DENT 5302 TOPICS IN DENTAL BIOCHEMISTRY 6 April 2007 Anticaries Mechanism of Fluoride The Effect on De/Remineralization Objectives: • Role of structural-bound vs topical fluoride • The effect of fluoride on demineralization • The effect of fluoride on remineralization
Outline • Caries resistance concept vs Current philosophy • Why it was believed that structurally-bound F was important? • What are the conflicting evidences? • How fluoride inhibits demineralization • How fluoride enhances remineralization
Historical perspective Fluoride presented during tooth formation provided 'caries resistance' Current philosophy Caries-reducing effect of fluoride is from its presence during active caries development to alter the dynamics of de- and remineralization Why do we want to know how fluoride prevents dental caries? Basis to develop effective ways of using fluoride Systemic F for the maximum benefit (less soluble enamel) Risk of developing (mild) fluorosis Posteruptive effect Topical fluorideapplication
Historical perspective: Fluoride & Caries Resistance Caries Resistance Concept Fluoride present during tooth formation provided 'caries resistance' Systemic incorporation of fluoride into enamel during development ‘More perfect’ enamel crystals Less acid soluble • Structurally-bound fluoride is life-long protection. • The more fluoride incorporated, the better the cariostatic effect. Treatment strategy according to this concept: Systemic F for the maximum benefit (less soluble enamel) Consequence Risk of developing (mild) fluorosis
Water fluoridation (10 years) reduced DMF Fluoride incorporated in tooth structure increases caries-resistance Is that true?
Non- fluoridated area Fluoridated area Why was fluoride believed to make teeth more resistant to caries attack? F in water supplies Lower caries prevalence 2.5 ppm Teeth formed in fluoridated area Increased F content in surface enamel But….2000 vs 3000 ppm F is too small for 50% reduction in DMF! Comm Dent Oral Epid 1985;13:65-7. No correlation between DMFT and enamel fluoride concentration
Human + rinse Human Shark F in tooth structure is not crucial • Shark enamel (almost pure fluorapatite; 30,000 ppm F) developed caries lesions in an in situ model (4 wks), although less severe • Human enamel + 0.2% NaF rinse (daily, 4 wks) ~ Shark enamel Ögaard B et al. Scand J Dent Res 1991;99:372-377 FAP has only a moderate caries protective potential, ~ daily F-rinse.
Human Shark Human Shark + Rinse + Rinse • Shark enamel + 0.2% NaF rinse was not as good as human enamel + 0.2% NaF rinse does not provide enough Ca? (Ca is firmly bound) Human enamel: CaF2-like globules Shark enamel: Nothing observed 1 • CaF2-like material: caries inhibition effect of topical fluoride Ögaard B et al. Scand J Dent Res 1991;99:372-377 & 1988;96:209-211.
Calcium fluoride-like material • Forms on tooth surface exposed to high level of fluoride • Slightly soluble in water, dissolves in strong mineral acids and KOH high level F : >300 ppm at pH 7.2 or >100 ppm at pH 5 x Rapidly dissolve • Retain on enamel > 2 weeks Unwanted phosphate Oral environment Tooth surface + high level F CaF2 F- pH 4-5 • Phosphate 'shell' reduces solubility • Fluoride reservoir; releases F in acidic environment pH 4-5 more soluble release F ten Cate. Eur J Oral Sci 1997;105:461-5.
Fluoridated water 8.92 + 4.79 Nonfluoridated water 10.73 + 5.48 DMFT NS Clinical evidence: F in tooth structure is not crucial Okinawa study No difference in caries status in young adults (18-22 years old) who received fluoridated water only until about 5-8 years old (13 years discontinued) vs those who never received fluoridated water. Kobayashi et al, Comm Dent Oral Epid 1992 Fluoride in the tooth structure cannot give a life-long protection.
Fluoridated water 8.92 + 4.79 15.02 + 9.14 Nonfluoridated water 10.73 + 5.48 20.36 + 13.43 DMFT DMFS NS P < 0.05 Discussion: (group of 6-8) From this Okinawa study, although DMFT between 2 groups were not different which is the main conclusion of the study, DMFS were significantly different. How can you explain the result? Kobayashi et al, Comm Dent Oral Epid 1992
= 27 % • = 26 % • = 20 % Clinical evidence: F in tooth structure is not crucial Children that had water fluoridation started at age 12 (teeth already formed; no extra structural F) showed significant reduction in caries prevalence. Harwick et al. Br Dent J 1982 Low level topical F is more important than F in the tooth structure.
Current philosophy: Fluoride & Caries Control Caries Controlled Concept The caries-reducing effect of fluoride is primarily achieved by its presence during active caries development at the plaque/enamel interface where it directly alters the dynamics of mineral dissolution and reprecipitation, and to some extent, affects plaque bacteria. Primary mode of action of fluoride is post-eruptive topical effect. Treatment (preventive) strategy according to this concept: Topical fluoride; low level, frequent exposure, life-long Maximize benefit (throughout life) with minimal adverse effects
Major mechanisms of fluoride on caries process: 1. Affect bacterial metabolism Require high concentration of fluoride 2. Inhibit demineralization Fluoride present at the crystal surfaces during acid challenge 3. Enhancing remineralization Form a layer of fluorapatite-like material on the crystal surfaces Featherstone JDB. The science and practice of caries prevention. JADA 2000;131:887-899
Dissolution of 3 wt% carbonated apatite in presence of fluoride 3 wt % Initial dissolution rate of CAP 1 ppmF in acid buffer Initial dissolution rate of HAP F in the aqueous phase Adsorbed to the crystal surface Protect against acid dissolution Featherstone JDB et al. J Dent Res 1990;69:620-5 Fluoride in the solution inhibits demineralization • 1 ppmF in the acid buffer reduced the dissolution rate ~ 1/3 (to the same level as HAP) • 3 ppm F reduces ~ 40% (log) No measurable reduction in solubility of 3% CAP (~ enamel) with 1000 ppmF incorporated 3 ppmF in acid buffer
Fluoride in the solution inhibits demineralization Enamel samples subjected to solutions varying in pH and F conc. Fluoride (even low concentration) reduces rate of mineral dissolution Mineral loss (Calcium) pH ~ caries formation Fluoride, 1-10 ppm ten Cate JM, van Loveren C. Fluroide Mechanisms. Dent Clin N Am 1999;43:713-742.
Enamel crystal (Carbonated apatite) Acid Demin Partially dissolved crystal Ca, P, F Remin FAP-like ‘veneer’ Adapted from Featherstone JDB JADA 2000;131:887-99. Fluoride enhances remineralization Partially demineralized crystals = nucleators Fluoride ions adsorb to the crystal surface Attract Ca, P new mineral formation • The newly formed FAP-like ‘veneer’ • Exclude carbonate • Composition between HAP and FAP • Low solubility Crystal surfaces become less soluble This FAP-like coating precipitated in the crystal surface, not F incorporated during tooth formation, is the major contribution to reduce enamel solubility
Arrested enamel caries Remineralized area has higher acid resistance Acquired Acid Resistance 2nd Demin Arrested enamel caries 2nd Demin Acid challenge Arrested enamel lesion had higher resistance to acid challenge than the adjacent area Lesion surface Higher F content Koulourides T, Cameron B J Oral Pathol 1980;9:255-269
Fluoride has greater effect on lesion progression than initiation Culemborg (no water F; 0.1 ppm) Tiel (Fluoridation; 1 ppm) Backer Dirks O. J Dent Res 1966;43:503 (n=436) (n=406) Age 9 Age 15 Total Age 9 Age 15 Total 241 186 23 54 263 318 244 17 10 271 Sound 45 22 14 59 25 18 21 64 54 81 White spot (arrested) 123 26 11 26 1 64 34 27 14 8 0 49 White spot (active) 4 7 22 2 1 2 13 12 45 0 0 5 Cavity
Summary: F & De/Remineralization Principal mechanisms of fluoride actions rely on • F in saliva • F in the plaque fluid and tooth interface • F in the fluid among the mineral crystals in the lesion Primary action of fluoride • Topical; after tooth eruption • Benefits continue throughout life • (as long as F is available)
Summary: F & De/Remineralization To optimize clinical effects of fluoride: • Delivery methods that bring F to the tooth surface, saliva, plaque fluid • The frequency of fluoride exposure F incorporated into the mineral during tooth development has only minor effect
Discussion: (group of 3-4) Give some examples of topical source that can provide low level of F continuously.
Recommended references 1. Ten Cate JM, van Loveren C. Fluoride Mechanisms. Dent Clin North Am 1999;43(4):713-742. 2. Featherstone JD. The science and practice of caries prevention. J Am Dent Assoc 2000;131:887-899. 3. Ten Cate JM. Current concepts on the theories of the mechanism of action of fluoride. Acta Odontol Scand 1995:57:325-329. 4. Fejerskov O. Changing paradigms in concepts on dental caries: Consequences for oral health care. Caries Res 2004;38:182-191. 5. ADA Reports. Position of the American Dietetic Association: The impact of fluoride on health. 2005;105:1620-1628.
Discussion: (group of 6-8) If structurally bound fluoride is no longer believed to be the major mode of anticaries mechanism of fluoride, why the ADA still recommend children live in non-fluoridated area to have supplement fluoride tablets?