Low-Dose Doxycycline Plus Additional Therapies may Lower Systemic Inflamation in Postmenopausal Women with Periodontitis

Abstract

Enrollment and study protocols took place between June 2002 and October 2005. This study was a supplemental project of a larger trial of cohorts recruited from university settings in Lincoln, Nebraska, and Stony Brook, New York. Female postmenopausal participants who had osteopenia and a history of moderate to advanced chronic periodontitis comprised the test group (n = 51; at baseline, n = 63) and placebo group (n = 62; at baseline, n = 64) after a 2-year study period. Participants were allocated to a test group or a placebo group. Participants who belonged to the test group received subantimicrobial-dose-doxycycline (SDD)(20 mg of doxycycline hyclate) twice daily for 2 years. Participants in the control group received a look-alike placebo twice a day for 2 years. In addition, all patients received periodontal maintenance (every 3-4 months for the duration of the study) and were provided with a supply to be taken twice daily for the duration of the study of calcium (1200 mg) and vitamin D (400 IU). Markers of systemic inflammation (hs-CRP, myeloperoxidase, MMP-8, TIMP-1, MMP-9, MMP-2, IL-6, TNF-α, and IL-1β) and lipid profiles (total cholesterol, HDL, LDL and VLDL cholesterol, and triglycerides). The combined treatment modalities (SDD + periodontal maintenance + dietary supplement) reduced hs-CRP levels as expressed by ratio of medians (SDD/placebo) by 18% compared with placebo (periodontal maintenance + dietary supplement) (0.82; confidence interval [CI] = 0.700.97; P = .02) after the 2-year study period when adjusting for the use of concomitant medications (statin, diuretics, aspirin). The combined treatment modalities significantly reduced MMP-9 (mean scanning units of treatment minus placebo) relative to placebo over the 2-year protocol (-28.44; CI = -40.17 to -16.72, P < .001). There were no statistically significant differences of lipid profiles between the combined treatment modalities and placebo group after a 2-year protocol. SDD when used as an adjunctive to periodontal maintenance plus dietary supplement significantly lowers serum biomarkers of inflammation in postmenopausal women with history of periodontitis.