Association Between Serum Inflammatory Biomarkers and Progression of Periodontitis

Objective:   To determine whether concurrent or baseline measures of systemic inflammation (serum C-reactive protein [CRP]), matrix metalloproteinase (MMP-2 and MMP-9) are associated with loss of alveolar bone density (ABD) or height (ABH) or progression of periodontitis (relative clinical attachment level [RCAL]), among postmenopausal women with osteopenia.

Method:   Secondary analyses were performed from a two-year randomized, double-blind, placebo-controlled, clinical trial examining efficacy/safety of subantimicrobial dose doxycycline (20 mg bid) in 113 postmenopausal osteopenic women receiving periodontal maintenance for moderate-advanced chronic periodontitis who consented to serum biomarker analysis.    Posterior vertical bite-wings were taken at baseline, one and two years.  ABD was determined by computer-assisted densitometric image analysis (CADIA), ABH by the Hausmann et al. method, and RCAL (threshold for significant change:  +/- 1.5 mm) by Florida Probe (every 6 months).  Serum was collected at baseline, one and two years.  CRP (mg/L) was analyzed using a high-sensitivity ELISA. MMPs were measured by gelatin zymography using denatured type I collagen as substrate and purified MMP-2 (72kDa) and MMP-9 (92kDa) as standards.  Gelatinolytic bands were scanned densitometrically.  Generalized Estimating Equations were used to fit logistic regression models investigating the association between concurrent and baseline measures of inflammation, expressed in tertiles (lowest tertile reference), and categorical measures of disease progression.

Result:    Changes in ABH were generally unassociated with systemic inflammation. Elevated odds of ABD loss were associated at 24 months with high levels of baseline CRP (OR=1.95, 95% CI:1.13-3.34, p=0.016);  with intermediate (but not high) baseline levels of MMP9 (OR=2.19, 95% CI:1.28-3.73, p=0.0039); and with high concurrent levels of MMP9 (OR=2.40, 95% CI:1.44-4.01, p=0.0008).  Odds of RCAL loss were elevated at 24 months with high concurrent levels of MMP2 (OR=1.95, 95% CI:1.08-3.54, p=0.027).

Conclusion:   Loss of ABD and RCAL, but not ABH, are associated with high serum inflammatory biomarker levels.  Supported by NIDCR grants R01DE012872, R03DE019805-01A1.