title: Systemic MMP inhibition for periodontal wound repair: results of a multi-centre randomized-controlled clinical trial.
abstract: OBJECTIVE
  This multi-centre, prospective, controlled trial was designed to examine the biological response of the matrix metalloproteinase(MMP) inhibitor subantimicrobial dose doxycycline (SDD) combined with access flap surgery on periodontal wound repair in patients with chronic severe periodontitis.
  
  
  METHODS
  Seventy subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate disease response to 6 months therapy and "wash-out" of either placebo+surgery or SDD (20 mg b.i.d.)+surgery. Primary outcome measure included clinical attachment levels (CAL) and secondary outcomes included probing depth (PD), bleeding on probing (BOP), as well as gingival crevicular fluid bone marker assessment [collagen telopeptides (ICTP)]. These measurements were taken at baseline through 12 months post-surgery and drug administration.
  
  
  RESULTS
  Patients treated with SDD and surgery demonstrated stronger reductions in PD in surgically-treated sites of >or=7 mm as well as gains in CAL (p<0.004). Furthermore, SDD+surgery resulted in short-term reductions in ICTP levels compared with placebo. Rebounds in ICTP levels and clinical parameters occurred when SDD was withdrawn.
  
  
  CONCLUSIONS
  The results from this multi-centre study suggests that SDD in combination with surgery improves the short-term response of periodontal therapy by reducing PD, increasing CAL gain and inhibiting early stage bone resorption.
authors.affiliation: Michigan Center for Oral Health Research and Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48106, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gapski
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Oringer
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D055113:Chronic Periodontitis / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery*; D024042:Collagen Type I / Q000032:analysis; D004311:Double-Blind Method; D004318:Doxycycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D011446:Prospective Studies; D019714:Tissue Inhibitor of Metalloproteinases / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D010455:Peptides; D019714:Tissue Inhibitor of Metalloproteinases; C052929:collagen type I trimeric cross-linked peptide; D020782:Matrix Metalloproteinases; D004318:Doxycycline