Modulation of Periodontal Wound Healing by Subantimicrobial Doxycycline Hyclate in Patients with Advanced Periodontitis

Objectives: Previous investigations have shown the effects on wound healing of subantimicrobial dose doxycycline (SDD) regimen in conjunction with non-surgical therapy in periodontal patients. The aim of this study is to evaluate the effect of SDD therapy on the modulation of wound repair following periodontal surgery. Materials and Methods: Twenty-four patients were included in a 12-month placebo-controlled, double-masked trial. At baseline, patients received periodontal access flap surgery (AFS) and were randomly assigned to either to AFS + SDD (20 mg Doxycycline hyclate bid for 6 month), or AFS + placebo. Clinical measurements including probing depth (PD), clinical attachment levels (CAL), bleeding upon probing (BOP) and microbial assessment (by evaluating level and proportion of 40 different pathogens) were performed at baseline, 3, 6, 9 and 12 months. In addition, biochemical analyses for a bone-specific marker (C-telopeptide) and relative changes in proteinases were conducted by using radioimmunoassay and gelatin zymmography, respectively. Results: Results demonstrated that either test or control groups gave clinical improvements in all PD strata. Using a subject-based analysis, patients treated with SDD + AFS showed improvements in PD reduction (3.3 mm Vs 2.1 mm; P < 0.05) and CA gains (1.8 mm vs 1.1 mm; NS) comparing to SDD + Placebo at 6 months. In addition, there was no statistical difference between SDD and placebo groups in mean counts for any bacteria analyzed during this trial. Biochemical analysis showed a greater reduction in C-telopeptides levels with SDD therapy compared to placebo. Finally, levels of collagenase type IV were reduced in SDD therapy (by 7.2%) while in placebo controls, a 5% increasing in expression was noticed. Conclusion: The utilization of post-surgical therapy SDD appeared to enhance efficacy compared to placebo, by evaluating either clinical and biochemical analysis. SDD therapy showed no effect on the periodontal microflora for any pathogen analyzed.