Bis-enoxacin Inhibited Alveolar Bone Loss and Gingival Inflammation in Rats

Objectives: Enoxacin, a fluoroquinolone antibiotic, possesses anti-osteoclastic properties and stimulates miRNA expression. Similarly, enoxacin-linked bisphosphonate, bis-enoxacin, inhibits osteoclast formation and bone resorption. Periodontal diseases are complex and multifactorial caused by polymicrobial subgingival pathogens including Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf). This study was designed to test the efficacy of bis-enoxacin, enoxacin, and alendronate in inhibiting osteoclast alveolar bone resorption (ABR) in a polymicrobial periodontal disease rat model. 

Methods: Sprague-Dawley rats were orally infected with Pg FDC 381, Td ATCC 35404, and Tf ATCC 43037 strains for 4 days consecutively every other week for 12 weeks.  A mixture of 10⁹ cells (Pg 3.3X10⁸+Td 3.310⁸+Tf 3.3X10⁸) mixed with 4% carboxymethylcellulose was administered orally.  Bis-enoxacin (5, 25mg/kg), enoxacin (25 mg/kg), alendronate (1, 2.5mg/kg), and doxycycline (5mg/day) were administered subcutaneously after 6 weeks of polymicrobial infection. Periodontal disease parameters were assessed (oral plaque, serum antibody, gingival inflammation, and ABR).  Systemic infection of heart, aorta, spleen, liver, lungs and kidneys with periodontal pathogens was also examined by PCR.

Results: Pg, Td and Tf genomic DNA were detected in oral plaque and also in systemic tissues of polymicrobal infected rats, indicating oral colonization and bacteremia, respectively.  Polymicrobial infected rats elicited significantly higher levels of IgG antibodies than the sham-infected control and treatment with enoxacin and bis-enoxacin resulted in even higher antibody levels.  Polymicrobial infection induced an increase in total ABR and intrabony defects while treatment with enoxacin and bis-enoxacin significantly decreased the incidence of both compared to infected and untreated controls.  Preliminary histologic examination reveals enhanced gingival inflammation in infected rats and a decrease in apical migration and inflammation in bis-enoxacin and enoxacin treated rats. 

Conclusions: This is the first study examining anti-osteoclastic effects of bis-enoxacin, enoxacin, and alendronate in a polymicrobial periodontal disease model.