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Periodontal-Systemic Interrelationships Antonio J. Moretti ...


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Periodontal-Systemic Interrelationships Antonio J. Moretti ...

  1. 1. Periodontal-Systemic Interrelationships Antonio J. Moretti, DDS, MS The University of Texas Houston Health Science Center Dental Branch
  2. 3. Periodontal Diseases and Systemic Diseases <ul><li>A “two-way street” </li></ul><ul><li>Is the old focal infection theory rearing its head? </li></ul><ul><li>Are we getting closer to become true oral physicians? </li></ul>
  3. 4. Periodontal Diseases and Systemic Diseases <ul><li>Dentists need to know more about systemic diseases and physicians need to increase their knowledge of oral diseases </li></ul>
  4. 5. Periodontal Disease <ul><li>10 to 15% of US adults have severe periodontal disease </li></ul><ul><li>The same is true for the rest of the world </li></ul><ul><li>Factors other than chance or poor dental habits predispose people to periodontal disease </li></ul>
  5. 6. Moderate to Severe Periodontitis with at least 28 teeth present 72 cm 2 of pocket epithelium in contact with biofilms Roy Page,1998
  6. 7. Systemic conditions as risk factors for periodontal disease <ul><li>Diabetes </li></ul><ul><li>Smoking </li></ul><ul><li>HIV </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Menopause </li></ul><ul><li>Angst-Related Psychosocial Factors </li></ul>
  7. 8. Diabetes - short review <ul><li>IDDM (type 1): </li></ul><ul><ul><li>5 to 15% of cases. Abrupt onset, commonly at puberty </li></ul></ul><ul><ul><li>Destruction of insulin production beta cells in the pancreas via autoimmune process </li></ul></ul><ul><li>NIDDM (type 2): </li></ul><ul><ul><li>2 to 3% of population. Recognized only 50% of cases </li></ul></ul><ul><ul><li>Reduced insulin production </li></ul></ul><ul><ul><li>Control with diet, hypoglycemic drugs, or combination </li></ul></ul>
  8. 9. Diabetes Mellitus - Hypothesis <ul><li>Hyperglycemia produces oxidation of protein and lipids. This will result in a dvanced g lycation e nd products (AGE) </li></ul><ul><li>AGEs are primarily responsible for collagen cross-links leading to macrovascular complications (hardening of arteries) </li></ul><ul><li>AGEs bind to endothelial cells and macrophages </li></ul><ul><li>Macrophages that interact with AGE will increase secretion of TNF-  , IL-6, and IL-1  </li></ul>
  9. 11. Diabetes Mellitus - Hypothesis <ul><li>Interaction of AGE and endothelial cells will result in endothelin-1 (a potent vasoconstrictor) </li></ul><ul><li>The previous cellular reactions may take place in the periodontium, thus accounting for increased risk for severe attachment loss </li></ul><ul><li>Tissues from retina, kidney, and nerves have shown permeability to glucose </li></ul><ul><li>Pathogenesis of periodontal disease in diabetics might also be glucose-mediated </li></ul>
  10. 13. Diabetes <ul><li>IDDM and NIDDM are risk factors for periodontal disease </li></ul><ul><li>Progression is faster and tooth loss is higher in poorly controlled patients </li></ul><ul><li>PMN function might be impaired </li></ul><ul><li>Thickening of the basement membrane and the vessel walls </li></ul>
  11. 14. Diabetes <ul><li>Interference with delivery of nutrients </li></ul><ul><li>Decreased oxygen diffusion </li></ul><ul><li>Decreased elimination of metabolic waste </li></ul><ul><li>Increased collagen breakdown </li></ul><ul><li>Altered collagen synthesis </li></ul>
  12. 15. Diabetes <ul><li>Well-controlled diabetics who receive regular periodontal care and have good oral hygiene are NO more likely to develop severe periodontitis than non diabetics. </li></ul><ul><li>Seppala et al., 1993 and 1994 </li></ul><ul><li>Well-controlled diabetics have been shown to respond equally as well to periodontal therapy as non diabetics. </li></ul><ul><li>Westfelt et al., 1996 Telervo et al., 1997 </li></ul>
  13. 16. Effect of Periodontitis on Diabetes <ul><li>Hypothesis: </li></ul><ul><ul><li>Bacterial infection releases hormones that increase glucose levels </li></ul></ul><ul><ul><li>Inflammatory mediators (TNF-  and IL-1  ) induce cell resistance to insulin </li></ul></ul>
  14. 17. Effect of Periodontitis on Diabetes <ul><li>Periodontal treatment might improve the metabolic control of the disease </li></ul><ul><li>Williams and Mahan, 1960; Miller et al., 1992; </li></ul><ul><li>Aldridge et al., 1996; Grossi et al., 1997 </li></ul><ul><li>Severe Periodontitis has been associated with a 6 fold increased risk of poor glycemic control Taylor et al., 1996 </li></ul>
  15. 18. Cigarette Smoking <ul><li>Accounts for approximately half the cases of periodontitis in young adults </li></ul><ul><li>Smokers are, in average, close to three times more likely to show severe periodontal disease </li></ul><ul><li>Current smokers are 3.3 times more likely to attend a periodontist’s office </li></ul>
  16. 19. Smoking <ul><li>Light smokers have a relative risk of developing periodontal disease that is 2 times higher than non smokers </li></ul><ul><li>Heavy smokers have a relative risk of developing periodontal disease that is 7 times higher than non smokers </li></ul><ul><li>Grossi et al. 1994, 1995 </li></ul>
  17. 20. Smoking <ul><li>Decreases cell-mediated and humoral immune responses </li></ul><ul><li>Alters PMN function </li></ul><ul><li>Decreases serum IgG 2 </li></ul><ul><li>Modulates subgingival microbiota </li></ul><ul><li>Increases levels of certain microorganisms </li></ul>
  18. 21. Smoking Cessation <ul><li>Seems to yield periodontal benefits </li></ul><ul><li>Long term studies are still missing </li></ul><ul><li>After a year, gingival tissues revert from fibrotic to normal anatomy and contour </li></ul><ul><li>Haber, 1996 </li></ul>
  19. 22. HIV <ul><li>Conflicting evidence to be considered a risk factor for conventional periodontal disease </li></ul><ul><li>Small percentage of HIV+ patients develop a severe rapidly progressive form of gingivitis/periodontitis (NUG/NUP) </li></ul><ul><li>Lesions are usually associated with pronounced immunosuppression </li></ul>
  20. 24. HIV <ul><li>Regulation of PMN recruitment in GCF is hindered </li></ul><ul><li>Suggested that PMN dysfunction allows subgingival colonization of Candida and subsequent risk increase for periodontal destruction </li></ul><ul><li>Lamster et al., 1998 </li></ul>
  21. 25. Candidiasis and Periodontal Disease
  22. 28. Short-Term Success of Osseointegrated Dental Implants in HIV-Positive Individuals <ul><li>Riano PC, Stevenson GC, Engelmeier RL, Flaitz CM, Moretti AJ, Nichols CM </li></ul>Master of Sciences Thesis at UTDB Houston
  23. 29. Hypothesis <ul><li>The null hypothesis for this study was: “There are no differences between the HIV infected and uninfected populations in the clinical behavior and biologic integration of endosseous dental implants as measured by descriptive parameters of assessment. </li></ul>
  24. 30. Study Information <ul><li>Prospective, cohort, multi-center pilot study </li></ul><ul><li>Compare short-term success rate of osseointegrated dental implants in HIV infected versus uninfected populations to justify the use of implants in the HIV positive population </li></ul><ul><li>Clinical study to glean other important clinical information related to implant dentistry in HIV infected individuals to assist dentists in contributing to the improvement of the quality of life for these individuals </li></ul>
  25. 31. Materials and Methods <ul><li>15 HIV+ patients </li></ul><ul><li>8 HIV- patients </li></ul><ul><li>Inclusion criteria: </li></ul><ul><ul><li>>18 years old, edentulous for at least 2 years </li></ul></ul><ul><ul><li>Occlusion type I or III </li></ul></ul><ul><ul><li>Minimum of 10mm crestal height </li></ul></ul><ul><ul><li>Hemoglobin >8g/dl </li></ul></ul><ul><ul><li>Absolute neutrophil count >750 cells/L </li></ul></ul><ul><ul><li>Platelet count >75,000/L </li></ul></ul><ul><ul><li>AST<5 times the upper limit of normal (ULN) </li></ul></ul><ul><ul><li>Bilirrubin <2.5 times ULN </li></ul></ul><ul><ul><li>Alkaline phosphatase <5.0 times ULN </li></ul></ul><ul><ul><li>Creatinine <2.5 mg/ml </li></ul></ul>
  26. 32. Materials and Methods <ul><li>Exclusion criteria: </li></ul><ul><ul><li>Heavy smoking (>30 cigarettes/day) </li></ul></ul><ul><ul><li>Individuals with high recurrence of opportunistic infections </li></ul></ul><ul><ul><li>Patients with uncontrolled diabetes mellitus </li></ul></ul><ul><ul><li>Pregnant patients </li></ul></ul><ul><ul><li>Occlusion class II and/or bruxism </li></ul></ul><ul><ul><li>Inadequate bone availability </li></ul></ul><ul><ul><li>Poor oral hygiene </li></ul></ul>
  27. 33. Materials and Methods <ul><li>Panoramic radiograph </li></ul><ul><li>Surgical drill guide for mandible only </li></ul><ul><li>Amoxicillin 500mg/chlorhexidine rinses </li></ul><ul><li>Mandibular right and left block anesthesia </li></ul><ul><li>Full thickness flaps </li></ul><ul><li>Two BioHorizons ® implants Maestro ™ System (#s 22 and 27) length: 11 or 12 mm, diameter: 3.5 to 5.0mm </li></ul><ul><li>Conventional surgical protocol according to Branemark </li></ul>
  28. 38. Tooth Loss and Osteoporosis <ul><li>Systemic bone loss can be a risk for edentulism Daniell et al., 1983 </li></ul><ul><li>In a 7-year longitudinal study, the rate of systemic bone loss was a predictor for tooth loss in menopausal women Krall et al., 1996 </li></ul><ul><li>Women that are at risk for or suffer from osteoporosis are also at risk for tooth loss </li></ul><ul><li>Grossi et al., 2000 </li></ul>
  29. 39. Periodontal Disease and Osteoporosis <ul><li>Mandibular bone mass is not related to age but to skeletal bone mass Kribbs et al., 1990 </li></ul><ul><li>Controversy still exists on the association between osteoporosis and periodontal disease: </li></ul><ul><ul><li>Small sample size, age of population </li></ul></ul><ul><ul><li>Definitions of diseases, methods used </li></ul></ul><ul><ul><li> Grossi et al., 2000 </li></ul></ul>
  30. 40. Menopause <ul><li>Postmenopausal women with no hormonal replacement have shown greater tooth loss </li></ul><ul><li>Grodstein et al., 1996 </li></ul><ul><li>Women who received estrogen replacement had much lower risk for edentulism </li></ul><ul><li>Pagaini-Hill, 1995 </li></ul>
  31. 41. Menopause <ul><li>Alendronate has shown to lower the risk of bone height and density loss by half </li></ul><ul><li>This difference was shown to remain for at least three months after stopping treatment </li></ul><ul><li>Jeffcoat and Reddy, 1996 </li></ul>
  32. 42. Angst-Related Psychosocial Factors <ul><li>Chronic stress </li></ul><ul><li>Depression </li></ul><ul><li>Financial problems </li></ul><ul><li>Social Isolation </li></ul>
  33. 43. Angst-Related Psychosocial Factors <ul><li>People with good coping strategies show less periodontal disease </li></ul><ul><li>Moss et al., 1996; Marcenes and Sheiham, 1992 </li></ul><ul><li>Genco et al., 1999 </li></ul><ul><li>Studies needed: establish the time course of stress, distress, and inadequate coping with respect to onset and progression of periodontal disease </li></ul>
  34. 44. Periodontal disease as a risk factor for systemic conditions <ul><li>Cardiovascular Disease </li></ul><ul><li>Pregnancy </li></ul><ul><li>Respiratory </li></ul>
  35. 45. Cardiovascular Disease <ul><li>Increased risk for atherosclerosis and thromboembolisms due to periodontal disease </li></ul><ul><li>Men with periodontitis is 25% more likely to develop coronary heart disease (CHD) </li></ul><ul><li>The risk is particularly high for men under age 50 with a relative risk for CHD </li></ul><ul><li>DeStefano et al., 1993 </li></ul>
  36. 47. Mechanisms by which infections contribute to atherosclerosis <ul><li>Direct effects of infectious agents in atheroma formation </li></ul><ul><li>Indirect or host-mediated effects triggered by infection </li></ul><ul><li>Common genetic predisposition to periodontal disease and atherosclerosis </li></ul><ul><li>Common risk factors such as life style </li></ul>
  37. 48. Direct effects of infectious agents in atheroma formation <ul><li>P. gingivalis has been found in carotid and coronary atheromas </li></ul><ul><li>Haraszthy et al. 1998; Chiu et al., 1999 </li></ul><ul><li>P. gingivalis has shown to invade and proliferate in endothelial cells </li></ul><ul><ul><li>Deshpande et al., 1998 </li></ul></ul><ul><li>P. gingivalis is able to induce aggregation of platelets </li></ul><ul><li> Herzberg and Meyer, 1996 </li></ul>
  38. 49. Indirect or host-mediated effects triggered by infection <ul><li>Periodontitis induces production of C-reactive protein and fibrinogen </li></ul><ul><li>Periodontal microorganisms contain proteins which cross-react with the heart </li></ul>
  39. 50. Common genetic predisposition to periodontal disease and atherosclerosis <ul><li>Beck et al., 1996 proposed a model of genetically determined hyperinflammatory macrophage phenotype in periodontal disease, which contributes to the susceptibility for atherosclerosis </li></ul>
  40. 51. Cardiovascular Disease <ul><li>Meta-analyses of prospective studies on coronary heart disease (CHD) and periodontal disease: Danesh, 1999 </li></ul><ul><ul><li>Five main studies with 2369 cases </li></ul></ul><ul><ul><li>Weighted mean age at baseline of 55 years </li></ul></ul><ul><ul><li>Weighted mean follow-up of 12 years </li></ul></ul>
  41. 53. Cardiovascular Disease <ul><ul><li>Different methods to measure disease (including self reported) </li></ul></ul><ul><ul><li>Different criteria based on clinical examination (e.g., missing teeth, alveolar bone loss, attachment loss, probing depth) </li></ul></ul><ul><ul><li>There was no significant heterogeneity among the 5 articles (p > .1) </li></ul></ul>
  42. 54. Cardiovascular Disease <ul><ul><li>This analyses did not find any strong correlation between periodontal disease and CHD </li></ul></ul><ul><ul><li>Reliable investigation requires: </li></ul></ul><ul><ul><ul><li>larger sample size </li></ul></ul></ul><ul><ul><ul><li>socially homogeneous population </li></ul></ul></ul><ul><ul><ul><li>serial measurements of infective agents </li></ul></ul></ul><ul><ul><ul><li>studies of early-onset cases </li></ul></ul></ul>
  43. 55. Pregnancy <ul><li>Fetuses of pregnant hamsters infected with P. gingivalis weighted up to 25% less than the fetuses of healthy controls </li></ul><ul><li>124 pregnant mothers with periodontal disease were seven times more likely to deliver a preterm low-birth weight (PLBW) baby </li></ul><ul><li>Offenbacher et al., 1996 </li></ul>
  44. 56. Pregnancy <ul><li>F. nucleatum is the most frequent isolate from the amniotic fluid (AF) </li></ul><ul><li>F. nucleatum may spread to the AF via a transient bacteremia in the presence of periodontal disease </li></ul><ul><li>IL-1, IL-6, and TNF-  may target the placenta </li></ul>
  45. 58. Pregnancy <ul><li>Mothers with a higher mean of GCF-PGE 2 level were 9 times more likely to be in PLBW </li></ul><ul><li>There is also a trend of higher mean of GCF-IL-1  level and an increase in PLBW </li></ul><ul><li>Offenbacher et al., 1998 </li></ul>
  46. 59. Respiratory <ul><li>Hospitalized or nursing home patients may increase the risk for bacterial pneumonia </li></ul><ul><li>Scannapieco et al., 1998 </li></ul><ul><li>There is evidence of correlation between increased alveolar bone loss and increased risk for chronic obstructive pulmonary disease </li></ul><ul><li>Hayes et al., 1998 </li></ul>
  47. 60. Evaluation of Oral Soft Tissue Lesions in Ventilated Patients <ul><li>Moretti AJ, Flaitz CM, Peninger M, Rex JH, Milano M, Harrison N, and Nates JL </li></ul>UTHSC-H Dental Branch and Medical School, Memorial Hermann Hospital, Houston, TX
  48. 61. Purpose <ul><li>To document the frequency of oral soft tissue lesions in ventilated patients, who were receiving care in a tertiary care and level I trauma center. This report is part of a larger study on oral hygiene care for these patients, using the oral suction toothbrush and oral swab. </li></ul>
  49. 62. Materials and Methods <ul><li>Study features: </li></ul><ul><ul><li>Pilot study, convenience sample, short term </li></ul></ul><ul><ul><li>Neurosurgical Intensive Care Unit patients </li></ul></ul><ul><ul><li>Treatment groups: oral hygiene by two-sided sponge or sponge/toothbrush </li></ul></ul><ul><ul><li>Oral hygiene q 4-6 h. or minimum 3 x/day </li></ul></ul><ul><ul><li>Initial evaluation by oral pathologist and periodontist within 24 hours </li></ul></ul><ul><ul><li>Follow up q 3-4 days </li></ul></ul><ul><ul><li>High intensity light, mouth mirror, cheek retractors, photos of accessible lesions </li></ul></ul>
  50. 63. Materials and Methods <ul><li>Inclusion criteria: </li></ul><ul><ul><li>Assisted ventilation >48 h. </li></ul></ul><ul><ul><li>Age >18 years-old </li></ul></ul><ul><ul><li>> 2 teeth </li></ul></ul><ul><li>Exclusion criteria: </li></ul><ul><ul><li>Non-ventilated patients </li></ul></ul><ul><ul><li>Trauma to jaws or neck to limit oral access </li></ul></ul><ul><ul><li>Transfer to another unit in less than 24 h. </li></ul></ul><ul><ul><li>Life expectancy less than 24 h. </li></ul></ul><ul><ul><li>Edentulous patients </li></ul></ul>
  51. 64. Materials and Methods <ul><li>Parameters: </li></ul><ul><ul><li>Plaque Index (Silness and L ö e, 1964) </li></ul></ul><ul><ul><li>Gingival Index (L ö e and Silness, 1963) </li></ul></ul><ul><ul><li>Tongue assessment (amount, distribution and color of coating) </li></ul></ul><ul><ul><li>Halitosis (Organoleptic scores, Rosenberg et al 1991) </li></ul></ul><ul><ul><li>Trauma associated oral lesions </li></ul></ul><ul><ul><li>Other oral and perioral lesions </li></ul></ul>
  52. 68. Ventilated Patient Swab & Toothbrush
  53. 69. Herpes Labialis Purpura/Sloughing
  54. 70. NUP/Candidiasis Spontaneous bleeding
  55. 72. Summary of Results <ul><li>At least one lesion per patient </li></ul><ul><li>Observation time was similar for all patients </li></ul><ul><li>More male patients in toothbrush group </li></ul><ul><li>Similar PI and GI for both groups </li></ul><ul><li>No difference in improvement of halitosis </li></ul><ul><li>No difference in lesions in both groups </li></ul>
  56. 73. Weaknesses of Study <ul><li>Very small sample size and limited time of observation </li></ul><ul><li>Periodontal status not assessed prior to randomization </li></ul><ul><li>More males in toothbrush group. Males usually have decreased periodontal health in comparison to females </li></ul><ul><li>Limited accessibility to evaluate parameters </li></ul>
  57. 74. Conclusions <ul><li>Lesions were very common but not associated with the oral hygiene devices </li></ul><ul><li>Potential for oral lesions and periodontal disease to contribute to systemic complications exists because many of these lesions are ulcerative and infectious </li></ul><ul><li>Medical and nursing staff needs to recognize and manage a variety of oral lesions for improved patient care and quality of life for ventilated patients </li></ul>
  58. 76. Future knowledge in Periodontal Systemic Interrelationships <ul><li>In vitro studies </li></ul><ul><li>Animal studies </li></ul><ul><li>Intervention studies </li></ul>
  59. 77. Modulation of Host Inflammatory Mediators as a Treatment Strategy for Periodontal Diseases Antonio J. Moretti, DDS, MS
  60. 78. Historical Review <ul><li>Until 1970s bacteria and their products were seen as the most important factors in periodontal diseases. </li></ul><ul><li>Page & Schroeder (1976): pathogenesis of inflammatory periodontal disease. </li></ul><ul><li>Inflammatory mediators (i.e., arachidonic acid metabolites and cytokines) directly cause local tissue destruction. </li></ul><ul><li>Matrix metalloproteinases imbalance. </li></ul>
  61. 79. Pharmaceutical Inhibition of Host Response Pathways <ul><li>NSAIDs </li></ul><ul><li>Cytokine receptor antagonists </li></ul><ul><li>Anti-collagenolytic agents </li></ul>
  62. 82. Modulation of Arachidonic Acid Metabolites <ul><li>Vane (1971) published landmark discovery that aspirin and NSAIDs blocked cyclooxygenase. </li></ul><ul><li>El Attar (1976) PGE 2 levels were observed 20 times higher in the inflamed gingiva. </li></ul><ul><li>Offenbacher et al. (1981) found elevated PGE 2 levels in the GCF of periodontitis patients. </li></ul>
  63. 83. Modulation of Arachidonic Acid Metabolites <ul><li>Williams et al. (1985) NSAIDs in animal model. </li></ul><ul><li>Williams et al. (1989) NSAIDs in humans showed significant lower bone loss rates up to 24 months. </li></ul><ul><li>Jeffcoat et al. (1995) NSAID rinse with positive results. </li></ul>
  64. 85. Modulation of Arachidonic Acid Metabolites <ul><li>Standard NSAIDs inhibit both cyclooxygenase 1 and 2. </li></ul><ul><li>Side effects : gastrointestinal tract, kidney, and platelets. </li></ul><ul><li>New classes of agents (i.e., cyclooxygenase 2 inhibitors and lipoxins) might selectively inhibit the isoenzyme associated with inflammation rather than that of tissue homeostasis. </li></ul>
  65. 86. Modulation of Host Cytokines <ul><li>Cytokines literally “cell proteins” transmit information from one cell to another. </li></ul><ul><ul><li>IL-1  </li></ul></ul><ul><ul><li>TNF-  </li></ul></ul><ul><li>Assuma et al. (1998) animal research on cytokine (i.e., IL-1  and TNF-  ) receptor antagonists found 80% inhibition. </li></ul>
  66. 88. Modulation of Other Host Inflammatory Mediators <ul><li>Nitric Oxide (NO)- free radical with important physiological functions including cardiovascular, nervous system and immune homeostasis. </li></ul><ul><li>NO is elevated in inflammation to protect against antigens. It causes deleterious host effects such as DNA damage, peroxidation, protein damage, and release of cytokines. </li></ul>
  67. 89. Modulation of Other Host Inflammatory Mediators <ul><li>Lohinai et al. (1998) - animal study with injection of mercaptoethylguanidine. Test group exhibited less plasma extravasation and less bone loss as compared with controls. </li></ul>
  68. 91. Matrix Metalloproteinases (MMPs) <ul><li>MMPs are a family of at least 12 Ca ++ and Zn ++ dependent enzymes that degradate extracellular matrix macromolecules (i.e., interesticial and basement membrane collagens, fibronectins, laminin, and proteoglycan core proteins). </li></ul>
  69. 92. MMPs <ul><li>Matrix metalloproteinases are produced by both infiltrating and resident cells of periodontium. </li></ul><ul><li>They play a role in both physiological (i.e., tooth eruption) and pathological (i.e., periodontitis) events. </li></ul>
  70. 93. Tetracyclines <ul><li>Non-antimicrobial properties have application in the treatment of: </li></ul><ul><ul><li>Cancer </li></ul></ul><ul><ul><li>Complications of diabetes </li></ul></ul><ul><ul><li>Arthritis </li></ul></ul><ul><ul><li>Wound healing </li></ul></ul>
  71. 94. MMPs (studies) <ul><li>Golub et al. 1980 – tetracycline binding to Zn ++ and Ca ++ on collagenases. </li></ul><ul><li>Animal studies (Ciancio et al. 1998) </li></ul><ul><li>Human studies (Caton et al. 1997, 2000) </li></ul>
  72. 96. Sub antimicrobial dose doxycycline (SDD) <ul><li>20 mg bid (no antimicrobial action) </li></ul><ul><li>No change in bacterial flora after 18 months </li></ul><ul><li>No induction of resistance after 18 months </li></ul><ul><li>Side effect profile similar to placebo </li></ul>
  73. 98. Sub antimicrobial dose doxycycline (drawbacks) <ul><li>Compliance </li></ul><ul><li>Cost </li></ul><ul><li>Statistical x Clinical Significance </li></ul>
  74. 101. Modulation of Host Inflammatory Mediators - Conclusions <ul><li>Animal and human studies support the basic hypothesis that inhibition of local arachidonic acid metabolites with NSAIDs slows periodontal disease progression. </li></ul><ul><li>Data on modulation of cytokines and Nitric Oxide appear promising. </li></ul>
  75. 102. Modulation of Host Inflammatory Mediators - Conclusions <ul><li>Despite the finding that SDD provides some benefit in arresting periodontal disease progression, there are numerous issues that need to be addressed before its widespread use with any form of periodontitis. </li></ul>
  76. 103. Modulation of Host Inflammatory Mediators - Conclusions <ul><li>Clinicians need to decide which patients are at greatest risk of future disease progression. We still lack proper diagnostic tools for this matter. </li></ul><ul><li>These adjunctive forms of therapy may become a valid option for a small percentage of our patients. </li></ul>