Medication-Related Osteonecrosis of the Jaw (MRONJ): Equivalent Dose and Threshold Dose Risk Metrics

Q: What were the main objectives of the study?

To investigate clinical characteristics and risk factors associated with MRONJ and to introduce two metrics—equivalent dose and threshold dose—as predictive risk assessment tools.

Q: How was the study conducted and what data were analyzed?

A retrospective review analyzed 193 patient records from Shahab Clinic and Mashhad Dental School (2017–2023). Patients were categorized into MRONJ stages (0–3) and an at-risk group, and demographics, comorbidities, clinical presentations, and medication profiles were analyzed.

Q: What factors were significantly associated with advanced MRONJ stages?

Advanced stages were significantly linked to higher equivalent doses, prolonged medication use, and key risk factors including oncologic diseases, medication type and route of administration, comorbidities, age, and surgical interventions such as extractions and ill-fitting dentures.

Jul 10, 2026

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Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious complication linked to a wide range of medications, initially associated with bisphosphonates and later broadened to anti-angiogenic, cytotoxic, and newer targeted therapies. A retrospective study analyzed 193 patient records from Shahab Clinic and Mashhad Dental School (2017–2023) to define clinical characteristics and risk factors and to introduce equivalent dose and threshold dose as predictive tools. MRONJ occurred in 40.4% and at-risk patients in 59.6%, with advanced stages tied to cumulative exposure and major clinical risks.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

Objectives and rationale

Medication-related osteonecrosis of the jaw (MRONJ)

Study design and data sources

Patient cohort and timeframe

Data collection and staging

Risk assessment metrics

Equivalent dose

Threshold dose

Statistical analysis and outcomes

Prevalence and staging associations

Predictive performance and implications

Shahab Dental Clinic (Oral Medicine and Special Care Dentistry) Oral & Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences Community and Family Medicine Department,, Faculty of Medicine, Mashhad University of Medical Sciences Community and Family Medicine Department,, Faculty of Medicine, Mashhad University of Medical Sciences Vice Chancellor for Health, Sabzevar University of Medical Science Mashhad University of Medical Sciences Shahab Dental Clinic (Oral Medicine and Special Care Dentistry) Kavian Institute of Higher Education Mike Petryk School of Dentistry Petry School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta Centro de Oncologia Molecular, Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês February 6th, 2025 [https://doi.org/10.21203/rs.3.rs-5922241/v1](https://doi.org/10.21203/rs.3.rs-5922241/v1) 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Competing interest reported. PMM serves as the Scienti«c Mentor at Shahab Clinic. SS and Parham Aghasizadeh Sharbaf are research assistant at Shahab Clinic. Other authors have no competing interests. A version of this preprint was published at Supportive Care in Cancer on July 6th, 2025. See the published version at [https://doi.org/10.1007/s00520-025-09649-6](https://doi.org/10.1007/s00520-025-09649-6) . To investigate the clinical characteristics and risk factors associated with medication-related osteonecrosis of the jaw (MRONJ) and to introduce two metrics—equivalent dose and threshold dose—as predictive risk assessment tools. This retrospective study reviewed 193 patient records from Shahab Clinic and the Oral Medicine Department of Mashhad Dental School (2017–2023) . Patients were categorized into MRONJ stages (0– 3) and an "at-risk" group. Data on demographics, comorbidities, clinical presentations, and detailed medication pro«les were analyzed. Equivalent dose was standardized to four years of oral alendronate use, and threshold dose provided a cumulative risk cut-off. Statistical analyses( T-tests, ANOVA, Chisquare tests,.) were applied . MRONJ was identi«ed in 40.4% of cases, while 59. 6% were classi«ed as at-risk. Advanced stages were signi«cantly associated with higher equivalent doses, prolonged medication use, and key risk factors, including oncologic diseases, medication type and route of administration, comorbidities, age, and surgical interventions such as extractions and ill-«tting dentures (p < 0 .001) . The novel metrics demonstrated strong predictive value, with higher equivalent doses correlating closely with MRONJ severity (R = 0 .46, p < 0 .001) This study offers critical insights into MRONJ risk strati«cation, highlighting the cumulative impact of medication dose alongside clinical risk factors. The introduction of equivalent and threshold doses represents a transformative advancement in MRONJ risk prediction, enabling precise prevention strategies and guiding clinical management toward standardized care protocols. Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious condition characterized by jawbone necrosis. Initially recognized in 2003 as an adverse effect of bisphosphonates—drugs used to regulate bone metabolism—MRONJ has since been associated with a broader range of medications. These include anti-angiogenesis agents, cytotoxic drugs, and newer therapies such as CDK4/6 inhibitors, adalimumab, and pembrolizumab. Emerging evidence also suggests that medications like ocrelizumab, recently introduced for the treatment of multiple sclerosis, may contribute to MRONJ development. [ 1–7] Understanding MRONJ requires a detailed analysis of its clinical features and risk factors across diverse patient populations. Despite the growing body of research, descriptive studies focusing on the frequency and characteristics of MRONJ within large cohorts in Iran remain scarce. This s

FAQs

What were the main objectives of the study?

To investigate clinical characteristics and risk factors associated with MRONJ and to introduce two metrics—equivalent dose and threshold dose—as predictive risk assessment tools.

How was the study conducted and what data were analyzed?

A retrospective review analyzed 193 patient records from Shahab Clinic and Mashhad Dental School (2017–2023). Patients were categorized into MRONJ stages (0–3) and an at-risk group, and demographics, comorbidities, clinical presentations, and medication profiles were analyzed.

What factors were significantly associated with advanced MRONJ stages?

Advanced stages were significantly linked to higher equivalent doses, prolonged medication use, and key risk factors including oncologic diseases, medication type and route of administration, comorbidities, age, and surgical interventions such as extractions and ill-fitting dentures.

Jul 10, 2026

Upload by Jiven