Amine Fiuoride Regimens.
Animal studies on caries inhibition are usually short term and involve too few subjects for meaningful analysis, however, Schmid et al. (1984b) carried out a pooled statistical analysis on 56 independant caries studies on Osbourne- Mendel rats, resulting in analysis based on 1938 rats. The analysis showed that toothpaste containing amine fluoride was significantly superior to MFP containing preparations with respect to caries prevention on smooth surfaces. In the case of initial and advanced fissure caries there was no statistically significant difference between amine fluoride and MFP preparations although both were statistically superior to the water and fluoride free toothpaste controls.
Human clinical trials on the influence of amine fluoride toothpaste on caries incidence are few (Appendix 2, Table 1) and the early trials did not meet the requirements of controlled clinical trials of caries preventive agents as adopted by the FDI in 1981 (Ainamo, 1982). Although later studies fulfilled these requirements the trials varied in design, methodology and data presentation. Results of individual trials are therefore not comparable. This is frustrating as trials have usually compared the amine fluoride regimen with fluoride free placebo. Variations in design mean that they cannot be used to evaluate the relative efficiency of various formulations against trials carried out with other fluoride regimens.
Nevertheless, clinical trials in children and adolescents using various amine fluoride toothpastes unsupervised (Marthaler, 1965, 1968, 1974; Patz and Naujoks, 1970) found a reduction in caries incidence of 7 to 30% compared to the use of non-fluoridated paste.
The effect of amine fluoride toothpaste used twice daily (with supervised brushing in school) was also investigated in a community preventive programme (Pakhomov at al. 1997). The toothpaste was provided to 12,500 children aged 3 to 12 years for 3 years. Random samples of children were selected from the programme and from a reference community at the start of
the study and after 3 years. A statistically significant reduction in mean DMFT scores was noted in 6 and 12 year olds in the programme (86% and 25% respectively) whereas 9 year olds and all three age groups in the reference community had non-significant differences in mean DMFT. Unfortunately the use of toothpaste by children In the reference community is not recorded making it difficult to draw conclusions other than that a community based fluoride toothpaste implemented programme successfully improved the caries status of children.
Two trials have been conducted against positive control toothpaste (Appendix 2, Table 1C). A 36 months clinical trial comparing amine fluoride and monoflurophosphate toothpaste (Cahen et a/., 1982) in 6 to 8 year olds showed a highly significant reduction in DMFS scores for both products compared to a placebo paste. The amine fluoride group performed notably better, but the statistical difference between the products is not reported. However Ringelberg
at al. (1979) reporting on an eighteen month clinical study on the use of amine fluoride and stannous fluoride toothpastes by school children found neither dentifrice to be significantly superior to a fluoride free control. The composition of pastes used in this trial is not reported.
It may be concluded that the use of amine fluoride toothpaste in children and adolescents, while proving beneficial compared to fluoride free pastes in preventing caries development, have not yet been established as beneficial compared with positive controls.
The use of higher concentrations of amine fluorides at less frequent intervals have also reported to have an effect on caries incidence in a wider age range (Appendix2, Table 3). Obersztyn etal. (1979, 1984) investigated military cadets aged 19 and 20 and found 6 monthly prophylaxis with a stannous fluoride paste followed by application of a stannous fluoride solution or weekly brushing with an amine fluoride gel to be highly statistically significant in reducing DMFS scores compared with no prophylaxis. However, despite the difference in frequency of the fluoride regimens the difference in effectiveness of the two was non-significant. Denes and Gabris (1991) found, in teenagers, that weekly brushing with Elmex® gel over 3 years to be significantly more effective than
use of fluoride free toothpaste alone unlike 2 to 3 weekly professional application of Elmex® fluid. However, the fluoride concentration or composition of the respective treatments was not recorded.
Ran et al., (1991) examined 112 children aged 13 and found a group brushing with Elmex® gel (1.25% F") had a significant decrease in DMFS compared with a group brushing with Elmex® toothpaste (0.125% F"). There was no significant difference between the reduction in DMFS scores between children using a placebo gel, a 0.4% F" gel and the 1.25%F" gel. Only the latter, however, resulted in no increase in DMFS score. The differences however were lost 6 months following cessation of the gel, suggesting that long term use is required for continuation of the protective effect.
Kunzel et al. (1977) reported on a 7 year study, on children aged 6 and 7, receiving professional applications of amine fluoride solutions and using amine fluoride toothpaste which resulted in a reduction of caries incidence by 42% compared to use of a placebo paste. Lincir and Rosin-Grgret (1993) and Rosin- Grgret and Lincir (1995) studied children aged 3 to 4 and 9 to 10 receiving professional applications of amine fluoride solutions. Those treated with 0.5%F' solutions monthly or 1.0%F" solutions once every two months had significant reductions in DMFS compared to those treated with solutions of lower fluoride concentration, applied less frequently. Brambilla et al. (1997) carried out an investigation on 6 year olds using a 1% fluoride toothpaste and receiving professional application of either Elmex® fluid or a non-fluoride placebo fluid twice yearly. A highly significant reduction in DMFT (23%) in first permanent molars was found in the children using the Elmex® fluid.
These investigations highlight the increased anti-caries activity obtainable by increasing the concentration or frequency of fluoride applications. But, additional benefit from the use of such topical applications in conjunction with amine fluoride toothpaste has been established (Marthaler 1970); although this was significant only for the first year, in the three year trial, when applications of amine fluoride gel were applied weekly. Ringelberg et al. (1979) also found the use of amine fluoride mouthrinse in conjunction with amine fluoride toothpaste to be more effective than either used alone (Appendix 2, Table 2). In addition
this regimen was more effective than a stannous fluoride toothpaste and sodium fluoride mouthwash combination. This is the only investigation that has shown an amine fluoride regimen to be superior to a positive control regimen but a sodium fluoride mouthrinse and placebo toothpaste regimen was equally effective.
Stannous Fluoride Regimens.
The use of stannous fluoride toothpastes in over 40 clinical trials has been estimated to result in mean caries reduction of 22% (Mellberg, 1991) and 25% (Richards and Banting, 1996) compared to placebo preparations. The variability in results has been suggested to be due to instability of the stannous ion (Richards and Banting, 1996). A few in vivo investigations on the anti-caries activity of stabilised stannous fluoride preparations have been reported (Appendix 2, Table 2B)
Klock et al. (1985) found twice daily rinsing with 0.1% Snp2 over 2 years resulted in a 33% reduction in caries compared to NaF rinsing.
Faller at si. (1995) reported on a rodent caries incidence trial. A stabilised stannous fluoride toothpaste resulted in a significantly greater reduction in caries than an unstabilised stannous fluoride toothpaste and placebo toothpaste but sodium fluoride toothpaste resulted in a similar reduction.
Human clinical trials have not yet been reported for the toothpaste. However, stabilised 0.4% stannous fluoride gel was more effective at preventing décalcification in adolescents wearing fixed orthodontic appliances, especially when brushed daily, than use of toothpaste alone (Stratemann and Shannon, 1974) and than daily mouthrinsing with 0.05% sodium fluoride mouthrinse (Boyd, 1993). Furthermore the gel, when applied 3 to 4 monthly, resulted in a trend towards decreased root caries indices following periodontal surgery compared to 5% sodium fluoride varnish (Ravald and Birkhead, 1992).
Amino-Stannous Fluoride Regimens.
Amino-stannous fluoride preparations have not been tested in clinical caries trials except for two studies on root caries (Appendix 2, Table 3). Ueberschar and Gunay (1991) found root caries incidence to be reduced post-periodontal surgery in patients using AmF 297/Snp2 rinse compared to a control group. This was close to significance (p = 0.06). Bânôczy and Names (1991) and Names et al. (1992) also found a AmF 297/Snp2 toothpaste/mouthrinse regimen to produce a reduction in root caries indices compared to a sodium fluoride toothpaste/mouthrinse regimen but the reduction was not statistically significant.
Summary
These products have not been fully investigated in controlled clinical caries trials against positive controls. Furthermore the regimens have been investigated for their effect on enamel caries, largely in children. The effect on root caries in older populations has not been investigated yet this is recognised as a high risk group and one that is expanding (Section 3).
While, the amine fluoride regimens have been established as effective against enamel caries this has largely been in comparison to fluoride free placebos. When comparing anti-microbial properties of toothpaste (Addy at a/., 1992) and using in situ models to test fluoride containing systems (Faller at si. 1995), it has been suggested that new preparations should be tested against a toothpaste commonly available to the general public. This has been termed a “benchmark control” (Addy at a/., 1992) or “gold standard” (Duckworth, 1995) and is required to assess the effect of the test product over and above that achieved by such a product. Furthermore, if the control could be standardised then comparison of agents would be simplified (Binney at a/.,1996).
It would seem rational to apply this to clinical caries trials. However, it is possible that different active systems exhibit their anti-caries effects in different ways, the choice of this control is therefore important if the assessment of a new product is to be meaningful. An alternative is to compare the test product with a control identical to the test product except for substitution of the active
ingredient. The control active ingredient needs to be carefully selected so that it is, not only compatible with the other ingredients in the product, but is also recognised as the current accepted standard regimen. As discussed previously (Section 3) this would arguably be sodium fluoride with a suitably compatible abrasive. This product has indeed been recognised as a reference standard by the American Dental Association to which other toothpastes in the United States are compared (Faller etal. 1997).