Death of Parts of the Jaw Bone With Osteoporosis Drugs Such As Alendronate (FOSAMAX)

A recent review of medical literature shows there have been 368 reported cases of osteonecrosis of the jaw (death of jawbone tissue) linked to drugs commonly used to treat osteoporosis.

According to the review, published in the May 16 Annals of Internal Medicine, 94 percent of the patients who developed osteonecrosis of the jaw were those with cancers such as multiple myeloma, as well as patients with cancers that have spread to bone who are receiving intravenous (IV) bisphosphonate.

Bisphosphonates are most commonly used for osteoporosis — alendronate (FOSAMAX) is the best-known member of this family. These drugs are also Food and Drug Administration (FDA)-approved for conditions such as hypercalcemia of malignancy (elevated levels of calcium in the blood), Paget’s bone disease, and the spread of cancer to the bone (metastases) in certain cases. See table for the list of FDA-approved bisphosphonates currently in the U.S. market.

Bones — including jawbones — are living tissue, normally in a constant state of breakdown and rebuilding. But bisphosphonates are powerful inhibitors of bone breakdown, thereby disturbing the delicate balance between breakdown and rebuilding. In fact, the researchers in this most recent study suggest that bisphosphonate-associated osteonecrosis of the jaw is the result of this marked suppression of bone breakdown.  

The typical signs and symptoms of osteonecrosis of the jaw may include pain, swelling or infection of the gums, loosening of the teeth, poor healing of the gums, numbness or a feeling of heaviness in the jaw, drainage and exposed bone. Patients with the least serious form of this condition may not show any symptoms, but in the most serious cases, some patients may require the removal of sections of the jaw.  

In this study, the lower jaw (mandible) was more commonly affected than the upper jaw (maxilla). The ratio is two cases in the lower jaw to one case in the upper jaw. The majority of reported cases, 60 percent, were preceded by a dental surgical procedure.

The authors of the Annals of Internal Medicine review were academic dentists from the Brigham and Women’s Hospital, Harvard School of Dental Medicine, the University of Iowa College of Dentistry and The Ohio State University College of Dentistry. The researchers reported that they received no outside funding for their work.

Worst Pills, Best Pills reports on bone death

The August 2005 Worst Pills, Best Pills News reported that the FDA had advised dentists and cancer physicians on May 5, 2005, that the package inserts for injectable bisphosphate drugs zoledronic acid (ZOMETA) and pamidronate (AREDIA) had been revised to warn about the possibility of osteonecrosis of the jaw with the use of these drugs. At this time the FDA advised:

• That patients receive a dental examination prior to beginning treatment with the IV bisphosphonates pamidronate and zoledronic acid.

• That patients avoid invasive dental procedures while receiving bisphosphonate treatment with pamidronate and zoledronic acid.

• That for patients who develop osteonecrosis of the jaw while on bisphosphonate treatment with pamidronate and zoledronic acid, dental surgery may make the condition worse.

The August 2005 newsletter also contained a review of research conducted by staff from the Division of Oral and Maxillofacial Surgery of the Long Island Jewish Medical Center. The group had published a report on cases of osteonecrosis of the jaw observed in their oral surgery clinic in the May 2004 Journal of Oral and Maxillofacial Surgery.

These researchers reviewed the medical records of all patients who were seen in their clinic between February 2001 and November 2003 who had both a diagnosis of jaw infection and a history of chronic bisphosphonate treatment. Of the 63 identified cases, 56 had received an injectable bisphosphonate such as zoledronic acid or pamidronate for at least one year. Seven patients had been on chronic oral bisphosphonate therapy with alendronate or risedronate.

The question of major concern for the millions of women being prescribed an oral bisphosphonate such as alendronate, risedronate, or ibandronate is their risk of osteonecrosis of the jaw. On this question, the Annals of Internal Medicine reviewers said:

The degree of risk for osteonecrosis [of the jaw] in patients taking oral bisphosphonates, such as alendronate, for osteoporosis is uncertain and warrants careful monitoring.

What You Can Do

You should inform your dentist, in addition to your physician and pharmacist, about all drugs that you are taking. Patients taking a bisphosphonate should carefully monitor themselves for any sign of jaw problems resembling those described in this article.