What Is Osteonecrosis of the Jaw?
Osteonecrosis of the jaw (ONJ) is a condition in which a section of jawbone loses its blood supply, dies, and becomes exposed through the overlying gum tissue. The exposed bone fails to heal, often persisting for 8 weeks or longer. The condition primarily affects the jaw because the jawbones have a higher rate of bone turnover than other bones in the body and are in constant contact with the bacteria-rich environment of the mouth.
The current accepted term is medication-related osteonecrosis of the jaw (MRONJ), which was adopted by the American Association of Oral and Maxillofacial Surgeons (AAOMS) in 2014 to reflect the growing list of medications linked to the condition. Earlier names included bisphosphonate-related osteonecrosis of the jaw (BRONJ).
For a diagnosis of MRONJ, all three of the following criteria must be present: the patient has current or previous treatment with an antiresorptive or antiangiogenic medication, exposed bone or bone that can be probed through an opening in the gum tissue has been present for more than 8 weeks, and there is no history of radiation therapy to the jaw.
Stages of MRONJ
MRONJ is classified into stages based on the severity of signs and symptoms. Staging guides treatment decisions.
- At risk: No exposed bone. The patient is taking or has taken an associated medication but has no clinical evidence of disease.
- Stage 0: No exposed bone, but the patient has nonspecific symptoms such as jaw pain, loose teeth, or a sinus tract (drainage pathway) that may suggest early bone involvement.
- Stage 1: Exposed or necrotic (dead) bone is present, but there is no pain or sign of infection.
- Stage 2: Exposed bone with evidence of infection, including pain, redness, swelling, or pus. This is the most commonly diagnosed stage.
- Stage 3: Exposed bone with infection that extends beyond the immediate area. May include pathologic fracture, extraoral fistula (a drainage tract through the skin), or bone loss extending to the lower border of the jaw or sinus floor.
What Medications Cause MRONJ?
MRONJ is associated with several classes of medications that affect bone metabolism or blood vessel formation. The risk varies significantly based on the drug, its dose, how it is administered, and how long it has been used.
Bisphosphonates
Bisphosphonates are the most commonly implicated medications. They work by slowing the natural process of bone breakdown (resorption), which helps maintain or increase bone density.
- Oral bisphosphonates for osteoporosis: alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva). The risk of MRONJ with oral bisphosphonates is low, estimated at 0.01% to 0.1%.
- Intravenous bisphosphonates for cancer: zoledronic acid (Zometa), pamidronate (Aredia). These are given at much higher doses to cancer patients with bone metastases, and the MRONJ risk is significantly higher, estimated at 1% to 15% depending on duration of use and other risk factors.
Other Medications Linked to MRONJ
- Denosumab (Prolia for osteoporosis, Xgeva for cancer): A different type of antiresorptive that also increases MRONJ risk. Unlike bisphosphonates, denosumab does not accumulate in bone, so its effects diminish after the drug is stopped.
- Antiangiogenic drugs: Medications that block new blood vessel formation, such as bevacizumab (Avastin) and sunitinib (Sutent). These are used in cancer treatment and have been linked to MRONJ, sometimes in combination with bisphosphonates.
- Romosozumab (Evenity): A newer osteoporosis medication that has been associated with rare cases of ONJ in post-marketing reports.
Dental Triggers and Risk Factors
Most cases of MRONJ are triggered by a dental procedure that disrupts the bone, most commonly a tooth extraction. The bone's ability to heal after the extraction is impaired by the medication, leading to exposed, non-healing bone.
- Tooth extractions account for 50% to 60% of MRONJ cases
- Dental implant placement and other bone surgery
- Ill-fitting dentures that create chronic pressure sores on the gum tissue over bone
- Periodontal (gum) disease with bone involvement
- Spontaneous cases (no identifiable dental trigger) account for roughly 25% to 30% of cases
Signs and Symptoms of MRONJ
MRONJ can develop gradually, and early symptoms may be subtle. Knowing what to watch for can lead to earlier diagnosis and better treatment outcomes.
Early Warning Signs
- A tooth extraction socket that is not healing as expected after 8 weeks or more
- Exposed white or yellowish bone visible through an opening in the gum tissue
- Pain or aching in the jaw that does not have another obvious cause
- Numbness, tingling, or heaviness in the jaw
- Loosening of teeth in an area without obvious gum disease
- Swelling, redness, or pus around an area of exposed bone
Advanced Symptoms
As the condition progresses, symptoms become more pronounced and can significantly affect quality of life.
- Persistent infection around the exposed bone, sometimes requiring repeated courses of antibiotics
- A fistula (abnormal drainage pathway) through the gum tissue or through the skin of the face or neck
- Pathologic fracture of the jaw (a fracture through weakened, dead bone)
- Difficulty eating and speaking due to pain and infection
- Chronic foul taste or odor in the mouth
Treatment and Management
Treatment for MRONJ depends on the stage of the disease and the patient's overall health. The goals are to control infection, minimize the progression of bone death, and improve quality of life. In some cases, complete resolution is achievable, while in others, the focus is on managing the condition long-term.
Conservative (Nonsurgical) Treatment
For Stage 0 through Stage 2, conservative management is often the first-line approach.
- Antimicrobial mouth rinses (typically chlorhexidine 0.12%) used daily to reduce bacterial load around the exposed bone
- Antibiotic therapy to control active infection, often with penicillin-based or clindamycin antibiotics
- Pain management with appropriate medications
- Gentle removal of loose bone fragments (superficial debridement) without disturbing healthy attached bone
- Regular follow-up visits to monitor the size of the exposed area and watch for signs of progression
Surgical Treatment
For Stage 3 disease or cases that do not respond to conservative treatment, surgical intervention may be necessary. Surgery involves removing the dead (necrotic) bone until healthy, bleeding bone margins are reached (a procedure called sequestrectomy or marginal resection). In severe cases, a larger segment of jawbone may need to be removed (segmental resection) and reconstructed with a bone graft or reconstruction plate.
Newer approaches combining surgery with adjunctive therapies like PRF (platelet-rich fibrin), low-level laser therapy, and pentoxifylline/tocopherol (a drug-vitamin combination that improves blood flow to bone) have shown promising results in improving healing outcomes.
Drug Holiday Considerations
The question of whether to temporarily stop the offending medication (a drug holiday) before dental procedures is controversial and must be decided on a case-by-case basis with the prescribing physician. For oral bisphosphonates taken for less than 4 years, the risk of MRONJ is very low and a drug holiday may not be necessary. For patients on IV bisphosphonates for cancer, the oncologist must weigh the risk of disease progression against the MRONJ risk.
Denosumab has a more favorable profile for drug holidays because it does not accumulate in bone. However, stopping denosumab can lead to a rapid rebound in bone loss, so the decision must be made carefully with the prescribing physician.
Cost of MRONJ Treatment
The cost of MRONJ treatment varies widely based on severity and the type of treatment required. These are general estimates and actual costs depend on your location, provider, and insurance. Always confirm costs with your provider before proceeding.
Conservative management (office visits, antibiotics, and antimicrobial rinses) may cost $200 to $1,000 over several months. Surgical treatment ranges from $2,000 to $5,000 for minor debridement to $15,000 to $50,000 or more for major jaw resection and reconstruction.
Insurance Coverage
Because MRONJ is a medical condition caused by prescribed medications, treatment is typically covered under medical insurance rather than dental insurance. Surgical procedures, hospital stays, and prescription medications are generally covered as medically necessary. However, coverage details and out-of-pocket costs vary by plan, so verify your benefits before treatment.
When to See a Specialist About MRONJ
If you are taking any of the medications listed above and notice any changes in your mouth, prompt evaluation by a specialist can make a significant difference in outcomes.
Seek Evaluation If You Notice
- Exposed bone in your mouth that persists for more than 2 weeks after a dental procedure
- Jaw pain, swelling, or a feeling of heaviness in the jaw that does not resolve
- A tooth extraction site that is not healing normally
- Pus or drainage from the gums, especially in an area where dental work was recently performed
- Loose teeth without an obvious cause like gum disease or trauma
- Any new numbness or tingling in the jaw or chin area
Preventive Steps Before Starting At-Risk Medications
The most effective way to reduce MRONJ risk is to have a thorough dental evaluation and complete any necessary invasive dental work before starting bisphosphonates, denosumab, or antiangiogenic medications. This includes extracting teeth that cannot be saved, treating active infections, and ensuring dentures fit properly. A 2-to-3 week healing period after dental procedures is recommended before beginning the medication.
Find an Oral Surgeon Experienced With MRONJ
If you have been diagnosed with MRONJ or are at risk, seek care from an oral and maxillofacial surgeon experienced in managing this condition. Academic medical centers and hospital-based oral surgery departments typically have the most experience with complex MRONJ cases.
Your oncologist, rheumatologist, or primary care doctor can provide referrals. When contacting a surgeon's office, ask specifically about their experience treating MRONJ and whether they coordinate care with the physician managing your bone medication.
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