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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (6): 1190-1195. doi: 10.19723/j.issn.1671-167X.2022.06.022

• 论著 • 上一篇    下一篇

药物相关颌骨骨坏死的病理特点及临床治疗策略

郭玉兴1,张建运2,王佃灿1,郭传瑸1,*()   

  1. 1. 北京大学口腔医学院·口腔医院口腔颌面外科，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，口腔数字医学北京市重点实验室，国家卫生健康委员会口腔医学计算机应用工程技术研究中心，国家药品监督管理局口腔生物材料重点实验室，北京 100081
    2. 北京大学口腔医学院·口腔医院口腔病理科，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，口腔数字医学北京市重点实验室，国家卫生健康委员会口腔医学计算机应用工程技术研究中心，国家药品监督管理局口腔生物材料重点实验室，北京 100081
  • 收稿日期:2020-03-19 出版日期:2022-12-18 发布日期:2022-12-19
  • 通讯作者: 郭传瑸 E-mail:guodazuo@sina.com
  • 基金资助:
    北京大学口腔医院青年科研基金(PKUSS20160115);国家自然科学基金(81900979)

Analysis of pathological characteristics of medication-related osteonecrosis of the jaw and discussion of clinical treatment strategies based on the pathological analysis results

Yu-xing GUO1,Jian-yun ZHANG2,Dian-can WANG1,Chuan-bin GUO1,*()   

  1. 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China
    2. Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China
  • Received:2020-03-19 Online:2022-12-18 Published:2022-12-19
  • Contact: Chuan-bin GUO E-mail:guodazuo@sina.com
  • Supported by:
    the Research Foundation of Peking University School and Hospital of Stomatology(PKUSS20160115);the National Natural Science Foundation of China(81900979)

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摘要：

目的: 总结药物相关颌骨骨坏死(medication-related osteonecrosis of the jaw, MRONJ)标本病理特点，结合患者不同手术方案治疗效果进行综合分析，为临床工作中有效治疗MRONJ提供思路。方法: 收集2014年6月至2015年12月北京大学口腔医院口腔颌面外科采用颌骨刮治术和颌骨区段截骨术进行治疗的23例MRONJ患者临床病理资料，总结MRONJ病理特点，并结合手术治疗方式，探讨基于病理表现特征下的临床治疗策略。MRONJ诊断标准和疾病分期依据2014年美国口腔颌面外科学会专家共识进行判定。结果: 本组患者5例采用颌骨区段截骨治疗，均为Ⅲ期；18例采用颌骨刮治治疗，其中Ⅱ期5例，Ⅲ期13例。5例颌骨区段截骨术的MRONJ标本病理特征从浅至深分为炎症区、骨硬化区、骨反应带，为更好分析颌骨刮治术的标本病理表现特征，我们将仅包括炎症区的表现定义为Ⅰ类病理特征，包括炎症区和骨硬化区的表现定义为Ⅱ类病理特征，而包括炎症区、骨硬化区和骨反应带的表现定义为Ⅲ类病理特征。18例颌骨刮治术患者病理特征分布如下：Ⅰ类38.9%(7/18)，Ⅱ类44.4%(8/18)，Ⅲ类16.7%(3/18)。5例患者采用颌骨区段截骨术治疗，术后完全愈合。18例患者采用颌骨刮治术治疗，术后完全愈合的患者中病理特征分别为Ⅰ类2例，Ⅱ类和Ⅲ类各1例；而术后出现MRONJ复发的患者中病理特征分别为Ⅰ类5例，Ⅱ类7例和Ⅲ类2例。结论: MRONJ病变由浅至深的病理表现可分为炎症区、骨硬化区、骨反应带；颌骨刮治术治疗MRONJ复发的常见原因可能为术中未充分去除骨硬化区，而遗留的骨硬化区可能阻断了骨创愈合所需要的血运、营养因子及间充质干细胞。

关键词: 药物相关颌骨骨坏死, 病理特征, 颌骨刮治术, 颌骨区段截骨术

Abstract:

Objective: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work. Methods: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper. Results: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery. Conclusion: Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.

Key words: Medication-related osteonecrosis of the jaw, Pathological characteristics, Jaw curettage, Jaw segmental osteotomy

中图分类号: 

  • R782.4

表1

患者临床资料"

Items Clinical data (n=23)
Male/female, n 11/12
Age/years
  Mean 61.04
  Range 44-81
≥50 years, n 16
< 50 years, n 7
Type of cancer, n
  Breast 9
  Kidney 6
  Prostate 2
  Lung 2
  Bladder 2
  Esophageal 1
  Multiple myeloma 1
Antiresorptive therapy/month
  Mean duration of antiresorptive therapy before first visit 41.13±25.26(range: 10-96)
Type of antiresorptive therapy, n
  Zoledronate 10
  Pamidronate 10
  Zoledronate + pamidronate 3
Mean duration of clinical symptoms before treatment/month 13.78±19.84(range: 2-96)
Trigger of MRONJ lesion, n
  Extraction 17
  Spontaneous 6
MRONJ location, n
  Maxilla 8
  Mandible 11
  Both maxilla and mandible 4
MRONJ stage, n
  Grade 2 5
  Grade 3 18
Treatment methods, n
  Jaw curettage 18
  Jaw segmental osteotomy 5
Mean duration until MRONJ relapse post treatment/month 5.71±4.08(range: 1-15)

图1

药物相关颌骨骨坏死病理特征及分类"

图2

药物相关颌骨骨坏死手术标本病理特征分类与临床分期、治疗方法的相关性分析"

图3

牙源性感染引起药物相关颌骨骨坏死发病过程示意图"

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