Bisphosphonate-Related Osteonecrosis of the Jaw

Updated: Mar 08, 2017
  • Author: Remy H Blanchaert, Jr, DDS, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
  • Print
Overview

Background

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a condition found in patients who have received intravenous and oral forms of bisphosphonate therapy for various bone-related conditions. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) manifests as exposed, nonvital bone involving the maxillofacial structures. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is thought to be caused by trauma to dentoalveolar structures that have a limited capacity for bone healing due to the effects of bisphosphonate therapy. See the image below.

Exposed, necrotic bone in the left anterior maxill Exposed, necrotic bone in the left anterior maxilla.

The 2014 update of a position paper from the American Association of Oral and Maxillofacial Surgeons recommended changing the name of bisphosphonate-related osteonecrosis of the jaw (BRONJ) to medication-related osteonecrosis of the jaw (MRONJ), owing to the increased number of maxillary and mandibular osteonecrosis cases that have been linked to other antiresorptive (denosumab) or antiangiogenic treatments. [1]

See Cancer Chemotherapy: Keys to Diagnosing Common Toxicities, a Critical Images slideshow, to help recognize some of the more common complications of chemotherapy.

Next:

History of the Procedure

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is relatively new to the medical and dental literature. See Surgical therapy.

Previous
Next:

Epidemiology

Frequency

The true incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has yet to be determined. The estimated incidence, according to a package insert in a special mailing by Merck Pharmaceuticals, is 0.7 per 100,000 persons per year. [2, 3] Most reports and experts disagree with this figure. Several recent studies of patients with multiple myeloma and patients with breast cancer who received intravenous aminobisphosphonate therapy for metastatic bone lesions demonstrated 6-11% of the patients developed bisphosphonate-related osteonecrosis of the jaw (BRONJ). The incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been strongly correlated with the aminobisphosphonates pamidronate (Aredia) and zoledronic acid (Zometa) and is even higher in patients who have had recent dental extractions. [4, 5]

Kahn et al evaluated the association of osteonecrosis of the jaw with bisphosphonate use. Data that links the incidence of osteonecrosis of the jaw and its etiologic factors are limited, and the incidence of osteonecrosis of the jaw in the general population (ie, those not taking bisphosphonates) is unknown. Evidence is insufficient to confirm a causal link between low-dose bisphosphonate use in osteoporosis with osteonecrosis of the jaw. Osteonecrosis of the jaw is primarily associated with high-dose bisphosphonate use in cancer patients. [6]

Previous
Next:

Etiology

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a condition in which bones of the maxillofacial skeleton, in particular the tooth-bearing areas, become necrotic and exposed to the oral cavity. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can be spontaneous, commonly appearing in the mylohyoid ridge area. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may also be caused by trauma, such as a tooth extraction or dental surgery. Exposed alveolar bone, which may be painful, is noted on examination.

A retrospective study by Choi et al indicated that previous dental extraction is the greatest risk factor for bisphosphonate-related osteonecrosis of the jaw. The study involved 133 patients with multiple myeloma who had undergone bisphosphonate therapy, with bisphosphonate-related osteonecrosis of the jaw found in nine of them. Among these patients, 6 had a history of extraction, with the investigators suggesting that extraction-related jaw damage is the “most potent trigger” for bisphosphonate-related osteonecrosis of the jaw. [7]

Previous
Next:

Pathophysiology

Bisphosphonates are believed to bind to osteoclasts and interfere with bone remodeling. They interfere with the cholesterol biosynthesis pathway by inhibition of farnesyl diphosphate synthase. In time, the cytoskeleton of the osteoclast becomes dysfunctional and the ruffled border needed for bone resorption is unable to form. Aminobisphosphonates have also been shown to have antiangiogenic properties. The overall effect is a decrease in bone turnover and inhibition of the bone’s reparative ability. [8, 9] Injury to the bone in these patients via tooth extraction, dental surgery, or mechanical trauma is thought to initiate bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Previous
Next:

Presentation

Symptoms may include the following:

Physical findings may include the following:

  • Mandibular and or maxillary bone exposure
  • Pathologic fracture
  • Oral-cutaneous fistula
  • Clinical infection
Previous
Next:

Indications

Gross examination reveals a varied amount of exposed, nonvital bone of the maxilla, mandible, or both.

Previous
Next:

Relevant Anatomy

Please see the Medscape Reference article Facial Bone Anatomy.

Previous