Dental Application of Bisphosphonates

我们已经报道了全身应用双膦酸盐可以预防实验性牙周炎大鼠牙槽骨吸收。我们还报道了全身和局部施用双膦酸盐对大鼠正畸牙齿移动具有有效的锚定和固位作用。这些结果表明，双膦酸盐可能是有用的代理人在各种牙科治疗，其中预防牙槽骨吸收是必不可少的。然而，当考虑双膦酸盐的临床牙科应用时，在牙槽骨的特定局部部位局部使用而不产生全身效应将是可取的，因为正常的全身骨代谢不应受到局部牙科治疗的影响。本研究的目的是（1）确定局部施用双膦酸盐是否有效预防牙周炎或正畸牙齿移动引起的牙槽骨吸收;（2）阐明双膦酸盐对骨吸收的预防作用模式。获得了以下结果。(1)局部注射氯膦酸二钠或利塞膦酸二钠到邻近目标牙齿的骨膜下区域可以有效地防止大鼠牙周炎或正畸牙齿移动时发生的骨吸收。(2)利塞膦酸钠离子导入对预防牙周炎引起的牙槽骨丢失也有效，但效果不明显。(3)二膦酸盐对骨吸收的抑制作用不是由于抑制破骨细胞的募集，而是由于抑制破骨细胞的功能，如诱导细胞凋亡和抑制酸性磷酸酶。

We have reported that systemic administration of bisphosphonates could prevent alveolar bone resorption in rats with experimental periodontitis. We have also reported that both systemic and topical administration of bisphosphonates have potent anchorage and retentive effects on the orthodontic tooth movement in rats. These results suggest that bisphosphonates could be useful agents in the various dental therapies in which prevention of alveolar bone resorption is essential. However, when clinical dental application of bisphosphonates is considered, localized use at specific local site of alveolar bone without systemic effect would be desirable, since normal systemic bone metabolism should not be affected by the local dental therapies. The objectives of the present study were (1) to determine whether topical administration of bisphosphonates is effective on the prevention of alveolar bone resorption incident to periodontitis or orthodontic tooth movement and (2) to clarify the mode of preventive action of bisphosphonates on the bone resorption. The following results were obtained. (1) Topical injection of clodronate or risedronate into the sub-periosteum area adjacent to target teeth were effective in preventing bone resorption incident to periodontitis or orthodontic tooth movement in rats. (2) Iontophoretic administration of risedronate were also effective in the prevention of alveolar bone loss in the periodontitis, but the effect was small. (3) The inhibitory action of bisphosphonates on bone resorption is not due to the inhibition of osteoclast recruittment, but rather to the inhibition of osteoclast function, such as an induction of apoptosis and inhibition of acid phosphatase.