DENT 53 TOPICS IN DENTAL BIOCHEMISTRY 4 April 8 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 Objectives: Role of structural-bound vs topical fluoride The effect of fluoride on demineralization The effect of fluoride on 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 ) Posteruptive effect Risk of developing (mild) fluorosis Topical fluoride application Historical perspective vs current philosophy It was thought that fluoride had to be present during tooth formation to provide 'caries resistance' to the teeth. Current philosophy believes that the cariesreducing effect of fluoride is primarily achieved by its presence during active caries development by altering the dynamics of mineral dissolution and reprecipitation. The question of how fluoride prevents dental caries is significant because that is the basis for developing effective ways to use fluoride. Along with the former caries resistant concept, systemic fluoride was necessary for the maximum benefit to have enamel with less acid solubility. But the ingested fluoride comes with a risk of developing (mild) fluorosis. The current concept, which emphasizes the 'topical' or posteruptive effect of fluoride has changed the principle of how fluoride should be used. Caries resistant concept 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 When fluoride is incorporated into the enamel crystals, the crystals (fluroapatite or fluoridatedhydroxyapatite) are more perfect and less acid soluble. Therefore it was thought that fluoride had to present during tooth formation to make teeth more resistant to caries attack. Structurally-bound fluoride was believed to give lifelong protection. The more fluoride incorporated, the better the cariostatic effect. Treatment strategy according to this concept is to give systemic fluoride (e.g., vitamin) when the child is young and teeth are forming. The consequence of this treatment strategy is potential of developing mild fluorosis, which is worth if dental caries is prevented.
Why was fluoride believed to make teeth more resistant to caries attack? Fluoridated area Nonfluoridated area F in supplies Lower caries prevalence.5 ppm Teeth formed in fluoridated area Increased F content in surface enamel Water fluoridation ( years) reduced DMF Fluoride incorporated in tooth structure increases caries-resistance But. vs 3 ppm F is too small for 5% reduction in DMF! Comm Dent Oral Epid 985;3:65-7. No correlation between DMFT and enamel fluoride concentration This concept of fluoride incorporated in the tooth structure increasing caries-resistance sounds true. And it seems to work, because fluoridation substantially reduced the number of cavities in children. Teeth formed in fluoridated area had an increased F content in surface enamel. However, the increased F content in surface enamel, ppm in non-fluoridated area vs 3 ppm in fluoridated area, cannot responsible for the 5% reduction in DMF. In addition, an epidemiology study did not find any correlation between DMF and enamel fluoride concentration. Shark enamel (almost pure fluorapatite; 3, ppm F) developed caries lesions in an in situ model (4 wks), although less severe Human enamel +.% NaF rinse (daily, 4 wks) ~ Shark enamel Mineral loss F in tooth structure is not crucial 8 5 9 6 3 Ögaard B et al. Scand J Dent Res 99;99:37-377 Human Shark Human + + rinse Rinse Shark + Rinse FAP has only a moderate caries protective potential, ~ daily F-rinse. Mineral loss 8 5 9 6 3 Human enamel: CaF -like globules Human Human Human Shark Shark Shark + Rinse + + Rinse + Rinse Shark enamel: Nothing observed Shark enamel +.% NaF rinse was not as good as human enamel +.% NaF rinse does not provide enough Ca? (Ca is firmly bound) CaF -like material: caries inhibition effect of topical fluoride Ögaard B et al. Scand J Dent Res 99;99:37-377 & 988;96:9-. Fluoride in tooth structure is not crucial in caries prevention F in the tooth structure is not that important to inhibit dental caries. Shark enamel, which is almost pure fluorapatite (3, ppmf) representing the structurally bound fluoride, developed caries lesions in an in situ model, although less severe than human enamel. Researchers placed shark or human enamel in a removable appliance worn in the mouth to undergo the caries process. The results showed that after 4 weeks on normal diet (non-disturbed plaque accumulation), both human and shark enamel developed caries lesions, although less severe in shark. When subjects rinsed with.% NaF daily, which represented the topical effect of fluoride, the caries lesion was inhibited to a similar level as shark enamel. This study showed that fluroapatite has only a moderate caries protective potential, which can be obtained by daily F- rinse. In other words, topical fluoride is as effective as pure fluorapatite. Surprisingly, when the group with shark enamel had the same NaF mouthrinse, the demin was not inhibited. Why? Scanning electron microscopy showed that CaF -like material did not form on shark enamel after treated with NaF solution, but it was found on human enamel. CaF cannot form on shark enamel because shark enamel cannot provide enough Ca, which is firmly bound in the crystals. This part of the study indicated that CaF -like material plays a role in the caries inhibition effect of topical fluoride.
Oral environment Calcium fluoride-like material Forms on tooth surface exposed to high level of fluoride high level F : >3 ppm at ph 7. or > ppm at ph 5 x Slightly soluble in, dissolves in strong mineral acids and KOH Rapidly dissolve Retain on enamel > weeks phosphate Tooth surface + high level F CaF ph 4-5 F - Calcium fluoride-like material Calcium fluoride-like material is formed on the surface when teeth are exposed to high concentrations of fluoride (>3 ppm at ph 7. or > ppm at ph 5). CaF is slightly soluble in and buffers, and dissolves in strong mineral acids and KOH. CaF was unwanted in the past for preventive strategy Phosphate 'shell' reduces solubility Fluoride reservoir; releases F in acidic environment because it was thought to be rapidly lost from the oral ph 4-5 more soluble release F cavity. Later it was found that CaF is retained on ten Cate. Eur J Oral Sci 997;5:46-5. tooth enamel for more than weeks. When CaF is formed in the oral environment, phosphate ions may adsorb to the surface, forming a 'shell' and reducing the solubility. The solubility is ph dependent, more soluble at ph 4-5. Therefore, CaF serves as a fluoride reservoir which releases F in acidic environment. Clinical evidence: F in tooth structure is not crucial Okinawa study No difference in caries status in young adults (8- years old) who received fluoridated only until about 5-8 years old (3 years discontinued) vs those who never received fluoridated. DMFT Fluoridated 8.9 + 4.79 Nonfluoridated.73 + 5.48 NS Discussion: (group of 6-8) From this Okinawa study, although DMFT between groups were not different which is the main conclusion of the study, DMFS were significantly different. How can you explain the result? DMFT DMFS Fluoridated 8.9 + 4.79 5. + 9.4 Nonfluoridated.73 + 5.48.36 + 3.43 NS P <.5 Kobayashi et al, Comm Dent Oral Epid 99 Kobayashi et al, Comm Dent Oral Epid 99 Fluoride in the tooth structure cannot give a life-long protection. Clinical evidences: Fluoride in tooth structure is not crucial in caries prevention Okinawa study: There was no difference in caries status (DMFT) in young adults who received fluoridated only until about 5-8 years old and those who never received fluoridated. The subjects were 8- years old at the time of the study, which was 3 years after discontinuation of fluoridation. This study shows that fluoride in the tooth structure cannot give a life-long protection. Clinical evidence: F in tooth structure is not crucial Children that had fluoridation started at age (teeth already formed; no extra structural F) showed significant reduction in caries prevalence. DMFS 8 6 4 Harwick et al. Br Dent J 98 Δ= % Δ= 6 % Δ= 8 % Control Fluoride 3 4 5 Year Low level topical F is more important than F in the tooth structure. Study by Harwick et al: Children that moved into a area with fluoridation, or the fluoridation started when their teeth had already formed showed significant reduction in caries prevalence. In this study, fluoridation started when this group of children were at age (teeth fully formed, no structural fluoride). The number of carious surfaces developed afterwards was less compared to those lived in area without fluoridated. The differences between the groups increased every year, became 8% less after 4 years in the group moved to area with fluoridation at years old. 3
The caries reduction is a result of the topical effect alone, no additional fluoride in the tooth structure because the teeth were fully formed. Therefore, low level topical fluoride is more important than structurally-bound fluoride. 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 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. The primary caries-preventive mode of action of fluoride is post-eruptive topical mechanism. According to this concept, the best strategy to control caries is topical fluoride at low concentration, life-long, and frequent exposure. This concept delivers the maximum benefit of fluoride throughout life with minimal adverse effects. Major mechanisms of fluoride on caries process:. Affect bacterial metabolism Require high concentration of fluoride. 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 ;3:887-899 The major mechanisms of fluoride on the caries process are:. The effect on bacterial metabolism, which requires high concentration of fluoride. Inhibiting demineralization when fluoride is present at the crystal surfaces during acid challenge. 3. Enhancing remineralization and forming a layer of fluorapatite-like material on the crystal surfaces. Fluoride in the solution inhibits demineralization Dissolution of 3 wt% carbonated 3 wt % apatite in presence of fluoride Initial dissolution rate of CAP ppmf in acid buffer Initial dissolution rate of HAP 3 ppmf in acid buffer Featherstone JDB et al. J Dent Res 99;69:6-5 ppmf in the acid buffer reduced the dissolution rate ~ /3 (to the same level as HAP) 3 ppm F reduces ~ 4% (log) No measurable reduction in solubility of 3% CAP (~ enamel) with ppmf incorporated F in the aqueous phase Adsorbed to the crystal surface Protect against acid dissolution F inhibits demineralization This study measured the dissolution of 3 wt% carbonated apatite (similar to tooth enamel) in the presence of fluoride in the acid solution. Low level of F (e.g., ppm) in an acid solution reduced the dissolution rate of carbonated HAP to the same level as pure hydroxyapatite. 3 ppm F in the acid reduced 4% of the dissolution rate (logarithmic relationship). When F is present in the aqueous solution, it is adsorbed strongly to the surface of the crystals and acts as a potent protection mechanism against acid dissolution. In contrary, when ppm F was incorporated into the carbonated apatite, no measurable reduction in the solubility is observed. This study showed that fluoride ions in the fluid phase are much more effective in inhibiting demineralization than fluoride incorporated into the crystals at levels found in enamel. 4
Enamel samples subjected to solutions varying in ph and F conc. Mineral loss (Calcium) Fluoride in the solution inhibits demineralization Fluoride, - ppm ph ~ caries formation Fluoride (even low concentration) reduces rate of mineral dissolution A series of experiments investigated fluoride in solution (between - ppm) in the ph range that caries occurs (ph 4-5). Enamel specimens were subjected to solutions varying in ph and F concentration. The amount of mineral lost during demineralization is a function of ph and fluoride. Fluoride (even low concentration) is an important determinant of the rate of mineral dissolution. ten Cate JM, van Loveren C. Fluroide Mechanisms. Dent Clin N Am 999;43:73-74. F enhances remineralization Enamel crystal (Carbonated apatite) Partially dissolved crystal FAP-like veneer Acid Ca, P, F Demin Remin Adapted from Featherstone JDB JADA ;3:887-99. 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 When enamel dissolves in acid, the partially demineralized crystals act as nucleators for crystal growth. Fluoride enhances remineralization by adsorbing to the crystal surface, and attracting calcium ions, followed by phosphate ions, leading to new mineral formation. The newly formed 'veneer' excludes carbonate and has a composition between HAP and FAP. The new 'veneer' crystals have low solubility similar to that of acid-resistant mineral fluorapatite. Hence the crystal surfaces become much less soluble. This FAP-like coating precipitated in the crystal surface is the major contribution to reduce enamel solubility, not structurally-bound F incorporated during tooth formation. Arrested enamel caries Remineralized area has higher acid resistance Arrested enamel caries nd Demin nd Demin Arrested enamel lesion had higher resistance to acid challenge than the adjacent area Koulourides T, Cameron B J Oral Pathol 98;9:55-69 Lesion surface Higher F content Remineralized area has higher acid resistance. It was observed that arrested enamel lesions had higher acid resistance than the adjacent sound enamel. Acquired acid resistance is the phenomenon of decalcified dental tissue remineralizes and obtains fluoride, thus inheriting protection to further demineralization. In this experiment, reserachers put teeth with natural arrested lesions in acid. The adjacent sound enamel developed a new lesion, but the area of arrested caries was fine. The lesion area, especially at the surface, has higher fluoride content than the adjacent sound enamel. 5
Fluoride has greater effect on lesion progression than initiation Backer Dirks O. J Dent Res Culemborg (no F;. ppm) (n=436) Tiel (Fluoridation; ppm) (n=46) 966;43:53 Age 9 Age 5 Total Age 9 Age 5 Total Sound 4 86 3 54 63 38 44 7 7 White spot (arrested) 59 5 8 64 54 45 4 8 White spot (active) 3 6 6 64 34 7 4 8 49 4 7 Cavity 3 45 5 Fluoride has greater effect on lesion progression than lesion initiation: This study done in two Dutch towns, one had fluoridation, the other did not. Culemborg, without fluoridated, showed that 45 teeth (from total of 436 teeth) progressed into the cavities when the children were followed from age 8 to 5. In Tiel, with fluoridated, only 5 from 46 teeth (.5%) progressed to cavities, compared to 45 teeth (~%) in Culemborg. In both cities, more than % of the sound teeth had developed white spot lesions. But the number of lesions progressed to active white spot were smaller in Tiel where the was fluoridated. The lesion appearance was different. In Culemborg, the lesions had white, chalky surfaces, while the lesions in Tiel tended to have shiny, glossy surfaces. Summary: 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) Principal mechanisms of fluoride actions rely on the presence of fluoride in saliva, in the plaque at the tooth surface, and in the fluid among the crystals in the subsurface lesion. Primary action of fluoride occurs topically after tooth eruption and the benefits continue throughout life as long as F is delivered to the microenvironment of the teeth. 6
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 The clinical effect of fluoride can be optimized by using delivery methods that bring F to the tooth surface or into the plaque, rather than incorporating F into the mineral during tooth development. The frequency of fluoride exposure to the tooth surface is important. These delivery methods are topical sources that continually provide low levels of F in beverages and foods, dental products, and drinking. Discussion: (group of 3-4) Give some examples of topical source that can provide low level of F continuously. Beverages and foods Toothpastes Mouthrinse Drinking Recommended references. Ten Cate JM, van Loveren C. Fluoride Mechanisms. Dent Clin North Am 999;43(4):73-74.. Featherstone JD. The science and practice of caries prevention. J Am Dent Assoc ;3:887-899. 3. Ten Cate JM. Current concepts on the theories of the mechanism of action of fluoride. Acta Odontol Scand 995:57:35-39. 4. Fejerskov O. Changing paradigms in concepts on dental caries: Consequences for oral health care. Caries Res 4;38:8-9. 5. ADA Reports. Position of the American Dietetic Association: The impact of fluoride on health. 5;5:6-68. 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? 7