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From Gums to Guts:Periodontal Medicine

KEY SLIDES

UCSF Osher Mini-Medical School

October 15, 2015

Mark I. Ryder DMD

Professor and Chair of Periodontology

Director, Postgraduate Program in Periodontology

Mark.Ryder@ucsf.edu

AlveolarBone

(Offenbacher S. Scientific American 2006 (October);Special Supplement, pp. 24-29.)

ToothEnamel(Crown)

Root ofTooth

DentalBiofilm

(Dental Plaqueand Calculus)

Periodontal Pocket(with ulcerated wall)

bacteria diseasehost response

environmental factors(smoking)

genetic factors(IL-1 beta)

systemic factors(diabetes)

psychological factors(stress)

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1. Systemic conditions and medications that have oral manifestations

2. Factors that affect the oral cavity and other areas of the body with similar mechanisms

3. Periodontal/Oral conditions that may have systemic effects

Systemic conditions, diseases and medications (e.g. pregnancy, diabetes,

HIV, etc.)

Periodontal Diseases

Systemic conditions diseases (e.g.

cardiovascular diseases, diabetes, pregnancy

outcomes, etc.)

Periodontal Diseases

Systemic conditions, diseases

Periodontal Diseases

Tobacco, Age, etc..

.

Systemic conditions, diseases and medications (e.g. pregnancy, diabetes,

HIV, etc.)

Periodontal Diseases

.

1. Systemic conditions and medications that have oral manifestations

2. Factors that affect the oral cavity and other areas of the body with similar mechanisms

3. Periodontal/Oral conditions that may have systemic effects

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Systemic conditions, diseases

Periodontal Diseases

Tobacco, Age, etc.

1. Systemic conditions and medications that have oral manifestations

2. Factors that affect the oral cavity and other areas of the body with similar mechanisms

3. Periodontal/Oral conditions that may have systemic effects

Systemic conditions diseases (e.g.

cardiovascular diseases, diabetes, pregnancy

outcomes, etc.)

Periodontal Diseases

.

Kurt H. Thoma (1883-1972)

Thoma KH. Secondary complications (Chapter VIII). In:Oral Abscesses, Ritter & Company, Boston, 1916, pp. 84-143.

circa 1950 )

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Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(still unresolved)

• Heart DiseasesCoronary heart disease (Atherosclerosis)

• Adverse Pregnancy OutcomesPreterm birth; PreeclampsiaFetal growth restriction

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes(stronger evidence up to one year ago, now

unresolved)

• Diabetes Mellitus (Onset & Control)

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(stronger evidence)

• Pulmonary DiseasesAspiration & Ventilator-associated pneumoniaChronic obstructive pulmonary disease

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(older and newer directions)

• GI diseases and conditions• Rheumatoid Arthritis• Neurological Diseases

Cerebrovascular disease (nonhemorrhagic stroke)Brain abscessesAlzheimer’s diseaseMeningitis

• HIV and Dementia

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How do we determine a direct relationship vsa casual association?

• Association Studies

• Biological Mechanisms

• Effects of Periodontal Treatment

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(still unresolved)

• Heart DiseasesCoronary heart disease (Atherosclerosis)

• Adverse Pregnancy OutcomesPreterm birth; PreeclampsiaFetal growth restriction

How do we determine a direct relationship vsa casual association?

• Association Studies

• Biological Mechanisms

• Effects of Periodontal Treatment

Forest Plot from Meta-Analysis of Studies Dealing with the Associationof Periodontitis as a Risk Factor for Coronary Heart Disease

Khader et al. J Periodontol 2004;75:1046-1053.

Greater risk with periodontitis

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How was the disease measured?1. Self reported?2. Loss of clinical attachment, radiographic bone

loss?3. Plaque and Inflammation?

Pretreatment One-year post SRP & 3-monthrecalls

Dr. Robert Parr Dr. Robert Parr

Levels of inflammation/Gingval Index and Bleeding on Probing

How was the disease measured?1. Self reported?2. Loss of clinical attachment, radiographic bone

loss?3. Plaque and Inflammation?

How do we determine a direct relationship vsa casual association?

• Association Studies

• Biological Mechanisms

• Effects of Periodontal TreatmentHansson et al. Nature Reviews Immunology 6, 508-519 (July 2006) | doi:10.1038/nri1882

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Hansson et al. Nature Reviews Immunology 6, 508-519 (July 2006) |

doi:10.1038/nri1882

IL-1, IL-6, CRP, Collagenase (MMP’s)

Hansson et al. Nature Reviews Immunology 6, 508-519 (July 2006) | doi:10.1038/nri1882

(Data from: Tonetti et al. N Engl J Med 2007;356:911-920.)

**

* P < 0.05(Between Groups)

0 Day 1 Day 2 1 Mo 2 Mo 6 Mo

Flow-mediated dilatation was used as theprimary outcome and is considered an

index of endothelial dysfunction.

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Common Risk Factors/ Risk Indicators for Periodontal Diseases and Cardiovascular Diseases

1. Age2. Gender3. Educational Status4. Tobacco Use5. Hypertension6. C-reactive Protein Levels7. LDL/ cholesterol levels8. Genetics/ Inflammatory response

True Endpointsvs.

Surrogate Endpoints

For Periodontology: Loss of tooth due to periodontal disease

vs. loss of clinical attachment

For Cardiovascular Disease: Heart Attack or Stroke

vs.Levels of CRP ,Lipid Profiles, etc.

“Observational studies to date support an association between Periodontal Diseases and Atherosclerotic Vascular Diseases independent of known confounders. They do not, however, support a causative relationship.

Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent Atherosclerotic Vascular Diseases or modify its outcomes”

AHA Scientific Statement

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?A Scientific Statement From the American Heart Association

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(still unresolved)

• Heart DiseasesCoronary heart disease (Atherosclerosis)

• Adverse Pregnancy OutcomesPreterm birth; PreeclampsiaFetal growth restriction

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From Offenbacher Scientific American 2006

Meta-analysis plot for overall adverse pregnancy outcome (preterm birth <37 weeksand spontaneous abortions/stillbirths). Polyzos et al. BMJ 2010;341:c7017.

Treatment No Treatment(Events/Total) (Events/Total)

López et al. 2002 15/200 20/200López et al. 2005 25/580 21/290Sadatmansuri et al. 2006 0/15 3/15Offenbacher et al. 2006 9/40 14/34Tarranum & Faizuddin 2007 55/120 70/100Oliveira et al. 2010 29/122 35/124SUBTOTAL 133/1077 163/763

Jeffcoat et al. 2003 5/123 11/123Michalowicz et al. 2006 49/413 52/410Offenbacher et al. 2009 98/903 80/903Newnham et al. 2009 54/546 55/541Macones et al. 2010 81/376 68/380SUBTOTAL 287/2361 266/2357

TOTAL ALL STUDIES 420/3438 429/3120

Courtesy of Gary Armitage

Odds Ratio (95% CI)

“LOW QUALITY”TRIALS

“HIGH QUALITY”TRIALS

0.1 0.2 0.5 1 2 5 10Favors Treatment Favors No Treatment

68%69.6%

45.9%

10%

BASELINEBASELINE 6 MONTHS~ 6 MONTHSApatzidou & Kinane. J ClinPeriodontol 2004;31:132-140.

Michalowicz et al. N Engl JMed 2006;355:1885-1894.

RESULTS OFPERIODONTAL

TREATMENTIN OPT STUDY

TYPICAL(EXPECTED)RESULTS OFSCALING &

ROOT PLANING

N = 20N = 413

HOW EFFECTIVE WAS THE PERIODONTAL TREATMENT?

Special Thanks to Gary Armitage for this slide

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(stronger evidence)

• Pulmonary DiseasesAspiration & Ventilator-associated pneumoniaChronic obstructive pulmonary disease

• Diabetes Mellitus (Onset & Control)

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Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes(stronger evidence up to 3 weeks ago, now

unresolved)

• Diabetes Mellitus (Onset & Control)

DiabetesPeriodontal Diseases

infection inflammatory mediators (IL-1, IL-6, TNF-alpha)

insulin resistance

glucose

HbA1C

AGE’s (advanced glycation end products)

AGE-protein

thickening of blood vessel wallsinflammatory mediators (IL-1, IL-6, TNF-alpha)oxidative stress

proteins

hemoglobin

% reduction in Glycated Hemoglobin

• Periodontal Treatment 0.4-1.0

• Injected Insulin (1921) ≥2.5

• Inhaled Insulin (2006) 1.5

• Sulfonylureas (1946) 1.5

• Metformin (Bisguanide) (1995) 1.5

• Rosiglitazone (1999) 0.8-1.0

• DPP-IV Inhibitors (2006) 0.5-0.9

Modified from From Nathan DM 2007, NEJM

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(From: Engebretson et al. J Am Med Assoc 2013; 310:2523-2532.)

“Nonsurgical periodontal therapy did not improve glycemic control in patientswith type 2 diabetes and moderate to advanced chronic periodontitis. Thesefindings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c.”

DiabetesPeriodontal Diseases

Obesity

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(stronger evidence)

• Pulmonary DiseasesAspiration & Ventilator-associated pneumoniaChronic obstructive pulmonary disease

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(older and newer directions)

• GI diseases and conditions

• Rheumatoid Arthritis• Neurological Diseases

Cerebrovascular disease (nonhemorrhagic stroke)Brain abscessesAlzheimer’s diseaseMeningitis

• HIV and Dementia

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Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(older and newer directions)

• GI diseases and conditions• Rheumatoid Arthritis

• Neurological DiseasesCerebrovascular disease (nonhemorrhagic

stroke)Brain abscessesAlzheimer’s diseaseMeningitis

• HIV and Dementia

Potential Associations Between Periodontal Infections and Adverse Systemic Outcomes

(older and newer directions)

• GI diseases and conditions• Rheumatoid Arthritis• Neurological Diseases

Cerebrovascular disease (nonhemorrhagic stroke)Brain abscessesAlzheimer’s diseaseMeningitis

• HIV and Dementia

Cognitive Function/Dementia

Periodontal Diseases

HIV

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Inflammatory Cytokines

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F. NucleatumT. DenticolaP. Gingivalis

F. NucleatumT. DenticolaP. Gingivalis

Inflammatory Cytokines