Subantimicrobial Dose Doxycycline Efficacy as a Matrix Metalloproteinase Inhibitor in Chronic Periodontitis Patients Is Enhanced When Combined With a Non‐Steroidal Anti‐Inflammatory Drug

• DOI: 10.1902/jop.2004.75.3.453
• Publication Date: 2005-02-02T12:52:16Z
• Authors: Hsi‐Ming Lee; Sebastian G. Ciancio; Gülay Tüter; Maria E. Ryan; Eugene Komaroff; Lorne M. Golub
• Keywords: Matrix metalloproteinase inhibitor

Background: Administration of subantimicrobial dose doxycycline (SDD) to chronic periodontitis (CP) patients has repeatedly been found reduce mammalian collagenase and other matrix metalloproteinase (MMP) activity in gingival tissues crevicular fluid, association with clinical efficacy, without the emergence antibiotic‐resistant bacteria either orally or extra‐orally. More recently, SDD adjunctive repeated mechanical debridement resulted dramatic improvement (>50% smokers) generalized aggressive periodontitis. As an additional pharmacologic approach, non‐steroidal anti‐inflammatory drugs (NSAIDs) can inflammation alveolar bone resorption, at least under experimental conditions. In current study, we determined effect administering a combination (combination) these two host‐modulating (SDD plus low‐dose NSAID) CP patients, on selected neutral proteinases gingiva, enzymes believed mediate periodontal breakdown. Earlier preliminary studies humans bullous pemphigoid, which is also associated excessive levels host‐derived including MMPs, indicated improved efficacy therapy. Methods: Nineteen scheduled for mucoperiosteal flap surgery bilaterally maxillary arch, were randomly distributed into three groups administered 1) flurbiprofen (LDF) alone, 50 mg q.d.; 2) (20 b.i.d.) alone; 3) LDF (combination). The biopsied during from right left posterior sextants, before after 3‐week regimen medication, respectively. then extracted, extracts partially purified, analyzed endogenous proteinase inhibitor, α1‐PI, its breakdown product, metalloproteinases (i.e., collagenases, gelatinases) neutrophil elastase activities. Results: Short‐term therapy alone produced significant reduction no proteinases. However, statistically synergistic collagenase, gelatinase, serpinolytic (α1‐PI degrading) activities (69%, 69%, 75% reductions, respectively) lesser serine proteinase, (46%). Conclusions: Consistent previous animal models destructive disease (e.g., rheumatoid arthritis), NSAID synergistically suppressed MMP gingiva patients. A mechanism, suggested by earlier studies, involves NSAID, regimen, increasing uptake tetracycline‐based inhibitor inflammatory lesion, thus enhancing this medication. J Periodontol 2004;75:453‐463 .