What are the recent guidelines for managing Medication-Related Osteonecrosis of the Jaw (MRONJ) in patients on bisphosphonates or denosumab (Prolia)?

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Last updated: November 14, 2025View editorial policy

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Recent Guidelines for Managing Medication-Related Osteonecrosis of the Jaw (MRONJ)

All patients scheduled to receive bisphosphonates or denosumab should undergo a comprehensive dental examination with radiographs before starting therapy, complete any necessary dental procedures with full mucosal healing, and avoid elective invasive dental surgery during active treatment. 1

Definition and Diagnosis

MRONJ requires all three diagnostic criteria to be present: 1

  • Current or previous treatment with a bone-modifying agent (bisphosphonate or denosumab) or angiogenic inhibitor
  • Exposed bone or bone probeable through an intraoral/extraoral fistula in the maxillofacial region persisting >8 weeks
  • No history of radiation therapy to the jaws or metastatic disease to the jaws

Risk Stratification by Medication Schedule

The incidence of MRONJ varies dramatically based on dosing regimen: 1

  • Oncologic doses (monthly IV bisphosphonates or subcutaneous denosumab): 1-9% incidence, increasing substantially after 2 years of treatment
  • Osteoporosis doses (every 6 months): 0-1% incidence
  • Oral bisphosphonates: 0-0.5% incidence

Prevention Protocol

Pre-Treatment Dental Assessment

Before initiating bone-modifying agents in non-urgent settings, perform: 1

  • Comprehensive dental and periodontal examination
  • Panoramic radiograph and/or full-mouth intraoral radiographs
  • Complete all medically necessary dental procedures before starting therapy
  • Ensure full mucosal coverage of bone before initiating bisphosphonates or denosumab

Critical caveat: In urgent oncologic situations (rapidly progressive bone disease, acute hypercalcemia), the benefits of promptly starting therapy may outweigh MRONJ risk, and partial dental evaluation is acceptable. 1

Modifiable Risk Factors to Address

The multidisciplinary team must address these factors before starting therapy: 1

  • Poor oral health and dental disease
  • Uncontrolled diabetes mellitus
  • Tobacco use
  • Ill-fitting dentures

Ongoing Dental Care During Treatment

Patients on bone-modifying agents require: 1

  • Routine dental follow-up every 6 months
  • Maintenance of excellent oral hygiene
  • Patient education about MRONJ risk, especially with tooth extractions and invasive procedures
  • Notification to dental practitioners about their medication status

Management of Dental Procedures During Treatment

Elective Procedures

Elective dentoalveolar surgery (non-medically necessary extractions, alveoloplasties, dental implants) should NOT be performed during active therapy with bone-modifying agents at oncologic doses. 1

Exceptions may be considered only when a dental specialist with MRONJ expertise has reviewed risks/benefits with the patient and oncology team. 1

Necessary Dental Surgery

If dentoalveolar surgery must be performed: 1

  • Evaluate the patient every 6-8 weeks until complete mucosal coverage occurs
  • Maintain communication between dental specialist and oncologist regarding healing status
  • Consider deferring the next bone-modifying agent dose until healing is complete (at treating physician's discretion)

Important limitation: There is insufficient evidence to support or refute mandatory discontinuation of bone-modifying agents before dental surgery—this decision remains at the treating physician's discretion after discussion with the patient and oral health provider. 1

Treatment of Established MRONJ

Initial Conservative Management

Conservative measures comprise the first-line approach: 1

  • Antimicrobial mouth rinses
  • Systemic antibiotics when clinically indicated
  • Effective oral hygiene maintenance
  • Conservative surgical interventions (removal of superficial bone spicules only)

Refractory Disease

Aggressive surgical interventions (mucosal flap elevation, block resection of necrotic bone, soft tissue closure) may be used if: 1

  • MRONJ causes persistent symptoms despite conservative treatment
  • MRONJ affects function
  • Do NOT perform aggressive surgery for asymptomatic bone exposure

The multidisciplinary team must thoroughly discuss risks and benefits before aggressive intervention. 1

Medication Management During Active MRONJ

There is insufficient evidence to mandate discontinuation of bone-modifying agents in patients with established MRONJ—administration may be deferred at the treating physician's discretion after discussion with the patient and oral health provider. 1

The dental specialist should communicate objective healing status (resolved, improving, stable, or progressive) to the oncologist, as this may affect decisions about cessation or recommencement of therapy. 1

Monitoring Requirements

Before Starting Therapy

All patients require: 1

  • Serum calcium measurement
  • Renal function assessment (for IV bisphosphonates)
  • Dental examination where feasible

During Treatment

Monitor for: 1

  • Serum calcium levels (especially in first weeks of therapy)
  • Renal function and serum creatinine (for IV bisphosphonates)
  • Signs/symptoms of MRONJ at routine dental visits

Provide calcium and vitamin D supplementation unless contraindicated (oral bisphosphonates and calcium should be separated by at least 2 hours). 1

Special Populations

Cancer Patients on Adjuvant Therapy

For postmenopausal women with breast cancer receiving adjuvant bisphosphonates, the same prevention strategies apply, though MRONJ risk is substantially lower (0-1.8%) compared to oncologic dosing. 1

Multiple Myeloma Patients

Baseline dental examination and ONJ monitoring are mandatory for all patients receiving bone-modifying agents, with continuation of therapy for up to 2 years recommended; beyond 2 years should be based on clinical judgment. 1

Critical Practice Points

The risk of ONJ increases with frequency, dose, and duration of administration—risk is substantially lower with osteoporosis-indicated schedules compared to oncologic doses. 1

Staging should be performed by a clinician experienced in MRONJ management. 1

Ongoing collaboration among dentist, dental specialist, and oncologist is essential to optimal patient care. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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