O'uchi N, Nishikawa H, Yoshino T, Kanoh H, Motoie H, Nishimori E, Shimaoka T, Abe T, Shikama H, Fujikura T, Matsue M, Matsue I
Pharmacology Laboratories, Yamanouchi Pharmaceutical Co. Ltd, Ibaraki, Japan.
J Periodontal Res. 1998 May;33(4):196-204. doi: 10.1111/j.1600-0765.1998.tb02191.x.
This study examined the efficacy of YM175 [disodium dihydrogen (cycloheptylamino) methylene-1, 1-bisphosphonate] in reducing alveolar bone loss caused by experimental periodontitis in beagle dogs. Thirty-six dogs were used and divided into 6 groups. Periodontitis was induced in 30 dogs (groups 2-6) by ligating the bilateral mandibular third and fourth premolar teeth with silk ligatures and by feeding a soft diet. Six dogs were sham-operated (group 1). Saline (placebo), flurbiprofen (0.02 mg/kg) and YM175 (0.01, 0.1 and 1.0 mg/kg) were administered to the dogs (groups 2-6) 5 d/wk for 25 wk. Radiographic and morphometric analyses were performed. In placebo-treated animals (group 2), the ligation caused a significant decrease in the alveolar bone height by 0.57 and 1.91 mm at 2 and 25 wk, respectively. YM175 (1.0 mg/kg) prevented the decrease in bone height by 47 and 31% at 2 and 25 wk. YM175 (0.1 mg/kg) and flurbiprofen tended to prevent bone loss after 15 wk. Although the ligation elicited no significant change in bone mineral density, it significantly decreased bone volume. YM175 (1.0 mg/kg) and flurbiprofen tended to increase the bone volume. The number of formative or resorptive Haversian canals and the bone turnover through the periosteal bone surface were increased by the ligation, indicating the increased turnover of the cortical bone. YM175 (1.0 mg/kg) reduced the increased bone turnover. The gingival index was maximally increased at 2 wk and was suppressed by YM175. These results suggest that YM175 prevents alveolar bone loss by reducing the increased alveolar bone turnover in dogs with periodontitis.
本研究检测了YM175（环庚基氨基亚甲基-1,1-二磷酸二钠）对减少比格犬实验性牙周炎所致牙槽骨丧失的疗效。使用了36只犬并将其分为6组。通过用丝线结扎双侧下颌第三和第四前磨牙并喂食软食，在30只犬（第2 - 6组）中诱导牙周炎。6只犬接受假手术（第1组）。向犬（第2 - 6组）每周5天给药生理盐水（安慰剂）、氟比洛芬（0.02 mg/kg）和YM175（0.01、0.1和1.0 mg/kg），持续25周。进行了影像学和形态学分析。在接受安慰剂治疗的动物（第2组）中，结扎分别在第2周和第25周导致牙槽骨高度显著降低0.57和1.91 mm。YM175（1.0 mg/kg）在第2周和第25周分别使骨高度降低减少了47%和31%。YM175（0.1 mg/kg）和氟比洛芬在15周后倾向于预防骨丧失。尽管结扎未引起骨矿物质密度的显著变化，但它显著降低了骨体积。YM175（1.0 mg/kg）和氟比洛芬倾向于增加骨体积。结扎增加了形成或吸收的哈弗斯管数量以及通过骨膜骨表面的骨转换，表明皮质骨转换增加。YM175（1.0 mg/kg）减少了增加的骨转换。牙龈指数在第2周时最大程度升高，并被YM175抑制。这些结果表明，YM175通过减少牙周炎犬增加的牙槽骨转换来预防牙槽骨丧失。
