Risk factors

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The most significant risk factor for MRONJ is the underlying medical condition for which the patient is being treated, with patients being treated for cancer considered at higher risk than those being treated for osteoporosis.

Patients who have had a previous episode of MRONJ, irrespective of their underlying medical condition, are also considered as being at higher risk.

Other risk factors are discussed in more detail below and in the full guidance.

Dental treatment

MRONJ is an adverse effect of treatment with anti-resorptive or anti-angiogenic drugs and although invasive dental treatment is a risk factor, it does not cause the disease.

MRONJ can occur 'spontaneously' without the patient having undergone any recent invasive dental treatment.

Dental procedures that impact on bone are considered a risk factor for MRONJ, with tooth extraction a common precipitating event.

The incidence of MRONJ after tooth extraction is estimated to be 2.9% in patients with cancer and 0.15% in patients being treated for osteoporosis.

Around 60% of patients who develop MRONJ have had a recent tooth extraction.

There is some evidence that dental infection and untreated periodontal disease may increase the risk of MRONJ. 

Dental trauma, including mucosal trauma from ill-fitting dentures or other appliances, is also considered a risk factor.

Duration of bisphosphonate drug therapy

The risk of MRONJ in patients being treated with bisphosphonate drugs is thought to increase as the cumulative dose of the drug increases, as a consequence of the long half-life of this drug class.

This may explain the increased MRONJ risk in patients being treated with high dose bisphosphonate drugs for the management of cancer compared to those being treated with lower doses for the management of osteoporosis or other non-malignant diseases of the bone.

However, even in this lower risk patient group, the MRONJ risk may be influenced by the length of time that a patient has been exposed to the drug.

One study found a higher prevalence of MRONJ in patients who had taken oral bisphosphonates for more than four years compared to those who had taken the drugs for less than this time period.

Other concurrent medication

Chronic systemic glucocorticoid use has been reported in some studies to increase the risk for MRONJ when taken in combination with anti-resorptive drugs. However, the association has not been observed in other studies. 

The combination of bisphosphonates and anti-angiogenic agents has also been associated with increased risk of MRONJ. The risk appears to be increased if the drugs are taken concurrently or if there has been a history of bisphosphonate use.

Previous treatment with anti-resorptive or anti-angiogenic drugs

There is currently no evidence to inform the assessment of risk for patients who have previously taken anti-resorptive or anti-angiogenic drugs.

The bisphosphonates are known to remain in the body for a significant amount of time after the patient stops taking them. Therefore, if a patient has taken bisphosphonate drugs in the past but is no longer taking them for whatever reason (i.e. completed or discontinued the course or taking a drug holiday), they should be allocated to a risk group as if they are still taking the drugs.

The effect of denosumab on bone turnover diminishes within nine months of treatment completion.

Anti-angiogenic drugs are not thought to remain in the body for extended periods of time.