Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis

Objectives: The therapeutic effects of doxycycline and other tetracyclines in the treatment of periodontitis involve, at least in part, mechanisms tha t are unrelated to their antimicrobial activity. Previous clinical studies have shown that doxycycline administered orally, at doses below those neede d for antimicrobial efficacy, to human subjects with adult periodontitis re sulted in significantly reduced collagenase activity in gingival crevicular fluid (GCF) and in extracts of inflamed gingival tissues. The purpose of t he present study was to identify clinically effective dosing regimens using subantimicrobial dose doxycycline (SDD) as an adjunctive therapy in patien ts with adult periodontitis. Material and Methods: A total of 75 adult men and women qualified for enrol lment into the three-part, placebo-controlled, double-blind, parallel-group study. Patients were stratified based on repeatedly exhibiting pathologic levels of periodontal attachment (ALv) and GCF collagenase activity at seve ral appointments prior to baseline. Patients were administered a scaling an d prophylaxis, then 1 of 5 treatment schedules for 12 weeks (part I), follo wed by a 12-week period of no drug therapy (part II), a second scaling and prophylaxis, and 12 additional weeks of treatment (part In). Primary determ inants of efficacy included reductions in GCF collagenase activity and chan ges in relative ALV. Results: 66 patients completed the Ist 12 weeks (part I) of the 3-part, 36- week study; 51 patients completed the entire 36-week study. From baseline t o week 12 (part I), treatment with specially formulated SDD capsules (20 mg ) 2x daily (Ix every 12 h) for up to 12 weeks was shown to significantly re duce GCF collagenase activity and to improve ALV, effects not seen in patie nts treated with placebo. Continuous drug therapy over the 12-week treatmen t period was needed to maintain and maximize the reduction in GCF collagena se and the improvement in ALv. Improvements in periodontal disease paramete rs occurred without the emergence of doxycycline-resistant micro-organisms. In patients administered an "on-off-on" regimen of SDD over 36 weeks (part s I-III), essentially no attachment loss occurred in patients receiving the highest of these SDD regimens (20 mg 2X daily during part I and 20 mg 1X d aily in part III), whereas patients administered placebo capsules experienc ed a mean attachment loss of approximately 0.8 mm at the 24- and 36-week ti me periods. Conclusions: Doxycycline administered at subantimicrobial doses led to impr ovements in disease parameters, with no apparent side effects, and appears to have significant potential as an oral adjunctive therapy in the long-ter m management of adult periodontitis.