GCF MMP-8 in Postmenopausal Women: Association with Progressive Attachment Loss

Objective: To evaluate the association between gingival crevicular fluid (GCF) matrix metalloproteinases (MMPs) and clinical attachment loss (CAL) in a clinical trial of an MMP inhibitor. Methods: Postmenopausal osteopenic, estrogen-deficient women on periodontal maintenance therapy (PMT) for moderate-advanced periodontitis participated in a two-year double-blind, placebo-controlled, randomized clinical trial with MMP-inhibitor subantimicrobial dose doxycycline (SDD; 20 mg bid, n = 64) or placebo (n = 64) treatment arms. The following changes were measured from baseline at 1 year and 2 years at posterior interproximal sites: GCF collagenase activity (high-performance liquid chromatography), MMP 8 (Western blot) and CAL (threshold for significant change: ± 1.5 mm; Florida Probe). GCF samples were collected from 2 pocket sites (5-9 mm in depth) and pooled per subject. The exploratory associations between tertiles of MMP changes and CAL were examined by Generalized Estimating Equations. Results: There was no significant association between 1 year changes in collagenase activity and progressive CAL over 2 years (test for linear trend p = 0.6). However, increases in MMP-8 during the first year of the trial were associated with a 50% increase in the odds of progressive CAL by year 2 when comparing subjects in the upper tertile of MMP-8 change to subjects in the lowest tertile (OR = 1.50, 95% CI: 1.06 to 2.13, p = 0.02), driven by the placebo group. Conclusions: Postmenopausal osteopenic patients with moderate-severe periodontitis and compliant with 3-4 month PMT, yet who experience increased GCF MMP-8, are more likely to demonstrate future progressive attachment loss, similar to our previously-reported findings with GCF IL-1b. SDD also was previously shown to reduce GCF MMP-8 and odds of CAL. Supported by NIDCR/NIH grant (R01DE012872).