Guideline sources The following summarized guidelines for the evaluation and management of medication-related osteonecrosis of the jaw (MRONJ) are prepared by our editorial team based on guidelines from the Multinational Association of Supportive Care in Cancer (MASCC/ISOO/ASCO 2019) and the American Cancer Society (ACS 2016). 1 2 Guidelines 1. Screening and diagnosis Diagnosis: As per ASCO 2019 guidelines: Use the term MRONJ when referring to bone necrosis associated with pharmacologic therapies. B Confirm the presence of all of the following criteria to establish a diagnosis of MRONJ: current or previous treatment with a bone-modifying agent or angiogenic inhibitor https://web.pathway.md/diseases/recUMmAyQnJ6qeu01 1/4 6/30/23, 1:01 AM Medication-related osteonecrosis of the jaw Pathway exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for > 8 weeks no history of radiotherapy to the jaws or metastatic disease to the jaws. B As per ACS 2016 guidelines, monitor survivors of head and neck cancer for swelling of the jaw and/or jaw pain indicating possible osteonecrosis. B 2. Classification and risk stratification Staging: Use a well-established staging system to quantify the severity and extent of MRONJ and to guide management decisions, such as: 2014 AAOMS staging system CTCAE version 5.0 2017 International Task Force on Osteonecrosis of the Jaw staging system. B Show 2 more 3. Medical management Conservative management: As per ASCO 2019 guidelines, offer conservative measures for the initial management of MRONJ, including: antimicrobial mouth rinses antibiotics when clinically indicated effective oral hygiene conservative surgical interventions (such as removal of a superficial bone spicule). B As per ACS 2016 guidelines, offer conservative treatment such as broad-spectrum antibiotics and daily saline or aqueous chlorhexidine gluconate irrigations for early-stage lesions. Refer patients to a head and neck surgeon for consideration of hyperbaric oxygen therapy for early and intermediate lesions. B Discontinuation of bone-modifying agents: insufficient evidence to recommend for or against discontinuation of the bone-modifying agent in patients diagnosed with MRONJ while on bone- modifying agent therapy. Consider deferring the administration of the bone-modifying agent at the discretion of the treating physician, in conjunction with a discussion with the patient and the oral health provider. I 4. Perioperative care Perioperative planning for elective dentoalveolar surgery: do not perform elective dentoalveolar surgical procedures (such as nonmedically necessary extractions, alveoloplasties, and implants) during active therapy with a bone-modifying agent at an oncologic dose. Consider performing procedures when a dental specialist with expertise in the prevention and treatment of https://web.pathway.md/diseases/recUMmAyQnJ6qeu01 2/4 6/30/23, 1:01 AM Medication-related osteonecrosis of the jaw Pathway MRONJ has reviewed the benefits and risks of the proposed invasive procedure with the patient and the oncology team. D Show 2 more 5. Surgical interventions Indications for surgery: As per ASCO 2019 guidelines, consider performing aggressive surgical interventions (such as mucosal flap elevation, block resection of necrotic bone, or soft tissue closure) in patients with persistent symptoms or dysfunction despite initial conservative treatment. C Show 2 more As per ACS 2016 guidelines, refer patients to a head and neck surgeon for debridement of necrotic bone while undergoing conservative management, or for external mandible bony exposure through the skin. B 6. Preventative measures Oral care assessment: Obtain oral care assessment (including a comprehensive dental, periodontal, and oral radiographic evaluation when feasible) before initiating bone-modifying agents in patients with cancer in a non-urgent setting. B Develop and implement a dental care plan based on the assessment. Coordinate the care plan between the dentist and the oncologist to ensure that medically necessary dental procedures are undertaken before the initiation of bone-modifying agent therapy. Follow-up by the dentists on a routine schedule (such as every 6 months) once therapy with a bone-modifying agent has commenced. B Management of modifiable risk factors: Address the following modifiable risk factors for MRONJ with the patient by members of the multidisciplinary team as early as possible: poor oral health invasive dental procedures ill-fitting dentures uncontrolled diabetes mellitus tobacco use. B 7. Follow-up and surveillance Assessment of treatment response: ensure that the dentist/dental specialist communicates with the medical oncologist during the course of MRONJ treatment regarding the objective and subjective status of the lesion: resolved, improving, stable, or progressive. Consider making local https://web.pathway.md/diseases/recUMmAyQnJ6qeu01 3/4 6/30/23, 1:01 AM Medication-related osteonecrosis of the jaw Pathway and/or systemic treatment decisions with respect to cessation or re-commencement of bone- modifying agents depending on the clinical course of MRONJ. B Clinical findings Symptoms Past medical history Facial pain CKD Mouth sores Diabetes mellitus Tooth mobility Hyperthyroidism Toothache Malignancy Osteoporosis Medication history Past surgical history Antiangiogenic therapy Antiresorptive therapy Dentoalveolar surgery Bisphosphonates Social history Corticosteroids Tobacco use Family history Dental exam Breast cancer Dentures Head and neck exam Poor dental health Exposed jaw bone Hematological findings Oral mucosal erythema Oral ulcers Anemia Lab findings C-terminal telopeptide References 1. Ezra E W Cohen, Samuel J LaMonte, Nicole L Erb et al. American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016 May;66 3 203 39. Open 2. Noam Yarom, Charles L Shapiro, Douglas E Peterson et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol. 2019 Sep 1;37 25 2270 2290. Open https://web.pathway.md/diseases/recUMmAyQnJ6qeu01 4/4