Osteonecrosis of the Jaw and Fosamax Risks — 2009 Updates

Fosamax (generic name alendronate) is the most popular drug of a class of drugs called bisphosphonates that are used to treat a variety of conditions affecting the bones. Fosamax itself is primarily prescribed to combat osteoporosis, bone loss that makes the bones fragile, and osteopenia, a less severe thinning of the bones (full discussion of the differences at Spine Universe). With 190 million Fosamax prescriptions dispensed worldwide, it is important to know what the risks of taking Fosamax are and what negative side effects are associated with taking Fosamax long term.

Beginning in 2004, the drug company Novartis issued a warning of a link between intravenous bisphosphonates and osteonecrosis of the jaw. In 2005, that warning was broadened to include oral bisphosphonates like Fosamax. The medical community was initially divided on whether Fosamax and other oral bisphosphonates could cause osteonecrosis of the jaw (ONJ), but according to a 2009 Position Paper from the American Association of Oral and Maxillofacial Surgeons (AAOMS), the evidence is now relatively strong that some cases of ONJ are in fact due to oral doses of bisphosphonates.

What Are the Risks?

As just mentioned, the big concern in recent years has been with bisphosphonates causing osteonecrosis of the jaw (ONJ) or, literally, jaw death or jawbone death. ONJ is essentially a condition where bone in the jaw is exposed and refuses to heal for a long time. The American Association of Oral and Maxillofacial Surgeons considers a patient to have ONJ caused by bisphosphonates if all three of these criteria are met:

1. Current or previous treatment with a bisphosphonate.
2. Exposed bone in the maxillofacial region that has persisted for more than 8 weeks.
3. No history of radiation therapy to the jaws.

The caution, however, that there are other medical conditions that can be confused with ONJ from bisphosphonates. These "commonly misdiagnosed conditions can include, but are not limited to, alveolar osteitis, sinusitis,
gingivitis/periodontitis, caries, periapical pathologic findings, and temporomandibular joint disorders." So, as for any such condition, it's important to get a complete and valid diagnosis from a qualified physician.

The AAOMS considers that emerging studies "have established a firm foundation for a strong association between monthly IV bisphosphonate therapy and the development of BRONJ [bisphosphonate-related osteonecrosis of the jaw]." Note, however, that conclusion only concerns intravenous doses of bisphosphonates, usually used in cancer treatment, and does not include oral bisphosphonates used to treat osteoporosis.

Is Fosamax Dangerous?

Here's where things get more difficult. There are documented cases of ONJ being associated with treatment oral bisphosphonates. Note, however, that there is still not great evidence about how strong the cause and effect relationship is. Merck, the manufacturer of Fosamax (alendronate), has estimated that the incidence of ONJ related to alendronate is 0.7 cases per 100,000 patient years. In other words, you would expect that for every 143,000 patients taking Fosamax for a year, one patient would get ONJ because of taking Fosamax. A study of 13,000 Kaiser Permanente patients who were long-term users of Fosamax estimated 0.06% of patients, or one patient for every 1,700 on Fosamax, would get ONJ at some point. Studies in Germany and Australia found generally lower risks.

Patients have to balance these risks against the risk of breaking a bone — an elderly person who breaks a hip may never return to the active lifestyle he or she knew. So no patient should discontinue bisphosphonate therapy without consulting his or her medical team.

Safety Measures and Precautions

ONJ can happen spontaneously or after minor trauma, but most documented cases ONJ related to oral bisphosphonates were in patients who were

• long-term users
• had dental surgery

Given that, the AAOMS recommends the following:

• Before going on Fosamax, patients should have a complete dental exam and get any dental work done before beginning a course of treatment, provided other conditions allow.
• Patients who have been on Fosamax for three years or more, should consider a "drug holiday" for three months before and after oral surgery, provided that their condition allows such a holiday.
• Patients who are taking bisphosphonates and oral corticosteroids (e.g. prednisone) should also consider a three-month bisphosphonate holiday if possible, which may not be the case.

Disclaimer

The authors of the AAOMS 2009 Position Paper caution:

The Position Paper is informational in nature and is not intended to set any standards of care. AAOMS cautions all readers that the strategies described in the Position Paper are not intended as practice parameters or guidelines and might not be suitable for every, or any, purpose or application. This Position Paper cannot substitute for the individual judgment brought to each clinical situation by the patient’s oral and maxillofacial surgeon.

In short, the position paper is a summary of the state of knowledge at the time of the writing and suggests treatment courses, but leaves specific situations up to each physician in consultation with their patients. There are still many unknowns with respect to bisphosphonates and ONJ.