The aim of the present study was to investigate the effect of the local administration of three kinds of bisphosphonates -etidronate, alendronate, and pamidronate- on orthodontic root resorption. Both the right and left molars of 7-week-old male Sprague Dawley rats were experimentally moved by interproximal insertion of the elastic band according to Waldo's method. Each bisphosphonate solution was injected into the palatal subperiosteum area adjacent to the upper first molar every third day during experimental period. Rats were sacrificed after 1, 3, 7, and 14 days of elastic band insertion, and samples prepared from tissues were histomorphometrically analyzed by light or scanning electron microscopy (SEM). The SEM analysis revealed that the local injection caused a significant reduction in mechanically induced root pit formation in all bisphosphonate treatment groups after 14 days. The root pit formation was parallel with the reduction in the number of odontoclasts in histological examination for tartrate-resistent acid phosphatase activity. However, on day 3, treatment with etidronate and alendronate transiently increased the root pit formation due to the increase of the odontoclast number. Immunohistochemical study was performed to examine the effect of these bisphosphonates on the expression of proinflammatory cytokines, i.e., interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). On day 3, in etidronate- and alendronate-trearment groups, the strong immunoreactive signals of IL-1β and TNF-α were observed in odontoclasts, osteoclasts, and periodontal ligament cells compared with control groups. Pamidronate treatment did not affect the expression of IL-1β, TNF-α, and IL-6 during whole experimental period. Thus, topical application of bisphosphonates following experimental induction of tooth movement in rats reduced the root resorption and the number of odontoclasts. These results suggest that bisphosphonates may be useful for prevention of root resorption of teeth during orthodontic tooth movement. Moreover, the effect of etidronate and alendronate via IL-1β and TNF-α expression might be associated with odontoclast and osteoclast formation
