Establishing an animal model of bisphosphonate-related osteonecrosis of the jaw / 中国组织工程研究

ABSTRACT

BACKGROUND:Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is thought to be caused by trauma to dentoalveolar structures after dental extraction and implantation that have a limited capacity for bone healing followed by infection,suppuration and pain,further inducing equestration,but the pathogenesis is poorly understood.OBJECTIVE:To establish a stable animal model of BRONJ,and to observe its clinical manifestations,radiological changes and pathological characters,thereby paving ways for further understanding the pathogenesis of BRONJ.METHODS:Twenty-four female Sprague-Dawely rats were randomly allocated into experimental and control groups (n=12 per group).The rats in the experimental group were given the intraperitoneal injection of 0.2 mg/kg zoledronic acid,and the controls received the intraperitoneal injection of same volume of normal saline,three times weekly for consecutive 12 weeks.Subsequently,left first mandibular molars were extracted under general anesthesia,and the bone healing was observed.At 8 weeks after tooth extraction,all the rats were euthanized.The rat left jaws were examined by X-ray and micro-CT to explore the imaging changes.The histopathological characteristics of the mandibular soft and hard tissues were investigated by hematoxylin-eosin staining and Masson staining,to further testify the BRONJ model.RESULTS AND CONCLUSION:At 8 weeks after tooth extraction,the wound was unable to heal,and nonvital bone tissues were visible in the experimental group.The findings revealed on radiographies and pathological sections were in accordance with the characteristics of BRONJ.Masson staining results showed slender collagen fibrils around the dental extraction wound were slender in the experimental group.These results indicate that the intraperitoneal injection of zoledronate combined with tooth extraction can induce BRONJ in rats.The soft tissue toxicity and anti-angiogenesis of zoledronic acid can promote the occurrence of BRONJ,and the local acidic microenvironment caused by trauma probably is involved in the occurrence of BRONJ.