Effectiveness of Adjunctive Low‐Dose Doxycycline Therapy on Clinical Parameters and Gingival Crevicular Fluid Laminin‐5 γ2 Chain Levels in Chronic Periodontitis

Abstract

Laminin-5 (Ln-5) is involved in the apical migration of epithelial cells during the development of periodontal pockets. Low-dose doxycycline (LDD) can therapeutically modulate the host response with its non-antimicrobial properties. In the present randomized, double-blind, placebo-controlled, parallel arm study, the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid (GCF) Ln-5 gamma2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period. GCF samples were collected and clinical parameters including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index were recorded. Thirty chronic periodontitis patients were randomized either to low-dose doxcycline or placebo groups. LDD group received doxycycline (20 mg, b.i.d.) for 3 months plus scaling and root planing (SRP), while placebo group was given placebo capsules b.i.d. for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. All clinical parameters and GCF sampling were repeated at each visit. GCF Ln-5 gamma2 chain fragment levels were determined by Western immunoblotting using specific antibody and quantitated by computerized image analysis. Friedman test was used for intragroup comparisons followed by Wilcoxon signed rank test to analyze significance of changes over time. The Mann-Whitney test was used to determine differences between both LDD and placebo groups. Both groups revealed significant improvements in all clinical parameters over the 12-month period (P < 0.0125). LDD group showed a significantly greater reduction in the mean PD scores at 9 and 12 months and in the mean GI scores at all time points than the placebo group (P < 0.05). In the LDD group, GCF Ln-5 gamma2 chain fragment levels were significantly reduced at 3 months (P < 0.0125) and then slightly increased during the rest of the study period. In the placebo group, GCF 45 and 70 kDa Ln-5 gamma2 chain fragments tended to decrease at 3 months compared to baseline, but did not reach significance; these levels continued to increase throughout the remainder of the study period. GCF Ln-5 gamma2 chain fragment levels in LDD group were significantly lower than those of the placebo group during the study period (P < 0.05). The present data indicate that LDD therapy in combination with SRP therapy can reduce GCF Ln-5 gamma2 chain fragment levels and improve clinical periodontal parameters in patients with chronic periodontitis. Since matrix metalloproteinases (MMP)-mediated fragmentation of laminin-5 can contribute to pocket formation by stimulating epithelial cell migration, the reduction of Ln-5 gamma2 chain fragment levels could provide a new mechanism by which LDD, adjunctive to SRP, inhibits periodontal disease more effectively than SRP alone. Thus, these results provide extended and additional information about the effectiveness of the LDD therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease.