Inhibitory effects of YM175, a bisphosphonate, on the progression of experimental periodontitis in beagle dogs.
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.
Pharmacology Laboratories, Yamanouchi Pharmaceutical Co. Ltd, Ibaraki, Japan.
N
N
O'uchi
H
H
Nishikawa
T
T
Yoshino
H
H
Kanoh
H
H
Motoie
E
E
Nishimori
T
T
Shimaoka
T
T
Abe
H
H
Shikama
T
T
Fujikura
M
M
Matsue
I
I
Matsue
D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001641:Bicuspid; D015519:Bone Density; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004285:Dogs; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000627:therapeutic use; D006253:Haversian System / Q000187:drug effects / Q000378:metabolism; D008334:Mandible; D010012:Osteogenesis / Q000187:drug effects; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010521:Periosteum / Q000187:drug effects / Q000378:metabolism; D010919:Placebos; D011859:Radiography; D012965:Sodium Chloride
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004164:Diphosphonates; D010919:Placebos; C071542:cimadronate; D012965:Sodium Chloride; D005480:Flurbiprofen