How do I Manage a Patient with Biphosphonate-related Osteonecrosis of the Jaw (BRONJ)

May 16, 2016

Biphosphonate-related osteonecrosis of the jaw (BRONJ)

  • Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been defined as exposed jaw bone for longer than 8 weeks in a patient who has received current or previous treatment with a bisphosphonate medication without evidence of local malignancy or prior radiotherapy to the site.
  • Bisphosphonates inhibit bone resorption by decreasing the action of osteoclasts, which are cells that break down bone. Also, bisphosphonates inhibit the increased osteoclastic activity and skeletal calcium release into the bloodstream induced by various stimulatory factors released by tumours.
  • It is expected that bisphosphonates will arrest bone loss and increase bone density, decreasing the risk of pathologic fracture resulting from progressive bone loss.
  • Osteonecrosis is progressive and may lead to extensive areas of bony exposure and dehiscence.

Presentation

Population

  • The patient group at greatest risk includes those who are on intravenously administered bisphosphonates for malignancies, such as multiple myeloma, and disease, such as breast or prostate cancer, that have metastasized to the bones.
  • Patients who are on oral bisphosphonates for osteopenia or osteoporosis may also be at risk at a much lower rate.
  • BRONJ can present as early as 1 year after initiation of intravenous drugs and 3 years after the start of oral drugs, depending on the patient's medical and dental comorbidities and other medications and on whether surgical trauma of the jaw has occurred.
  • BRONJ is more likely to occur in the mandible than the maxilla.

Signs

  • Loosening of teeth that can't be explained by chronic periodontal disease.
  • Periapical/periodontal fistula that is not associated with pulpal necrosis due to caries.
  • Pain is often related to the sharpness of the exposed bone irritating adjacent soft tissues, with the exposed bone itself being asymptomatic.
  • With secondary infection, there may be pain, swelling, difficulty chewing, bad taste and fetid odor.
  • Paresthesia, altered neurosensory functions and extraoral fistulas are late signs indicating the extent of disease progression, as with osteomyelitis.

Symptoms

  • The most common initial complaint is the sudden presence of intraoral discomfort and the presence of roughness that may progress to traumatize the oral soft tissues surrounding the area of necrotic bone. Initially, patients may be asymptomatic or have nonspecific jaw pain (i.e., no tooth-related causes can be identified).
  • Exposed, nonhealing bone (e.g., large tori) occurring after invasive dental surgery (e.g., extraction, periodontal or endodontic surgery) or trauma.
  • Purulent discharge without bone exposure after extraction or other oral surgery.

Investigation

  1. Obtain a detailed history:
    • Ask about the patient's bisphosphonate therapy. Is it intravenous or oral? What is the name of the drug? When did the therapy start, and for how long is it prescribed? Bisphosphonates have a very long half-life, and the risk of BRONJ increases with the duration of therapy.
    • Ask about the reason for the bisphosphonate therapy. If the medication is administered intravenously, it is important to ascertain the stability and severity of the malignancy to determine the patient's overall prognosis. Widespread disease that has metastasized to the bones usually connotes palliative care with or without additional chemotherapy. However, maintenance bisphosphonate therapy after treatment for multiple myeloma may not indicate such a guarded prognosis. Oral bisphosphonates for the treatment of osteoporosis would indicate a lower risk of non-healing.
    • Ask about any history of radiation therapy, and do a thorough review of systems of the malignant disease. This should include diagnosis, date, treatment and degree of follow-up with the oncologist.
    • Ask about any concurrent illnesses, conditions and medications used. Comorbidities, such as renal failure, diabetes mellitus, smoking, steroid use and maintenance chemotherapy, have been shown to increase the risk of BRONJ.
  2. Perform a complete extraoral and intraoral examination (examine all oral mucosal surfaces):
    Extraoral exam
    • Complete a thorough head and neck lymph node examination.
    • Look for any extraoral draining sinuses or scars.
    • Intraoral exam
  3. Examine the exposed bone and look at the surrounding tissues for signs of inflammation. If there is no bone exposure, look closely for small pinpoint areas of purulent drainage with a periodontal probe. Radiographic examination
  4. Perform a radiographic examination, including periapical, panoramic and, occasionally, occlusal radiographs (to see the location of sequestra). In early stages, the architecture of the bony trabeculae are destroyed, and radiolucent areas result. In addition, there can be alveolar bone loss or resorption not attributable to chronic periodontal disease, thickening or obscuring of the periodontal ligament and inferior alveolar canal narrowing. The radiographic features vary from none when just the cortical bone is involved in the exposure to features characteristic of acute osteomyelitis to chronic osteomyelitis.
  5. Advanced imaging may be recommended by a specialist to observe the extent of destruction and location and number of sequestra. Limited field of view cone beam computed tomography may be useful.

Diagnosis

The diagnosis of BRONJ is based on the medical and dental history of each patient and on the observation of clinical signs and symptoms.

Differential Diagnosis

May include osteomyelitis, which can occur in the absence of bisphosphonates and for which an etiology is often not found.

Treatment

Common Initial Treatments

  • Minor debridement, including minor sequestrectomy with elimination of sharp bone edges and sharp tooth surfaces if these are symptomatic.
  • Advise the patient to maintain local hygiene in areas of exposed bone (chlorhexidine gluconate 0.12%, 20 mL for 30 seconds 3 times daily).
  • For bacteremia, prescribe systemic antibiotics to control bacterial infection. The recommended antibiotic is penicillin V potassium, 500 mg (1 tablet 4 times daily for 7 days). Alternatively, you can prescribe amoxicillin, 500 mg (1 tablet 3 times daily for 7 days) or clindamycin, 150 mg or 300 mg (1 capsule 4 times daily for 7 days). The prescriptions listed above represent a minimum dose. The addition of 250 mg of metronidazole 3 times daily may be indicated if anaerobic infection is suspected. In refractory patients or in severe cases, prescribe amoxicillin/clavulanate potassium (Augmentin®), 500 mg (1 tablet 3 times a day). It is important NOT to prescribe systemic antibiotic therapy if there is no infection (most commonly evidenced by pain) to prevent the development of resistant bacterial strains.
  • Conservative, noninvasive sequestrectomy performed periodically over the long term, with systemic antibiotics prescribed for flare-ups of infection and pain, may be the optimal therapy.
  • For pain control prescribe analgesics (acetaminophen, 325 mg, taken 6 times daily). The maximum cumulative dose recommended for acetaminophen is 4 g in 24 hours. Patients will require opioid analgesia if pain is severe (oxycodone 5 mg with acetaminophen 325 mg [Percocet®]; 1 tablet every 4–6 times daily).
  • Mobile segments of bony sequestrum should be removed without exposing uninvolved bone. Necrotic bone cannot be resorbed by the osteoclasts (bisphosphonates inhibit osteoclastic activity) and will inhibit healing, so it's important to remove it.
  • The extraction of symptomatic teeth within exposed, necrotic bone also should be considered (it is unlikely that the extraction will exacerbate the established necrotic process).

Advice

  • All dental and periodontal procedures should be completed prior to the administration of bisphosphonates.
  • Patients should be educated on how to maintain good oral hygiene.
  • For patients undergoing bisphosphonate therapy, there is insufficient evidence to suggest successful placement of dental implants.

Suggested Resources

  1. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone and Mineral Res. 2007;22(10):1479-91.
  2. Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F, et al. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol.2008;35(7):1391-7.
  3. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw--2009 update. J Oral Maxillofac Surg. 2009;67(5 Suppl):2-12.

THE AUTHOR

 

 

Dr. Auluck is a clinician research fellow with the British Columbia Oral Cancer Prevention Program, Vancouver, BC.

 

Acknowledgement: I am grateful to Dr. Michele Williams for her help in creating and revising this article. Michele was an oral medicine specialist and clinical professor in dentistry at the University of British Columbia and an oral medicine leader at the BC Oral Cancer Prevention Program. She passed away in January 2015.

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