RESUMO
PURPOSE: This study was conducted to histomorphologically determine the quantity of bone formation induced by TAK-778, a 3-benzothiepin derivative, (Takeda Pharmaceutical Co.Ltd.), in various amounts, using b-tricalcium phosphate granules (beta-TCP; OLYMPUS Corp.) as a carrier for the osteogenetic agent. METHODS: Ten-week-old female SD rats were used. An incision was made over the parietal region of the head. The cranial periosteum was ablated and a titanium tube was fixed with an adhesive resin cement to the central part of the head, through which a mixture of TAK-778 and beta-TCP was implanted under various conditions. Tissue specimens were prepared at 4, 8, and 16 weeks after the implantation for histomorphological examination, and the proportion of new bone formation was compared at fixed time points using the NIH imaging software. The amount of new bone formation was examined every week after the implantation of TAK-778 at various doses, and the mean values were compared using Fisher's PSLD test (P< 0.05). RESULTS: The histomorphological observations revealed new bone formation in all the groups, irrespective of the amount and the duration of implantation of TAK-778. A comparative study revealed that the amount of new bone formation was the largest at 16 weeks following the implantation of a mixture of beta-TCP and 100 mg of TAK-778. CONCLUSIONS: 1. The present study confirmed the acceleration of new bone formation soon after TAK-778 implantation. 2. The results suggested that the action of TAK-778 could be maintained over time if the agent was used in combination with beta-TCP. 3. The time-course of bone formation differed depending on the proportion of TAK-778 and beta-TCP in the mixture used. 4. TAK-778 at the dose of 10 mg or 50 mg was more effective than that at the dose of 100 mg for the early formation of new bone. These results indicate that TAK-778 accelerates the formation of new bone and that beta-TCP is a useful carrier for TAK-778.
