Medication-Related Osteonecrosis of the Jaw

Publication Date: July 22, 2019
Last Updated: December 15, 2022

Diagnosis

It is recommended that the term “medication-related osteonecrosis of the jaw" (MRONJ) be used when referring to bone necrosis associated with pharmacologic therapies. ( FC , Ins , W )
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Clinicians should confirm the presence of all three of the following criteria in order to establish a diagnosis of MRONJ: 1) Current or previous treatment with a BMA or angiogenic inhibitor, 2) Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks, and 3) No history of radiation therapy to the jaws or metastatic disease to the jaws. ( FC , Ins , W )
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Risk Reduction

Coordination of Care

For cancer patients scheduled to receive a BMA in a non-urgent setting, oral care assessment (including a comprehensive dental, periodontal, and oral radiographic exam when feasible to do so) should be undertaken prior to initiating therapy. Based on the assessment, a dental care plan should be developed and implemented. The care plan should be coordinated between the dentist and the oncologist to ensure that medically necessary dental procedures are undertaken prior to initiation of the BMA. Follow-up by the dentist should then be performed on a routine schedule (e.g., every six months) once therapy with a BMA has commenced. ( EB , L , M )
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Modifiable Risk Factors

Members of the multidisciplinary team should address modifiable risk factors for MRONJ with the patient as early as possible. These risk factors include poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use. ( FC , Ins , M )
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Elective Dentoalveolar Surgery

Elective dentoalveolar surgical procedures (e.g., non-medically necessary extractions, alveoloplasties, and implants) should not be performed during active therapy with a BMA at an oncologic dose. Exceptions may be considered when a dental specialist with expertise in prevention and treatment of MRONJ has reviewed the benefits and risks of the proposed invasive procedure with the patient and the oncology team. ( EB , I , M )
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Dentoalveolar Surgery Follow-Up

If dentoalveolar surgery is performed, patients should be evaluated by the dental specialist on a systematic and frequently scheduled basis (e.g., every 6-8 weeks) until full mucosal coverage of the surgical site has occurred. Communication with the oncologist regarding status of healing is encouraged particularly when considering future use of BMA (Table 2). ( FC , Ins , M )
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Temporary Discontinuation of BMAs Prior to Dentoalveolar Surgery

For patients with cancer who are receiving a BMA at an oncologic dose, there is insufficient evidence to support or refute the need for discontinuation of the BMA prior to dentoalveolar surgery. Administration of the BMA may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. (, , )
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Staging

A well-established staging system should be used to quantify the severity and extent of MRONJ and to guide management decisions. Options include the 2014 AAOMS staging system, the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and the 2017 International Task Force on ONJ (osteonecrosis of the jaw) staging system for MRONJ. The same system should be used throughout the patient’s MRONJ course of care. Diagnostic imaging may be used as an adjunct to these staging systems. ( FC , Ins , W )
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Optimally, staging should be performed by a clinician experienced with the management of MRONJ. ( FC , Ins , W )
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Treatment

Initial Treatment of MRONJ
Conservative measures comprise the initial approach to treatment of MRONJ. Conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical interventions (e.g., removal of a superficial bone spicule). ( FC , Ins , M )
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Treatment of Refractory MRONJ
Aggressive surgical interventions (e.g., mucosal flap elevation, block resection of necrotic bone, soft tissue closure) may be used if MRONJ results in persistent symptoms or impacts function despite initial conservative treatment. Aggressive surgical intervention is not recommended for asymptomatic bone exposure. In advance of the aggressive surgical intervention, the multidisciplinary care team and the patient should thoroughly discuss the risks and benefits of the proposed intervention. ( FC , Ins , W )
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Temporary Discontinuation of BMAs
For patients diagnosed with MRONJ while being treated with BMAs, there is insufficient evidence to support or refute the discontinuation of the BMAs. Administration of the BMA may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. ( FC , Ins , W )
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Outcome Measures
During the course of MRONJ treatment, the dentist/dental specialist should communicate with the medical oncologist the objective and subjective status of the lesion – resolved, improving, stable or progressive. The clinical course of MRONJ may impact local and/or systemic treatment decisions with respect to cessation or recommencement of BMAs. ( FC , Ins , W )
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Recommendation Grading

Overview

Title

Medication-Related Osteonecrosis of the Jaw

Authoring Organizations

American Society of Clinical Oncology

Multinational Association of Supportive Care in Cancer

Publication Month/Year

July 22, 2019

Last Updated Month/Year

October 2, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To provide guidance regarding best practices in the prevention and management of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer.

Target Patient Population

Adult patients with cancer who are receiving bone-modifying agents (BMAs) for any oncologic indication.

Target Provider Population

Oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners

PICO Questions

  1. What are the recommended best practices for preventing and managing medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer?

  2. What is the preferred terminology and definition for osteonecrosis of the jaw associated with pharmacologic therapies in oncology patients?

  3. What steps should be taken to reduce the risk of MRONJ in patients with cancer?

  4. What outcome measures should be used in clinical practice to describe the response of the MRONJ lesion to treatment?

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Clinical researcher, dentist, nurse, nurse practitioner, health systems pharmacist, physician, physician assistant

Scope

Management, Prevention

Diseases/Conditions (MeSH)

D059266 - Bisphosphonate-Associated Osteonecrosis of the Jaw, D010020 - Osteonecrosis

Keywords

medication-related osteonecrosis of the jaw, jaw osteonecrosis, Osteonecrosis, supportive care, MRONJ, bone-modifying agents, BMAs

Source Citation

DOI: 10.1200/JCO.19.01186 Journal of Clinical Oncology 37, no. 25 (September 01, 2019) 2270-2290.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
132
Literature Search Start Date
January 1, 2003
Literature Search End Date
December 31, 2017
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Specialties Involved
Internal Medicine General, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See full-text
Description of Study Criteria
See Supplement
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100