A bisphosphonate for periodontitis with anti-bone-resorbing and anti-inflammatory activities

据报道，双膦酸类药物的药理特性取决于连接在P-C-P键碳原子上的侧链的不同。TRK-530是一种新型的具有抗氧化剂甲硫基苯硫基侧链的合成双膦酸脂。这种化合物被认为既有抗炎作用，又有抗骨吸收作用。这种化合物可以有效地治疗伴随炎症的过度骨吸收疾病。我们一直在研究这种化合物作为牙周炎的潜在治疗剂。在本研究中，我们发现：1)TRK-530抑制动物破骨细胞性骨吸收和骨器官培养；2)局部腹膜下注射TRK-530可引起动物牙槽骨骨密度持续显著增加；3)全身和局部应用TRK-530均可防止实验性牙周炎动物的牙槽骨丢失；4)TRK-530通过抑制COX-2mRNA的表达而阻止PGE2的合成。以上结果提示TRK-530有可能用于治疗牙周炎的牙槽骨丢失。

It has been reported that the pharmacological characteristics of bisphosphonates vary depending on the side chain attached to the carbon atom of the P-C-P bond. TRK-530 is a novel synthetic bisphosphonate with an anti-oxidant methylthio-phenylthio side chain. This compound has been suggested to have both anti-inflammatory and anti-bone-resorbing effects. Such a compound could be effective for the treatment of diseases with excessive bone resorption accompanied by inflammation. We have been studying this compound as a potential therapeutic agent for periodontitis. In the present research, we found that 1) TRK-530 inhibited osteoclastic bone resorption in animals and in bone organ culture, 2) topical sub-peritoneal injection of TRK-530 induced a long-lasting and prominent increase in the bone mineral density of alveolar bone in animals, 3) both systemic and topical administration of TRK-530 prevented alveolar bone loss in animals with experimental periodontitis, and 4) TRK-530 prevented PGE2 synthesis by inhibiting the expression of COX-2 mRNA. The above results suggest that TRK-530 might be useful for the treatment of alveolar bone loss in periodontitis.