title: Effect of locally delivered minocycline microspheres on markers of bone resorption.
abstract: BACKGROUND
  Gingival crevicular fluid (GCF) biomarkers associated with bone resorption may be useful to determine periodontal disease status and response to therapy. The pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a bone-specific degradation product, and interleukin 1-beta (IL-1), a potent bone-resorptive cytokine, have both been associated with periodontal disease activity. Minocycline is a tetracycline derivative possessing antimicrobial effects on periodontal pathogens and inhibitory properties on matrix metalloproteinases (MMPs) associated with tissue destruction. The aim of this study was to evaluate the effect of periodontal treatment in the form of scaling and root planing (SRP) and locally administered minocycline microspheres on the GCF levels of ICTP and IL-1.
  
  
  METHODS
  Forty-eight chronic periodontitis patients were randomly assigned to 2 groups (SRP plus subgingival application of vehicle control [SRP + V], or SRP plus subgingival application of minocycline microspheres [SRP + M]) and monitored at 8 sites per subject at baseline and 1, 3, and 6 months. Four shallow (PD < or = 3 mm) and 4 deep (PD > or = 5 mm) sites were evaluated for both marker levels and for probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Eight periodontally healthy control subjects with no probing depths >3 mm and no loss of attachment were also monitored at the same time intervals. GCF levels of ICTP and IL-1 were determined using radioimmunoassay and enzyme-linked immunosorbent assay techniques, respectively.
  
  
  RESULTS
  Significant differences (P<0.001) in GCF levels of ICTP and IL-1 were found between deep and shallow sites at all time points in both treatment groups. In addition, healthy subjects demonstrated significantly reduced levels of both markers compared to both shallow and deep sites in periodontitis patients (P <0.001). Only the SRP + M treated patients exhibited significant reductions (P <0.05) in both ICTP and IL-1 levels 1 month after treatment. Furthermore, the SRP + M group demonstrated significantly lower IL-1 levels (P <0.02) at 1 month compared to the SRP + V group.
  
  
  CONCLUSIONS
  Results of this study indicate that GCF levels of ICTP and IL-1 correlate with clinical measures of periodontal disease and may aid in assessing disease status and response to periodontal therapy. Furthermore, local administration of minocycline microspheres led to a potent short-term reduction in GCF IL-1 levels. Additional studies are needed to address whether repeated administration of scaling and root planing along with minocycline microspheres will achieve long-term reductions in GCF ICTP and IL-1 levels.
authors.affiliation: Department of Periodontics, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Oringer
authors.forename: K F
authors.initials: KF
authors.lastname: Al-Shammari
authors.forename: W A
authors.initials: WA
authors.lastname: Aldredge
authors.forename: V J
authors.initials: VJ
authors.lastname: Iacono
authors.forename: R M
authors.initials: RM
authors.lastname: Eber
authors.forename: H L
authors.initials: HL
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Berwald
authors.forename: R
authors.initials: R
authors.lastname: Nejat
authors.forename: W V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001862:Bone Resorption / Q000188:drug therapy / Q000628:therapy*; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis* / Q000187:drug effects; D024042:Collagen Type I; D012534:Dental Scaling; D005260:Female; D005500:Follow-Up Studies; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D005884:Gingival Hemorrhage / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis*; D008297:Male; D016555:Matched-Pair Analysis; D008863:Microspheres; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D010455:Peptides / Q000032:analysis* / Q000187:drug effects; D017622:Periodontal Attachment Loss / Q000188:drug therapy / Q000628:therapy; D010514:Periodontal Pocket / Q000188:drug therapy / Q000628:therapy; D010518:Periodontitis / Q000188:drug therapy / Q000628:therapy*; D016745:Root Planing; D016037:Single-Blind Method; D013223:Statistics as Topic
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D024042:Collagen Type I; D007375:Interleukin-1; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D008911:Minocycline