• Role of fluoride on dental caries

• Role of fluoride on the prevalence of dental fluorosis

• The effect of fluoride on plaque bacteria

Objectives:

DENT 5302 TOPICS IN DENTAL BIOCHEMISTRY

4 April 2007

Outline

Overview of fluoride

Fluoride, dental caries, and fluorosis: Historical perspective

Structural-bound fluoride

Calcium fluoride-like material

Fluoride in saliva and dental plaque

How does fluoride work? (anticaries mechanisms)

Effect of fluoride on plaque bacteria

Potent inhibitor of many enzymes

Elimination by kidneys

Avid calcified tissue seeker

Inhibit and even reverse the formation of dental caries

Fluoride

Halogen group

The most electronegative element

13th most abundant in the crust of the earth

Found in virtually all inanimate and living things

F- + H+ HF Hydrofluoric acid (pKa ~ 3.4)

Fluorine:

Fluoride:

Fluoride: ionic form of fluorine

Remarkable decline in dental caries

Systemic and topical fluoride

F: The cornerstone of modern preventive dentistry

Dental fluorosis

Reversible gastric disturbances

Skeletal fluorosis

Death

when large doses are taken acutely

when lower doses are taken chronically

Fluoride is a hazardous substance

Water fluoridation

Top 10 great public health achievements

of the 20th century (CDC)

Regular consumption of drinking water with fluoride

Reduction of dental caries

Mottled enamelEndemic in several regions of the southwestern USA

McKay FS. The relation of mottled enamel to caries. J Am Dent Assoc 15:1429-1437, 1928.

“…these mottled enamel cases…are singularly

free from caries.”

Colorado Springs

? substance in drinking water ?

Mottled enamel = Dental fluorosis

Fluoride, Dental Caries, and Fluorosis

F

Dean HT et al., Domestic water and dental caries: V. Additional studies of the relation of fluoride domestic waters to dental caries experience in 4425 white children, aged 12-14 years, of 13 cities in 4 states.

Public Health Rep 57:1155-1179, 1942.

Water fluoride level ~ 1 ppm

Dean et al: various levels of fluoride in most water supplies

Caries prevention

Low prevalence of dental fluorosis

Dental FluorosisHypomineralization of enamel from excessive fluoride ingestion

during tooth development

Mild fluorosis (common) Severe fluorosis (rare)

Minor cosmetic defect Increased caries risk: Pitting & Loss outer enamel

Overintake of fluoride from 0-6 year old

Generally less in primary teeth (develop prenatally)

Most critical between 15-30 months of age: maxillary central incisors

Optimal water F level (~ 1 ppm)

20 % prevalence of very mild or mild fluorosis

Dentistry: Mild fluorosis is an acceptable tradeoff for

caries prevention

Esthetic: ‘mild’ cosmetic defect ?

Why are we concerned about dental fluorosis?

The prevalence of fluorosis has increased

No fluorosis: 27 % dissatisfied with their tooth color

Mild fluorosis: 50% dissatisfied

Water Fluoridation

EPA (Environmental Protection Agency)

Max. Contaminant Level (Primary Drinking Water Standards) = 4 ppm F

Naturally existed F in some municipal water & wells : 4-8 ppm F or higher

1945

Grand Rapids

Michigan

1948: Grand Rapids had 60% less DMFT than Muskegon ‘control’ city

Optimal level: 0.7 - 1.2 ppm F

Colder climates drink less water need higher fluoride level

USA: 67% (170 millions) on public water

system receive fluoridated water

Centers for Disease Control and Prevention, 2002

Halo effect

Persons not residing in fluoridated communities

Foods and beverages produced with fluoridated

water

The most cost-effective community-based approach for caries prevention

Direct annual cost of fluoridation: $ 0.68-3.0 per person per year

$1 invested in water fluoridation saves > $38 in treatment costs

Discussion: (group of 6-8)

1. The optimal level of fluoride in water as determined by this graph is 1 ppm.

What are the rationales?

2. Why in Minnesota the level of added fluoride in water varies from 0.7 to

1.2 ppm?

How does fluoride work?

Systemic incorporation into enamel during development

‘More perfect’ enamel crystals

Less acid soluble

Historical perspective

The more fluoride incorporated, the better cariostatic effect

Shark enamel (100% fluoroapatite) can develop caries lesion!

Øgaard B et al. Scand J Dent Res 96:209, 1988. Microradiographic study of demineralization of shark enamel in a human caries model.

Cariostatic effect of fluoride

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, affect

plaque bacteria.

Current philosophy

Change tooth morphology

Effect on plaque bacteria

Inhibit demineralization and enhance remineralization process

Goal: Try to maximize benefit with minimal adverse effects

MORE IS NOT NECESSARILY BETTER!

Controversial and not universally accepted

Debatable: need much higher concentration of fluoride to be effective

Cariostatic Mechanism of Fluoride

Effect of fluoride on plaque bacteria

1940: Fluoride inhibited carbohydrate metabolism in pure cultures of

streptococci and lactobacilli.

Bibby BG, van Kesteren M. The effect of fluoride on mouth bacterial.

J Dent Res 1940:19;391-402.

Fluoride affects oral bacteria and dental plaque ecology

IMPLY a reduced risk of caries

F inhibits bacterial adsorption

F reduces proportion of cariogenic bacteria in dental plaque

F decreases acid production

In vitro: 9500 ppm F in solution inhibit bacterial adsorption to hydroxyapatite

Clinical: rinses & toothpaste with Sn or amine F reduce plaque deposit

Clinical: only high concentration of fluoride works!

No difference in subjects from area upto 21 ppm F in water

Reduced MS in plaque after daily use of APF gel (12,300 ppm F)

Chemostat: 19 ppm F prevent MS from growing to a larger proportion

Fluoridated water or daily rinse with 0.2% (~900 ppm) NaF solution

Reduce 0.1 - 0.2 unit in pH drop after a sucrose challenge

No effect after 0.05 % (~200 ppm) rinse

Effect on dental plaque bacteriaEffect on dental plaque bacteria

Bound to enzymes

- Enolase

- Proton-extruding ATPase

Cytoplasmic acidification

H+ + F- HF

HF

HF forms when external pH is lower than pKa (3.4)

H+ + F-

Accumulation of H+

Accumulation of fluoride

Fluoride enters cell as HF (not F-)

Antimicrobial effect of FAntimicrobial effect of F

1122

‘Fluoride has inhibitory effects on plaque metabolism’

In vitro: 9500 ppm F in solution inhibit bacterial adsorption to hydroxyapatite

Reduced MS in plaque after daily use of APF gel (12,300 ppm F)

Fluoridated water or daily rinse with 0.2% (~900 ppm) NaF solution

reduced 0.1 - 0.2 unit in pH drop after a sucrose challenge

No effect in pH drop after 0.05 % (~200 ppm) NaF rinse

No reduction of MS in plaque in subjects from area upto 21 ppm F

in drinking water

How much fluoride is needed for antimicrobial effect?How much fluoride is needed for antimicrobial effect?

To what extent do these effects contribute to caries prevention?

Effective at a few ppm F

ppm F to reduce solubility << ppm F for antimicrobial effect

At pH 4-5

Fluoride in solution

reduces the amount of

enamel dissolved

The most important cariostatic mechanism of F: De- and Remineralization

How much fluoride is needed to reduce enamel solubility?How much fluoride is needed to reduce enamel solubility?

Lower dissolution rate

F- substitute OH-

Decrease crystal

dimension(F- is smaller)

Strong attraction with calcium(F: the most

electronegative)

Stabilize the lattice structure

Hydroxyapatite lattice structure

FOHCa

Improve the crystallinity

• F- fill vacancy• H-bond with O

H-bond

F

Fluoride in HAP crystal:Fluoride in HAP crystal:Structurally-bound FStructurally-bound F

‘Fluorhydroxyapatite’ ‘Fluoridated hydroxyapatite’ ‘Fluoroapatite-like material’

Range from 5-50 ppm wet weight

1% is available as fluoride ion

15-75% is ionizable

Some firmly-bound fluoride (bacterial uptake?)

Plaque matrix concentrate fluoride from saliva:

How much fluoride is in dental plaque?

+ve charges in matrix & on bacterial surface attract Ca2+

Ca2+ bind fluoride.

Calcium fluoride

Oral mucosa?

Plaque fluid F and Saliva F after 1-min rinse with

NaF ( 900 ppm) or MFP ( 1000 ppm)

Plaque fluid F

Saliva F

F decreases exponentially

Elevated for ~ 3 hours

Clinical study:

F level in saliva and

plaque remained for 18 h

F reservoir

Ekstrand J. Enhancing effects of fluoride. Cariology for the nineties, 409-420.

ten Cate JM, van Loveren C. Fluroide Mechanisms. Dent Clin N Am 1999;43:713-742.

Adapted from Sjögren T, Birkhed D. Caries Res 1993;27:474.

Age 26 + 8 24 + 8

Male / female 9 / 14 13 / 11

Salivary flow (ml/min) 1.5 + 0.3 1.5 + 0.5

MS (log CFU/ml saliva) 4.2 + 1 5.3 + 1

Lactobacilli (log CFU/ml saliva) 3.8 + 0.8 4.5 + 1.2

Brushing time (min) 2.8 + 1.6 2.6 + 2

Amount of toothpaste (g) 1.1 + 0.5 1.2 + 0.6

DMFT 4.8 + 5 * 18.9 + 7.3

Decay surface 0 * 3.8 + 3.1

Rinse frequency 1.5 + 0.7 * 3.6 + 1.9

Amount of water to rinse (ml) 70 + 60 * 190 + 10

F in saliva (immediate) (mM) 0.6 + 0.4 * 0.3 + 0.3

F in saliva (accumulate) (mM·min) 6.9 + 3.9 * 3.9 + 2.9

CharacteristicsLow

Caries-Active High

Caries-Active

Discussion: (group of 6-8) What characters affect caries development?

Discussion: (group of 6-

8)

I believe that the main anticaries effect of fluoride is by

changing the equilibrium towards remineralization,

not antimicrobial effect.

Why?

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. Gordon Nikiforuk. Understanding Dental Caries 1. Etiology and Mechanisms, Basic and Clinical Aspects. Basel; New York: Karger 1985. Chapters 4.

4. Gordon Nikiforuk. Understanding Dental Caries 2. Prevention, Basic and

Clinical Aspects. Basel; New York: Karger 1985. Chapters 3.

5. van Loveren C. Antimicrobial activity of fluoride and its in vivo importance:

Identification of research questions. Caries Res 2001;35(suppl 1):65-70.

6. Fejerskov O. Changing paradigms in concepts on dental caries:

Consequences for oral health care. Caries Res 2004;38:182-191.

7. Ten Cate JM. Review on fluoride, with special emphasis on calcium fluoride mechanisms in caries prevention. Eur J oral Sci 1997;105:461-465.