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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."

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