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This study aims to evaluate the healing process of autografted mandibular bone defects in rats treated with zoledronate (ZOL). A total of 180 Wistar rats were divided into four groups: group L received intravenous infusion of two doses of 0.06 mg/kg ZOL, nine weeks apart; group H received 0.06 mg/kg ZOL, while groups C and NC received normal saline at three-week intervals for nine weeks. Three weeks following the last infusion, a unilateral mandibular bone defect (5 mm) was created. Except in the NC group, all defects were repaired with autologous iliac bone graft. Fifteen animals from each group were sacrificed on postoperative Day 20, Day 40, and Day 60. Graft healing was scored using a histological grading system (ranging from 1 to 6). Histological evaluations performed on postoperative Day 60 showed that the mandibular defects were mainly repaired with fibrous tissue in the NC and H groups (93.00% ± 7.51% and 82.67% ± 13.08%, respectively) and with bone in the C and L groups (75.33% ± 14.20% and 92.67% ± 8.84%, respectively). The percentage of fibrous tissue and bone as well as the healing score of the NC and H groups were significantly different (P = 0.001) from those of the C and L groups. However, these were not different between neither the NC and H groups nor the C and L groups. Based on the results of the present study the hypothesis can be established that there also might be a dose-dependent effect of ZOL on the healing of bone grafts in humans. This hypothesis has to be verified or rejected in clinical trials. • After intravenous infusion of two doses of 0.06 mg/kg zoledronate, 9 weeks apart, autografted mandibular bone defect healed normally in rats. • Intravenous infusion of four doses of 0.06 mg/kg zoledronate at 3-week intervals resulted in healing of autografted mandibular bone defects with fibrous tissue. • Low, cumulative doses of zoledronate do not affect healing of autografted mandibular bone defects in rats, while high, cumulative doses severely impair healing. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the effects of short-term teriparatide administration on healing of autologous bone graft in mandibular critical-size defects. Subjects and methods A 5-mm mandibular bone defect was created and iliac bone graft was harvested in 135 rats. Rats were randomly divided into 3 groups of negative control (NC), control (C), and study (S). In groups S and C, iliac graft was placed in defect and 2 μg/kg/day teriparatide or saline, respectively, was administered for 20 days. In group NC, iliac graft was not transferred to the defect and saline was injected for 20 days. Twenty, 40, and 60 days after surgery, 15 rats in each group were euthanized and the healing process was histologically evaluated and scored using a grading system (1–6). Results In group NC, defects did not heal or were predominantly filled with fibrous tissue. At day 20, bone defects in both C and S groups contained a large area of graft particles, numerous collagen fibers and some areas of new trabeculae. At the day 40, defects in group S showed a larger bone graft area, more new bone formation, smaller connective tissue area, and a higher healing score compared to group C (P < 0.05). At day 60, most of the defect in group S was filled with graft particles and mature bone while in group C, new trabecular bone formation was still underway (P < 0.05). Conclusion Teriparatide therapy improves healing of bone defects reconstructed with autograft by reducing bone graft resorption and enhancing new bone formation and maturation. Highlight • Daily administration of a low-dose teriparatide for a period of 20 days enhances the healing process of grafted mandibular defect in rats. • Bone defects in teriparatide-treated rats have more new bone formation and bone maturation and shorter healing time than in control rats. • Beneficial effects of low-dose teriparatide therapy appear only at late stages of bone healing. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate fracture healing in mandible of rats under zoledronate therapy.Methods: A total of 135 Wistar rats were randomly allocated into 3 groups. Group L received two intravenous infusion of 0.06 mg/kg zoledronate 6 weeks apart. Group H received the same dose of zoledronate as group L once a week for 6 weeks and group C were treated with normal saline. Seven days after the last infusion, rats underwent unilateral mandibular osteotomy to replicate a fracture. Fifteen rats from each group were sacrificed 2, 4, and 6 weeks after surgery. Fracture calluses were examined and scored using a histological grading system (1 to 10).Results: After 2 weeks, substantial woven bone and some lamellar bone were seen in control and L groups. In group H, healing was delayed and consisted of fibrous and cartilaginous tissue and some woven bone. After 4 weeks, most of woven bone in control group was replaced with lamellar bone but in group L, comparatively less bone remodeling occurred. In group H, healing process was nearly the same as that at 2 weeks. After 6 weeks, complete bone remodeling was seen in control group. In group L, bone remodeling was under way and in group H, histological findings were nearly the same as those at 2 and 4 weeks. Except for L and control groups at 2 weeks, healing score was significantly different between all corresponding groups.Conclusion: Zoledronate therapy delayed healing process of mandibular fracture in rats in a dose-dependent manner. [ABSTRACT FROM AUTHOR]