relative risks(RR) and 95% confidence intervals (CIs) were estimatedto assess the proportion of children who developed cariesin primary teeth and aesthetically objectionable fluorosisin permanent teeth. Numbers needed to treat for an ad-ditional harmful outcome (NNTH), which correspondsto the number of children that needed to use low-fluoride toothpaste as opposed to standard fluoridetoothpaste in order for 1 child to be harmed, i.e., to de-velop at least 1 dentin caries lesion, were derived by apply-ing the pooled RR of caries to three different scenarios:1

high (70%), medium (50%), and low (20%) 5-year cariesincidence; 95% CIs were derived by applying the 95% CIsof the pooled RR.2 No meta-analyses of the difference inmeans were performed when the surface was consideredbecause data regarding caries incidence at the surfaceand tooth level were highly skewed. The paucity of studiesprevented the use of meta-regression to assess the influ-ence of study characteristics on the treatment effect, aswell as the assessment of publication bias. The resultsshowed that in non-fluoridated or non-optimally fluori-dated areas, the use of low-fluoride toothpastes did notprotect preschoolers from developing moderate to severeforms of fluorosis in upper permanent anterior teeth andincreased the risk of caries in the primary dentition.

ConclusionsThe authors found no evidence to support the use of low-fluoride toothpastes by preschoolers because they in-creased the risk of caries in the primary dentition anddid not decrease the risk of aesthetically objectionablefluorosis in upper permanent anterior teeth.

COMMENTARYANDANALYSIS

We partially contradict the authors’ conclusion. As re-ported in the systematic review,3 which is the most recentand complete systematic review in the field, the use ofstandard fluoride toothpastes by young children wassignificantly associated with an increase in fluorosis inthe permanent anterior teeth (TFI > 0 and Dean’sclassification > questionable). In addition, in the system-atic review of Walsh et al.4 the use of standard fluoridetoothpastes is recommended for caries prevention in chil-dren. However, from the 85 independent studies includedin this review that analyzed the permanent dentition(DMFS), only two compared toothpastes containing 440to 550 ppm to placebo. Considering the primary dentition(ceos), which is the outcome that really matters in respectto the prevention of both dental caries and fluorosis, sincethe permanent upper central incisors develop in the first

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3 years of life,4,5 only four studies were included, andfrom them two compared 440- to 550-ppm fluoride with1055- to 1450-ppm fluoride toothpaste. One of these stud-ies,6 which was also reported in the present systematicreview, was the only one showing that children usinglow-fluoride toothpaste had a significant increase in themean caries incidence at tooth level compared to those us-ing standard fluoride toothpastes. However, in this study,children were living in non-fluoridated areas and were athigh risk for dental caries. The other four included studiesdid not find any significant difference between low-fluoride and standard fluoride toothpastes in preventingcaries in primary teeth (high variation between the dmfsvalues). The conclusion of Santos and co-authors wasbased on the mean RR value of 1.13 (I2 = 0.0%, p = 0.77).Despite the lowheterogeneity, therewas only 13% increasein caries risk associated with the use of low-fluoride tooth-paste compared to the standard toothpaste. In respect todental fluorosis, only two studies, which were performedin non-fluoridated or non-optimally fluoridated areas,were statistically analyzed, with mean RR values of 0.32(I2 = 76.3%, p = 0.04). The RR values of the two studiesare highly discrepant: RR = 0.097 and RR = 0.8.8 Both stud-ies presented a different baseline age of the patients andtime of follow-up. Therefore no final conclusion can begiven due to the low number of studies and also to thefact that there is no study evaluating the fluorosis inci-denceby theuseof low-fluoride toothpaste in afluoridatedarea. It is important to point out that the use of fluoridatedtoothpastes is related to mild fluorosis incidence and notto moderate/severe fluorosis. This issue should be consid-ered in the interpretation of the data. Furthermore, forboth variables (caries and fluorosis), the selected studiespresented some bias, since high rates of losses in thefollow-up were found and no baseline caries balance wasreported. Another limitation is that the tested toothpastespresented different formulations (fluoride salt, concen-tration, and pH) among the studies. All limitations foundin the clinical studies may reduce the contribution of thissystematic review to evidence-based dentistry, especially bythe fact that thepresent conclusionmay influence readers’clinical practices. We recommend that more appropriaterandomized controlled trials (RCTs) (with a low risk ofbias) be conducted to allow more consistent conclusionthat really makes a key contribution to evidence-baseddentistry. We agree that there is no evidence supportingthe use of low-fluoride toothpastes for caries preventionin primary dentition because of the low number ofRCTs on children <7 years old (>2 years of follow-up).However, there is still no consensus in respect to the anti-caries effect of low-fluoride toothpaste based on the pa-tient’s risk assessment. Finally, there is also no evidencethat low-fluoride toothpaste leads to the same risk of den-tal fluorosis as standardfluoride toothpaste, with lack of in-formation in fluoridated areas. Finally, the impact of theamount of toothpaste applied on toothbrush should also

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JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE

be an issue to be studied further in respect to both dentalcaries and fluorosis, since according to the review byWonget al.1 no association was found between the amount oftoothpaste loadedonto the toothbrush and the risk of den-tal fluorosis.

REFERENCES

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BMJ; 2001. p. 386-99.2. Altman DG. Confidence intervals for the number needed to treat. Br

Med J 1998;317:1309-12.3. Wong MC, Glenny AM, Tsang BW, Lo EC, Worthington HV,

Marinho VC. Topical fluoride as a cause of dental fluorosis in chil-

dren. Cochrane Database Syst Rev 2010;(1):CD007693.4. Walsh T, Worthington HV, Glenny AM, Appelbe P, Marinho VCC,

Shi X. Fluoride toothpastes of different concentrations for preventing

dental caries in children and adolescents. CochraneDatabase Syst Rev

2010;(1):CD007868.5. Bardsen A. ‘‘Risk periods’’ associated with the development of dental

fluorosis inmaxillary permanent central incisors: ameta-analysis. Acta

Odontol Scand 1999;57(5):247-56.

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6. Hong L, Levy SM, Warren JJ, Broffitt B, Cavanaugh J. Fluoride intakelevels in relation to fluorosis development in permanent maxillarycentral incisors and first molars. Caries Res 2006;40(6):494-500.

7. Davies GM, Worthington HV, Ellwood RP, et al. A randomised con-trolled trial of the effectiveness of providing free fluoride toothpastefrom the age of 12 months on reducing caries in 5- to 6-year old chil-dren. Community Dent Health 2002;19:131-6.

8. Tavener JA, Davies GM, Davies RM, Ellwood RP. The prevalence andseverity of fluorosis in children who received toothpaste containingeither 440 or 1,450 ppm F from the age of 12 months in deprivedand less deprived communities. Caries Res 2006;40(1):66-72.

9. Holt RD, Morris CE, Winter GB, Downer MC. Enamel opacities anddental caries in children who used a low fluoride toothpaste between2 and 5 years of age. Int Dent J 1994;44(4):331-41.

REVIEWERS

Mar�ılia Afonso Rabelo Buzalaf, PhDCristiane de Almeida Baldini Cardoso, PhDAna Carolina Magalh~aes, PhDDepartment of Biological Sciences, Bauru Dental School,University of S~ao Paulo, Al. Oct�avio Pinheiro Brisolla, 9-75,Bauru, SP 17012-901, Brazil, Tel.: þ55 14 32358346;fax: þ55 14 32271486mbuzalaf@fob.usp.br

December 2013