The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial

Abstract

Background: Periodontitis has been reported to be associated with coronary artery disease (CAD). Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases.

Methods: The study registrar randomly assigned 128 eligible postmenopausal women with chronic periodontitis to a twice-daily regimen of subantimicrobial-dose-doxycycline (SDD) or placebo tablets for two years as an adjunct to periodontal maintenance therapy. Through a supplement to the main trial, in which they investigated alveolar bone and clinical attachment level changes, the authors assayed inflammatory mediators and lipid profiles in baseline, one-year and two-year serum samples. The authors analyzed the data by using generalized estimating equations.

Results: In the intent-to-treat analysis across two years, SDD treatment reduced median high-sensitivity C-reactive protein (hs-CRP) by 18 percent (primary outcome; P = .02) and reduced serum matrix metalloproteinase (MMP)-9 (92 kilodalton gelatinase; difference in mean scanning units, -28.44; P < .001), with no significant effect on serum lipids. However, in women more than five years postmenopausal, SDD elevated the level of high-density lipoprotein (HDL) cholesterol (difference in means [milligrams per deciliter], 5.99; P = .01).

Conclusion: A two-year SDD regimen in postmenopausal women significantly reduced the serum inflammatory biomarkers hs-CRP and MMP-9 and, among women more than five years postmenopausal, increased the HDL cholesterol level.

Clinical implications: SDD significantly reduced the systemic inflammatory biomarkers hs-CRP and MMP-9. More research is needed to determine whether SDD has a role in managing the care of patients at risk of developing CAD.

Conflict of interest statement

DISCLOSURES OF INTERESTS

Dr. Golub is listed as an inventor on patents on the test medication in this clinical trial and those have been fully assigned to his institution, Stony Brook University. He is also a consultant to Galderma Research and Development (Lausanne, Switzerland) which has licensed a series of tetracycline patents from the State University of New York. No other conflicts of interest exist with the other authors.

Figures

Figure 1. Flow diagram in compliance with Consolidated Standards of Reporting Trials

Diagram shows flow of subjects through each stage of the two-year clinical trial. An additional subject, the 65th subject in the SDD group, was randomized and was deemed ineligible at the baseline visit, as she did not meet inclusion criteria.

Figure 2. SDD effects on serum hs-CRP over the two-year clinical trial

SDD reduced median hs-CRP levels by 18% compared to placebo over the two-year protocol after adjustment for baseline hs-CRP level, smoking status, study center, study visit and batch effects, which was statistically significant (p=0.02, intent-to-treat analysis). The lower edge of the box represents the 25th percentile of the observed distribution, while the center line and upper edge of the box represent the 50th and 75th percentiles of the observed distribution, respectively. The number of subjects analyzed at each time point in the placebo group is as follows: 62 at baseline, 61 at the 1-year visit (serum sample not available for one subject) and 62 at the two-year visit. 51 subjects were analyzed at each time point in the SDD group. hs-CRP = high-sensitivity C-reactive protein.

Figure 3. SDD effects on serum MMP-9 over the two-year clinical trial

SDD significantly reduced mean serum MMP-9 (92 kDa) by 28.44 scanning units over the two-year protocol relative to placebo after adjustment for the baseline MMP-9 (92 kDa) level, smoking status, study center, study visit and batch effects (p