Spherical beta-tricalcium phosphate (b-TCP) granules synthesized using a unique dropping slurry method expressed good osteoconductivity with prominent bone apposition and bioresorbability when implanted into the rat femur (Gonda et al., Key Eng. Mater. 361-363:1013-1016, 2008). The spherical b-TCP granules were implanted into the bone defect created in the distal end of the right femur of each 8-week-old female Wistar rat. To analyze performance of the spherical b-TCP granules as bone substitute in the bone with reduction in osteogenic potential, the right sciatic neurectomy was performed after implantation and the right hind limb was kept unloaded for 2 weeks before euthanization. Four weeks after implantation, some spherical b-TCP granules with resorption in part were surrounded by newly formed bone. Eight and 12 weeks after implantation, most of the residual b-TCP granules were embedded in newly formed bone, and total volume of the implant and newly formed bone was more than the other portions of the bone or the bone of control animals. Osteoclast activity in the implanted area was also higher than the other portions of the bone or the bone of control animals. Replacement of the intraosseous residual b-TCP granules for bone progressed at 12 weeks after implantation compared to those at 8 weeks after implantation. These data suggested that the spherical b-TCP granules stimulated osteogenesis and osteoclast activity of the unloaded bone.