MRONJ risk and dental treatment

The drugs (MHRA safety-update list, March 2024)

The March 2024 supplement also lists drugs with a possible association reported in case studies — including romosozumab, several protein kinase inhibitors and some biologics — but with insufficient evidence to estimate risk or base advice on. They are not part of the risk assessment below.

How risk is assessed (Figure 3.1)

A patient is at higher risk of MRONJ if any of the following applies:

• A previous diagnosis of MRONJ
• The drugs are taken as part of the management of cancer
• A bisphosphonate taken for more than 5 years
• A bisphosphonate (any duration) or denosumab taken with a concurrent systemic glucocorticoid

Otherwise — a bisphosphonate for under 5 years, or denosumab, for osteoporosis or other non-malignant bone disease, without concurrent glucocorticoids — the patient is at low risk.

The memory rules

• Patients who have taken bisphosphonate drugs at any time in the past are allocated to a risk group as if they are still taking the drug — bisphosphonates persist in skeletal tissue for years.
• Patients who have taken denosumab in the last nine months are allocated to a risk group as if they are still taking it — its effect on bone turnover diminishes within nine months.
• A low risk patient who continues to take bisphosphonate drugs after their five-year medication review should be reclassified as higher risk.

How rare is it?

• Cancer patients on anti-resorptive / anti-angiogenic drugs: ~1% (1 in 100) in the 2017 guidance; the 2024 supplement notes most recent studies report rates under 5%, with wide variation.
• Osteoporosis patients on anti-resorptive drugs: 0.01–0.1% (1–10 per 10,000); the 2024 supplement reports typically <0.05% for bisphosphonates, and 0.04–0.3% for denosumab taken up to 10 years.

Discuss the risk with the patient, but ensure they are not discouraged from taking their medication or undergoing dental treatment — the risk is small.

Low risk patients

• Carry out all routine dental treatment as normal and continue to provide personalised preventive advice.
• If an extraction or another procedure that impacts on bone is required: discuss the risks and benefits with the patient to ensure valid consent, then proceed with the treatment as clinically indicated.
• Do not prescribe antibiotic or antiseptic prophylaxis unless required for other clinical reasons.
• Advise the patient to contact the practice if they have any concerns, such as unexpected pain, tingling, numbness, altered sensation or swelling in the extraction area.
• Review healing. If the extraction socket is not healed at 8 weeks and you suspect MRONJ, refer to an oral surgery / special care dentistry specialist as per local protocols.

Higher risk patients

• Carry out most routine dental treatment as normal and continue to provide personalised preventive advice.
• If an extraction is indicated, explore all possible alternatives where teeth could potentially be retained — e.g. retaining roots in the absence of infection.
• If extraction remains the most appropriate treatment: discuss the risks and benefits with the patient to ensure valid consent, then proceed as clinically indicated.
• Do not prescribe antibiotic or antiseptic prophylaxis unless required for other clinical reasons.
• For medically complex patients, including higher risk patients treated for cancer, consider consulting an oral surgery / special care dentistry specialist for clinical assessment and treatment planning.
• Advise the patient to contact the practice if they have any concerns, such as unexpected pain, tingling, numbness, altered sensation or swelling in the extraction area.
• Review healing. If the extraction socket is not healed at 8 weeks and you suspect MRONJ, refer to an oral surgery / special care dentistry specialist as per local protocols.

No antibiotic prophylaxis for MRONJ

Do not prescribe antibiotic or antiseptic prophylaxis following extractions or other bone-impacting treatments specifically to reduce the risk of MRONJ. (Strong recommendation; low quality evidence)

Drug holidays

There is no evidence that MRONJ risk is reduced if the patient temporarily or permanently stops taking bisphosphonate drugs before invasive dental procedures — the drugs persist in skeletal tissue for years. The decision to initiate a drug holiday is the responsibility of the prescribing physician, and dental practitioners should not discourage patients from continuing their medication.

For osteoporosis patients on six-monthly denosumab injections, an acceptable option is to delay non-urgent invasive dental treatment of an asymptomatic tooth until the month before the next scheduled injection, and to delay resumption of denosumab until the soft tissues / extraction socket have healed. This requires close liaison with the patient’s medical practitioner.

Prevention advice for every at-risk patient

• Have a healthy diet and reduce sugary snacks and drinks.
• Maintain excellent oral hygiene.
• Use fluoride toothpaste and fluoride mouthwash.
• Stop smoking.
• Limit alcohol intake.
• Attend regular dental checks.
• Report any symptoms such as exposed bone, loose teeth, non-healing sores or lesions, pus or discharge, tingling, numbness or altered sensation, pain or swelling as soon as possible.

When to refer

• Extraction socket not healed at 8 weeks with MRONJ suspected → refer to oral surgery / special care dentistry as per local protocols.
• Suspected spontaneous MRONJ → refer to oral surgery / special care dentistry as per local protocols.
• Consider reporting any suspected MRONJ case to the MHRA via the Yellow Card Scheme, and encourage the patient to do likewise.