Effect of systemic matrix metalloproteinase inhibition on periodontal wound repair: a proof of concept trial

BACKGROUND: The adjunctive use of matrix metalloproteinase (MMP) inhibitors with scaling and root planing (SRP) promotes new attachment in patients with periodontal disease. This pilot study was designed to examine aspects of the biological response brought about by the MMP inhibitor low dose doxycycline (LDD) combined with access flap surgery (AFS) on the modulation of periodontal wound repair in patients with severe chronic periodontitis. METHODS: Twenty-four subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate clinical, biochemical, and microbial measures of disease in response to 6 months therapy of either placebo capsules + AFS or LDD (20 mg b.i.d.) + AFS. Clinical measures including probing depth (PD), clinical attachment levels (CAL), and bleeding on probing (BOP) as well as gingival crevicular fluid bone marker assessment (ICTP) and microbial DNA analysis (levels and proportions of 40 bacterial species) were performed at baseline and 3, 6, 9, and 12 months. RESULTS: Patients treated with LDD + AFS showed more potent reductions in PD in surgically treated sites of >6 mm (P<0.05, 12 months). Furthermore, LDD + AFS resulted in greater reductions in ICTP levels compared to placebo + AFS. Rebounds in ICTP levels were noted when the drug was withdrawn. No statistical differences between the groups in mean counts were found for any pathogen tested. CONCLUSIONS: This pilot study suggests that LDD in combination with AFS may improve the response of surgical therapy in reducing probing depth in severe chronic periodontal disease. LDD administration also tends to reduce local periodontal bone resorption during drug administration. The use of LDD did not appear to contribute to any significant shifts in the microbiota beyond that of surgery alone.