唑来膦酸对大鼠颌面骨和外周骨创伤后骨改建的影响

doi:10.13591/j.cnki.kqyx.2022.07.003

Abstract

Abstract: Objective To evaluate and compare the effects of zoledronate on bone remodeling of maxillofacial and peripheral bones after trauma in rats. Methods Sprague-Dawley rats were randomly divided into experimental group and control group, and then injected intravenously with zoledronate (80 μg/kg every week) and PBS via the tail vein, respectively. Two weeks later, the first molar from maxilla was extracted, and cylindrical bone defect was prepared on the ipsilateral tibia under general anesthesia. Drugs were continuously injected for 1, 4, and 12 weeks after surgery. Thereafter, rats were sacrificed by parcel, and bone samples were collected. New bone formation in the bone defect area was investigated with Micro-CT. Soft tissue healing, new bone formation, inflammatory response, dead bone formation and other indicators were observed using HE and Masson staining. The expressions of RANKL and OPG involved in bone remodeling were detected using ELISA. Results Rats in experimental maxillofacial group showed non-healed bone defect and exposed necrotic bone, while rats in control group exhibited continuous cortical bone and normal bone remodeling according to Micro-CT results. The experimental tibial bones showed thicker bone cortex, denser mineral density and faster bone remodeling progress than that of the control group. BV/TV ratio in the experimental tibial group 4 weeks and 12 weeks after surgery increased significantly compared with the control group (P<0.05), while the difference between the two groups in maxillofacial bones has no statistical significance. Histological staining presented major clinical and histopathological manifestations of the human bisphosphonate-related osteonecrosis of the jaw(BRONJ), including non-healed or delay-healed mucosa, exposed necrotic bone, osseous sclerosis and inflammatory infiltration in zoledronate-treated rats. While rats in control group exhibited normal reepithelialization and bone remodeling, the experimental tibial bones showed increased cortical thickness, bone formation, trabecular bone volume and bone mineral density compared with the control group. Cytokines results showed that RANKL/OPG ratio in the experimental maxillofacial bones decreased significantly compared with the control group (P<0.05), while RANKL/OPG ratio in the experimental tibial bones increased significantly (P<0.05). Conclusion Zoledronate suppresses maxillofacial bone remodeling after tooth extraction, and causes BRONJ-like disease in rats, but promotes peripheral bone remodeling after bone trauma. RANKL/OPG ratio may play an essential role in the occurrence of BRONJ.

Key words: zoledronate, bone remodeling, maxillofacial bone, peripheral bone, RANKL/OPG, rat

CLC Number:

R782.4
R914

GONG Xue, QIAN Wenhao, SU Jiansheng. Effects of zoledronate on bone remodeling of maxillofacial and peripheral bones after trauma in rats[J]. Stomatology, 2022, 42(7): 587-592.

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Effects of zoledronate on bone remodeling of maxillofacial and peripheral bones after trauma in rats

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