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2-D The Importance of Oral Health Systemic Health Connections ...


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2-D The Importance of Oral Health Systemic Health Connections ...

  1. 1. University of Manitoba Faculty of Dentistry Traditions of Excellence: Horizons of Change Anthony M. Iacopino Dean Professor, Restorative Dentistry
  2. 2. Periodontitis and Systemic Disease “The Perio-Systemic Connection” Alzheimer Society of Manitoba Winnipeg – March 10, 2008 Basic Overview
  3. 3. Relationship Between Periodontitis and Systemic Diseases/Conditions Grand Rounds in Oral Systemic Medicine Gapski and Cobb 1(1):14-23, 2006; Moritz and Mealy 1(2):13-21, 2006; Iacopino 1(3):25-37, 2006; Paquette 1(4):14-25, 2006; Tae-Ju Oh et al., 2(1):10-21, 2007 <ul><li>osteoporosis </li></ul><ul><li>diabetes </li></ul><ul><li>heart disease </li></ul><ul><li>adverse pregnancy outcome </li></ul><ul><li>stroke </li></ul><ul><li>Alzheimer’s disease </li></ul><ul><li>arthritis </li></ul><ul><li>respiratory disease </li></ul>
  4. 4. Periodontal Disease: Periodontitis <ul><li>Chronic inflammatory disease </li></ul><ul><ul><li>primarily gram negative anaerobic oral infection </li></ul></ul><ul><ul><li>gingival inflammation </li></ul></ul><ul><ul><li>destruction of periodontal supporting tissues </li></ul></ul><ul><ul><li>exfoliation of teeth in severe cases </li></ul></ul><ul><ul><li>organisms within microbial flora of dental plaque are the major etiologic agents ( Porphyromonas gingivalis, Bacteriodes forsythus, and Treponema denticola ) </li></ul></ul><ul><ul><li>microorganisms and endotoxins generate localized host-mediated tissue destructive immune response (cellular, inflammatory cytokines) </li></ul></ul><ul><ul><li>(Socransky et al., J Periodontol 63:322-331, 1992; Liljenberg et al., J Clin Periodontol 21:720-727, 1994) </li></ul></ul>
  5. 5. Periodontitis: Systemic Effects <ul><li>Transient bacteremia/endotoxemia </li></ul><ul><ul><li>demonstrations of periodontitis-induced bacteremia/endotoxemia linked to periodontitis severity and periods of progression/exacerbation </li></ul></ul><ul><ul><li>organisms invade deep connective tissues/endothelium and coronary vasculature </li></ul></ul><ul><ul><li>tissue destructive responses not limited to oral cavity </li></ul></ul>
  6. 6. Periodontitis: Systemic Effects <ul><li>Transient bacteremia/endotoxemia </li></ul><ul><ul><li>creates systemic “exposure” </li></ul></ul><ul><ul><li>elevation of serum pro-inflammatory cytokines and acute phase reactants have many biologic effects </li></ul></ul><ul><ul><ul><li>leads to elevations of serum lipid levels (FFA, LDL/TRG) </li></ul></ul></ul><ul><ul><ul><li>“ systemic inflammatory state” may adversely effect many organ systems leading to systemic diseases/conditions associated with chronic inflammation </li></ul></ul></ul>
  7. 7. Periodontitis: Systemic Effects <ul><li>Link to systemic health </li></ul><ul><ul><li>determined prevalence of systemic diseases/conditions in patients with periodontitis </li></ul></ul><ul><ul><li>420 random patients over a two-year period with periodontal disease) </li></ul></ul><ul><ul><li>hypertension, respiratory disease, diabetes, and arthritis significantly more prevalent in subjects with periodontitis (p < 0.05) </li></ul></ul><ul><ul><li>subjects with more severe periodontitis were four times more likely to have three or more systemic conditions </li></ul></ul>(Al-Emadi et al., Quintessence Int 37: 761-765, 2006)
  8. 8. Periodontitis: Systemic Effects <ul><li>Link to medical costs </li></ul><ul><ul><li>investigated effect of periodontal treatment on medical expenditures for diabetes, cardiovascular disease, and cerebrovascular disease </li></ul></ul><ul><ul><li>measured per member per month costs for 144,225 enrollees of a PPO by aggregating ICD-9 expenditures over a two-year period </li></ul></ul><ul><ul><li>controlled for differences in disease burden between groups with and without history of periodontal care </li></ul></ul><ul><ul><li>periodontal treatment significantly decreases medical costs (p < 0.05) with greater reductions when care is provided earlier in life </li></ul></ul>(Albert et al., BMC Health Services Res 6: 103-109, 2006)
  9. 9. Periodontitis Causes Systemic Inflammation <ul><li>Treatment of periodontitis reverses systemic inflammation </li></ul><ul><ul><li>65 healthy subjects with severe generalized PD </li></ul></ul><ul><ul><li>blinded randomized control clinical trial </li></ul></ul><ul><ul><li>measured CRP, IL-6, LDL cholesterol at baseline and two months after treatment (standard therapy) </li></ul></ul><ul><ul><ul><li>at baseline, markers were significantly elevated </li></ul></ul></ul><ul><ul><ul><li>after treatment, significant reductions in CRP (p=0.03), IL-6 (p=0.006), and LDL (p=0.002) </li></ul></ul></ul><ul><ul><ul><li>reductions were independent of age, gender, BMI, ethnicity </li></ul></ul></ul>(D’Aiuto et al., J Clin Perio 34:124-129, 2007)
  10. 10. Respiratory Disease <ul><li>Direct linkages through aspiration </li></ul><ul><ul><li>aspiration pneumonia </li></ul></ul><ul><ul><ul><li>major cause of morbidity, hospitalization, and mortality in institutional settings (~50% of all infections) </li></ul></ul></ul><ul><ul><ul><li>tremendous health care costs and decreased quality of life </li></ul></ul></ul><ul><ul><ul><li>frequently caused by gram negative organisms in dental plaque around diseased teeth/poorly maintained dentures </li></ul></ul></ul><ul><ul><ul><li>indisputable evidence and acceptance by medical community </li></ul></ul></ul><ul><ul><ul><li>requires changes in interprofessional patient management </li></ul></ul></ul>
  11. 11. Rheumatoid Arthritis <ul><li>Some preliminary studies indicate: </li></ul><ul><ul><li>patients with PD and RA exhibit similar pro-inflammatory cytokine profiles </li></ul></ul><ul><ul><li>periodontal pathogens may initiate formation of rheumatoid factor immune complexes </li></ul></ul><ul><ul><li>patients with moderate to severe periodontitis are at higher risk for rheumatoid arthritis </li></ul></ul><ul><ul><li>dose-response relationship between PD and RA </li></ul></ul><ul><ul><li>periodontal treatment reduces the severity of rheumatoid arthritis </li></ul></ul><ul><ul><li>requires further investigation, may warrant closer monitoring of periodontal status of RA patients </li></ul></ul>
  12. 12. Stroke/CVA/TIA <ul><li>Several credible studies indicate PD is a significant risk factor for CVAs, especially stroke </li></ul><ul><ul><li>dose-response relationship (gingivitis, PD severity) </li></ul></ul><ul><ul><li>closely tied to mechanisms underlying initiation and progression of atherosclerosis </li></ul></ul><ul><ul><ul><li>dysregulation of lipid metabolism </li></ul></ul></ul><ul><ul><ul><li>interaction of periodontal pathogens with vascular walls </li></ul></ul></ul><ul><ul><ul><li>endothelial cell dysfunction and damage </li></ul></ul></ul><ul><ul><ul><li>initiation and/or exacerbation of atheroma formation </li></ul></ul></ul><ul><ul><ul><li>thickening of intimal-medial vessel walls </li></ul></ul></ul>
  13. 13. Stroke/CVA/TIA <ul><li>Periodontitis associated with stroke in the elderly, even partially edentulous patients </li></ul><ul><ul><li>NHANES III database for patients aged ≥ 60 years </li></ul></ul><ul><ul><li>used “new” index to account for number of teeth </li></ul></ul><ul><ul><ul><li>weighs “exposure burden” based on past periodontitis </li></ul></ul></ul><ul><ul><li>periodontitis significantly associated with stroke </li></ul></ul><ul><ul><ul><li>relationship just as strong for subjects with few teeth </li></ul></ul></ul><ul><ul><ul><li>“ cumulative effects” of periodontitis are important </li></ul></ul></ul><ul><ul><li>(Lee et al., J Periodontol 77:1744-1754, 2006) </li></ul></ul>
  14. 14. Cardiovascular Disease <ul><li>8 separate longitudinal studies from 2000-2004 indicated that PD is associated with the onset of coronary heart disease </li></ul><ul><ul><li>controlled for other established risk factors </li></ul></ul><ul><ul><li>periodontitis associated with intimal-medial wall thickness (a measure of sub-clinical atherosclerosis) </li></ul></ul><ul><ul><li>links between systemic inflammation, PD, and atherosclerosis/CHD as gingival index and dental infections (microbial burden) were positively correlated to onset of new CHD events </li></ul></ul>
  15. 15. Cardiovascular Disease <ul><li>Since 2000: </li></ul><ul><ul><li>16 associative studies linking PD to presence of vascular plaques </li></ul></ul><ul><ul><li>9 studies demonstrating presence of periodontal pathogens in atheromas </li></ul></ul><ul><ul><li>16 associative studies concerning inflammatory PD-cardiovascular mechanistic link </li></ul></ul><ul><ul><ul><li>significant association between PD-induced elevations in serum inflammatory biomarkers (pro-inflammatory cytokines, CRP, fibrinogen) and CHD </li></ul></ul></ul><ul><ul><ul><li>levels of inflammatory biomarkers and extent of CHD directly proportional to PD severity </li></ul></ul></ul><ul><ul><ul><li>treatment of PD reduces levels of serum inflammatory biomarkers </li></ul></ul></ul>
  16. 16. Diabetes <ul><li>The most well defined perio-systemic connection </li></ul><ul><ul><li>The “sixth major complication” of diabetes </li></ul></ul><ul><ul><li>similar changes in systemic physiology and blood biochemistry (a bi-directional relationship between pro-inflammatory cytokines and serum lipids) </li></ul></ul><ul><ul><li>definitive evidence that uncontrolled diabetes exacerbates PD and that PD exacerbates some diabetic complications (reversible with treatment of PD) </li></ul></ul><ul><ul><li>preliminary evidence that untreated PD may actually cause diabetes in otherwise healthy patients </li></ul></ul>
  17. 17. Periodontitis and Insulin Resistance <ul><li>Recent studies demonstrate links between PD and insulin resistance (case control and randomized trials) </li></ul><ul><ul><li>PD causes insulin resistance and significant elevations in serum glucose/HbA1c levels (degree of insulin resistance directly related to severity of PD) </li></ul></ul><ul><ul><li>treatment of PD improves glycemic status in diabetic patients (significant decreases in serum glucose/HbA1c levels, reduced insulin requirements, effects more pronounced for severe PD) </li></ul></ul><ul><ul><li>significantly more PD in non-diabetic patients with documented insulin resistance </li></ul></ul><ul><ul><li>documented relationship between PD and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) </li></ul></ul>
  18. 18. Osteoporosis <ul><li>Conflicting results from initial studies for: </li></ul><ul><ul><li>periodontal status and systemic bone mineral density </li></ul></ul><ul><ul><li>BMD and number of remaining teeth </li></ul></ul><ul><ul><li>systemic bone loss as a predictor of risk for alveolar bone loss (vice-versa) </li></ul></ul><ul><li>Positive studies outnumber negative studies for associations/relationships </li></ul><ul><li>Both conditions involve physiologic mechanisms mediated through pro-inflammatory cytokines </li></ul><ul><li>Current thought is that patients would benefit from “bi-directional” screening </li></ul>
  19. 19. Alzheimer’s Disease <ul><li>Inflammatory hypothesis (no biologic evidence) </li></ul><ul><ul><li>systemic inflammation associated with signals that cross blood-brain barrier via perivascular macrophages/microglia </li></ul></ul><ul><ul><li>activated macrophages/microglia initiate a neuro-inflammatory process </li></ul></ul><ul><ul><li>resultant neuro-inflammatory responses and secretion of neurotoxic factors cause cell injury/death </li></ul></ul><ul><ul><li>chronic inflammation in the brain destroys sufficient neurons to cause the clinical signs of dementia </li></ul></ul><ul><ul><li>several recent population-based, prospective cohort studies have demonstrated that serum CRP and pro-inflammatory cytokine levels are increased prior to the clinical onset of dementia </li></ul></ul>
  20. 20. Periodontitis Elevated Serum Pro-Inflammatory Cytokines Hyperlipidemia Diabetes Bacteremia Endotoxemia Insulin Resistance β -Cell Destruction Cardiovascular/ Cerebrovascular Disease Arthritis Respiratory Infection Aspiration Dementia Microglia Activation Synovial Inflammation Atherosclerosis Altered Lipid Metabolism Rheumatoid Factor Atherosclerosis Vascular Endothelium Linkage Between PD and Systemic Diseases/Conditions in the Elderly Iacopino, Grand Rounds Oral-Sys Med 1(3):25-37, 2006
  21. 21. University of Manitoba Faculty of Dentistry Questions, Comments, Concerns? Traditions of Excellence: Horizons of Change