Pathobiology of Caries

DENT 5301Introduction to Oral BiologyDr. Joel Rudney

Major concepts

Caries is a process, not a disease Driven by biofilm, but initiated by the host Closely linked to specific microenvironments

The process is dynamic and reversible Oral ecological shifts are normal and cyclical

Many factors influence the outcome Microbes are necessary, but not sufficient

Understanding the process

Enamel is a unique hard tissue Enamel is 95% mineralized

Minimal protein content Enamel is acellular and non-vital

Cannot repair itself Enamel is permeable

Water and small molecules

Enamel is in dynamic chemical equilibrium with the oral environment Enamel caries is primarily a chemical process

http://dentistry.uic.edu/CraniofacialGenetics/ResearchTED.htm

Equilibrium at normal pHSaliva is supersaturated with respect to enamel

Saliva

Enamel

Ca10(PO4)6OH2

[Ca] [PO4][Ca] [PO4]

Ca+statherin Ca+aPRP

Demineralization

Saliva

Enamel

Ca10(PO4)6OH2

[Ca] [PO4][Ca] [PO4]

Ca+statherin Ca+aPRP

Dietary CHO + biofilm = lactic acid; diffusion into enamel = local pH drop

Enamelsolubilityincreases

[Ca][PO4]exit tosaliva

CHO CHO CHO

[H+]

[H+]

[H+][H+]

[H+]

Remineralization

Saliva

Enamel

Ca10(PO4)6OH2

[Ca] [PO4][Ca] [PO4]

statherin Ca+aPRP

Saliva flow clears CHO; salivary HCO3 returns pH to normal

Enamel becomeslesssoluble

[Ca][PO4]move intoenamel

CHO

CHO

[HCO3]

[HCO3][HCO3]

Alternating cycles of de/re-min

Break even - sound enamel or arrested caries

Net loss Subsurface demineralization New caries Progression of old lesions

Net gain - remineralization of existing lesions

http://www.uiowa.edu/~ocrdent/crown%20model.htm

Enamel caries

Begins as discrete lesions in the enamel of specific sites (reservoirs) Occlusal pits and fissures of Interproximal contacts molars and premolars between adjacent teeth

(usually posterior)

Caries risk varies greatly between tooth sites Micro-environments account for this variation

http://www.dentsply.de/products/esthet_x/ http://www.dent.ucla.edu/ce/caries

Enamel caries

http://www.dent.ohio-state.edu/radiologycarie

http://www.st-andrews.ac.uk/~amc/research/medical.htm

http://www.uic.edu/classes/peri/peri343/WsptPrev02/wspt7.htm

White spot lesions• Intact surface• Subsurface demineralization

Advanced enamel caries• Intact surface• “Sticky” fissures• Visible in radiographs• Dentin defensive reaction

Enamel caries can be remineralized

Dentinal caries

http://www.st-andrews.ac.uk/~amc/research/medical.htm

http://www.dent.umich.edu/research/loeschelabs

Love et al. Infect. Immun. 68:1359

• Cavitation• Demineralization + proteolysis• Bacteria move down tubules• Pulpal involvement• Major damage if unchecked

Can be arrested, but generallymust be restored

Risk factors

http://wwwsam.brooks.af.mil/af/files/fsguide/HTML/Graphics/fig_12-06.gif

The initiation and progression of caries is the outcome of interaction between:• Microbial factors• Host factors• Behavioral/dietary/environmental factors• Institutional factors

Cariogenicity of microbes

Streptococcus mutans/sobrinus Major source of demineralization Cariogenic properties

Highly acidogenicHighly aciduricExtracellular polysaccharide from sucrose - insolubleAdheres to pellicle

• So do most oral strepTransmisible - mother/caregiver to child

• So are all oral bacteria Microcolonies - localized zones of high acidity in protected sites

Occlusal pits and fissures; interproximal contacts

http://www.dokidoki.ne.jp/home2/saishika/caries01.htm

Microbes as risk factors

Necessary, but not sufficient High S. mutans levels in saliva/plaque increase risk

Longitudinal studiesMost people who get new lesions will have “high” levels BUTMany people with “high” levels won’t get new lesions

The majority of oral streptococci belong to non-mutans species S. mutans is a minority streptococcus - not a good competitor High % of acidogenic/aciduric non-mutans = increased risk? Low % of acidogenic/aciduric non-mutans = decreased risk?

Other species may moderate risk Are high levels of Veillonella related to lower lactate levels?

Antimicrobial strategies

Targeted attacks on mutans streptococci Fundamental concept - S. mutans is the main demineralizer Caries vaccines - results not impressive

Secretory immune system (S-IgA) is tolerant of oral microbes Topical antibodies - results not impressive NEW Antimicrobial peptides combines w/ S. mutans pheromones

Broad-spectrum attempts to eliminate/limit biofilm Allows for the possibility of other acidogenic species Systemic antibiotics (fungal overgrowth) Chlorhexidine rinses or varnishes (recolonization from reservoirs) NEW Antimicrobial peptides (a “natural” defense system) NEW Quorum sensing inhibitors

Replacement with “probiotics”, natural or genetically engineered All approaches have limitations, possible risks

Host factors - teeth

Genetics (twin studies) Occlusal morphology

Predisposing• Complexity (e.g. buccal pits)

Simplicity may be protective

Environment (diet, prevention) Resistance to demineralization Replacement ions in hydroxyapatite

Fluoride, strontium - protectiveSelenium - predisposing

http://www.zahntechnik-online.de

Host factors - no saliva

Saliva is an important regulator of the caries process Xerostomia due to radiation therapy or Sjogren’s syndrome

Very high S. mutans levels + rampant cariesDecay in unusual sites in multiple teeth

http://www.eastman.ucl.ac.uk/climages/ © Eastman Dental Institute

Host factors - normal saliva

What is the effect of individual variation in saliva? Variation in flow rate

High flow rate - protective; low (normal) flow rate - predisposing Not considered a major risk factor by itself

Variation in salivary buffering capacity (HCO3) High HCO3 - protective; Low HCO3 - predisposing Not considered a major risk factor by itself

Variation in antimicrobial protein concentrations S-IgA, peroxidase, lysozyme, lactoferrin and others Expectation: High [ ] - protective; Low [ ] - predisposing Studies results are inconsistent, sometimes contradictory

Diet and behavior

Sucrose and refined CHO - predisposing Archeological and historical evidence define major changes Effect of smaller fluctuations more difficult to measure

Intraoral plaque pH studies of cariogenicity Hard cheeses - protective BUT NOT HEART-HEALTHY Artificial sweeteners (xylitol) - protective The Happy Tooth logo in Europe - plaque pH ≥ 5.7

“Stickiness” - resistance to clearance - how long does pH stay low? Frequency of intake - how many demineraliztion episodes/day

The extremes of Vipeholm The reality of shifting dietary patterns

Oral hygiene (F- products), dental visits, parental oversight

“Social demineralization”

Affecting caries prevalence at the population level Institutional “remineralizing” factors

Public health programs - water fluoridation and sealants Research on prevention - NIDCR, IADR, and ADA Dental education and outreach - dental insurance Corporate introduction of fluoride oral health products Dramatic declines in caries prevalence during the ‘80s

Institutional “demineralizing” factors Lifestyle change - high frequency use of high CHO foods Mass-marketing of junk foods - the school budget dilemma Budget cuts - decreases in prevention, access to care Will this be a decade of demineralization?

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