the relative caries-inhibiting efficacy of amine fluoride and

Preventive Dentistry

The relative caries-inhibiting efficacy of amine fluoride and sodiumfluoride in compatible dentifrices-Results of a consensus conferenceJohannes Einwag*/Elmar HeUwig**/Peter Hotz***/Peter Städtler****

A conference concerning the caries-inhibiting efficacy of dentifrices that contain amineand sodium fluorides cotnpared relevant clinical studies and found that bothfltioridecompotmds contribute to the tnaintenance ofdental health. Because ofthe differing testconditions, the study restdts cannot, however, be compared. Thus, there is no definite scientificproof of the superiority of one fluoride compound, and no such proof will exist until dentifricescontaining amine fiuorlde and sodium fluoride are tested in a direct clinical comparison.(Quintessence Int 1995:26:707-7/3.)

Introduction

For decades there have been countless dentifrices onthe market that contain fluoride for caries prevention.The efficacy of fluoride in caries prevention is gener-ally well documented and indisputable. In view ofthemultitude of available products, it is often very difficultto recommend a specific dentifrice to a patient.

This article contains a summary of the mostimportant factors for consideration and relevant clini-cal data on the subject. In addition, this article presentsthe results of a conference at which the results ofstudies of dental cleaning with dentifrices containingsodium fluoride or amine fluoride were compared.

At the moment, most dentifi-ices on the market con-tain either sodium monofluorophosphate (NaMFP),sodium fluoride (NaF), or amine fluoride (AtnF). In

' Zahnärztliches Fortbildungszentriim, Landes ZahnärztekammerBaden-Wjrttemberg, Stuttgart, Germany.

-* PoliMitiik fiir Zahrerhaitiingskunde. Klinik für Zahn , Mund- undKieferheilkunde, Universität Freiburg, Freiburg, Germany.

" * Klinikfür Zahnerhaltung, Zahnmedizinische Kliniken, LlniversitätBeni, Bern, Switzerland.

- " ' Deparlment fiir Konservierende Zahnheilkunde, LJniversitätsklinikfür Zahn-, Mund- und Kieferheilkunds, Graz, Austria.

Reprint requests: Prof Dr Johannes Einwag, Zahnärztliches Fortbil-dungszantrjm, Landesiahnárztekammer Bad en-Württemberg, Herdweg50, D-70174 Stuttgart, Germany.

western European countries, dentifrices containingNaMFP are most common, followed by productscontaining NaF and AmF.

Based on direct clinical comparative studies, Stookeyet al' came to the conclusion that NaF in a compatibledentifrice is significantly more effective than NaMFP.Compatible means that the fluoride used in the pastebase is available to act on the surface ofthe tooth and isnot rendered inactive by the other paste ingredients.The authors judged the difference in efficacy betweenthe two fluoride compounds to be clinically importantand statistically significant. In the light of these results,they recommended the use of dentifrices containingNaF, if this was contained in a compatible manner.

In contrast, in Germany, Austria, Switzerland, andthe Benelux countries, dentifrices containing AmF areoften recommended. This recommendation is foundedon the belief that amine fluoride is superior to the othertwo fluorides.

A consensus conference was held in Frankfiirt/Main, Germany, to discuss and compare scientificallythe caries-inhibiting efficacy of dentifrices containingAmF with that of dentifrices containing NaF incompatible formulations. The following points werediscussed at this conference;

I. Is caries still a problem; eg. with today's drasticallyreduced degree of distribution ofthe disease, is theefficacy of dentifrices still a relevant issue fordiscussion?

Quintessgpco lijlarnalional- 10/1995 707


Sodiumfluoride

Na® F® StannoLSfluoride

2F

Sodium mono-fluorophosphate 0 = P - F

2©

Olafluoride

H.C - {CHJ,.- CHj p© F© CH,- CKOH\ © © /NH-CH, -CH, -CH, -NH

/ \HOCHj - CHg CHj-

N'-Ocladecyll(imelhylenecliamine-N,N,N'-lri5(2-ethanol]-dihyd[OtlLioride

Fig 1 Structural formulas for fluorides used in dentilnces.

Table 1 Average DMFS values in differentcountries*

Country

Deimiark (N)Germany^Gennany*Italy (R)France (R)Netherlands (N)Switzerland (N)United States"

Yeart

1990] 1988]198919921990(1985]1990199019881985-1987

Age ¡2 y .

1,3

4.r-3,3+«431,7•yj

1,8

\ge 35-44 y

17,8*16,713.413.8-

17,4•'2,3

14,3

' Adapted from ELnwag,^t Year in brackets ¡s the sludy year for the 35 io 44 age group,i In this study, 30 to 39 year olds were examined,§ Old federal states,' Data from Marthaler,^• Linear interpolation; 13 and 14 year olds were examined.# New federal stales,N - national average^ R = representative study.

2. A short summary of the mechanism of action ofdentifrices containing fluoride and the productingredients that can adversely affect efficacy waspresented,

3. How can the caries-inhibiting efficacy ofa denti-frice be clinically demonstrated or proven?

4. What clinical proof is available for the efficacy ofdentifrices containing AmF or NaF in compatibleformulations, and to what extent can the cariesincidence be reduced?

5, Can the caries inhibition of the two systems becompared? If so, is the difference clinically rele-vant?

Caries—Still a problem?

Despite encouraging developments with respect to theprevalence and severity of caries in the last 10 to 15years, caries is stiil a widespread disease, A look at theaverage prevalence in different countries shows thatthe problem has decreased but is stiil not solved (Table1). Moreover, despite its reduced prevalence, cariesstill incurs very high costs. In Germany, for example,the financial outlay for the dental care of the popula-tion totaled DM 16,8 million last year, with DM 8,6million of this being spent on the treatment of cariesand the consequences of caries damage (Source;German Federal Health Office),

The fear is being increasingly voiced that theprevalence of caries is rising to previous figures again.First, preventive programs are becoming more andmore difficult to finance, because caries is no longerregarded as a problem. Second, preventive programsare difficult to conduct, because the potential partic-ipants, who do not yet suffer from caries, do not regardparticipation in such a program as necessary. Third, itis becoming more and more difficult to motivatepatients, especially children, to maintain good oralhygiene on an individual basis because they have neverexperienced the effects of caries. On top of thesefactors are economic measures taken by the authoritiesand also the fear of fluorides. It is therefore moreimportant than ever to continue with caries prophy-iaxis or at least to maintain it in its current state.

Signiñcance of fluoride dentifrices for cariesprevention

One ofthe factors responsible for the decline in caries,and for many people maybe the most important, isfluoride, a substance that is especially effective whenapplied locally to the teeth on a regular basis, Dcntifrices are an ideal vehicle for this application (Fig I),

The first fluoride compound to be utilized andclinically tested for caries prophylaxis was NaF,However, its clinical efficacy was proven only after thatof AmF and NaMFP, The poor results of initial clinicalstudies on the efficacy of dentifrices containing NaFcan today be traced back to incompatibility of theactive ingredient with the other ingredients of thedentifrice, especially the polishing agent. Polishing

708 Quintessence International Volume 26, Number IO/1995


Fig 2 The carious process-aquestion of equilibrium. (Adaptedfrom Slookey.'')

BACTERIA * SUBSTRATE

Acids

HEALTHY PA^P.^I^^H^^m ^ CARIOUSENAMEK- - ENAMEL

Remineralization

Acid ---^^''^'^^^ FLUORIDEBuffer ___

SALIVA

Calcium andPhosphorus

agents formerly used in dentifrices, were calcium, inthe form ofcalcium carbonate, calcium phosphate, or amixture of dicalcium phosphate and insoluble precip-itates, including calcium fluoride and ñuorapatite.Sodium fluoride can also react witb various aluminumsalts, which were also used as polishing agents. Thisadversely affected the caries-inhibiting efficacy of thedentifrice. For NaF to be effective in a dentifrice,fluoride ions, which can react with the tooth enamel,must be present in ample quantities. Today, compatiblepohshing Events, mostly silica hydrates, are used inmost dentifrices on the market. However, calciumpyrophosphate, sodium bicarbonate, and acrylic par-ticles are also used in clinically tested products.

Amine fiuoride was first used successfully as anadditive to dentifrices at the end of the 1950s. Theresults of the first clinical studies were published hi1965. The substance is only used on the Europeanmainland.

Sodium monofluorophosphate has heen a commonadditive to dentifrices since the beginning ofthe 1960s.It is relatively easy to integrate into a dentifrice and iscompatible with a whole range of polishing agents.

Despite extensive research, the mechanism of ac-tion of fiuodde in relation to caries prophylaxis is notyet fully understood. Its efficacy in the prophylaxis ofcaries may result ñrom its influence on the develop-ment of the morphology of the tooth structure, theformation or the metabolism of plaque, or the demin-eralizarion or remineralization of the teeth. The lasteffect may be due to reactions in the enamel with thesaliva. It is now generally assumed that the decisiveefficacy of fluoride applied iocally in a dentifrice arisesfrom its influence on the demineralization and remin-eralization ofthe enamel. Independent of its mechanism

of action, fluoride must, in any case, swing theequilibrium that governs demineralization and retnin-eralization (which is not static but dynamic) in such away as shown in Fig 2 ); ie, toward better conditions forthe integrity ofthe tooth enamel.

Assessing the caries-inhibiting efficacy of a dentifrice

In vitro tests and animal experimentsBecause ofthe use to which they aspire, dentifrices forcaries prevention must be tested under conditions thatcorrespond to real-life circumstances. Tbe best test ofthe efficacy of a caries-inhibiting agent is the conduc-tion of a suitably designed clinical dental cleaningstudy. Animal experiments and in vitro tests shouldonly be used to show trends. They can be very useful inthe development of a product, hut the results of suchtests must be validated by means of clinical dentalcleaning studies under realistic conditions.

The results of in vitro comparisons between NaFand NaMFP could be confirmed by clinical studies.For NaF and AmF, however, there are no directclinical comparisons that can be used for vahdation. If,for example, the fiuoride absorption from AmF intothe enamel is measured under laboratory conditions,ie, in a watery medium, the results with respect tobioavailability are optimum. If the conditions are mademore realistic by the addition of saliva, the availabilityis considerably less.' The results of in vitro tests andanimal experiments with NaF and AmF must thereforenot be overinterpreted with respect to theh: effect in thehutnan oral cavity.

Clinical testing

The result of a clinical study may be influenced bycountless variables, amotig them the following examples.

Quintessgpce i'^*"""' ' '"""!. V"liimp?fl Mnmh^r 10/1995 709


Product properties

The optimization ofthe fluoride effect in a dentifrice isvery important. For example, NaF could react with theabrasive system. Poor compatibility between NaF andthe abrasive system adversely affects the bioavailabilityof fluoride, producing a less-than-expccted resuh, giventhe formulation. As a result of this factor, the con-clusions with respect to the caries-inhibiting efficacy ofthese products are in general unreliable.

Another problem arises if a dentifrice is not usedbecause, for example, it has a bad taste, but the subjectremains within the study to the end and yields falseresults. The investigator must also document thereasons why participants drop out of the study andinclude in the evaluation only those subjects who haveremained in the study from beginning to end.

Finally, apart from the absence of the activehigredient, there should be no great difference betweenthe test product and the placebo. Otherwise it cannotbe ascertained to what any difference in efficacy can beattributed.

Study participants

The participants in caries studies may belong todifferent age groups. The age of most subjects isbetween 6 and 16 years or older. The number ofendangered teeth, varying necessarily with the varyingage group, must be taken into consideration in the finalevaluation.

The prevalence of caries in the population isexpressed by the value of decayed, missing, and fliledsurfaces (DMFS). This is, however, an instantaneousvalue that does not indicate the caries progression ofthe group. A caries test should measure the inhibitingeffect of fluoride on the incidence of caries for theduration ofthe study This is, however, independent ofthe respective baseline values and is, as per expec-tations, low with low baseline values and high withhigh baseline values. As a result, different basehnevalues lead to different results for the caries-inhibitingefficacy of fluoride.

Participants ofa caries study can also take fluoridein other ways than in dentifrice, eg, in fluoridatedwater, fluoride tablets, fluoridated common salt, and/or fluoridated mouthwashes. in an evaluation of suchstudies, these other fluoride sources must be taken intoconsideration, because experience has shown that theeffect of a fluoride dentifrice alone is not as great as acombination of different supplements.

Study design

Studies lasting at least 30 months often yield morereliable results than do shorter ones. This, of course,very much depends on the caries incidence in therespective study population; with higher incidence ashorter time is necessary, and with lower incidence alonger time, before a difference is visible.

The investigators may instruct the participantsdifferently and if necessary check the frequency withwhich the participants are to clean their teeth; theinstructions range from "as often as you want" to"twice a day," In interpretation of results of clinicalcaries studies, the cooperation ofthe participants is, ofcourse, of decisive importance.

The investigators in caries studies turn mostly to acombination of clinical and radiologie examination inthe evaluation, because this combination provides themost powerful expression of caries prevalence. Theactual evaluation criteria, however, are not yet stan-dardized. Thus a comparison ofthe results of differentstudies, even if the evidence of each individual study issound, appears to be very difficult.

Results of clinical studies on amine fluoride andsodium fluoride dentifrices

With the help of a computer search program, allclinical studies on the efficacy of AmF dentifrices andNaF dentifrices in compatible formulations wereselected. Because there were no studies in whichdentifrices containing AmF and NaF were tested indirect clinical comparison, only placebo-controlledstudies, in which the absolute caries-inhibiting valuesfor both products were ascertained, were selected.

Many studies have been pubhshed on the efficacy ofAmF. However, there are only six published studies inwhich a dentifrice containing AmF was compared witha nonfiuoride placebo. In all other studies, a dentifi'icecontaining AmF was compared with a gel with a veryhigh fluoride content, highly concentrated F" prepara-tions, with a fluoride mouthwash, or with fluoridetablets. Therefore only the following six studies wereincluded in the review: Marthaler,* Marthaler et al,'Patz and Naujoks,* Marthaler,' Ringelberg et al,'° andCahenet al."

A great number of clinical studies have comparedthe caries-inhibiting efficacy of NaF to that of aplacebo. However, as already mentioned, it is nowknown that certain paste bases adversely aifect thebioavailability of free fluoride. Studies with non-

710 Quintessence International Voiume 26, Number 10/19^5


Table 2 Clinical studies in which dentifrices containing amine fiuorides were compared with a placebo'

Study

Marthaler'(1968)''

Patz andNaujoks^(1970)

Matt haieretal'(197O)t

Marthater'(1974/

Ringelberaetal"'(1979)

Cahenet al" (1982)

Duration(mos)

36'

36

36

4S

72

30

36

Location

Zutich

Würzburg

Zurich

Kilchberg

Horida

Strass-bourg

Dentifriceusage

Not checked

Not checked

Not checked

Uncheckedbut verywell trained

Checked

Linche ekedbut withmonthlyinstructions

OtherfluorideSQtirce

LJnknown

Unknown

0.3 mg/d

Salt plushighlyconcentratedgel

None

Unknown

Subjectage atstart ofstudy (ys¡

6-9

11-14

15-18

6-7

7.5(meanvalue)

11(meanvalue)

6-8

Dentifnce(ppmfluoride)

AmF(1250)Placebo(0)AmF(1250)Placebo(0)

AmF(1250)Placebo(0)

AmF(1230)Placebo(0)AmF(1250)Placebo(0)

AmF(125Q)Placebo(0)

AmF(1250)Placebo(0)

AmF(1500)Placebo

BaselinevalueDMFS[DMFrl

6.60[3,73]6.7513.49]28.88114.57]29.50[15.59]

23.30

23,69

4.07

4.26

7,39

9-1

7.IB13.0217.3413.511

3,69[2.1514,95[2 72]

Unknown

Unknown

Increase inDMFS[DMhTI

B.26[3.85111.72[5 24112,7114,02116,Bl

14.381

9.99

10.75

8.07

8,96

10.13

14.3

13.90[6.94118.34[B.20]

5.1212.81]5.99[3,211

3,25[1.4514.05I I 8 5 I

% reductionvs placeboDMFS[DMFTl

30[26]

24[8] (NS)

7.1 (NS)

9 (NS)

16 (NS)

33[151

18.1116.91

20.14[21.62]

' The preparations cnntainiitg amine nuonde and the placebit The Marthaler index was used lo assess caries.t The study was conducted over 7 yearsNS = not significant.

IDS used in the various studies i

compatible formulations were therefore not consid-ered. At the end ofthe 1960s, Koch"* used poly(me-thyl methacrylate) (PMMA) as an abrasive agent in adentifrice and obtained optimal fluoride avaiiability,because PMMA does not react with fluoride. How-ever, PMMA has only a very limited polishing effect,which meant that this dentifrice had a poor cieaningeffect. For this reason, ß-calclum pyrophosphate wasdeveloped as a new abrasive agent for dentifrices. Thisled to better, but not optimal, fluoride availability. The

specially treated silica compounds that are used todayas abrasive agents are fully compatible with NaF. Thereare four placebo-controlled clinical studies in whichNaF was used in a compatible toothpaste: Koch,'^Zacherl,'^ Lu et al,''' and Jensen and Kohout,'^

Tables 2 and 3 summarize the most important studyconditions under which the respective caries-in-hibiting effect was observed. A comparison of thefluorides is very diificult. The various studies with thesame l\vs of fluoride are not even comparable, because

n, .in Intprnational Volume 26, Number 10/1995 711


Table 3 Clinical studies in which dentifrices cotitaining sodium fiuoridein a compatible formulation werecompared with a placebo*

Study (mos) LocationDentifriceusage

Otherfluoridesource

Subjectage atstarl ofstudy (ys)

Dentifrice(ppmfluoride)

BaselinevalueDMFSIDMFTI

Increase inDMFS[DMFTI

% reduction

vs placeboDMFS[DMFTI

Koch'- 36(1967)^

Zacheri" 36(1981)

Lu et al''' 12(198S)*

JensenandKohut'*(1988)'

Malmö Checked Unknown 9

Not checked Unknown

Taipei

Not checked None

NaF(1000)Placebo(0)NaF(1000)Placebo(0)

NaF(1100)Plai;ebo(0)

NaF(11001Placebo(0)NaF(1100)Placebo(0)

NaF

Placebo(0)NaF(1100)Placebo(0)

11.2817.28111,27[7.10]18.32[11,30121.07[12.431

5,6513.49]5.59[3.441

14.88

15.25

12.03

12,6

53.09

53.57enamel3.90root3.S3root

11.45[6.08119.17[9.32111.87[5.05]22.97[7.181

3.57[1.94]6.02[3.26]

2.08

3.78

0.59

1.22

0.73

1.24enamel0.14root0.43root

40.3134.81

48.3[29.7]

40.7[40.5]

25.9

51.6

41Enamelareas

67root

' The preparations containing sodium fluoride used in the variou; srudii"f" Study used own carles index.t One study but w o investigalors.

the conditions and the methods of investigation weredifferent in each case. For exampie, the yeariy increasein the incidence of caries in the various piacebogroups, a rough estimate for the increase in the generalpopulation, varied between 1.35 and 3.90 DMFS forthe products containing AtnF and between 1.24 and7.65 DMFS for the products containing NaF. Of evengreater significance is the variation in the age of thesubjects and with that the number of endangered teeth:6 to 18 years in the studies with products containingAmF and 6 to 93 years in those with productscontaining NaF.

However, it can be concluded that dentifrices that

contain sodium or amine fluoride have a sigttificantcaries-inhibiting effect. Both types of fluoride contri-bute to the maintenance of dental health. The cor-responditig figures in the studies are all valid, as longas the exact conditions under which the results wereachieved are known. Because the test conditions are sodifferent, however, it is not possible to calculateaverage values for both fluorides and to compare thesevalues with each other. This also means that there is nodefinite scientific proof for the superiority of onefluoride compound until dentifrices containing aminefluoride and sodium fluoride are tested in directclinical comparison.

712 Quintessence International Volume 26, Number 10/1005


References

1, Slookey GK, DePaola PF, Featherstone JDB, Fejerskov O, MóllerIJ, Rotberg S, et al, A eritiCLil review of the relative anticariei ericacyof sodium fluoride and sodium mo no fluoro phosphate dentifrices.Caries Res 1993;27;337-.160.

2. EinwagJ, Ausmaß der Karies und ihre Folgen in der BundesrepublikDeutsehland, Zahnärzll Pra\ I992;43:126-L'O.

slaluR m Europe and predictions of futuÎ. Manhaler TM, Catrends. Caries Res

4. Stookey GK. Are all dentiftiees (he same? [n: Wei SHY fed). ClinicalUses of Fluoride. Philadelphia: Lea & Febiger, 1985:105-131

5. Faller RV, Agrícola FO, White DJ, Salivary effects on the in viUoaetivity of sodium lluoride (NaF) and amine fluoride (Amp)dentifriees. Caries Res I99I;15:23L

6. Maithaler TM, Caries.Inhibition after seven years of unsuperviseduse of ar amine fluoride dentifrice Br Dent J 1968;124:510-515,

7. MarthaleiTM, König KCMuhlemannHR, The etffeet ofa fluoridegel used for supervised toothbrushing 15 or iO times per year, HtlvOdontoi Acta 1970:14:67-77,

8. Pati V Naujoks R, Die kariesprophylaktische Wirkung einer amin-tluoridhaltigen Zahnpasta bei Jugendlichen nach dreijährigem uti-aberwachten Gebrauch, Dtsch Zahnärztl Z l970;25:617-625.

9. Manhaier TM, Caries, in h i bit ion by an amine fluoride dentifrice.Results after 6 years in children with low caries activity, HelvOdontoi Aeta 1974;l8(Süppl S):35-44.

10, Ringelberg ML, Webster DB.Dixon DO, LeZotte DC, "fhe caries-prevention effect of amine fluorides and inorganic fluorides in amouthrinse or dentifrice after 30 months of use, J Am Dent Assoc1979:98:202-208.

11, Cahen PM, Frank RM, Turlot JC, Jung MT, Comparative unsuper-vised clinical trial on caries inhibition effect of monofiuorophos-phate and amine fluoride dentifrices after 3 years in Strasbourg,France. Community Dem Oral Epidemiol l982aO:238-241,

12, Koch G. Effect of daily supervised toothbrushing with a sodiumfluoride dentifrice, A 3.year double-blind clinical test, Odontol RevI967:18(suppl 12):48-66.

13, Zacherl DPH, A three year el in ical caries evaluation ofthe effect ofasodium fluoride-silica abrasive dentifrice. Pharmacol Ther Dent1981:6:1-7.

14, Lu KH, Yen DJC, Zacherl WA, et al. The effect of a nuoridedentifrice containing an anti-calculus agent on denial earies inchildren. J Dent Chiid 19S3;52:449-'li 1.

Í5. Jensen ME, Kohout F, The effect ofa fluoridated dentifrice on rootand coronal caries in an older adult population, J Am Dent Assoc19S8Jl7:S29-332. G

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