Transcript Slide 1

DENT 5302 TOPICS IN DENTAL BIOCHEMISTRY
4 April 2007
Objectives:
• Role of fluoride on dental caries
• Role of fluoride on the prevalence of dental fluorosis
• The effect of fluoride on plaque bacteria
Outline
Overview of fluoride
Fluoride, dental caries, and fluorosis: Historical perspective
How does fluoride work? (anticaries mechanisms)
Effect of fluoride on plaque bacteria
Structural-bound fluoride
Calcium fluoride-like material
Fluoride in saliva and dental plaque
Fluoride
Fluoride: ionic form of fluorine
Fluorine:
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)
Fluoride:
Potent inhibitor of many enzymes
Elimination by kidneys
Avid calcified tissue seeker
Inhibit and even reverse the formation of dental caries
F: The cornerstone of modern preventive dentistry
Remarkable decline in dental caries
Systemic and topical fluoride
Water fluoridation
Top 10 great public health achievements
of the 20th century
(CDC)
Fluoride is a hazardous substance
when large doses are taken acutely
when lower doses are taken chronically
Dental fluorosis
Reversible gastric disturbances
Skeletal fluorosis
Death
Fluoride, Dental Caries, and Fluorosis
Mottled enamel
Endemic in several regions of the southwestern USA
Colorado Springs
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.”
Mottled enamel = Dental fluorosis
F
? substance in drinking water ?
Regular consumption of drinking water with fluoride
Reduction of dental caries
Dean et al: various levels of fluoride in most water supplies
Water fluoride level ~ 1 ppm
Caries prevention
Low prevalence of dental fluorosis
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.
Dental Fluorosis
Hypomineralization of enamel from excessive fluoride ingestion
during tooth development
Mild fluorosis (common)
Minor cosmetic defect
Severe fluorosis (rare)
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
Why are we concerned about dental fluorosis?
The prevalence of fluorosis has increased
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 ?
No fluorosis: 27 % dissatisfied with their tooth color
Mild fluorosis: 50% dissatisfied
Water Fluoridation
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
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
USA: 67% (170 millions) on public water
system receive fluoridated water
Centers for Disease Control and Prevention, 2002
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
Halo effect
Persons not residing in fluoridated communities
Foods and beverages produced with fluoridated
water
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?
Historical perspective
Cariostatic effect of fluoride
Systemic incorporation into enamel during development
‘More perfect’ enamel crystals
Less acid soluble
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.
Current philosophy
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.
Cariostatic Mechanism of Fluoride
Change tooth morphology
Controversial and not universally accepted
Effect on plaque bacteria
Debatable: need much higher concentration of fluoride to be effective
Inhibit demineralization and enhance remineralization process
Goal: Try to maximize benefit with minimal adverse effects
MORE IS NOT NECESSARILY BETTER!
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
Effect on dental plaque bacteria
F inhibits bacterial adsorption
In vitro: 9500 ppm F in solution inhibit bacterial adsorption to hydroxyapatite
Clinical: rinses & toothpaste with Sn or amine F reduce plaque deposit
F reduces proportion of cariogenic bacteria in dental plaque
Chemostat: 19 ppm F prevent MS from growing to a larger proportion
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)
F decreases acid production
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
Antimicrobial effect of F
HF forms when external pH is lower than pKa (3.4)
H+ + F-
HF
Fluoride enters cell as HF (not F-)
HF
H+ + FAccumulation of fluoride
Accumulation of H+
1
2
Bound to enzymes
Cytoplasmic acidification
- Enolase
- Proton-extruding ATPase
‘Fluoride has inhibitory effects on plaque metabolism’
To what extent do these effects contribute to caries prevention?
How much fluoride is needed for antimicrobial effect?
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 to reduce enamel solubility?
ppm F to reduce solubility << ppm F for antimicrobial effect
At pH 4-5
Fluoride in solution
reduces the amount of
enamel dissolved
Effective at a few ppm F
The most important cariostatic mechanism of F: De- and Remineralization
Fluoride in HAP crystal:
Structurally-bound F
F- substitute OHDecrease
crystal
dimension
(F- is smaller)
Strong attraction
with calcium
(F: the most
electronegative)
F
OH
Ca
Hydroxyapatite lattice structure
• F- fill vacancy
• H-bond with O
Stabilize the lattice structure
Improve the crystallinity
Lower dissolution rate
‘Fluorhydroxyapatite’ ‘Fluoridated hydroxyapatite’
‘Fluoroapatite-like material’
H-bond
F
How much fluoride is in dental plaque?
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:
+ve charges in matrix & on bacterial surface attract Ca2+
Ca2+ bind fluoride.
Plaque fluid F and Saliva F after 1-min rinse with
NaF (
900 ppm) or MFP (
1000 ppm)
F decreases exponentially
Elevated for ~ 3 hours
Plaque fluid F
Clinical study:
F level in saliva and
plaque remained for 18 h
Saliva F
F reservoir
Calcium fluoride
Oral mucosa?
Ekstrand J. Enhancing effects of fluoride. Cariology for the nineties, 409-420.
Discussion: (group of 6-8) What characters affect caries development?
Low
Caries-Active
High
Caries-Active
4.8 + 5 *
18.9 + 7.3
0*
3.8 + 3.1
Age
Male / female
Salivary flow (ml/min)
26 + 8
9 / 14
1.5 + 0.3
24 + 8
13 / 11
1.5 + 0.5
MS (log CFU/ml saliva)
Lactobacilli (log CFU/ml saliva)
Brushing time (min)
Amount of toothpaste (g)
4.2 + 1
3.8 + 0.8
2.8 + 1.6
1.1 + 0.5
5.3 + 1
4.5 + 1.2
2.6 + 2
1.2 + 0.6
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)
F in saliva (accumulate) (mM·min)
0.6 + 0.4 *
6.9 + 3.9 *
0.3 + 0.3
3.9 + 2.9
Characteristics
DMFT
Decay surface
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.
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.