Osteonecrosis of the Jaw and Breast Cancer Treatment

July 9, 2013

Osteonecrosis of the Jaw and Breast Cancer Treatment

  1. William J. Gradishar, MDAU1223

Adjuvant zoledronic acid was associated with low incidence of ONJ and did not affect oral quality of life.

  1. William J. Gradishar, MDAU1223

The prior, industry-supported AZURE trial (N Engl J Med 2011 Oct 13; 365:1396) demonstrated that the bisphosphonate zoledronic acid (ZA), in combination with standard adjuvant systemic therapy, had no effect on disease-free survival in the overall study population of patients with stage II or III breast cancer, although it significantly reduced the risk for recurrence and death in the subset of postmenopausal patients. Bisphosphonate therapy has also been associated with osteonecrosis of the jaw (ONJ), characterized by exposed bone, most commonly in the mandible, as well as by loose teeth, draining fistulas, secondary infections, and localized pain.

Now, investigators have evaluated the incidence and impact of ONJ in 3360 women in the AZURE trial. Patients were randomized to receive standard adjuvant systemic therapy alone (controls) or with ZA (4 mg for 19 doses over 5 years). All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. In addition, 362 study participants completed the Oral Health Impact Profile–14 to assess oral quality of life (QoL) around the time they completed 5 years of the study.

During a median follow-up of 73.9 months, 33 possible cases of ONJ were reported, all in ZA-treated patients; 26 were confirmed as consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1%. Neither the prevalence nor severity of oral QoL differed significantly between ZA-treated patients and controls.


The incidence of osteonecrosis of the jaw was low in the AZURE study and other trials (e.g., Ann Oncol 2012; 23:1341), but ONJ can be debilitating. Medical treatments and surgical debridement are used with variable success. The quality-of-life analysis in a subset of AZURE study patients indicates no compromise in outcome, but, importantly, this small analysis does not compare the QoL in patients with ONJ versus those without the diagnosis of ONJ. The possibility of ONJ should be discussed with all patients receiving either zoledronic acid or denosumab as a component of breast cancer treatment.

Editor Disclosures at Time of Publication

  • Disclosures for William J. Gradishar, MD at time of publication Consultant / Advisory board Biologics, Inc.; Celgene; Myriad; Novartis Grant / research support Breast Cancer Research Fund Editorial boards Clinical Breast Cancer; Journal of Clinical Oncology; Oncology


Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.