Living Well to 100: Role of Prevention and Treatment: Systemic Factors and Interactions with Perio Disease Flashcards
Theory of “Focal Infection”
Localized infections could lead to dissemination of pathogens throughout the circulatory system causing infection at distant sites (Kumar 2017)
Periodontitis definition
A chronic inflammatory disease affecting the supporting tissues of the teeth characterized by a pathologic interaction between the host inflammatory response and subgingival microflora (Kornman 2008)
5 Theories for how Chronic Periodontal Inflammation may influence systemic health
1: Dissemination of periopathogens and antigens into circulatory systems
2: Dissemination of inflammatory mediators and locally activated inflammatory cells from the periodontal tissues to the bloodstream – increasing systemic inflammation
3: Metabolic alterations / endothelial dysfunction / vascular inflammation
4: Systemic diseases resulting in modulation of periodontal microbiome causing increased pathogenicity
5: Trained immunity – the production of hyper-reactive inflammatory cells with enhanced destructive potential
Mammen et al. 2020
(Theory # ?)
Well accepted that oropharyngeal translocation of periodontal bacteria is associated with aspiration pneumonia - Possibly COPD/Cystic fibrosis/Asthma (Theory 1)
Kitamoto et al. 2020
(Theory # ?)
Orodigestive Translocation of periodontal bacteria associated with intestinal dysbiosis/gut-mediated systemic inflammation (Theory 1)
Wegner et al. 2010
(Theory # ?)
Protein citrullination by P.gingivalis may generate antigens that contribute towards autoimmune response in rheumatoid arthritis (Theory 1)
Hajishengallis and Chavakis 2021
(Theory # ?)
Reviewed the literature and discussed how locally primed T cells and myeloid cells migrate to distant sites to cause systemic inflammation
Theory 2
Despite some studies showing that periodontitis treatment improves surrogate markers of systemic conditions, strong evidence that periodontal treatment can decrease the risk of systemic conditions is lacking
Tonetti 2007
Theory #?
RCT
Evaluate the link between perio and endothelial function
Nonsurgical tx resulted in short term endothelial dysfunction and long term (6mo) improved clinical outcomes and endothelial function
Theory 3
Orlandi et al. 2020
Association between periodontitis, obesity, dyslipidemia, T2D, and CVD
Theory 3
Xiao et al 2017
Diabetes enhances pathogenicity of perio microbiome through increased IL-17 expression and other pro-inflammatory cytokines
Theory 4
Herrera et al. 2014
Peripheral blood monocytes from periodontitis patients are primed for enhanced osteoclastogenesis
Theory 5
S/s of Diabetes
increased thirst, urination, hunger, and weight loss
Type I diabetes
Often appears in childhood; autoimmune response to beta cells in pancreas - pancreas produces little to no insulin
Type II Diabetes
More common than type 1; often appears in adults >40; insulin resistance and/or insufficient insulin production
More evidence to show link between Type II and Perio than Type I
Should diabetes-associated perio be a distinct diagnosis?
No - no phenotypic features that are distinct to perio in diabetics
diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor (Jepsen et al. 2018 - World Workshop 2017 consensus)
Alagl 2017
Diabetes is associated with increased prevalence of periodontal abscess formation
Shlossman et al. 1990
Cross-sectional study (Pima indians)
Relationship between T2D and perio
In all age groups, diabetics had higher prevalence of perio
Diabetes is a risk factor for perio
Tsai et al. 2002
Cross-sectional study
Relationship between glycemic control in T2D and severe perio
Poorly controlled diabetes (>9%) is associated with higher prevalence of severe perio
D’Aiuto et al. 2018
RCT
Evaluate the effect of perio tx on glycemic control in T2D
Intensive perio therapy can reduce HbA1c (1yr follow-up)
Sanz et al. 2018
Consensus report from International Diabetes Federation and EFP
1) Diabetics with perio have higher HbA1c
2) Perio therapy can reduce HbA1c in diabetics
3) Perio patients have a higher risk of developing T2D, insulin resistance, and hyperglycemia
What systemic issues have the strongest evidence for a link with Periodontal disease?
Type II Diabetes
Pre-term low birth weight
Cardiovascular disease
Alzheimer’s Disease
Cancer
What are possible mechanisms of action for how Periodontitis influences Pre-term low-weight birth?
Basically Theories 1 and 2 Direct mechanism (1): Bacteremia - dissemination of microbes/byproducts through dental induced bacteremia into circulatory system which induce inflammatory response in the fetus/placenta. Indirect mechanism (2): enhanced secretion of inflammatory mediators produced in the periodontium impact inflammatory response in fetus/placenta (scarce evidence)
Sanz et al. 2013
EFP/AAP consensus report
Evaluated association between periodontitis and adverse pregnancy outcomes
Strength of association is modest and varies across different populations
What cardiovascular diseases have been associated with Periodontitis?
Atherosclerosis/coronary artery disease and infective endocarditis (Dhotre et al. 2017)
What is a possible mechanisms of action for how Periodontitis influences Cardiovascular Disease?
Farrugia et al. 2021
Pg-mediated endothelial cell damage
Gingipain dependent degradation of intercellular adhesion molecules -> increased vascular permeability -> exposure of underlying vascular connective tissue -> localized platelet activation/leucocyte recruitment
(loss of endothelial integrity and vascular damage = pathogenesis of CVD)
Farrugia et al. 2021
Pg-mediated endothelial cell damage
Gingipain dependent degradation of intercellular adhesion molecules -> increased vascular permeability -> exposure of underlying vascular connective tissue -> localized platelet activation/leucocyte recruitment
(loss of endothelial integrity and vascular damage = pathogenesis of CVD)
Bokhari et al. 2012
RCT
Evaluate effect of nonsurgical therapy on C-reactive protein, fibrinogen, and WBC count in coronary heart disease patients
Non-surgical therapy decreased systemic CRP, Fibrinogen, and WBC count in test group, and control had increase in CRP
What is a possible mechanism of action for how Periodontitis influences Alzheimer’s disease?
Reduced ability to conduct oral hygiene and attend dental visits due to cognitive decline
Dissemination of periopathogens past blood-brain barrier (theory 1)
Gil-Montoya et al. 2017 found increased systemic Amyloid-beta in severe perio patients
How is amyloid-beta related to Alzheimer’s disease?
extracellular Amyloid-beta plaques are found in Alzheimer’s patients.
Kantarci et al. 2020
In mice- ligature induced perio resulted in amyloid-beta accumulation in the brain.
Ide et al. 2016
Cohort study
Evaluate the association between perio and cognitive decline in Alzheimer’s patients
Perio was associated with an increased rate of cognitive decline in Alzheimer’s patients
What is a possible mechanism of action for how Periodontitis influences Cancer development?
Oro-digestive translocation leading to colorectal dysbyosis - Colorectal cancer Other malignancies (esophogeal, oral, lung, pancreatic, hepatic) also linked with oral microbe colonization but biologic mechanisms poorly understood (Sun et al. 2020)
Yachida et al. 2019
Colorectal cancer is characterized by increased microbial diversity compared with health with ectopic colonization of oral bacteria F.nucleatum and P.micra
Michaud et al. 2018
Prospective Cohort Study
7500 pts - 15yr follow-up
Severe perio is significantly associated with increased risk of cancer.
Strong association for non-smoking related lung cancer (4x greater risk) and colorectal cancer (80% greater risk)
What are the 4 types of risks? (Citation)
Robert (Bob) Genko
Risk FACTORS: supported by longitudinal studies and confirmed to be present before the onset of disease.
Risk INDICATORS: supported by cross-sectional/retrospective studies but not confirmed through longitudinal
Risk DETERMINANTS: a risk that cannot be modified (genetic, gender, age…)
Risk MARKERS: the outcomes of disease (increased PD, BOP, CALoss…)
Article to support stress impacting perio
Becker 1988
Green 1986
Genco et al. 1999
What does Becker 1988 say about stress an perio?
Patients that did not adhere to SPT had more stressful life events and poor interpersonal relationships
What does Green 1986 say about stress and perio?
Stressful events lead to a greater prevalence of periodontal disease
How does stress impact periodontal health?
Wang & Boyapati 2007
stress stimulates autonomous nervous system - hyper-release of epinephrine by the adrenal medulla - increased release of glucose - altered immunity
Genco et al. 1999
People who had high financial stress and poor coping ability had
OR 2.24 of severe attachment loss
OR 1.91 of severe alveolar bone loss
By what mechanism does obesity impact periodontitis?
Adipose tissue produces adipokines and pro-inflammatory cytokines.
Excessive in obese patients
May contribute to disease development
Genco 2005
Article supporting obesity impacts perio
Saito et al. 2001
OR based on BMI
22-24.9: 2.0
25-29.9: 3.3
>30: 4.3
Articles in support of link between RH and Perio
Marchesan & Giannobile 2013
Mercado et al. 2001
Marchesan & Giannobile 2013
Pg infection prior to arthritis induction (in mice) increased the immune response and accelerated disease development.
Majority of Pg’s impact was on the innate immune response (monocytes and dendritic cells)
upregulation of Th-17 and subsequent pro-inflammatory cytokines
Mercado et al. 2001
RA patients had 2x the issues
2x missing teeth
2x more bone loss
2x more 6mm pockets
How are RA and Perio related
Pathogenesis of RA relies on the citrullination of protines (post-translational modification of arginine residues to citrulline) and the bodies auto-immune respons driven by anti-citrullinated protein antibodies
Pg generates citrullinated proteins which may be distributed systemically through access to the blood stream
What is T-Score and Z-Score?
Bone density values
T-score compares your results to a healthy young adult 20-35
Z-score compares to same gender/age
What T/Z scores are diagnostic?
-1.5 to -2.4 = Osteopenia
Less than -2.5 = Osteoporosis
Why is the number 2.5 for osteoporosis?
2.5x the standard deviation
Standard deviation of 1
Article in support of osteoporosis impact on perio? Results?
Penoni et al. 2017
Systematic review and Meta-analysis - greater loss of periodontal attachment vs normal bone density
- *Osteopenia: 1.7 OR**
- *Osteoporosis: 3.4 OR**
How does age impact disease? Citation
Increased attachment loss seen in older individuals is because of prolonged exposure to other risk factors like plaque, smoking, mechanical trauma, brushing, repeated SRP, attrition, etc…
aging alone does not increase disease susceptibility
Papapanou & Lindhe 1992
How does Gender influence perio?
Men have poorer oral hygiene! and go to fewer dental appointments!
Albandar 2002
Emrich et al. 1991
Subjects with type 2 diabetes have an increased risk
OR: 2.81 when CALoss was used
OR: 3.43 when bone loss
How much increased risk is there for perio in diabetics? 2 citations
Emrich et al. 1991
OR 2.8 when CAL used
OR 3.4 when bone loss
Tsai et al. 2002
OR 2.9 for poorly controlled diabetics
NSSD with well controlled
are diabetics at higher risk for recurrence?
When adequate oral hygiene is maintained, no difference in terms of recurrence between
groups of diabetics and controls Five years of follow-up after Modified Widman Flap
(Westfelt et al., 1996)
How does alcohol impact perio?
OR 1.9 of perio if 8+/week vs <1/wk
(Ga et al., 2018)
How does stress impact perio?
increased glucocorticoid level (cortisol) and catecholamine
level (related with impairment of neutrophil function and initial phase of wound healing,
reduced growth hormone levels, altered cytokine profiles).
How is obesity related to perio?
Wood 2003
NHANES III, showed that there was a
significant association between Waste to Hip Ratio and periodontal disease, obese patients had a higher
percentage of sites with CALoss
