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  1. 1. From Gums to Guts: New Developments inDiagnosis and Treatment and Periodontal MedicineUtah Dental Association February 19, 2010Mark I. RyderProfessor And ChairDivision of PeriodontologyDirector, Postgraduate Program in PeriodontologyUniversity of California, San Francisco Mark.Ryder@ucsf.eduI) Introduction: The impact of Periodontal Diseases onHuman Health. Looking at the problem three ways: 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 effectsII) The Nature of the Beast we treat. Diagnosis and treatmentrelevant to Systemic Health A)Periodontal Diseases as the most common inflammatory/microbial conditions encountered by the body in one’s lifetime B) Understanding the concepts of periodontal risks and relation to overall healthCLASSIFICATION OF PERIODONTAL DISEASES (The New System) I. Gingival Diseases A. Dental Plaque-induced gingival diseases 1. Gingivitis associated with dental plaque only 2. Gingivitis Modified by Systemic Factors (endocrine changes, blood diseases) 3. Gingivitis Modified by Medications 4. Gingivitis Modified by Malnutrition B. Non-plaque-induced gingival lesions (specific bacteria, viruses, fungi, mucocutaneous disorders, allergic reactions, traumaticlesions, etc.) II. Chronic Periodontitis III. Aggressive Periodontitis A Localized
  2. 2. B. Generalized IV. Periodontitis as a Manifestation of Systemic Diseases V. Necrotizing Periodontal Diseases VI. Abscesses of the Periodontium VII. Periodontitis Associated with Endodontic Lesions VIII. Developmental or Acquired Deformities (mucogingival conditions, occlusal trauma, etc.) environm psych (smoking (stres bacteria host r dise geneti systemic (IL-1 (diabetes)B. Microbiological testing in the diagnosis of periodontal disease 1. Microscopic assays: motile vs. non motile forms 2. Culture assays predominance of Aggregitabacter actinomycetemcomitans Tanarella Forsythensis (Bacteroides Forsythus) Porphyromonas gingivalis Prevotella intermedia 3. DNA Probes 2
  3. 3. Principles of DNA probe analysis and how we use the results Introduction to the PERIODONTAL FINGERPRINTC. Crevicular fluid testing in the diagnosis of periodontal diseases Measuring products of inflammation, bacteria, and tissue breakdown Some Examples with Therapeutic implications: 1. Prostaglandins How they are made, role of Cyclooxygenase 1 and 2 Therapeutic use of Prostaglandin Inhibitors. 2. Elastase and Collagenase Therapeutic use of SYSTEMIC LOW DOSE DOXYCYCLINES Rationale, Clinical Studies, Practical Application Potential Systemic Benefits Potential Benefits for SmokersD. Genetic testing for Periodontal diseases interleukin -1β genetic markers: uses and limitationsE. The future of diagnostic markers . Impact on dental insuranceF . Relevant approaches to the treatment of periodontal diseases 1) Plaque Control 3
  4. 4. The concept of Dental Plaque as a BiofilmThe central role of mechanical removal of the biofilm as the foundation of treatmentthrough1. Home Care2. Mechanical debridement with hand instruments/ultrasonic instruments2) Chemical Control of Plaque3) Local delivery/irrigation with antimicrobials 1. Historical Background 2. Local Delivery of Tetracyclines and related antibiotics Doxycycline and Minocycline4) Site specific drug delivery/controlled release devices A) Justification: Why a high concentration over a short period of time may be desirable the problem of bacterial resistance biofilms drug sensitivity B) New developments in controlled delivery systems What is the difference between Statistical Significance and Clinical Significance? a. Periochip® (Chlorhexidine in a gelatin chip) clinical studies (of clinical significance) b. Atridox® (Doxycycline mixed into a liquid polylactic acid polymer that sets as a gel in the periodontal pocket) Clinical Studies 4
  5. 5. Benefits for Smokers Case Study c. Arestin® (Minocycline incorporated into polylactic acid microspheres that adhere to the pocket wall and tooth, and then dissolve. Clinical Studies Case StudiesCASE STUDIES USING COMBINATIONS OF DEBRIDEMENT, SYSTEMICANTIBIOTICS, CONTROLLED LOCAL DRUG DELIVERY, SYSTEMIC HOSTMODULATION, AND OF COURSE PLAQUE CONTROLTHE FUTURE: CUSTOMIZING YOUR ANTIMICROBIAL TREATMENT andCOMBINING ANTIMICROBIAL APPROACHES WITH ANTI-INFLAMMATORYAPPORACHESIII) Systemic conditions and medications that have oral manifestations:Some examples A) Pregnancy B) Nutritional Deficiencies: Vitamins from C to D C) Systemic Medications-the special case of gingival enlargements D) Effective Communication with PhysiciansIV) Factors that affect the oral cavity and other areas of the body withsimilar mechanisms A) Introduction: Tobacco and Periodontal Diseases from the perspective of thepatient, society, and global health 5
  6. 6. B) Tobacco as a major preventable risk factor in the incidence and severity ofperiodontal diseases. 1) Putting tobacco in perspective as a risk factor in the overall scheme of periodontal diseases 2) The Evidence for Tobacco Use a) the classic studies b) new longitudinal studies c) effects on tooth loss d) benefits of smoking cessation on the progression of periodontal diseases e) benefits of smoking cessation on treatment outcomes. Scaling and root planing, surgery, regeneration surgery, implant outcomes. C) Are Cigars, Pipes, Smokeless Tobacco Products or other smoking strategiessafer? D) The Influence of Advertising and other tobacco use campaigns on smokinghabits of different generations and the challenges of smoking cessation. E) The World-Wide Challenges for Smoking Cessation Programs. F) Strategies for reducing the damage from Tobacco Use and PeriodontalDiseases Public Health Policies that can reduce the overall incidence and Use of tobacco G) Smoking Cessation Programs for the Patient 1) The 5 A Approach i. Ask ii. Advise iii. Assess iv. Assist v. Arrange 2) The Challenges of Nicotine Addiction in Smoking Cessation i. Mechanisms of addiction ii. Value of nicotine replacement therapies iii. Pharmacological Agents, Value and Limitations 1. Antidepressants 2. Buproprion 3. Varenicline 3) The Big Reality Check on Smoking Cessation Approaches i. Short and Long Term Success Rates in Smoking Cessation Approaches 6
  7. 7. ii. The Unique Role of the Dental Practitioner in Improving Smoking Cessation Rates—Lessons from Heart Patients and how we can apply these messages to Periodontal Diseases H) When Smoking Cessation Strategies fall short—controlling the Damage to the Periodontal Support from Tobacco Use. 4) the role of Tobacco in the progression of Periodontal Diseases i. Effects on the Bacterial Flora ii. Effects on the Inflammatory Host Response 5) Using this information to treat the Periodontal Patient who uses tobacco products i. Benefits of Antimicrobial Therapies ii. Benefits of Host Modulation Therapies 1. Local Application of Doxycycline, Minocycline 2. Systemic Low Dose DoxycyclineV) Periodontal/Oral conditions that may have systemic effects A) Basic concepts: periodontal plaque and inflamed tissue as a reservoir of bacterial products and products of inflammation (prostaglandins, interleukins, etc.) that can invade the bloodstream B) Some Examples 1) Pulmonary Diseases and the “Reservoir” concept 2) Ulcers (reservoirs of heliobacter pylorii) 3) Cardiovascular Diseases Role of Bacteria in clot (thrombus) formation Role of bacteria and products of inflammation in the development of ATHEROSCLEROSIS The C-reactive protein story 7
  8. 8. Proposed Me ATHEROSCPeriodontally diseased tisLPSlipopolysaccha ( from period perioHeat Shock Pr ATHEROSDamaged Vesse Proposed Me ATHEROSC diseased tis Periodontally IL1-beta LPSTNF-alpha fromDensity bacteriaLowTriglyceridIL1-beta, TN ATHEROSDamaged Vesse 8
  9. 9. Proposed M ATHEROSC diseased tis Periodontally IL1-beta,perio lipopolysaccha LPS from TNF ( prostagland (A? ? C-REACT non-specific m ATHEROSCL NEW STUDIES ON THE BENFITS OF PERIODONTAL TREATMENT4) Role of the practitioner in diabetic control (how reducing periodontal infections maylower harmful glucose end products) infection IL (IL-1, insulin res glucose glycosyl hemog AGEÕs pr ( dvanced advanced a glycatio end AGE-RA thickening inflammato oxidative s 9
  10. 10. HOW ANTIMICROBIAL AND HOST MODULATION TREATMENTS INTHE MOUTH CAN ALSO AFFECT THE SYSTEMIC CONDITION OF DIABETES Proposed Low pe /Premat Birthwei 5) Low Birth Weight and Premature Births (the periodontal tissue as a reservoir of inflammatory mediators and bacterial products) Periodonta diseased LPS beta, T lipopolysac ( ) from PGE2 ( prostaglan IL-1 BLOODST Placenta PGE2 TNF-alpha5) SOME INTRUIGING NEW DEVELOPMENTS IN THE PERIO/SYSTEMIC LINK Periodontal Disease and Dementia/Alzheimer’s DiseaseCONCLUSIONS AND QUESTIONS AND ANSWERSCOMMONLY REQUESTED REFERENCES 10
  11. 11. Getting Patient Education and Office MaterialsAmerican Academy of Periodontology http://www.perio.orgThe New Classification System for Periodontal DiseasesGC Armitage. Development of a classification system for periodontal diseases andconditions. Ann Periodontol 1999; 4:1-6.Linkages of Periodontal Diseases and General HealthOral Health in America: A Report of the Surgeon General, Chapter 4: Linkages withGeneral Health; 95-132Pischon N, Heng N, Bernimoulin JP, Kleber BM, Willich SN, Pischon T.Obesity, inflammation, and periodontal disease.J Dent Res. 2007 May;86(5):400-9Ryder MI. An update on HIV and periodontal disease. J Periodontol. 2002Sep;73(9):1071-8.MI Ryder, R Fujitaki, G Johnson, W Hyun. Alterations of neutrophil oxidative burst byin vitro smoke exposure: Implications for oral and systemic diseases. Ann Periodontol1998; 3(1):76-87Hu W, Cao C, Meng H, Zhang J, Ma D, Zhang L. Detection and analysis of Helicobacterpylori in oral cavity and stomach from chronic gastritis patients.Zhonghua Yi Xue Za Zhi. 2002 Aug 10;82(15):1037-41GC Armitage. Periodontal infections and cardiovascular disease: how strong is theassociation. Oral Diseaes 2000; 6:335:350.Noack B, Genco RJ, Trevisan M, Grossi S, Zambon JJ, De Nardin E.Periodontal infections contribute to elevated systemic C-reactive protein level.J Periodontol. 2001 Sep;72(9):1221-7Mattila K, Vesanen M, Valtonen V, Nieminen M, Palosuo T, Rasi V, Asikainen S.Effect of treating periodontitis on C-reactive protein levels: a pilot study.BMC Infect Dis. 2002 Dec 10;2(1):30Lopez NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of pretermlow birth weight in women with periodontal disease: a randomized controlled trial.J Periodontol. 2002 Aug;73(8):911-24Scannapieco FA, Bush RB, Paju S Periodontal disease as a risk factor for adversepregnancy outcomes. A systematic review. Ann Periodontol. 2003 Dec;8(1):70-8.Scannapieco FA, Bush RB, Paju S. 11
  12. 12. Associations between periodontal disease and risk for nosocomial bacterial pneumoniaand chronic obstructive pulmonary disease. A systematic review.Ann Periodontol. 2003 Dec;8(1):54-69.Scannapieco FA, Bush RB, Paju S.Associations between periodontal disease and risk for atherosclerosis, cardiovasculardisease, and stroke. A systematic review.Ann Periodontol. 2003 Dec;8(1):38-53.Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJInflammation and Alzheimers disease: possible role of periodontal diseases. AlzheimersDement. 2008 Jul;4(4):242-50.Goldstein MR, Mascitelli L, Pezzetta F. Periodontitis, atherosclerotic cardiovasculardisease and vitamin D. Am J Cardiol. 2009 Oct 15;104(8):1164Benefits of Periodontal Treatment on Systemic HealthMealey BL, Oates TW Diabetes mellitus and periodontal diseases. J Periodontol. 2006Aug;77(8):1289-303.Tuter G, Kurtis B, Serdar M, Aykan T, Okyay K, Yucel A, Toyman U, Pinar S, Cemri M,Cengel A, Walker SG, Golub LM.Effects of scaling and root planing and sub-antimicrobial dose doxycycline on oral and systemic biomarkers of disease in patientswith both chronic periodontitis and coronary artery disease.J Clin Periodontol. 2007 Jun 21Tonetti MS, DAiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD,Vallance P, Deanfield J. Treatment of periodontitis and endothelial function.N Engl J Med. 2007 Mar 1;356(9):911-20Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE,Buchanan W, Bofill J, Papapanou PN, Mitchell DA, Matseoane S, Tschida PA; OPTStudy. Treatment of periodontal disease and the risk of preterm birth.N Engl J Med. 2006 Nov 2;355(18):1885-94Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, van der Geest S, van Tiel FH,Beysens AJ, de Leeuw PW, Stobberingh EE.Prevention of ventilator-associatedpneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study Am J Respir Crit Care Med. 2001 Aug 1;164(3):382-8DAiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS.Short-term effects of intensive periodontal therapy on serum inflammatory markers andcholesterol. J Dent Res. 2005 Mar;84(3):269-73Kiran M, Arpak N, Unsal E, Erdogan MF. 12
  13. 13. The effect of improved periodontal health on metabolic control in type 2 diabetesmellitus. J Clin Periodontol. 2005 Mar;32(3):266-72Taylor GW. A meta-analysis finds periodontal treatment provides a non-significantimprovement in glycemic control.J Evid Based Dent Pract. 2007 Jun;7(2):62Scheckler WE. Chlorhexidine gluconate for prevention of nosocomial infection in cardiacsurgery. JAMA. 2007 Mar 14;297(10):1059-60Altenative Drugs with less Gingival EnlargementG Hernandez, L Arriba, M Lucas, A de Andres. Reduction of severe gingival overgrowthin a kidney transplant patient by replacing cyclosporin A with Tacrolimus. J Periodontol2000; 71: 1630-1636.P Westbrook, EM Bednarczyk, M Carlson, H Sheehan, NF Bissada. Regression ofNifedipine-induced gingival hyperplasia following switch to a same class calciumchannel blocker, Isradipine. J Periodontol 1997; 68:645-650.O Oetiinger-Barak, S Barak, EE Machtei, L Ardekian, Y Baruch, and M Peled.Periodontal Changes in Liver Cirrhosis and Post-Transplantation Patients I: ClinicalFindings J Periodontol 2001; 72:1236-1240Effectiveness of Controlled Local Delivery SystemsGarrett S, Johnson L, Drisko CH, Adams DF, Bandt C, Beiswanger B, Bogle G, DonlyK, Hallmon WW, Hancock EB, Hanes P, Hawley CE, Kiger R, Killoy W, Mellonig JT,Polson A, Raab FJ, Ryder M, Stoller NH, Wang HL, Wolinsky LE, Evans GH, HarroldCQ, Arnold RM, Southard GL, et al.Two multi-center studies evaluating locally delivered doxycycline hyclate, placebocontrol, oral hygiene, and scaling and root planing in the treatment of periodontitis.J Periodontol. 1999 May;70(5):490-503Paquette D, Oringer R, Lessem J, Offenbacher S, Genco R, Persson GR, Santucci EA,Williams RC. Locally delivered minocycline microspheres for the treatment ofperiodontitis in smokers. J Clin Periodontol. 2003 Sep;30(9):787-94Ryder MI, Pons B, Adams D, Beiswanger B, Blanco V, Bogle G, Donly K, Hallmon W,Hancock EB, Hanes P, Hawley C, Johnson L, Wang HL, Wolinsky L, Yukna R, PolsonA, Carron G, Garrett S Effects of smoking on local delivery of controlled-releasedoxycycline as compared to scaling and root planing.J Clin Periodontol. 1999Oct;26(10):683-91 13
  14. 14. Williams RC, Paquette DW, Offenbacher S, Adams DF, Armitage GC, Bray K, Caton J,Cochran DL, Drisko CH, Fiorellini JP, Giannobile WV, Grossi S, Guerrero DM, JohnsonGK, Lamster IB, Magnusson I, Oringer RJ, Persson GR, Van Dyke TE, Wolff LF,Santucci EA, Rodda BE, Lessem J. Treatment of periodontitis by local administration ofminocycline microspheres: a controlled trial.J Periodontol. 2001 Nov;72(11):1535-44Microbial testing servicesUniversity of Southern California: Oral Microbiology Testing Laboratory (OMTL) Telephone: 213-740-3163 14