中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (11): 1699-1704.doi: 10.12307/2022.354

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

颌骨和股骨缺损模型大鼠注射唑来膦酸后骨坏死发生率的差异

鲍宏宇1，2，吕冬梅1，何  芸1，2，夏德林1，2，陈俊良1，2   

  1. 1西南医科大学口颌面修复重建和再生实验室，四川省泸州市   646000；2西南医科大学附属口腔医院口腔颌面外科，四川省泸州市   646000
  • 收稿日期:2021-04-27 修回日期:2021-04-29 接受日期:2021-06-03 出版日期:2022-04-18 发布日期:2021-12-11
  • 通讯作者: 陈俊良，博士，副主任医师，西南医科大学附属口腔医院口腔颌面外科，四川省泸州市 646000
  • 作者简介:鲍宏宇，男，1993年生，内蒙古自治区呼伦贝尔市人，汉族，西南医科大学在读硕士，主要从事口腔颌面外科方面的研究。
  • 基金资助:
    国家自然科学基金项目(11702231)，项目负责人：何芸；泸州市人民政府-西南医科大学联合项目(2020LZXNYDJ17)，项目负责人：陈俊良

Incidence of osteonecrosis in rats with jaw versus femoral defects following zoledronic acid injection

Bao Hongyu1, 2, Lü Dongmei1, He Yun1, 2, Xia Delin1, 2, Chen Junliang1, 2   

  1. 1Orofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Received:2021-04-27 Revised:2021-04-29 Accepted:2021-06-03 Online:2022-04-18 Published:2021-12-11
  • Contact: Chen Junliang, MD, Associate chief physician, Orofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • About author:Bao Hongyu, Master candidate, Orofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 11702231 (to HY); the Science and Technology Strategic Cooperation Program of Luzhou Municipal People’s Government and Southwest Medical University, No. 2020LZXNYDJ17 (to CJL) 

PDF

43

摘要：

文题释义：
双膦酸盐类药物：是一类由人工合成的具有P-C-P核心链结构的无机焦磷酸盐类似物。它被广泛用于临床治疗Paget骨病、恶性肿瘤的骨转移及骨质疏松等疾病。双膦酸盐类药物可导致颌骨坏死。2003年MARX首次发现并报道了通过服用双膦酸盐治疗嗜铬细胞瘤的患者发生了颌骨坏死，将其称为双膦酸盐相关性颌骨坏死。
对比研究：作为基本的科学实验方法之一，是把一组具有一定相似因素的不同性质物体或对象，放在一起进行对照比较，通过综合比较它们在构造方面的差异(因)及在性质方面的不同(果)，得出这种物体或对象的某些性质(果)是由什么、哪些因素(因)造成的。

背景：双膦酸盐类药物可导致颌骨坏死，但是双膦酸盐类药物对同一个体不同部位产生的作用可能是不同的，对同一个体有创伤和无创伤的颌骨或者股骨的影响也是不明确的。
目的：对比唑来膦酸对大鼠颌骨及股骨缺损愈合的影响，为临床指导唑来膦酸等药物的使用和预防药物相关性颌骨坏死的发生提供理论支持。
方法：8周龄雌性SD大鼠共40只，其中20只腹腔注射唑来膦酸溶液，20只注射生理盐水。给药10周后于大鼠左侧下颌骨及股骨做一2 mm× 2 mm×2 mm骨缺损，右侧不做任何处理，即可分为唑来膦酸+颌骨缺损组、唑来膦酸+股骨缺损组、唑来膦酸+颌骨未处理组、唑来膦酸+股骨未处理组、生理盐水+颌骨缺损组、生理盐水+股骨缺损组、生理盐水+颌骨未处理组、生理盐水+股骨未处理组。术后观察颌骨和股骨的愈合情况，术后第8周取材并行影像学和组织学检查。
结果与结论：①唑来膦酸+颌骨缺损组中有16个观察区域术后见下颌骨缺损愈合不佳，局部牙龈红肿、溢脓，术后8周软组织仍未完全愈合，颌骨术区仍可见死骨，骨坏死发生率为80%；其余各组均未见骨质坏死；②影像学结果：唑来膦酸+颌骨缺损组中发生骨坏死标本的X射线片显示，颌骨缺损区域未发生骨愈合，有骨质溶解性破坏；唑来膦酸+股骨缺损组缺损区域密度与周围骨组织相似；生理盐水+颌骨缺损组和生理盐水+股骨缺损组骨缺损处密度较周围组织稍低；③组织学结果：唑来膦酸+颌骨缺损组中发生骨坏死标本的组织学切片可见细胞核消失，骨小梁结构紊乱，并可见少量纤维组织；其余标本未见明显异常；④提示腹腔注射唑来膦酸后大鼠下颌骨缺损骨坏死的发生率很高，而股骨缺损及无缺损的颌骨和股骨不会发生骨坏死。
缩略语：双膦酸盐相关性颌骨坏死：bisphosphonate related osteonecrosis of the jaw，BRONJ

https://orcid.org/0000-0002-9631-4535 (鲍宏宇)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 颌骨, 股骨, 唑来膦酸, 双磷酸盐, 骨坏死, 大鼠

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

中图分类号: