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Myeloma Minute: Special Advisory On Osteonecrosis Of The Jaws
05.30.04

Osteonecrosis of the jaws is a condition whereby there is loss or destruction of the bone underneath the teeth. This loss of bone appears to be caused by a combination of poor blood supply and impaired bone remodeling or healing.

Two recent reports have raised the possibility that osteonecrosis (also referred to as avascular necrosis) of the jaws could be an unexpected complication of bisphosphonate therapy (1, 2). Language addressing this concern has recently been added to the FDA-approved labeling for Aredia® and Zometa®.

Excerpt from “Post Marketing Experience” section of the
FDA-approved labeling for
Aredia® and Zometa®.

Cases of osteonecrosis (primarily of the jaws) have been reported since market introduction.

Osteonecrosis of the jaws has other well documented multiple risk factors. It is not possible to determine if these events are related to Aredia, Zometa or other bisphosphonates, to concomitant drugs or other therapies (e.g., chemotherapy, radiotherapy, corticosteroid), to patient's underlying disease, or to other comorbid risk factors (e.g., anemia, infection, preexisting oral disease).

The implications of these new findings are quite diverse. Further studies are definitely required to clarify many aspects. Nevertheless, a number of basic recommendations can be made:

  1. Bisphosphonates remain a critical element of care to reduce bone destruction in myeloma patients. Patients should continue to use bisphosphonates as recommended by their physicians.

  2. Be alert and aware that bisphosphonate use can be associated with jaw or dental problems, including pain, bone loss, and poor healing. Problems are more likely with longer periods of bisphosphonate use (e.g. several years) and possibly more potent bisphosphonates (e.g. Zometa®).

  3. Be proactive if dental problems exist and/or if any dental or jaw interventions are planned. If feasible, dental evaluation and treatment prior to starting bisphosphonates would seem to be a good idea. Once bisphosphonate therapy has begun, dental extractions, placement of dental implants and/or any other major interventions must be undertaken with due caution. Although there are no conclusive data available at this point, stopping Aredia® or Zometa® for 2-4 months prior to a procedure can be considered. This may help even in the absence of any planned surgery.

  4. Conservative measures such as antibiotic treatment and mouth rinses (e.g. Peridex or hydrogen peroxide) would seem to be quite helpful and safe. Intravenous antibiotics may be required for more severe or acute secondary infections. Ongoing use of an antibiotic such as penicillin has also been recommended if problems persist. Major surgical intervention should be avoided if at all possible.

  5. If the osteonecrosis is severe, potential co-factors or co-triggering factors should be stopped or avoided. If at all feasible, steroids such as prednisone or dexamethasone should be discontinued or reduced. There should be no irradiation therapy involving the head/neck.

Further investigations are required to assess more accurately the causes and treatment for the osteonecrosis. For now, awareness is key. Proceed with caution whenever dental or jaw problems emerge. Seek a second opinion if recommendations for management are unclear or uncertain. If you are currently taking bisphosphonates, consider baseline dental evaluation as well as periodic check-ups and review. If you have further questions, you may want to contact the IMF hotline at 800-452-2873 or email TheIMF@myeloma.org.

References

  1. Marx RE. Pamidromate (Aredia) and Zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J. Oral Maxillofac Surg. 61: 1115-1118; 2003.
  2. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 62: 527-534; 2004.



 related articles
Salvatore L. Ruggiero, DMD, MD Talks About Osteonecrosis of the Jaw (ONJ)
AAOMS Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws
American Society for Bone and Mineral Research (ASBMR) Issues report on ONJ risk
Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone.
FDA Oncologic Drugs Advisory Committee Meeting On Aredia And Zometa
Journal of the National Cancer Institute
Mayo Clinic Consensus Statement for the Use of Bisphosphonates in Multiple Myeloma
NEJM Publishes Correspondence On ONJ
OSTEONECROSIS OF THE JAWS IN MYELOMA:
Time Dependent Correlation with AREDIA and ZOMETA Use
Osteonecrosis Web Survey Results Presented At 2004 ASH Meeting
Special Advisory: Osteonecrosis of the Jaw
Use of Bisphosphonates in Multiple Myeloma: IMWG Response to Mayo Clinic Consensus Statement
Wall Street Journal Article On Osteonecrosis Of The Jaws
Aredia/Zometa and osteonecrosis of the jaws
Food and Drug Administration (FDA) MedWatch Postings About Osteonecrosis Of The Jaw


You might also be interested in:

Salvatore L. Ruggiero, DMD, MD Talks About Osteonecrosis of the Jaw (ONJ)

AAOMS Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws
Bisphosphonate-related osteonecrosis of the jaw (BRON) adversely affects the quality of life and produces significant morbidity in afflicted patients. Oral and maxillofacial surgeons have been responsible for counseling, managing, and treating a majority of these patients. The strategies set forth in this position paper were developed by a Task Force appointed by the American Association of Oral and Maxillofacial Surgeons (AAOMS).

American Society for Bone and Mineral Research (ASBMR) Issues report on ONJ risk
The American Society for Bone and Mineral Research (ASBMR) announced today the publication of a report that examines the link between a class of widely prescribed drugs used to strengthen bones and the disorder known as Osteonecrosis of the Jaw (ONJ). The report, authored by an international, multidisciplinary task force, was convened by the ASBMR to look at the possible association between ONJ, a deterioration of the jawbone, and a class of drugs known as bisphosphonates, which in recent years have been linked to the condition.

Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone.
An article from Cancer, in which researchers from the College of Dental Medicine, Nova Southeastern University in Fort Lauderdale, Florida present results of a study of 17 patients with cancer with bone metastases and 1 patient with osteopenia who received treatment with bisphosphonates and who subsequently developed osteonecrosis of the mandible and/or maxilla.

FDA Oncologic Drugs Advisory Committee Meeting On Aredia And Zometa
The committee discussed safety concerns, specifically osteonecrosis of the jaw (ONJ), associated with two bisphosphonates, NDA 21-223, ZOMETA® (zoledronic acid) Injection and AREDIA®, NDA 20-036 (pamidronate disodium for injection), both from Novartis Pharmaceuticals Corp.

Journal of the National Cancer Institute
Intravenous Bisphosphonate Therapy andInflammatory Conditions or Surgery of the Jaw: A Population-Based Analysis

Mayo Clinic Consensus Statement for the Use of Bisphosphonates in Multiple Myeloma
A multidisciplinary panel consisting of hematologists, dental specialists, and nurses specializing in the treatment of myeloma reviewed available data concerning the use of bisphosphonates. Guidelines for the use of bisphosphonates in MM were developed. This link is to the full article.

NEJM Publishes Correspondence On ONJ
The New England Journal of Medicine published correspondence from Drs. Durie, Richardson, Duck and Tarassoff on Osteonecrosis of the Jaw in its July 7, 2005 issue (N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102.)

OSTEONECROSIS OF THE JAWS IN MYELOMA:
Time Dependent Correlation with AREDIA and ZOMETA Use
At the 2004 Annual Meeting of the American Society of Hematology, Dr. Durie presented the results of the web-based survey that many of you were kind enough to help us with. We are encouraged by the discussions that have ensued and are hopeful that this will help us raise awareness about this very serious issue and facilitate timely action.

Osteonecrosis Web Survey Results Presented At 2004 ASH Meeting

Special Advisory: Osteonecrosis of the Jaw

Use of Bisphosphonates in Multiple Myeloma: IMWG Response to Mayo Clinic Consensus Statement
Published in the Mayo Clinic Proceedings 2007;82:516-522

Wall Street Journal Article On Osteonecrosis Of The Jaws
You can also read a Wall Street Journal article that discusses this issue and includes a quote from Dr. Durie

Aredia/Zometa and osteonecrosis of the jaws

Food and Drug Administration (FDA) MedWatch Postings About Osteonecrosis Of The Jaw
FDA and Novartis notified healthcare professionals of revisions the PRECAUTIONS and ADVERSE REACTIONS sections of labeling for Aredia and Zometa