Collagenase activity in recurrent periodontitis: relationship to disease progression and doxycycline therapy

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Abstract
Previous reports have suggested that active progression of periodontitis may be correlated with increased collagenolytic activity, and that improved clinical conditions after tetracycline treatment may be explained by inhibition of host collagenase. Eighty‐two patients with a recent history of periodontal abscesses and/or loss of gingival attachment level (GAL) despite active periodontal therapy were enrolled in a double‐blind, randomized, placebo‐controlled trial. Clinical measurements, sampling of gingival crevicular fluid (GCF) and sub‐gingival scaling were performed every 2 months. If any site exhibited > 2 mm loss of GAL or a periodontal abscess, patients were administered either 100 mg doxycycline per day for 3 weeks or placebo. During 12 months of monitoring, 55 patients exhibited recurrent active disease and were then randomly assigned to either the doxycycline (n = 30) or placebo (n = 25) groups. Analysis of active collagenase and latent collagenase in GCF samples were determined by functional assays and quantitated after SDS‐PAGE and fluorography. Collagenase activities were assayed at sites exhibiting active destruction (study site), at sites with pocket depth comparable to the study site but without active destruction, and at healthy sites. Clinical measurements of GAL and collagenase activity were made at intervals between l wk and 7 months after completion of the drug regime. Within 7 months, 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on doxycycline. Collagenase activity exhibited large variations among patients and was analyzed as presence or absence of active collagenase with a logistic model. The frequency of study sites with active collagenase was 20% higher than that of comparable sites and was 60% higher than control sites. Collagenase activity remained elevated throughout the experimental period in spile of clinical remission from active destructive disease. There was no detectable difference between placebo and doxycycline groups of collagenase activity in vivo during or after the administration of the drug. Separate tests of reproducibility demonstrated that less than 8% of the total variability of the results was due to assay error, diurnal Variation or sampling errors. These data indicate that analysis of collagenase activity could provide an effective diagnostic method to detect the presence of progressive periodontal lesions.