Inhibitory effects of YM175, a bisphosphonate, on the progression of experimental periodontitis in beagle dogs

Abstract

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.

Bisphosphonate inhibits alveolar bone resorption in experimentally‐induced peri‐implantitis in dogs

“…Moreover, Shoji et al (1995) reported that Residronate inhibited alveolar bone resorption and the loss of bone mineral contents in a dose‐dependent fashion in elastic ring‐induced periodontitis in rats. Recently, O’uchi et al (1998) reported that YM175, disodium dihydrogen methylene‐1,1‐bisphosphonate, prevents alveolar bone loss by reducing increased alveolar bone turnover in ligature‐induced periodontitis in beagle dogs. However, the effect of bisphosphonate on peri‐implantitis has not been examined previously.…”

“…However, the effect of local application of the drug on the implant tissue should be examined in future studies. O’uchi et al (1998) reported that YM11 inhibited the inflammatory response in experimental periodontitis tissue, and suggested that YM11 might inhibit the production of prostaglandin E. This supports that bisphosphonate can also have the inhibitory effect of inflammatory reaction in peri‐implantitis.…”

Host response modulation in the management of periodontal diseases

“…Several animal studies have examined the effects of local or systemic bisphosphonate delivery on alveolar bone resorption by using the experimental periodontitis model (Brunsvold et al 1992, Weinreb et al 1994, Shoji et al 1995, Ouchi et al 1998, Alencar et al 2002, Mitsuta et al 2002, Tani‐Ishii et al 2003, Buduneli et al 2004), the naturally occurring periodontitis model (Reddy et al 1995) or after mucoperiosteal flap elevation (Yaffe et al 1995, 1997, 2000, 2003, Binderman et al 2000, Kaynak et al 2000, 2003).…”

Relationship between periodontal disease and osteoporosis

“…A very common treatment prescribed for osteoporosis is the bisphosphonate class of drugs. Bisphosphonates have been reported to inhibit periodontal bone loss in animal models in some papers, both with 27,32,82,83 and without concurrent experimental osteoporosis 84–90 . In humans however, somewhat conflicting results are seen, with no effect on periodontal condition beyond that achieved by non‐surgical therapy 91,92 or improvements in clinical periodontal parameters but not on periodontal bone mass 93 .…”