Caries Formation and the Effects of Various Fluorides in Treatment

1. Caries Formation and the Effects of Various Fluorides in Treatment ©iStockphoto.com ©iStockphoto.com/Günay Mutlu ©iStockphoto.com/Nina Shannon

2. Learning objectives • To summarise the caries formation process and fluoride mode of action • To discuss the different types of fluoride available and their relative efficacies

3. Caries development process ©iStockphoto.com ©Sciencephotolibrary.com ©iStockphoto.comPeter Nguyen

4. The five stages of caries development1,2 1 Initial subsurface demineralization Reversible lesion 1. Initial subsurface demineralization 2 Extension of demineralized zone towards dentine 3 Collapse of surface layer to form cavity Irreversible lesion 3. Collapse of surface layer to form cavity 4 Extension of caries lesion into dentine 5 Extension of caries into pulp Possible formation of apical abscess 1. Collins WJN, et al. A Handbook for Dental Hygienists. 3rd edition. Oxford: Wright, 1992.2. Clarkson BH, et al. Caries Res 1991;25:166-173.

5. Caries sites • Pit-and-fissure caries develop initially in the fissures of the teeth, but can spread into the dentine • Smooth-surface caries are most common on interdental surfaces, but can occur on any smooth surface of the tooth • Root caries attack the cementum and dentine, which becomes exposed as gums recede

6. Caries lesions Figure 1. Sectioned, extracted tooth with three caries lesions Figure 2. A single caries lesion showing bacterial invasion in dentinal tubules

7. Salivary [Ca2+] Low pH Salivary [PO43-] Salivary [F-] Demineralization and remineralization • Tooth enamel is involved in continuous demineralization and remineralization in the oral environment • The progression or reversal of caries depends upon the balance of demineralization and remineralization Demineralization Remineralization

8. The natural demineralization and remineralization process • Cyclical changes in the oral environment result in alternating periods of demineralization and remineralization at the tooth-plaque interface1 Adapted from Aoba T. Oral Dis 2004;10:249-257. 1. Gao XJ, et al. J Dent Res 2001;80:1834-1839.

9. Fluoride mode of action

10. Sources of fluoride • Topical agents • Fluoridated water • Other ingested sources ©iStockphoto.com ©iStockphoto.com/Adam Gryko ©iStockphoto.com/ Wolfgang Amri ©iStockphoto.com

11. F- Fluoride effect on remineralization and demineralization of enamel Promote remineralization1 Inhibit acid generation from plaque bacteria4 Reduce demineralization2,3 1. Silverstone LM. Clinical uses of fluoride 1985;153-175.2. Featherstone JD, et al. J Dent Res 1990;69:620-625.3. Aoba T. Crit Rev Oral Biol Med 1997;8:136-153.4. Briner WW & Francis MD. Arch Oral Biol 1962;7:541-550.

12. Fluoride inhibits demineralization: Formation of FAP • Fluoride prevents demineralization through formation of fluorohydroxyapatite (FAP)

13. Fluoride inhibits demineralization: Helps prevent mineral loss • Fluoride prevents demineralization through inhibition of mineral loss from enamel

14. Fluoride promotes remineralization: Formation of a fluoride reservoir • Fluoride promotes remineralization through formation of a fluoride reservoir

15. Fluoride promotes remineralization: Creation of supersaturated solutions • Fluoride promotes remineralization through creation of supersaturated solutions

16. Fluoride inhibits plaque bacteria invitro1-4 • At low pH, fluoride combines with hydrogen ions and diffuses into oral bacteria as hydrogen fluoride (HF) • Inside the cell HF dissociates, acidifying the cell and releasing fluoride ions • Fluoride ions inhibit glycolysis • As fluoride is trapped inside the cell this becomes a cumulative process 1. Hamilton IR, et al. Fluoride in dentistry. Copenhagen: Munksgaard; 1996. p23-51.2. Whitford GM, et al. Infect Immun 1977;18:680-687.3. Van Loveren C. J Dent Res 1990;69:676-681.4. ten Cate JM. Acta Odontol Scand 1999;57:325-329.

17. Types of fluoride

18. Types of fluoride overview • The use of fluoride dentifrices has reduced the incidence of caries by 9.7%–24.9%1 • Sodium fluoride (NaF) and sodium monofluorophosphate (MFP) are the most common sources of fluoride in dentifrices • These can be used alone or in combination 1. Twetman S, et al. Acta Odontologica Scandinavica 2003;61;6:347-355.2. Volpe AR, et al. Am J Dent. 1993;6:S13-S42.3. Sullivan RJ, et al. J Clin Dent. 1995;6:135-138.

19. Fluoride formulation factors and mode of action • Not all fluoride toothpastes are the same • Different fluoride source, pH and choice of formulation can affect fluoride uptake1,2 • Fluoride needs to be deposited and slowly released to be effective following brushing3 • The amount of fluoride released into saliva and adsorbed by enamel during the period after brushing is critical 1. Friberger P. Scand J Dent Res 1975:83;339-344.2. White DJ, et al. Caries Res 1986;20:332-336.3. ten Cate JM. Eur J Oral Sci 1997;105:461-465.

20. Factors that influence fluoride delivery • Fluoride source (NaF, MFP, stannous fluoride) • For example, MFP requires activation by hydrolysis by salivary phosphatase to release active F- • Fluoride concentration in formulation • Formulation properties • pH will drive different fluoride modes of action • Ingredients such as divalent cations (eg, Ca2+) can reduce the amount of available fluoride • Ingredients such as high levels of phosphates can reduce fluoride uptake

21. NaF vs MFP: Supporting studies • Fluoride ions are freely available in NaF whereas MFP requires hydrolysis by salivary phosphatase to release free fluoride, the biologically active species1,2 • In vitro, in situ, animal and clinical studies all support that NaF has superior anti-caries efficacy to MFP in an equivalent silica base formulation • A calcium carbonate-based MFP formulation contains abrasive particles which are thought to complement or enhance fluoride efficacy2 • Meta-analysis of 12 clinical studies: 6.8% clinically and statistically significant greater benefit with NaF vs MFP3 • Study in adolescents: 7% greater benefit with NaF than MFP4 1. Newby CS, et al. J Clin Dent 2006;17:94-99.2. Lynch RJ, et al. Int Dent J 2005;55:175-178.3. Bowen WH. J Royal Soc Med 1995;88:505-507.4. Stephen KW, et al. Int Dent J 1994;44:287-295.

22. Comparison of fluoride performance in dentifrices

23. Comparison of marketed NaF and MFP in an in situ caries model1 Results • Surface hardness recovery and fluoride uptake were significantly (p<0.001) greater with NaF (1100ppm F) than MFP (1100ppm F) after 14 days of treatment 1. Zero DT, et al. Caries Res 2007;41:268-334.

24. Efficacy of marketed NaF and MFP dentifrices in an in situ caries model1 Results • Remineralization potential and fluoride uptake were significantly greater for a dentifrice containing 1350ppm F NaF/silica base than for a dentifrice containing 1000ppm F MFP/450ppm F NaF/dicalcium phosphate base * * * * Data expressed as least square mean ± S.D. n=39*p<0.01 compared with 1000ppm F MFP/450ppm NaF • Zero DT, et al. Presented at the 85th General Session & Exhibition of the International Association for Dental Research (IADR), New Orleans, USA, 2007.

25. Surface microhardness changes and fluoride uptake with marketed NaF and MFP in an in vitro caries cycling model1 Results • At least 25% greater surface microhardness was observed with NaF than with MFP after 20 days of treatment (p<0.05), as a result of improved remineralization and increased fluoride uptake • NaF in silica base A gave greater surface microhardness and fluoride uptake after 20 days of treatment (p<0.05) than NaF in silica base B • All dentifrices tested contained 1100ppm F 1. Newby EE, et al. 54th ORCA Congress. July 2007. Caries Res 2007;41:328 (abs 173).

26. Conclusions from in situ and in vitro studies comparing NaF with MFP1–3 • NaF (1100ppm F/silica base) showed greater efficacy with regard to surface hardness recovery and fluoride uptake than MFP (1100ppm F/dicalcium phosphate base) in an in situ caries model1 • A second in situ study similarly demonstrated that NaF (1350ppm F) in a silica base provided greater remineralization potential and fluoride uptake than a combination of MFP (1000ppm F) and NaF (450ppm F) in a dicalcium phosphate base2 • This in situ evidence is supported by data from an vitro study.3 Taken together, these results suggest: • NaF in silica base provides superior anti-caries potential to MFP formulations • Different formulations of NaF in silica base have different remineralization potentials and fluoride uptake 1. Zero DT, et al. Caries Res 2007;41:268-334. 2. Zero DT, et al. Presented at the 85th General Session & Exhibition of the International Association for Dental Research (IADR), New Orleans, USA, 2007.3. Newby EE, et al. 54th ORCA Congress. July 2007. Caries Res 2007;41:328 (abs 173).

27. Summary • Dental caries is a progressive disease characterised by demineralization (dissolution) and destruction of enamel and dentine • Fluoride can reduce caries by preventing demineralization and promoting remineralization of tooth surfaces and can also inhibit plaque acid production • Four fluoride sources are used routinely in dentifrices: sodium fluoride (NaF); sodium monofluorophosphate (MFP); amine fluoride (AmF) and stannous fluoride (SnF2) • While investigations continue to reveal the relative benefits and mode of action of these different fluoride sources, there is a strong set of data which indicates that NaF is a superior anti-caries agent to MFP • Optimizing the base formulation can increase fluoride bioactivity without altering the fluoride level, with the potential to enhance anti-caries efficacy