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Special issues

Medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw

Recommendation 45


MRONJ is a rare complication of osteoporosis therapy and most patients will not be at increased risk of MRONJ. Consider a patient's risk of MRONJ prior to starting osteoporosis therapy and ensure high-risk patients receive dental review prior to therapy initiation. Given the long in vivo half-life of bisphosphonates, there is little benefit to their cessation prior to dental extraction. Invasive dental procedures in patients on denosumab should be performed just prior to the next six-monthly injection because the in vivo effect on bone suppression will be waning.


MRONJ is defined as an area of exposed bone in the maxillofacial region that has persisted for more than eight weeks in a patient receiving bisphosphonates, denosumab, or anti-angiogenic therapy for cancer, with no history of radiation therapy to the jaws or obvious metastatic disease.1

MRONJ occurs at a substantially lower incidence in patients undergoing osteoporosis therapy than in those with cancer being treated with antiresorptives to prevent malignancy-related skeletal adverse events. The reported prevalence is between 1 and 100 per 100,000 patient-years (with a ‘ceiling’ of 150 per 100,000 patient-years) in patients receiving oral bisphosphonate therapy for osteoporosis, marginally higher than the incidence in the general population.2–4

The duration of oral bisphosphonate therapy for osteoporosis is a risk factor for MRONJ, with a mean duration of greater than four years.5 This may be shortened if the patient is also being treated with long-term glucocorticoids or anti-angiogenic drugs.1 Compared with patients receiving higher doses of antiresorptives (e.g., zoledronic acid or denosumab) for cancer treatment, the risk of MRONJ for patients with osteoporosis exposed to antiresorptive medications is approximately 100-fold smaller.1

The aetiology of MRONJ is uncertain, but appears multifactorial and related to dose and duration of antiresorptive exposure, pre-existing oral disease profile, type of dentoalveolar oral surgery, and genetic polymorphisms.6

Because the dose and duration of antiresorptive therapy are of concern in the development of MRONJ, patients who have been on more than four years of antiresorptive therapy are at greater risk of MRONJ. Patients should be educated to inform their dental provider if they are taking antiresorptive agents (bisphosphonates or denosumab).

Invasive dental surgery, including extraction, implant insertion, and limited surgical intervention to treat dental infection/abscess, such as periodontal scaling and endodontic (root canal) therapy, have been associated with osteonecrosis of the jaw.

Consensus recommendations from the American Association of Oral and Maxillofacial Surgeons1 and the International Task Force on Osteonecrosis of the Jaw6 state that elective dentoalveolar oral surgery is not contraindicated in patients receiving antiresorptive therapy (bisphosphonate and denosumab) for osteoporosis. However, the identification and treatment of dental disease prior to the initiation of antiresorptive therapy, if possible, is recommended.6 Patients should be adequately informed of the very low risk of MRONJ.

The American Association of Oral and Maxillofacial Surgeons recommends that if systemic conditions permit, discontinuation of oral bisphosphonates for two months before and three months after elective invasive dental surgery may be considered to lower the risk of MRONJ.1 This guidance contrasts with that of the American Dental Association and the International Task Force on Osteonecrosis of the Jaw, both of which state there is insufficient evidence to recommend a break from antiresorptive drug therapy, or a waiting period before performing minor oral surgical treatment.6–8 However, the International Task Force on Osteonecrosis of the Jaw recommends that in those at high risk of MRONJ, pausing antiresorptive therapy following extensive oral surgery should be considered until the surgical site heals with mature mucosal coverage.

The decision to initiate a treatment pause should be made in consultation with the prescribing clinician and incorporate consideration of the individual patient’s fracture risk (refer to Section 3.2 regarding the risk of rebound vertebral fracture following denosumab cessation). Patients at lower risk of fracture may safely undertake a brief treatment pause if undergoing an invasive dental procedure. There is no evidence to support the use of serum C-telopeptide (a bone turnover marker) to guide the timing of dental procedures in patients receiving antiresorptive therapy.1,3

Optimising oral hygiene and addressing active dental disease prior to initiating antiresorptive therapy may reduce the incidence of MRONJ.6 Good dental hygiene and care are recommended for all patients undergoing antiresorptive therapy for osteoporosis, particularly in those on long-term bisphosphonates. There is a strong association between periodontitis and MRONJ due to the increased likelihood of extractions, the direct effects of bacterial infection, and delayed healing due to inflammation.8 Improved dental awareness and prophylactic intervention have significantly reduced the incidence of MRONJ in patients receiving antiresorptive therapy for bone-related cancer complications.9

However, the benefits of antiresorptive therapy in preventing fragility fractures in patients with osteoporosis and malignancy-related skeletal events significantly outweigh rare adverse events such as MRONJ. Importantly, patients with established MRONJ can be satisfactorily managed and risk minimised. For such patients, referral to a centre with experience in managing and mitigating MRONJ is indicated.

More research to understand the pathophysiology of MRONJ is required, and future recommendations may change to reflect improved knowledge of this condition. However, it is important to be aware of the proven benefits of antiresorptive therapy in fracture risk reduction compared with the very small risk of serious adverse events, such as MRONJ.

Using current evidence, Figure 2 illustrates key decision points in determining the risk of MRONJ when undertaking a dental procedure and considerations to mitigate this risk.

Figure 2

Figure 2

Figure 2. Practical considerations for patients on antiresorptive therapy undergoing an invasive dental procedure.1,2,9

  1. Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw – 2014 update. J Oral Maxillofac Surg 2014;72(10):1938–56.
  2. Lo JC, O'Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010;68(2):243-53.
  3. Therapeutic Guidelines. Medication-related osteonecrosis of the jaw: Dental considerations. Therapeutic Guidelines Limited, 2022 [Accessed 7 December 2023]
  4. Malden N, Lopes V. An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab 2012;30(2):171–82.
  5. Dodson TB. The frequency of medication-related osteonecrosis of the jaw and its associated risk factors. Oral Maxillofac Surg Clin North Am 2015;27(4):509–16.
  6. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus. J Bone Miner Res 2015;30(1):3–23.
  7. Damm DD, Jones DM. Bisphosphonate-related osteonecrosis of the jaws: A potential alternative to drug holidays. Gen Dent 2013;61(5):33–38.
  8. Hellstein JW, Adler RA, Edwards B, et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: Executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 2011;142(11):1243–51.
  9. Tsao C, Darby I, Ebeling PR, et al. Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg 2013;71(8):1360–66.
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