Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (6): 1190-1195. doi: 10.19723/j.issn.1671-167X.2022.06.022

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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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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

CLC Number: 

  • R782.4

Table 1

Patient clinical data"

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)

Figure 1

Pathological features observed by analyzing histological sections of MRONJ lesions A-C, histological sections from MRONJ samples; D, schematic drawing showing the histological changes resulting from MRONJ, black arrows indicate IR, SR, and NB. Type 1, labeled with the blue arrow, represents the IR region; type 2, labeled with the green arrow, represents the IR and SR region; type 3, labeled with the yellow arrow, represents the three regions IR, SR, and BRL. The black arrow points to BRL, filled with abundant cells. MRONJ, medication-related osteonecrosis of the jaw; IR, inflammation region; SR, sclerosis region; BRL, bone reaction layer; NB, normal bone; S, sequestrum. Scale bars, 100 μm. D, the sketch figure, no scale bars."

Figure 2

Relation of the MRONJ stage and treatment results with pathological types distribution A, pathological features of surgical specimens in MRONJ patients with stage Ⅱ and stage Ⅲ; B, pathological features of patients who completely healed after jaw curettage and the pathological features of patients who had recurrence after surgery; C, relapse timing in MRONJ patients with stage Ⅱ and Ⅲ after jaw curettage was similar (P > 0.05). MRONJ, medication-related osteonecrosis of the jaw."

Figure 3

Pathogenesis of odontogenic MRONJ A, pulpitis and periodontitis are common causes of alveolar bone inflammation; B, alveolar bone inflammation is associated with the production of osteoclasts, which are also the targets of anti-bone resorption drugs (mainly bisphosphonate drugs), then alveolar bone inflammation is surrounded by sclerotic region, characterized by bone sclerosis, micro-vessels, and osteoblasts decrease or disappearance; C, due to the blockage of blood flow in the peripheral bone sclerosis region, the healing of the teeth socket exposed by the spontaneous loss or extraction is delayed or impaired; D, further intensification of inflammation in the teeth socket will cause it to break through the bone sclerosis region, resulting in separation of the sequestrum, still, at this time, the outer periphery mixed with sequestrum and soft tissue inflammation will be further wrapped by a new bone sclerosis region. MRONJ, medication-related osteonecrosis of the jaw."

1 Sacco R , Sacco N , Hamid U , et al. Microsurgical reconstruction of the jaws using vascularised free flap technique in patients with medication-related osteonecrosis: A systematic review[J]. Biomed Res Int, 2018, 2018, 9858921.
2 Rupel K , Ottaviani G , Gobbo M , et al. A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ)[J]. Oral Oncol, 2014, 50 (11): 1049- 1057.
doi: 10.1016/j.oraloncology.2014.08.016
3 郭玉兴, 王佃灿, 王洋, 等. 二膦酸盐药物治疗乳腺癌骨转移发生颌骨坏死的临床特点[J]. 北京大学学报(医学版), 2016, 48 (1): 80- 83.
doi: 10.3969/j.issn.1671-167X.2016.01.014
4 Hayashida S , Soutome S , Yanamoto S , et al. Evaluation of the treatment strategies for medication-related osteonecrosis of the jaws (MRONJ) and the factors affecting treatment outcome: A multicenter retrospective study with propensity score matching analysis[J]. J Bone Miner Res, 2017, 32 (10): 2022- 2029.
doi: 10.1002/jbmr.3191
5 Ruggiero SL , Dodson TB , Fantasia J , et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw: 2014 update[J]. J Oral Maxillofac Surg, 2014, 72 (10): 1938- 1956.
doi: 10.1016/j.joms.2014.04.031
6 Basi DL , Hughes PJ , Thumbigere-Math V , et al. Matrix metalloproteinase-9 expression in alveolar extraction sockets of Zoledronic acid-treated rats[J]. J Oral Maxillofac Surg, 2011, 69 (11): 2698- 2707.
doi: 10.1016/j.joms.2011.02.065
7 Yamashita J , Koi K , Yang DY , et al. Effect of zoledronate on oral wound healing in rats[J]. Clin Cancer Res, 2011, 17 (6): 1405- 1414.
doi: 10.1158/1078-0432.CCR-10-1614
8 Marx RE . Pamidronate (aredia) and zoledronate (zometa) induced avascular necrosis of the jaws: A growing epidemic[J]. J Oral Maxillofac Surg, 2003, 61 (9): 1115- 1117.
doi: 10.1016/S0278-2391(03)00720-1
9 Ruggiero SL , Mehrotra B , Rosenberg TJ , et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases[J]. J Oral Maxillofac Surg, 2004, 62 (5): 527- 534.
doi: 10.1016/j.joms.2004.02.004
10 Lin JT , Lane JM . Bisphosphonates[J]. J Am Acad Orthop Surg, 2003, 11 (1): 1- 4.
doi: 10.5435/00124635-200301000-00001
11 Di Fede O , Panzarella V , Mauceri R , et al. The dental management of patients at risk of medication-related osteonecrosis of the jaw: new paradigm of primary prevention[J]. Biomed Res Int, 2018, 2018, 2684924.
12 Shintani T , Hayashido Y , Mukasa H , et al. Comparison of the prognosis of bisphosphonate-related osteonecrosis of the jaw caused by oral and intravenous bisphosphonates[J]. Int J Oral Maxillofac Surg, 2015, 44 (7): 840- 844.
doi: 10.1016/j.ijom.2015.03.013
13 Nicolatou-Galitis O , Papadopoulou E , Vardas E , et al. Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents[J]. Oral Dis, 2020, 26 (5): 955- 966.
doi: 10.1111/odi.13294
14 Guo Y , Guo C . Enhancement of bone perfusion through cortical perforations to improve healing of medication-related osteonecrosis of the jaw: A retrospective study[J]. Int J Oral Maxillofac Surg, 2021, 50 (6): 740- 745.
doi: 10.1016/j.ijom.2020.07.036
15 郭玉兴, 王佃灿, 刘筱菁, 等. 翻瓣联合骨管技术拔牙方案在药物相关性颌骨坏死潜在风险患者中的应用初探[J]. 中华口腔医学杂志, 2021, 56 (5): 452- 457.
doi: 10.3760/cma.j.cn112144-20210104-00003
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