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FACT SHEET: Medication-Related Osteonecrosis of the Jaw (also known as “MRONJ” and “osteonecrosis of the jaw associated with medications” [“ONJ”]; includes “antiresorptive agent-induced osteonecrosis of the jaw” [“ARONJ”] and its subset “bisphosphonate-related osteonecrosis of the jaw”1 [“BRONJ”; also known as “bisphosphonate-associated osteonecrosis of the jaw {“BON”, “BONJ”, and “BON of the jaw”} and bisphosphonate-induced osteonecrosis of the jaw” {“BIONJ”}], as well as antiangiogenic agent-related osteonecrosis of the jaw [“AARONJ”])

Date of Publication: July 7, 2016

Note:  This fact sheet concentrates on ARONJ (and particularly its subset BRONJ). AARONJ, a more recent and less common type of MRONJ, is periodically referenced for dental hygienist awareness.

Is the initiation of non-invasive dental hygiene procedures* contra-indicated?

  • Possibly, depending on severity of MRONJ and procedure being contemplated.

Is medical consult advised?  

  • Yes, for the patient/client taking a bisphosphonate (orally, by injection, or intravenously) or other antiresorptive bone drug (such as denosumab or romosozumab2 by subcutaneous injection) or antiangiogenic agent (such as, amongst many, bevacizumab intravenously or sunitinib, sorafenib, and cabozantinib orally), the patient/client’s physician should be consulted to determine medical diagnosis and types of drugs taken. Furthermore, the patient/client should be referred to a dentist pre-bisphosphonate use (particularly for high potency injectable/intravenous formulations) and before other antiresorptive/antiangiogenic agent use for consideration of selective teeth extraction (for nonrestorable or questionable teeth). Appropriate dental hygiene procedures, either non-invasive or invasive, should be informed by medical consultation.

Is the initiation of invasive dental hygiene procedures contra-indicated?**

  • Yes. This is an unstable (often progressive) oral health condition, which may affect appropriateness or safety (and be exacerbated by invasive procedures), and scaling of teeth and root planing, including curetting of surrounding tissue, are contraindicated until the patient/client is medically cleared. Bisphosphonate-related osteonecrosis of the jaw is a much more common complication of injected/intravenous (high dose) bisphosphonates, and it rarely occurs with oral administration.

Is medical consult advised? 

  • Yes; see above. Additionally, the consult should address whether antibiotic prophylaxis is required/advisable (see below).

Is medical clearance required? 

  • Yes, if MRONJ exists or is suspected.

Is antibiotic prophylaxis required?

  • No, for most low-risk patients/clients3 who are taking antiresorptive drugs (ARDs) and do not have MRONJ.4  
  • Possibly (although unlikely), for some high-risk patients/clients who are taking ARDs and do not have MRONJ. The use of an antimicrobial mouthwash and systemic antibiotics before and after the procedures may be a consideration.5  
  • Possibly, for patients/clients who have MRONJ.

Is postponing treatment advised?

  • Potentially. Ideally, all necessary invasive dental and dental hygiene treatments should be performed before administration of injectable/intravenous bisphosphonate drugs or other antiresorptive/antiangiogenic agents (similar to approach indicated for patients/clients undergoing head and neck radiation therapy). Cessation of at-risk medications prior to invasive procedures may or may not be indicated (less likely for invasive dental hygiene procedures as distinct from some invasive dental procedures), and should be informed by medical consultation. Informed by medical/dental consultation, routine scaling is usually indicated during bisphosphonate (or other antiresorptive/antiangiogenic) therapy to optimize oral health and reduce risk of MRONJ development. All procedures should be performed as atraumatically as possible, minimizing tissue damage, bleeding, and risk for post-procedural infection.

Oral management implications

  • In patients/clients who have received drug treatment for cancer or its sequelae, the dental hygienist should enquire if intravenous bisphosphonate therapy (e.g., etidronate, ibandronate, pamidronate, clodronate, or zoledronic acid)6 or other antiresorptive/antiangiogenic therapy was used. In particular, persons treated for breast cancer or prostate cancer may have received, or are receiving, bisphosphonate or other antiresorptive therapy (e.g., denosumab) for treatment-related (i.e., hormone ablation therapy7 induced) bone loss or for bone metastases.
  • Patients/clients at increased risk of MRONJ include those who smoke and those with diabetes mellitus, immunosuppressive drug use, cancer and any periodontal or other oral infection. A history of radiation to the jaw also elevates risk of osteonecrosis.
  • Prevention of MRONJ is very important so patients/clients can receive required cancer treatments. Caries should be eliminated, and oral health should be optimized during cancer and bisphosphonate (or other antiresorptive/antiangiogenic) treatments. During such treatments, patients/clients should practise good oral hygiene including daily brushing (often with high-strength fluoride toothpaste), flossing, and use of antibacterial oral rinses, and as well as undergo recommended dental/dental hygiene appointments, and denture fittings. Non-surgical periodontal therapy is strongly indicated for most patients/clients taking ARDs, and it should be carefully planned to regularly remove plaque and calculus. Particularly important for cancer patients/clients taking ARDs, this can reduce the number of bacteria-related pathologies in the oral cavity, thereby lowering the risk of developing MRONJ. 
  • In patients/clients who have been treated for osteoporosis or Paget’s disease8, the dental hygienist should enquire if oral bisphosphonate therapy (e.g., alendronate, risedronate, or ibandronate) or subcutaneous denosumab or subcutaneous romosozumab was used.
  • The dental hygienist should be alert for evidence of MRONJ ulcers during intraoral and extraoral examinations.
  • Other than palliative management, MRONJ is very difficult to treat. Surgical debridement, bone curettage, local irrigation with antibiotics, and hyperbaric oxygen therapy often prove disappointing. Antimicrobial rinses (e.g., chlorhexidine 0.12%) may provide benefit, and oral infection should be treated aggressively with systemic antibiotics. Cessation of bisphosphonate (or other antiresorptive/antiangiogenic) therapy may or may not be indicated, depending on the systemic condition.
  • The inability to manage MRONJ compromises oral care of affected patients/clients.

Oral manifestations

  • MRONJ is definitionally characterized by the following: 
    • current or previous treatment with antiresorptive or anti-angiogenic agents;
    • exposed bone or bone that can be probed through an intra-oral or extra-oral fistula(e) in the maxillofacial region that has persisted for more than eight weeks; and
    • no obvious metastatic disease to the jaws or history of radiation therapy to the jaws.
  • Due to bisphosphonate-induced reduction in bone remodeling, bone becomes brittle and unable to repair physiologic microfractures that occur with daily activity (e.g., common masticatory forces9). In patients/clients taking bisphosphonates or other antiresorptive agents, microdamage to the jaw is not repaired, setting the stage for oral osteonecrosis to occur. This often painful oral (or extraoral) condition may resemble an osteoradionecrosis lesion. 
  • Posterior sites of the jaw are more frequently affected than anterior sites, and the mandible is more often affected than the maxilla.
  • In the early stages of MRONJ, no radiographic changes can be seen. While patients/clients are usually asymptomatic, some persons develop severe pain because of necrotic bone becoming secondarily infected after exposure to oral bacteria and/or when surrounding soft tissues become inflamed.
  • The most common initial complaint is the sudden presence of oral discomfort and the presence of roughness, which may traumatize the oral soft tissues surrounding the area of necrotic bone.
  • Other early symptoms/signs may include:
    • odontalgia not explained by an odontogenic cause;
    • dull, aching bone pain in the body of the mandible, which may radiate to the temporomandibular joint region;
    • sinus pain;
    • poor gum healing;
    • loosening of teeth not explained by chronic periodontal disease; and 
    • periodontal/periapical fistula not associated with pulpal necrosis due to caries.
  • Early radiographic findings may include:
    • alveolar bone loss/resorption;
    • thickening or obscuring of the periodontal ligament on radiography; and 
    • inferior alveolar canal thickening.
  • The osteonecrosis is often progressive, leading to irregular ulceration of adjacent soft tissues and extensive areas of bone exposure and dehiscence. Osteonecrosis may appear as exposed yellow-white bone. When tissues are acutely infected, the patient/client may complain of swelling and drainage. Halitosis and trismus may be present. Severe pain or paresthesia (lack of sensory sensation) may indicate peripheral nerve compression.
  • In advanced MRONJ, exposed and necrotic bone extends beyond the region of alveolar bone (i.e., inferior border and ramus in the mandible, maxillary sinus, and zygoma in the maxilla), resulting in pathologic fracture, oral-cutaneous fistula formation, and establishment of oral antral-oral nasal communication.
  • Because bisphosphonates attach to the bone matrix, they may remain in the bone for several years. This prevents the jaw bones from undergoing the forming and reforming necessary for normal healing after trauma.10  
  • Spontaneous MRONJ, without predisposing dental treatment or other detectable trauma, most commonly appears in the mylohyoid ridge area of the mandible.

Related signs and symptoms

  • MRONJ is a relatively uncommon but serious side effect of treatment with osteoclast inhibitors (i.e., antiresorptive drugs) such as bisphosphonates (particularly high potency intravenous formulations), denosumab, and romosozumab. It can also be a complication of cancer therapy that targets angiogenesis. Up to 10% of patients/clients who take at-risk medications for cancer develop MRONJ, whereas risk drops to 1 in 10,000 for patients/clients whose drug indication is osteoporosis.
  • The majority of reported MRONJ lesions follow invasive dental procedures (such as extraction or implant placement), and they are less commonly associated with ill-fitting dentures or exostoses. However, MRONJ can also occur spontaneously in limited cases. Other factors that increase the risk of developing MRONJ include: age older than 65 years; diabetes; smoking; and periodontitis.11  
  • Intravenous bisphosphonates12 are used to treat various types of cancer, including primary bone lesions of multiple myeloma,13 as well as bony metastases of breast, prostate, lung and thyroid cancer. The drugs are given to patients/clients with cancer to control bone loss, pain, hypercalcemia14, and fracture risk resulting from skeletal lesions. Risk of MRONJ development increases with the amount and duration of bisphosphonate use, particularly when intravenous bisphosphonate therapy exceeds two years. 
  • Oral bisphosphonates are used to treat osteoporosis and Paget’s disease of the bone; they act by increasing bone density. They are less likely to cause MRONJ by virtue of their lower dose intensity compared with intravenous bisphosphonate formulations. 
  • MRONJ, often superimposed upon a cancer diagnosis, can have profound quality of life and therapeutic implications. The inability to manage MRONJ compromises oncologic and nutritional management of affected patients/clients.

References and sources of more detailed information

Date: March 30, 2016
Revised: May 21, 2021; July 7, 2023


1 In addition to bisphosphonates, other antiresorptive drugs (e.g., denosumab, a human monoclonal antibody that binds the cytokine RANKL, an essential factor initiating bone turnover; and romosozumab, a monoclonal antibody that is a sclerostin inhibitor) and antiangiogenic agents (e.g., bevacizumab, a monoclonal antibody, as well as tyrosine kinase inhibitors such as sunitinib, sorafenib, and cabozantinib) have been linked to mandibular and maxillary osteonecrosis. Sunitinib and sorafenib are typically used in the treatment of renal (kidney) cell carcinoma (with sorafenib also used in treatment of hepatocellular [liver] cancer), and cabozantinib is used to treat metastatic thyroid cancer. Bevacizumab is used to treat a wider range of advanced cancers, including renal, lung, colorectal, breast, and brain (glioblastoma).
2 Romosozumab has both antiresorptive and bone-formation properties.
3 Patients/clients at lower risk of developing MRONJ include those taking low potency oral bisphosphonate formulations rather than high potency intravenous formulations, those who are in a state of good oral health, and those who do not have cancer.
4 If a dental implant needs to be placed, clinicians should recommend the use of an antimicrobial mouthwash and systemic antibiotics before/after the procedure to reduce the risk of MRONJ.
5 For non-surgical endodontic treatment (as distinct from invasive dental hygiene procedures) in this patient/client population, antibiotic prophylaxis is a stronger consideration/recommendation.
6 Oral bisphosphonates (used primarily for treatment of osteoporosis to reduce risk of fractures) include alendronate and risedronate.
7 In men being treated for prostate cancer, hormone ablation therapy is commonly referred to as androgen deprivation therapy (ADT).
8 Paget’s disease is a chronic disorder that can result in enlarged, weakened, and misshapen bones. It is caused by excessive and disorganized bone remodeling.
9 The oral cavity is subjected to unique conditions of continual small traumas via mastication, sometimes exacerbated by poorly fitting dentures/prostheses or oral infection (e.g., apical abscesses and periodontitis).
10 In contrast to the bisphosphonates, denosumab — a more recently approved antiresorptive therapy for bone loss (U.S. Food and Drug Administration approved in 2011) — does not become embedded within bone tissue. It has a half-life of 26 days. Romosozumab (FDA-approved in 2019) has a half-life of 6–12 days.
11 Similar to ARONJ (which includes BRONJ), the major risk factors for onset of AARONJ are invasive dental procedures with manipulation of bone tissue, such as tooth extractions and periapical/periodontal surgery, in addition to local trauma, periodontal disease, and periapical infection. AARONJ, like ARONJ/BRONJ, can also occur spontaneously.
12 Bisphosphonates are synthetic analogues of inorganic pyrophosphate that have high affinity for calcium and which are also strong inhibitors of osteoclastic activity. Bisphosphonate compounds accumulate in the mineralized bone matrix and may remain in the body for years. As an alternative to oral bisphosphonate treatment, intravenous bisphosphonate therapy is sometimes used, but at lower dosages (and more intermittently) than is typical for cancer-related therapy.
13 Multiple myeloma is a systemic, malignant proliferation of plasma cells that cause destructive bone lesions.
14 Hypercalcemia may manifest as “moans” (gastrointestinal conditions including constipation, nausea, and abdominal pain), “stones” (kidney-related conditions including renal stones, flank pain, and urinary frequency), “groans” (psychological conditions including confusion, memory loss, and depression), and “bones” (bone-related conditions including bone pain, fractures, curvature of the spine, and loss of height).

* Includes oral hygiene instruction, fitting a mouth guard, taking an impression, etc.
** Ontario Regulation 501/07 made under the Dental Hygiene Act, 1991. Invasive dental hygiene procedures are scaling teeth and root planing, including curetting surrounding tissue.