From Gums to Guts: Periodontal Medicine KEY SLIDES. UCSF Osher Mini-Medical School October 15, /8/2015. environmental factors (smoking)

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1 From Gums to Guts: Medicine KEY SLIDES UCSF Osher Mini-Medical School October 15, 2015 Tooth Enamel (Crown) Dental Biofilm (Dental Plaque and Calculus) Pocket (with ulcerated wall) Mark I. Ryder DMD Professor and Chair of Periodontology Director, Postgraduate Program in Periodontology Root of Tooth Alveolar Bone (Offenbacher S. Scientific American 2006 (October);Special Supplement, pp ) environmental factors (smoking) psychological factors (stress) bacteria host response disease systemic factors (diabetes) genetic factors (IL-1 beta) 1

2 1. Systemic conditions and medications that have oral manifestations Systemic conditions, diseases and medications (e.g. pregnancy, diabetes, HIV, etc.) 2. Factors that affect the oral cavity and other areas of the body with similar mechanisms 3. /Oral conditions that may have systemic effects.. Systemic conditions, diseases Systemic conditions diseases (e.g. cardiovascular diseases, diabetes, pregnancy outcomes, etc.) Tobacco, Age, etc.. 1. Systemic conditions and medications that have oral manifestations Systemic conditions, diseases and medications (e.g. pregnancy, diabetes, HIV, etc.) 2. Factors that affect the oral cavity and other areas of the body with similar mechanisms 3. /Oral conditions that may have systemic effects 2

3 1. Systemic conditions and medications that have oral manifestations Systemic conditions, diseases Tobacco, Age, etc. 2. Factors that affect the oral cavity and other areas of the body with similar mechanisms 3. /Oral conditions that may have systemic effects. Systemic conditions diseases (e.g. cardiovascular diseases, diabetes, pregnancy outcomes, etc.) ) circa 1950 Kurt H. Thoma ( ) Thoma KH. Secondary complications (Chapter VIII). In: Oral Abscesses, Ritter & Company, Boston, 1916, pp

4 (still unresolved) (stronger evidence up to one year ago, now unresolved) Heart Coronary heart disease (Atherosclerosis) Adverse Pregnancy Outcomes Preterm birth; Preeclampsia Fetal growth restriction Diabetes Mellitus (Onset & Control) (stronger evidence) (older and newer directions) Pulmonary Aspiration & Ventilator-associated pneumonia Chronic obstructive pulmonary disease GI diseases and conditions Rheumatoid Arthritis Neurological Cerebrovascular disease (nonhemorrhagic stroke) Brain abscesses Alzheimer s disease Meningitis HIV and Dementia 4

5 How do we determine a direct relationship vs a casual association? (still unresolved) Association Studies Biological Mechanisms Effects of Treatment Heart Coronary heart disease (Atherosclerosis) Adverse Pregnancy Outcomes Preterm birth; Preeclampsia Fetal growth restriction How do we determine a direct relationship vs a casual association? Forest Plot from Meta-Analysis of Studies Dealing with the Association of Periodontitis as a Risk Factor for Coronary Heart Disease Greater risk with periodontitis Association Studies Biological Mechanisms Effects of Treatment Khader et al. J Periodontol 2004;75:

6 How was the disease measured? 1. Self reported? 2. Loss of clinical attachment, radiographic bone loss? 3. Plaque and Inflammation? How was the disease measured? 1. Levels Self reported? of inflammation/gingval Index and 2. Loss of clinical Bleeding attachment, on Probing radiographic bone loss? 3. Plaque and Inflammation? Dr. Robert Parr Pretreatment Dr. Robert Parr One-year post SRP & 3-month recalls How do we determine a direct relationship vs a casual association? Association Studies Biological Mechanisms Effects of Treatment Hansson et al. Nature Reviews Immunology 6, (July 2006) doi: /nri1882 6

7 IL-1, IL-6, CRP, Collagenase (MMP s) Hansson et al. Nature Reviews Immunology 6, (July 2006) doi: /nri1882 Hansson et al. Nature Reviews Immunology 6, (July 2006) doi: /nri1882 * * Flow-mediated dilatation was used as the primary outcome and is considered an index of endothelial dysfunction. 0 Day 1 Day 2 1 Mo 2 Mo 6 Mo * P < 0.05 (Between Groups) (Data from: Tonetti et al. N Engl J Med 2007;356: ) 7

8 Common Risk Factors/ Risk Indicators for and Cardiovascular 1. Age 2. Gender 3. Educational Status 4. Tobacco Use 5. Hypertension 6. C-reactive Protein Levels 7. LDL/ cholesterol levels 8. Genetics/ Inflammatory response True Endpoints vs. 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. AHA Scientific Statement Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association? A Scientific Statement From the American Heart Association Observational studies to date support an association between and Atherosclerotic Vascular 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 shortterm studies, there is no evidence that they prevent Atherosclerotic Vascular or modify its outcomes (still unresolved) Heart Coronary heart disease (Atherosclerosis) Adverse Pregnancy Outcomes Preterm birth; Preeclampsia Fetal growth restriction 8

9 Meta-analysis plot for overall adverse pregnancy outcome (preterm birth <37 weeks and spontaneous abortions/stillbirths). Polyzos et al. BMJ 2010;341:c7017. Treatment No Treatment (Events/Total) (Events/Total) Odds Ratio (95% CI) López et al /200 20/200 López et al /580 21/290 Sadatmansuri et al /15 3/15 Offenbacher et al /40 14/34 Tarranum & Faizuddin /120 70/100 Oliveira et al /122 35/124 SUBTOTAL 133/ /763 LOW QUALITY TRIALS Jeffcoat et al /123 11/123 Michalowicz et al /413 52/410 Offenbacher et al /903 80/903 Newnham et al /546 55/541 Macones et al /376 68/380 SUBTOTAL 287/ /2357 HIGH QUALITY TRIALS From Offenbacher Scientific American 2006 TOTAL ALL STUDIES 420/ /3120 Courtesy of Gary Armitage Favors Treatment Favors No Treatment HOW EFFECTIVE WAS THE PERIODONTAL TREATMENT? 69.6% 68% (stronger evidence) N = % RESULTS OF PERIODONTAL TREATMENT IN OPT STUDY BASELINE ~ 6 MONTHS Michalowicz et al. N Engl J Med 2006;355: N = 20 TYPICAL (EXPECTED) RESULTS OF SCALING & ROOT PLANING 10% BASELINE 6 MONTHS Apatzidou & Kinane. J Clin Periodontol 2004;31: Pulmonary Aspiration & Ventilator-associated pneumonia Chronic obstructive pulmonary disease Diabetes Mellitus (Onset & Control) Special Thanks to Gary Armitage for this slide 9

10 (stronger evidence up to 3 weeks ago, now unresolved) Diabetes Mellitus (Onset & Control) Diabetes infection insulin resistance proteins inflammatory mediators (IL-1, IL-6, TNF-alpha) glucose hemoglobin HbA1C AGE s (advanced glycation end products) AGE-protein thickening of blood vessel walls inflammatory mediators (IL-1, IL-6, TNF-alpha) oxidative stress % reduction in Glycated Hemoglobin Treatment Injected Insulin (1921) 2.5 Inhaled Insulin (2006) 1.5 Sulfonylureas (1946) 1.5 Metformin (Bisguanide) (1995) 1.5 Rosiglitazone (1999) DPP-IV Inhibitors (2006) Modified from From Nathan DM 2007, NEJM 10

11 Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA 1c. Obesity Diabetes (From: Engebretson et al. J Am Med Assoc 2013; 310: ) (stronger evidence) Pulmonary Aspiration & Ventilator-associated pneumonia Chronic obstructive pulmonary disease (older and newer directions) GI diseases and conditions Rheumatoid Arthritis Neurological Cerebrovascular disease (nonhemorrhagic stroke) Brain abscesses Alzheimer s disease Meningitis HIV and Dementia 11

12 (older and newer directions) (older and newer directions) GI diseases and conditions Rheumatoid Arthritis Neurological Cerebrovascular disease (nonhemorrhagic stroke) Brain abscesses Alzheimer s disease Meningitis GI diseases and conditions Rheumatoid Arthritis Neurological Cerebrovascular disease (nonhemorrhagic stroke) Brain abscesses Alzheimer s disease Meningitis HIV and Dementia HIV and Dementia HIV Cognitive Function/ Dementia 12

13 F. Nucleatum T. Denticola P. Gingivalis Inflammatory Cytokines ++ F. Nucleatum T. Denticola P. Gingivalis Inflammatory Cytokines 13