In a rat model of induced periodontal disease using gingival LPS injections, elevated levels of collagenase (MMP-8), gelatinase (MMP-9), elastase and alveolar bone loss were overcome by using a synergistic combination of sub-optimal doses of the chemically modified tetracycline CMT-8 and a biphosphonate, clodronate [86]; when sub-optimal doses of these agents were used individually, there were negligible effects on the above parameters. The gene discussed is MMP8; the disease is periodontal disorder.