Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats

Background: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α), leukotriene B₄ (LTB₄), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats. Methods: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE₂, PGF₂α, LTB₄, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Results: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE₂ and PGF_2α, (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB₄ and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05). Conclusions: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice.