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Medication-related osteonecrosis of the jaw in a minipig model: Parameters for developing a macroscopic,
B Nowicki1, D Nehrbass1, D Arens1
1AO Research Institute Davos, Davos Platz, Switzerland.
Objectives:
To devise a macroscopic, radiological, and histological scale for assessing pathological changes associated with medication-related osteonecrosis of the jaw in a minipig model.
Materials And Methods:
Medication-related osteonecrosis of the jaw was induced in Göttingen minipigs by weekly intravenous administration of bisphosphonate (zoledronic acid) combined with a tooth extraction procedure. Controls either did not receive zoledronic acid or did not undergo tooth extraction. After 20 weeks, minipigs were euthanized and underwent computed tomography and micro-computed tomography scanning. The mandible underwent additional histological examination.
Results:
The most consistent macroscopic findings in animals that had developed bisphosphonate-related osteonecrosis of the jaw (BRONJ) were necrotic, denuded bone, and formation of fistula and pus. Under radiological examination, impaired extraction socket healing, decrease in attenuation of bone beneath the extraction site, and periosteal reaction were observed. Under histological examination, demineralization of the extracellular bone matrix, denuding of bone, and osteonecrosis were recorded.
Conclusion:
These parameters were used to develop a scoring system for grading BRONJ.
Insights
Researchers developed a new scoring system to assess medication-related osteonecrosis of the jaw (MRONJ) in minipigs. This system uses macroscopic, radiological, and histological findings to grade the condition, aiding in future research and treatment strategies.
Area of Science:
- Oral and Maxillofacial Surgery
- Pharmacology
- Veterinary Pathology
Background:
- Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of certain medications, particularly bisphosphonates.
- Accurate assessment and grading of MRONJ are crucial for understanding its progression and evaluating treatment efficacy.
- Existing assessment methods may lack comprehensive integration of macroscopic, radiological, and histological features.
Purpose of the Study:
- To develop and validate a novel scoring system for evaluating pathological changes in medication-related osteonecrosis of the jaw (MRONJ).
- To establish a standardized method for assessing MRONJ in a preclinical minipig model, integrating multiple examination modalities.
- To provide a quantitative tool for future research on MRONJ pathogenesis and therapeutic interventions.
Main Methods:
- Medication-related osteonecrosis of the jaw (MRONJ) was induced in Göttingen minipigs using zoledronic acid and tooth extraction.
- Control groups were established with either no zoledronic acid or no tooth extraction.
- Post-mortem assessment included macroscopic, computed tomography (CT), micro-CT, and histological examination of the mandible after 20 weeks.
Main Results:
- Macroscopic findings included necrotic bone, exposed bone, fistula formation, and pus.
- Radiological signs encompassed impaired extraction socket healing, reduced bone attenuation, and periosteal reactions.
- Histological analysis revealed bone demineralization, exposed bone, and osteonecrosis.
Conclusions:
- The study successfully devised a scoring system integrating macroscopic, radiological, and histological parameters for grading bisphosphonate-related osteonecrosis of the jaw (BRONJ).
- This scoring system provides a comprehensive approach to assessing MRONJ in a preclinical model.
- The developed scale facilitates standardized evaluation and grading of MRONJ, supporting further research and clinical application.
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