Pathobiology of Caries DENT 5301 Introduction to Oral Biology Dr. 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 pH Saliva is supersaturated with respect to enamel Saliva Ca+aPRP Ca+statherin [Ca] [PO4] [Ca] [PO4] Enamel Ca10(PO4)6OH2

Demineralization Ca+aPRP Ca+statherin [Ca] [PO4] [Ca] [PO4] Dietary CHO + biofilm = lactic acid; diffusion into enamel = local pH drop Saliva Ca+aPRP [Ca] [PO4] exit to saliva Ca+statherin [Ca] [PO4] [Ca] [PO4] CHO CHO [H+] CHO [H+] [H+] Enamel [H+] Enamel solubility increases [H+] Ca10(PO4)6OH2

Remineralization Ca+aPRP statherin [Ca] [PO4] [Ca] [PO4] Ca10(PO4)6OH2 Saliva flow clears CHO; salivary HCO3 returns pH to normal Saliva [Ca] [PO4] move into enamel Ca+aPRP statherin [HCO3] CHO [Ca] [PO4] [Ca] [PO4] [HCO3] [HCO3] CHO Enamel Enamel becomes less soluble Ca10(PO4)6OH2

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 Enamel caries can be remineralized White spot lesions http://www.st-andrews.ac.uk/~amc/research/medical.htm http://www.dent.ohio-state.edu/radiologycarie 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 Can be arrested, but generally must be restored http://www.st-andrews.ac.uk/~amc/research/medical.htm Love et al. Infect. Immun. 68:1359 Cavitation Demineralization + proteolysis Bacteria move down tubules Pulpal involvement Major damage if unchecked http://www.dent.umich.edu/research/loeschelabs Can be arrested, but generally must 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 http://www.dokidoki.ne.jp/home2/saishika/caries01.htm Streptococcus mutans/sobrinus Major source of demineralization Cariogenic properties Highly acidogenic Highly aciduric Extracellular polysaccharide from sucrose - insoluble Adheres to pellicle So do most oral strep Transmisible - mother/caregiver to child So are all oral bacteria Microcolonies - localized zones of high acidity in protected sites Occlusal pits and fissures; interproximal contacts

Microbes as risk factors Necessary, but not sufficient High S. mutans levels in saliva/plaque increase risk Longitudinal studies Most people who get new lesions will have “high” levels BUT Many 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 - protective Selenium - 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 caries Decay 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 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? $