Living Well to 100: Role of Prevention and Treatment: Systemic Factors and Interactions with Perio Disease

Question 1

Theory of “Focal Infection”

Answer 1

Localized infections could lead to dissemination of pathogens throughout the circulatory system causing infection at distant sites (Kumar 2017)

Question 2

Periodontitis definition

Answer 2

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)

Question 3

5 Theories for how Chronic Periodontal Inflammation may influence systemic health

Answer 3

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

Question 4

Mammen et al. 2020

(Theory # ?)

Answer 4

Well accepted that oropharyngeal translocation of periodontal bacteria is associated with aspiration pneumonia - Possibly COPD/Cystic fibrosis/Asthma (Theory 1)

Question 5

Kitamoto et al. 2020

(Theory # ?)

Answer 5

Orodigestive Translocation of periodontal bacteria associated with intestinal dysbiosis/gut-mediated systemic inflammation (Theory 1)

Question 6

Wegner et al. 2010

(Theory # ?)

Answer 6

Protein citrullination by P.gingivalis may generate antigens that contribute towards autoimmune response in rheumatoid arthritis (Theory 1)

Question 7

Hajishengallis and Chavakis 2021

(Theory # ?)

Answer 7

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

Question 8

Tonetti 2007
Theory #?

Answer 8

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

Question 9

Orlandi et al. 2020

Answer 9

Association between periodontitis, obesity, dyslipidemia, T2D, and CVD
Theory 3

Question 10

Xiao et al 2017

Answer 10

Diabetes enhances pathogenicity of perio microbiome through increased IL-17 expression and other pro-inflammatory cytokines
Theory 4

Question 11

Herrera et al. 2014

Answer 11

Peripheral blood monocytes from periodontitis patients are primed for enhanced osteoclastogenesis
Theory 5

Question 12

S/s of Diabetes

Answer 12

increased thirst, urination, hunger, and weight loss

Question 13

Type I diabetes

Answer 13

Often appears in childhood; autoimmune response to beta cells in pancreas - pancreas produces little to no insulin

Question 14

Type II Diabetes

Answer 14

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

Question 15

Should diabetes-associated perio be a distinct diagnosis?

Answer 15

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)

Question 16

Alagl 2017

Answer 16

Diabetes is associated with increased prevalence of periodontal abscess formation

Question 17

Shlossman et al. 1990

Answer 17

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

Question 18

Tsai et al. 2002

Answer 18

Cross-sectional study
Relationship between glycemic control in T2D and severe perio
Poorly controlled diabetes (>9%) is associated with higher prevalence of severe perio

Question 19

D’Aiuto et al. 2018

Answer 19

RCT
Evaluate the effect of perio tx on glycemic control in T2D
Intensive perio therapy can reduce HbA1c (1yr follow-up)

Question 20

Sanz et al. 2018

Answer 20

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

Question 21

What systemic issues have the strongest evidence for a link with Periodontal disease?

Answer 21

Type II Diabetes
Pre-term low birth weight
Cardiovascular disease
Alzheimer’s Disease
Cancer

Question 22

What are possible mechanisms of action for how Periodontitis influences Pre-term low-weight birth?

Answer 22

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)

Question 23

Sanz et al. 2013

Answer 23

EFP/AAP consensus report
Evaluated association between periodontitis and adverse pregnancy outcomes
Strength of association is modest and varies across different populations

Question 24

What cardiovascular diseases have been associated with Periodontitis?

Answer 24

Atherosclerosis/coronary artery disease and infective endocarditis (Dhotre et al. 2017)

Question 25

What is a possible mechanisms of action for how Periodontitis influences Cardiovascular Disease?

Answer 25

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)

Question 26

Farrugia et al. 2021

Answer 26

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)

Question 27

Bokhari et al. 2012

Answer 27

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

Question 28

What is a possible mechanism of action for how Periodontitis influences Alzheimer's disease?

Answer 28

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

Question 29

How is amyloid-beta related to Alzheimer's disease?

Answer 29

extracellular Amyloid-beta plaques are found in Alzheimer's patients.

Question 30

Kantarci et al. 2020

Answer 30

In mice- ligature induced perio resulted in amyloid-beta accumulation in the brain.

Question 31

Ide et al. 2016

Answer 31

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

Question 32

What is a possible mechanism of action for how Periodontitis influences Cancer development?

Answer 32

``` 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) ```

Question 33

Yachida et al. 2019

Answer 33

Colorectal cancer is characterized by increased microbial diversity compared with health with ectopic colonization of oral bacteria F.nucleatum and P.micra

Question 34

Michaud et al. 2018

Answer 34

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)

Question 35

**What are the 4 types of risks? (Citation)**

Answer 35

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…)

Question 36

Article to support stress impacting perio

Answer 36

Becker 1988 Green 1986 **Genco et al. 1999**

Question 37

What does Becker 1988 say about stress an perio?

Answer 37

Patients that did not adhere to SPT had more stressful life events and poor interpersonal relationships

Question 38

What does Green 1986 say about stress and perio?

Answer 38

Stressful events lead to a greater prevalence of periodontal disease

Question 39

How does stress impact periodontal health?

Answer 39

Wang & Boyapati 2007 stress stimulates autonomous nervous system - hyper-release of epinephrine by the adrenal medulla - increased release of glucose - altered immunity

Question 40

Genco et al. 1999

Answer 40

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**

Question 41

By what mechanism does obesity impact periodontitis?

Answer 41

Adipose tissue produces adipokines and pro-inflammatory cytokines. Excessive in obese patients May contribute to disease development **Genco 2005**

Question 42

Article supporting obesity impacts perio

Answer 42

**Saito et al. 2001** OR based on BMI 22-24.9: **2.0** 25-29.9: **3.3** \>30: **4.3**

Question 43

Articles in support of link between RH and Perio

Answer 43

**Marchesan & Giannobile 2013** **Mercado et al. 2001**

Question 44

Marchesan & Giannobile 2013

Answer 44

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

Question 45

**Mercado et al. 2001**

Answer 45

RA patients had 2x the issues 2x missing teeth 2x more bone loss 2x more 6mm pockets

Question 46

How are RA and Perio related

Answer 46

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

Question 47

What is T-Score and Z-Score?

Answer 47

Bone density values T-score compares your results to a healthy young adult 20-35 Z-score compares to same gender/age

Question 48

What T/Z scores are diagnostic?

Answer 48

-1.5 to -2.4 = Osteopenia Less than -2.5 = Osteoporosis

Question 49

Why is the number 2.5 for osteoporosis?

Answer 49

2.5x the standard deviation Standard deviation of 1

Question 50

Article in support of osteoporosis impact on perio? Results?

Answer 50

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**

Question 51

How does age impact disease? Citation

Answer 51

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*

Question 52

How does Gender influence perio?

Answer 52

Men have poorer oral hygiene! and go to fewer dental appointments! Albandar 2002

Question 53

Emrich et al. 1991

Answer 53

Subjects with type 2 diabetes have an increased risk OR: 2.81 when CALoss was used OR: 3.43 when bone loss

Question 54

How much increased risk is there for perio in diabetics? 2 citations

Answer 54

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

Question 55

are diabetics at higher risk for recurrence?

Answer 55

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)

Question 56

How does alcohol impact perio?

Answer 56

OR 1.9 of perio if 8+/week vs \<1/wk (Ga et al., 2018)

Question 57

How does stress impact perio?

Answer 57

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).

Question 58

How is obesity related to perio?

Answer 58

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