Abstract: BACKGROUND: Bisphosphonate drugs are a class of synthetic inorganic pyrophosphate analogs that can cause osteonecrosis of the jaw. However, the effects of bisphosphonate drugs on different parts of the same individual may be different, and the effect on the jaws or femurs with and without trauma is also unclear.
OBJECTIVE: To compare the effect of zoledronic acid on the healing of rat jaw and femur defects, thereby providing theoretical support for the clinical use of zoledronic acid and other drugs as well as the prevention of medication-related osteonecrosis of the jaw.
METHODS: Forty female Sprague-Dawley rats aged 8 weeks were included in this study. Among them, 20 rats were injected intraperitoneally with zoledronic acid and the remaining 20 rats were injected with normal saline. Ten weeks later, a 2 mm×2 mm×2 mm bone defect was made on the left mandible and femur of each rat, and no treatment was done on the right side. Therefore, there were eight groups: zoledronic acid+jaw defect group, zoledronic acid+femoral defect group, zoledronic acid+jaw untreated group, zoledronic acid+femur untreated group, normal saline+jaw bone defect group, normal saline+femoral defect group, normal saline+jaw bone untreated group, and normal saline+femur untreated group. The healing of the jaw and femur was observed after operation. At 8 weeks after operation, the samples were taken and the radiological and histological examinations were performed.
RESULTS AND CONCLUSION: In the zoledronic acid+jaw defect group, 16 observation areas showed poor healing of mandibular defects, local gingival swelling and pus, soft tissues were still not fully healed at 8 weeks after surgery. The dead bone was still seen in the jaw defect area. The incidence rate of osteonecrosis was 80%. On the contrary, there was no osteonecrosis in the other groups. Radiological results: No bone healing was observed in the jaw defect area of the osteonecrosis specimens in the zoledronic acid+jaw defect group, while osteolytic destruction developed. The density of the defect area was similar to that of the surrounding bone in the zoledronic acid+femoral defect group. The density of the defect area was lower than that of the surrounding bone in the normal saline+jaw bone defect group and normal saline+femoral defect group. Histological results: The specimens with osteonecrosis in the zoledronic acid+jaw defect group demonstrated the disappearance of the nucleus, the disorder of the trabecular bone structure, and a small amount of fibrous tissue. The remaining specimens showed no obvious abnormalities. The above results suggest that the incidence of osteonecrosis in the mandible defect is very high after intraperitoneal injection of zoledronic acid, while there is no osteonecrosis in the femoral defect and non-defective jaw and femur.

Key words: jaw, femur, zoledronic acid, bisphosphonate, osteonecrosis, rat