Transcript CE/Technology Plan - Alzheimer Society of Manitoba

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