Tetracyclines inhibit Porphyromonas gingivalis‐induced alveolar bone loss in rats by a non‐antimicrobial mechanism

Tetracyclines have been widely used as adjuncts in periodontal therapy due to the antimicrobial efficacy of these drugs. Recently, their ability to inhibit host‐derived matrix metalloproteinases (collagenase and gelatinase) and bone resorption in organ culture has also been invoked as a therapeutic rationale. The current study was undertaken to determine whether tetracyclines can inhibit alveolar bone loss in vivo due to a non‐antimicrobial action of these drugs. Experimental periodontitis was induced by inoculating adult, male Sprague‐Dawley rats with P. gingivalis (strain 381) following kanamycin/ampicillin pretreatment. Doxycycline, non‐antimicrobial chemically‐modified tetracycline (CMT‐1) and vehicle alone were administered daily to 3 infected groups of rats (n=6 rats per group; each group housed in a sterilized inflatable isolator) beginning 10 days after P. gingivalis inoculation. The control group (n = 6; non‐infected rats) received only vehicle. After 5 weeks of daily drug administration by gastric intubation, the experiment was terminated and blood samples were taken from each animal to determine antibody levels against P. gingivalis . Plaque samples were collected from each group of animals before and after P. gingivalis inoculation and at the end of the experiment for microbiological examination. The jaws were removed from each rat, defleshed and then analyzed morphometrically and radiographically to assess bone loss. Serum antibody levels against P. gingivalis were significantly elevated in the 3 infected groups compared to the non‐infected controls. This, together with the microbiologic findings, indicated that these groups of rats were infected with P. gingivalis . Significantly greater bone loss was observed in the untreated P. gingivalis ‐infected group compared to the controls based on both morphometric and radiographic measurements. Oral administration of doxycycline or CMT‐1 to the P. gingivalis ‐infected rats completely inhibited this bone loss. As expected, CMT‐1 did not exhibit an antimicrobial effect against P. gingivalis . Therefore, this study indicates that tetracyclines can inhibit alveolar bone loss in vivo by a mechanism which is independent of the antimicrobial efficacy of these drugs.