COMMENTARY : remineralization potential of a fluoridated carbamide peroxide whitening gel

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*Dental Research Center; Pediatric Dentistry, University of North Carolina, School of Dentistry, Chapel Hill, NC, USA†Dental Research Center; Pediatric Dentistry, University of North Carolina, School of Dentistry, Chapel Hill, NC, USA‡Dental Research Center; Pediatric Dentistry, University of North Carolina, School of Dentistry, Chapel Hill, NC, USA

Remineralization Potential of a Fluoridated Carbamide Peroxide Whitening Gel

JASON GLADWELL, DDS*

DARRIN SIMMONS†

J . TIMOTHY WRIGHT, DDS, MS‡

ABSTRACTPurpose: Little knowledge exists regarding the potential remineralizing benefits of adding fluo-ride to carbamide peroxide-based whitening gels. The aim of this project was to evaluate whethera whitening system with fluoride will remineralize previously demineralized enamel.

Materials and Methods: Twenty-four extracted teeth were sectioned into quadrants labeled A toD. Tooth quadrants in groups A, B, and D were demineralized with a lactic acid, methyl-cellulosegel system to mimic incipient carious lesions. Group C was neither demineralized nor treated.Group D was demineralized, but not treated with a whitening gel. Groups A and B were exposedto one of two commercially prepared 10% carbamide peroxide whitening gels: one that was fluo-ride free (group A) and one that contained fluoride (0.463%NaF) (group B). Remineralizationwas evaluated histologically and analyzed statistically using paired t tests accepting p < 0.05 assignificant.

Results: Shade comparisons showed equal whitening efficacy of both gel A and B. Paired t testsshow a significant reduction in lesion depth after treatment with the fluoride containing gel (B:mean lesion depth = 100 µm; p < 0.01), while there was no difference for the gel lacking fluoride(A: mean lesion depth = 110 µm).

Conclusion: Under the conditions of this study, the addition of fluoride to a tooth whitening sys-tem does not affect the gel’s whitening efficacy. The addition of fluoride could provide remineral-ization properties to the gel. As tooth whitening therapies continue to grow and evolve, a strongfocus should rest on improving these materials in ways that will provide ever greater patient benefits. Coupling the esthetic benefits of whitening with the preventive benefits of fluoride is anatural step in this direction.

CLINICAL SIGNIFICANCETherapuetic quantities of fluoride can impact remineralization properties of commercially avail-able tooth whitening gels without altering whitening properties.

(J Esthet Restor Dent 18:206–213, 2006)

DOI 10.1111/j.1708-8240.2006.00021.x

I N T R O D U C T I O N

As seen through the recent intro-ductions of products such as

Crest White Strips (Procter &

Gamble, Cincinnati, OH, USA) andColgate Simply White (Colgate, Piscataway, NJ, USA), patients areincreasingly interested in enhancing

the esthetics of their smiles. Thepopularity of dentifrices marketedto decrease dental caries also indi-cates that consumers of dental

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products are concerned with keep-ing their mouth free of decay. Fromthese observations one can presumethat patients would regard awhitening system that also fightsdecay as being of higher value thanone that only whitens teeth. Basedon consumer trends of esthetic andtherapeutic dental products overthe past decade, it is highly likelythat commercial demand wouldexist for a material that would haveboth a bleaching and caries reduc-tion benefit.

There are currently numerous dif-ferent whitening systems available,ranging from those based on car-bamide peroxide to those withhydrogen peroxide.1 While theproduct names and marketing areslightly different, the underlyingmechanism of action is essentiallythe same: the lightening of a tooththrough the application of a chemi-cal agent to oxidize the organic pig-mentation in the tooth.2

Fortunately, extensive researchrelated to systems directed at nonvi-tal bleaching, vital bleaching, night-guard bleaching, anddentifrice-based whitening havebeen completed helping validate theeffectiveness and safety of theseapproaches. Based on these previ-ous works, it is evident that thewhitening effect of bleaching solu-tions is time and concentrationdependent.3

One problem with today’s whiten-ing systems is that as efforts have

been made to increase patient bene-fits in terms of better whiteningefficacy and ease of use, little hasbeen done with regard to strength-ening the teeth that are beingwhitened. Fluoride already has beenproven to be useful when added toother commonly used dental prod-ucts such as dentifrices and mouthrinses.4 These applications show theadded patient benefits of low-dosehigh-frequency fluoride, and lendcredibility to the argument ofadding fluoride to whitening sys-tems to aid in remineralization.5,6

The addition of fluoride has alsobeen shown to decrease tooth sensitivity often associated withwhitening, while not significantlychanging the efficacy of the gelused.7

This area of research is potentiallyvery important and could have sig-nificant clinical implications. Ifremineralization is possible throughthe use of a whitening system, thesesystems could serve the dual role ofimproving esthetics while also act-ing as a caries-preventive measure.Increasing the benefits from whiten-ing alone to whitening with thepossibility of decreasing a patient’scaries risk, as well as further limit-ing sensitivity experienced duringtreatment, are steps in the rightdirection, but should by no meansbe considered an end point. Thepresent study was aimed at deter-mining whether the addition of flu-oride to a whitening gel could

promote remineralization of simu-lated enamel demineralization.

M A T E R I A L S A N D M E T H O D S

Extracted teeth were collected overa period of a month through thecooperation of local oral and max-illofacial surgeons and the Univer-sity of North Carolina (UNC) Oraland Maxillofacial Surgery Depart-ment. The extracted third molarsused in this study were limited tothose without previous restorationsor fractures. Exclusion criteria alsoinclude teeth with fluorosis,enamel, or dentin defects. All teethwere scaled to remove tissue andother debris and kept hydrated in aphosphate buffered saline solution(PBS) until they were prepared fortesting. Twenty-four third molarteeth were used in the project. Thepretreatment shade was determinedusing a Vita Classical shade guide(Vita Zahnfabrik, Bad Sackingen,Germany). The pretreatment shadeswere established by one observerusing natural light to avoidmetamerism.8 In instances when atooth was between shades, thelighter of the two shades wasrecorded.

After the initial shades were deter-mined and recorded, the roots wereamputated and the crowns of theteeth were sectioned into quadrants.The teeth were sectioned using aslow speed dental handpiece anddiamond sectioning disk. Thecrowns were sectioned mesiodistally

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R E M I N E R A L I Z A T I O N P O T E N T I A L O F A F L U O R I D A T E D W H I T E N I N G G E L

and faciolingually in a manner thatwould allow each quarter to beapproximately the same size as theothers. Once sectioned, one quarterwas randomly assigned and desig-nated as belonging to either groupA, B, C, or D. This experimentalapproach allowed each tooth toserve as its own control therebyhelping reduce the effects of uncon-trollable confounders related toinherent differences in the structureand composition of individual teeth.

Figure 1 shows a flow chart of thesequence of treatment for each

tooth used in the study. Groups Aand B were treated with the de-mineralizing solution followed bytreatment with whitening gel (onegel with fluoride and the otherwithout fluoride). Group C was the untreated, nondemineralizedexperimental control. Because nofurther treatment other than sec-tioning would be necessary forgroup C, these sections remainedhydrated in individual containerswith 2mL PBS solution until theother groups were ready for histo-logic evaluation. Group D wastreated with the demineralizing

solution, but were not treated witheither whitening gel. Groups A, B,and D were then exposed for 1week to a 10% (w/v) methylcellu-lose gel acidified with 0.1m lacticacid-sodium lactate at pH 4.5 andhaving a hydroxyapatite content of0.05% (w/v). The sections wereplaced in individual glass containerswith 2mL of the demineralizingsolution. This same demineralizingsolution was used in past researchby Kotsanos, Levers, and Tyler, sim-ulating natural enamel caries invitro, which are indistinguishablefrom natural enamel caries whenexamined by polarized lightmicroscopy and contact microradiography.9

After 1 week, the tooth quadrantsfrom groups A, B, and D wereremoved from the demineralizingsolution, rinsed with deionizedwater, and cleaned with a soft-bristled toothbrush to remove anyresidual gel. The tooth quadrantswere then returned to individuallabeled containers containing 2mLPBS solution. Because no furthertreatment other than sectioningwould be necessary for group D,these sections remained hydrated inindividual containers with 2mLPBS solution until the other groups(A and B) had been treated with thewhitening gel and were ready to besectioned for histologic evaluation.

Tooth quadrants in groups A and Bwere treated for 8 hours per day for

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Figure 1. Flow chart illustrating the experimental design evaluating the differencein remineralization potential of whitening gels with and without fluoride.


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21 days with their correspondingwhitening gel. The whitening gelswere both 10% carbamide perox-ide-based gels (Opalescence, Ultra-dent Products, Inc., South Jordan,UT, USA). The gels were not identi-fied as to fluoride content so theinvestigator was masked as to thecontrol and experimental gel untilafter scoring of all samples. Thewhitening gels were purchased byProcter & Gamble and modified bythe addition of fluoride to one ofthe gels. Once fluoride was addedto one of the gels, both groups ofwhitening gels were repackaged andlabeled to maintain the blindness ofthe study. The concentration of fluo-ride in the study was used becauseof its close correlation to prescrip-tion strength products already usedin caries prevention today. Toothsamples in groups A and B were

brushed with a soft-bristled tooth-brush and deionized water aftereach 8-hour whitening treatment toremove residual gel and placed intothe PBS solution for 16 hours andthe whitening gel treatment thenrepeated for 21 days.

Final shade determination wasmade after the 21 treatments on alltooth quadrants using the sameVita shade guide with natural light(Figures 2 and 3). After all treat-ments and posttreatment shadedetermination, all tooth quadrantsamples were sectioned with aslow-speed sectioning saw withdeionized water coolant, polishedto appropriate thickness (approxi-mately 150 µm), and mounted onhistologic slides for evaluation of lesion depth with light microscopy.

Zones of enamel demineralizationwere measured using a computerimaging program. The width of thezone of demineralization was mea-sured at five different points, allequidistant, and then averaged todetermine the mean lesion depth foreach sample (Figure 4). Differencesin lesion depths between the groupswere evaluated using t tests accept-ing ≤0.05 as significant. After eval-uation of shade changes and lesiondepths, the fluoride content of thewhitening gels was determined.

R E S U L T S

Fluoride analysis revealed that gelA had no fluoride and gel B wasfluoridated. Differences in lesiondepths were significantly reduced (p = 0.002) in group B (Opalescence,10% carbamide peroxide with

Figure 2. Initial shade of a control sample in group Cshown next to the corresponding Vitapan shade tab. Thefinal shade of this same tooth from group A (no fluoride)shows a reduction in color from shade A3.5 to shade B1,which was the average shade change in both bleaching groups.

Figure 3. Section A of sample #5, postwhitening treatment.This shows the sample whitening to shade B1 on the Vitapan shade guide.

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0.463% NaF) compared with demineralization only (group D).As shown in Table 1, the meanlesion depth was less in group Acompared with the demineralized,no-bleach control group D; how-ever, the difference was not statisti-cally significant. The whiteningefficacy was not altered by theaddition of fluoride to gel B. Theteeth had a variety of pretreatmentshades ranging from A3 to C4.Both gels whitened teeth with anaverage starting shade of A3.5 to a

final shade of B1. The sample sizein this study included 24 extractedthird molars and used highly sensi-tive parametric measurements (con-tinuous measurement of lesiondepth), providing sufficient powerto identify significant differences of15% lesion depth at the 95% confi-dence level.

D I S C U S S I O N

This study reveals that the additionof fluoride to a 10% carbamide

peroxide whitening gel does impartsome potential for remineralizationof demineralized enamel. Althoughthis study did not attempt to pin-point the exact mechanism of how the fluoridated whitening gelwould remineralize tooth structure,it is believed by the authors thatfluoride efficacy might well bepotentiated by the bleaching com-ponents. Once the proteins thatadhere to the enamel crystallites are removed by the bleaching agent, the reactive fluoride ioncould interact with the freshlycleaned crystallites, thereby enhanc-ing the potential for remineraliza-tion. This mechanism could be ofbenefit in cases where the lack ofmineral results from demineraliza-tion as in the case of dental cariesor a developmental defect thatresults in enamel hypomineraliza-tion and protein retention. It is alsopossible that the addition of fluo-ride to a whitening gel thatenhances mineral deposition couldhelp reduce the tendency for teethto re-stain and darken over time.Increased mineral deposition wouldreduce the intercrystallite spaces inenamel, thereby reducing the poten-tial for the reintroduction of pro-teins that change the enamel opticalproperties.

This study did not identify thethreshold dose of fluoride needed toproduce these results. In this study,0.463% NaF was added to Opales-cence 10% carbamide peroxide


142 µm

217 µm

214 µm

127 µm

108 µm

Figure 4. Light micrograph of a thin section illustrating the five measurementstaken per sample section and the calibrated ruler used for determining the lesiondepth.

TABLE 1. SUMMARY OF SIGNIFICANT RESULTS

Experimental Results Sample Group A Group B Group D

Mean lesion depth (µm) (±SD) 24 109 ± 37.5 99 ± 43.3 127 ± 43.4

Fluoride treatment No Yes No

p value 0.07 0.002

These results show the changes in mean lesion depth of samples treated with the fluoridated gelB were statistically significant compared with the control group D. It also shows the samplestreated with the nonfluoridated gel A lacked statistical significance with respect to decrease inmean lesion depth.


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whitening gel and no other concen-trations of fluoride were examined.This study also examined only thirdmolars and could yield differentresults if anterior teeth were used.Future research should focus ondetermining the optimal concentra-tion of fluoride that would renderthe desired best clinical results.Future research may also expandupon the many previous works that examine surface changes andmicrohardness of teeth as related todifferent whitening products withand without the addition of fluo-ride in higher concentration thancurrently used. PBS solution wasused as the method of keeping eachsample hydrated throughout thelength of the study. Perhaps, eithernatural saliva or a natural salivasubstitute should be used as thehydrating medium to provide theminerals and environment that may better replicate the environ-ment of the oral cavity. Althoughall groups were exposed to thesame environment (except forgroups A and B, which were treated with the whitening gels), the experiment did not examine thepossibility of remineralization fromregular oral hygiene practices andthe natural environment of the oralcavity. Clearly, clinical trials to eval-uate the effect of fluoridatedwhitening gels are necessary to con-firm whether there is a potentialbenefit in caries protection orincreased stability of the bleachingeffect.

C O N C L U S I O N S

Under the conditions of this study,the whitening efficacy was notaltered by the addition of fluorideto the whitening gel. Simulatedareas of demineralization did, how-ever, show statistically significantlevels of remineralization whentreated with the whitening gel containing fluoride versus the gelwithout fluoride.

C L I N I C A L I M P L I C A T I O N S

A N D R E L E V A N C E

In an ever increasing estheticallyoriented society, it is the obligationof the dental care provider toensure that all necessary precau-tions are being taken to providemaximum benefit and safety to thepatient. This obligation extends toareas of elective care includingtooth whitening. As tooth whiten-ing therapies continue to grow inpopularity and evolve in therapeu-tic application, the focus shouldrest on improving the materials inways that will provide ever greaterpatient benefits by incorporatingfluoride into whitening products.However, the proven benefits of fluo-ride are still protested against anddebated by a small segment of thepopulation; the addition of fluorideto a whitening gel would probablynot be a welcomed benefit forthem. As with any fluoride-contain-ing product, care should always betaken to ensure that high fluoridelevels are not experienced duringcritical tooth developmental

periods, in which the adverse effectsof fluorosis may be experienced.The high concentration of fluorideadded to the whitening gel used inthe study could potentially beenough to cause fluorosis of thedentition if used for a long enoughperiod of time during tooth devel-opment. Benefits could include areduction in the potential cariesrisk, remineralization of incipientcarious lesions, reduction in enamelsolubility by increasing the fluoridecontent of the carbonate-substituted hydroxyapatite enamelcystallites, or decreasing sensitivity.Coupling the esthetic benefits ofwhitening with the preventativebenefits of fluoride is a natural stepin this direction.

D I S C L O S U R E

This study was funded in part bythe UNC School of Dentistry, theAADR/IADR Student Research Fellowships, and Procter & Gamble.

R E F E R E N C E S

1. Gerlach RW, Gibb RD, Sagel PA. A ran-domized clinical trial comparing a novel5.3% hydrogen peroxide whitening stripto 10%, 15%, and 20% carbamide perox-ide tray-based bleaching systems. Com-pend Contin Educ Dent Suppl 2000Jun;29:S22–8.

2. Roberson T, Heymann H, Swift E Jr. Sturdevant’s art and science of operativedentistry. 4th ed. St. Louis (MO): CVMosby, Inc. 2002.

3. Heymann HO. Tooth whitening: facts andfallacies. Br Dent J 2005;198:514.

4. Zimmer S, Jahn KR, Barthel CR. Recom-mendations for the use of fluoride in

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caries prevention. Oral Health Prev Dent2003;1(1):45–51.

5. Negri HM, Cury JA. Dose-response effectof a dentifrice formulation with low fluo-ride concentration—an in vitro study.Pesqui Odontol Bras. 2002;16(4):361–5.

6. Twetman S, Axelsson S, Dahlgren H, et al. Caries-preventive effect of fluoridetoothpaste: a systematic review. ActaOdontol Scand 2003;61(6):347–55.

7. Tam L. Effect of potassium nitrate andfluoride on carbamide peroxide bleaching. Quintessence Int2001;32(1):766–70.

8. Grajower R, Revah A, Sorin S.Reflectance spectra of natural and acrylicresin teeth. J Prosthet Dent1976;36(5):570–9.

9. Kotsanos N, Durling A, Leuers B, Tyler S.Simulation of natural enamel caries in

vitro with methylcellulose acid gels: effectof addition of calcium and phosphateions. J Biol Buccale 1989;17(3):159–65.

Reprint requests: Dr. J. Timothy Wright,DDS, MS, 301 Dental Research Center,School of Dentistry, UNC Chapel Hill, Pedi-atric Dentistry CB #7450, Chapel Hill, NC27599–7450; Tel.: (919) 966–8822; email:[email protected]

©2006 Blackwell Publishing, Inc.


COMMENTARY

REMINERALIZATION POTENTIAL OF A FLUORIDATED CARBAMIDE PEROXIDE WHITENING GEL

Van B. Haywood, DMD*

The authors have presented some interesting data concerning the potential for fluoride remineralization of demineral-ized enamel while effectively bleaching the tooth. Most interesting is the proposal that bleaching could improve the effi-cacy of the fluoride due to the cleaning nature of bleaching. They have correctly cited the limitations of this study inthat it is on extracted teeth and the teeth were not stored in artificial saliva. The lack of normal biological mediumsmay have exaggerated the potential benefit of the fluoride-containing product, as some benefits of remineralizationwould have occurred from saliva in the nonfluoride group.1 However, there are other articles citing the beneficial effectsof fluoride in bleaching solutions for which this article is an additional confirmation.2–6

It is unfortunate that the authors did not treat all the samples the same. According to figure 1, a group C was also eval-uated, yet table 1 gives no data as to the amount of or lack of demineralization. The text states that all groups wereevaluated, but the table does not indicate the outcome. The reason for this concern is that if the teeth were already de-mineralized to some degree, then the effect of the solution would be the amount of acid demineralization (D) minus theamount of existing demineralization (C), not D alone. We do not know if this would change the significance of thedata. Also, the authors did not brush D after demineralization of the tooth, but did brush both bleaching groups A andB. The concern here is that the lack of lesion depth on the bleached samples could be a result of the brushing away ofthe softened demineralized surface of A and B. We know nothing of the amount and time of brushing, the hardness ofthe brush, and the force of application. Without the positive control C, and with the nonbrushing of D, we do notknow if the reduced surface depth was due to the action of fluoride or the loss of depth from brushing.

The authors cite a statistical difference between the untreated demineralized group D and the fluoride-containingbleaching group B. However, we are not told whether there is any significant difference between bleaching product Awithout fluoride and bleaching product B with fluoride measurements. We can see that there is a numerical difference,but we do not know if this is statistically or clinically different. The authors also state the sample sites for measuringdepths were equidistant apart, but the figure shown does not demonstrate that claim. It is unknown how the startingpoint of the measurement was obtained, and what determined what sites were measured. When the difference in treatedand control are only 25 microns, small variances in technique could radically alter the outcome.


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The authors point out there is no difference in bleaching efficacy, which is an additional insight to the original article byTam and colleagues in Quintessence International in 1991 refuting the earlier concern that fluoride would hinder theefficacy of the bleaching treatment. Her article was a clinical study. In this laboratory study, the shade was taken priorto sectioning the teeth, which may alter the baseline. Apparently, group C was used as the color standard to demon-strate bleaching, although that is not cited in the text. It was good that each tooth served as its own control, as theresponse of individual teeth varies greatly.

What is most interesting is to note the variations in amount of demineralization on a single tooth surface when exposedto the most ideal condition. This insight helps explain to the dentist the somewhat random nature of demineralizationclinically, where the entire tooth is not being brushed but only one spot has caries. In some areas, the demineralizationwas twice as deep as on other areas.

We are not given a rationale for the 0.463% NaF that was added other than it is the amount typically used for cariesprevention. There is no reference to that statement, and this formulation used in this study may not be commerciallyavailable to the clinician, as the amount was added to Opalescence (Ultradent Products, Inc., South Jordan, UT). Theamount of fluoride in Opalescence PF bleaching material (Ultradent Products, Inc.) is 0.25% NaF, the amount in Flor-Opal Fluoride varnish (Ultradent Products, Inc.) is 5.0% NaF, and the amount in PreviDent 5000 (Colgate Oral Phar-maceuticals, Piscataway, NJ, USA) is 1.1% NaF. Gel-Kam Gel (Colgate Oral Pharmaceuticals) has 0.4% SnF2. We donot know how this percentage of fluoride compares to the ppm data for water and other materials, and what is theexpected remineralization from a topical application of fluoride done after the bleaching treatment. Another possibleuse for group C would have been to demineralize it as well, and then treat it with conventional fluoride after eachbleaching application to see if that was more effective than fluoride in the bleaching material.

The authors have pointed out the concern for too much fluoride by some people. It would seem the addition of fluoridefor the sake of remineralization would be applied in patients who have demineralized teeth, such as in poor oralhygiene and postorthodontic patients. There is also data showing some reduction in enamel hardness from some bleach-ing, for which the use of fluoride is most appropriate in bleaching. In summary, based on this work and the other arti-cles cited, the addition of fluoride seems to be a beneficial component of a bleaching material.

REFERENCES

1. Justino LM, Tames DR, Demarco FF. In situ and in vitro effect of bleaching with carbamide peroxide on human enamel. Oper Dent2004;29(2):219–25.

2. Basting RT, Rodregues AL Jr., Serra MC. The effect of 10% carbamide peroxide bleaching material on microhardness of sound anddemineralized enamel and dentin in situ. Oper Dent 2001;26:531–9.

3. Lewinstein I, Fuhrer N, Churaru N, Cardash H. Effect of different peroxide bleaching regimens and subsequent fluoridation on the hard-ness of human enamel and dentin. J Prosthet Dent 2004;92:337–42.

4. Clark LM, Barghi N, Summitt JM, Amaechi BT. Enamel fluoride uptake from fluoridated carbamide peroxide bleaching gel. AADRAbstract #0498 2006.

5. Al-Qunaian T. The effect of whitening agents on caries susceptibility on human enamel. Oper Dent 2005;30(2):265–70.6. Clark LM, Barghi N, Summitt JB, Amaechi BT. Influence of fluoridated carbamide peroxide bleaching gel on enamel demineralization.

IADR Abstract #0497 2006.

*Professor, director of Dental Continuing Education, Department of Oral Rehabilitation, School of Dentistry, Medical College of Georgia,Augusta, GA, USA

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COMMENTARY : remineralization potential of a fluoridated carbamide peroxide whitening gel