Effect of locally delivered minocycline microspheres on markers of bone resorption

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 less than or equal to3 mm) and 4 deep (PD greater than or equal to5 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.