Intramembranous and Endochondral Bone Changes Induced by a New Bisphosphonate (YM175) in the Beagle Dog

Oral treatment with a new bisphosphonate, YM175, for 13 wk resulted in increased bone tissue mass by both intramembranous and endochondral ossification processes in adult beagle dogs. Intramedullary bone formation due to intramembranous process was observed in dogs treated with a highly toxic dose of YM175. The newly formed woven bone trabeculae, showing immature to relatively mature figures, were present between the preexisting cancellous bone. The immature bone consisted of spindle-shaped mesenchymal cells with osteoid tissues. Many active osteoblasts surrounded the immature woven bone, while only few osteoclasts were seen on the surfaces of the new bone. Endochondral bone change was observed at the costochondral junction in all YM175-treated groups. Accumulation of unresorbed mineralized cartilage with its covering of bone at this site resulted in an increase in length of the area of primary spongiosa. Although the endochondral bone change induced by YM175 was due to a bisphosphonate-induced inhibitory effect on bone resorption, the intramedullary bone formation is unique to YM175.