Objective To prepare compound bone cement of silk fibroin/biphasic calcium phosphate/ alpha-calcium sulphate hemihydrate/recombinant human bone morphogenetic protein-2 (SF/BCP/ CSH/rhBMP-2) and to study its osteogenesis capacity for sheep vertebral defects. Methods Compound bone cement SF/BCP/CSH/rhBMP-2 was prepared and a cylindrical bone defect (6.0 mm in diameter and 10 mm in depth) was created at lumbar vertebrae 2, 3 and 4 by open operation in 12 sheep. The injured lumbar vertebrae in each sheep were randomly divided into 3 study groups. The experimental group was implanted with the SF/BCP/CSH/rhBMP-2, the control group with polymethylmethacrylate (PMMA), and the blank control group with nothing. At 3 and 6 months postoperation, 6 random sheep were sacrificed for radiological, histological and biomechanical tests to check the reparation of sheep vertebral defects. Results Radiological and histological examinations showed that the vertebral bone density in the experimental group was similar to that of a normal vertebral body and the bone defects were almost repaired at 3 months postoperation and completely repaired at 6 months postoperation. Loose union between the bone and PMMA was observed but no degradation of PMMA or no formation of new bone was observed in the control group at 3 and 6 months postoperatively. The bone defects in the blank control group were not repaired at either time points. Biomechanical tests showed that there were no statistically significant differences between the experimental group and normal vertebral bodies regarding compressive strength and rigidity at 3 and 6 months postoperatively. Conclusion SF/BCP/CSH/rhBMP-2 may become a biodegradable vertebral filler with osteogenesis for percutaneous vertebroplasty and kyphoplasty because it possesses a good capability of repairing vertebral bone defects and maintaining mechanical properties of a vertebral body in the process of bone formation. Key words: Silk fibroin; Vertebroplasty; Sheep; Bone cement; Filler