Abstract: BACKGROUND: Studies have found that risedronate sodium can influence bone remodeling by regulating osteoclast and osteoblast activity, thereby accelerating orthodontic tooth movement. However, its mechanism of action has not been fully elucidated.
OBJECTIVE: To investigate the effects of risedronate sodium on periodontal inflammation, osteoclasts, and the bone morphogenetic protein 2/Smad1 signaling pathway in rats with orthodontic tooth movement.
METHODS: Thirty Sprague-Dawley rats were used to establish orthodontic tooth movement models. At 24 hours after modeling, the rats were randomly divided into model group, high-dose risedronate sodium group, and low-dose risedronate sodium group, with 10 rats in each group. Another 10 Sprague-Dawely rats were set as the control group. The high- and low-dose risedronate sodium groups received intragastric administration of 1 and 0.5 mg/kg risedronate sodium, respectively, while the model group and control group received intragastric administration of normal saline, once daily for 21 consecutive days. At 24 hours after the final administration, the orthodontic tooth movement distance was measured. Serum levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 were detected by ELISA. The number of osteoclasts in periodontal tissue was detected by tartrate-resistant acid phosphatase staining. Maxillary tissue morphology was observed by hematoxylin-eosin staining. Protein expression of bone morphogenetic protein 2 and Smad1 in alveolar bone tissue was detected by western blot.
RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed significantly increased levels of interleukin 1β, tumor necrosis factor α, and interleukin 6, and a significantly increased number of osteoclasts (P < 0.05), while protein expression of bone morphogenetic protein 2 and Smad1 was significantly decreased (P < 0.05). Compared with the model group, the low-dose risedronate sodium group showed significantly decreased levels of interleukin 1β, tumor necrosis factor α, and interleukin 6, and a significantly decreased number of osteoclasts (P < 0.05), while orthodontic tooth movement distance and protein expression of bone morphogenetic protein 2 and Smad1 were significantly increased (P < 0.05). Compared with the low-dose risedronate sodium group, the high-dose risedronate sodium group showed significantly decreased levels of interleukin 1β, tumor necrosis factor α, and interleukin 6, and a significantly decreased number of osteoclasts (P < 0.05), while orthodontic tooth movement distance and protein expression of bone morphogenetic protein 2 and Smad1 were significantly increased (P < 0.05). (2) Hematoxylin-eosin staining showed normal maxillary bone structure in the control group. In the model group, the periodontal space on the pressure side was narrowed, the periodontal ligament on the tension side was widened, cementum resorption lacunae were increased, and bone remodeling was active. In the low- and high-dose risedronate sodium groups, the pressure side space was reduced, new bone deposition on the tension side was enhanced, and bone resorption was decreased. To conclude, these findings indicate that risedronate sodium inhibits inflammatory response and osteoclast activity in the periodontal tissue induced by orthodontic force, promotes bone formation by upregulating the bone morphogenetic protein 2/Smad1 signaling pathway, and accelerates the process of orthodontic tooth movement.

Key words: risedronate sodium, orthodontic tooth movement, periodontal inflammation, osteoclasts, bone morphogenetic protein 2, Smad1