Effect of Reveromycin A on experimental tooth movement in OPG-/- mice.

In osteoprotegerin-deficient (OPG-/-) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG-/- mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG-/- and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG-/- mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG-/- mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG-/- mice.