A new US study found that even short term use of oral bisphosphonates like Fosomax (alendronate), commonly used to treat osteoporosis, may leave the jaw vulnerable to devastating necrosis (death of bone tissue).

The study was the work of principal investigator Dr Parish Sedghizadeh, assistant professor of clinical dentistry with the University of Southern California (USC) School of Dentistry, and colleagues, and is published in the 1 January 2009 issue of the Journal of the American Dental Association (JADA).

Previous studies had already suggested that patients taking bisphosphonates like Fosomax orally were at higher risk of developing osteonecrosis (death of bone tissue) of the jaw, but this study shows the side effect may be more common than had previously been suggested.

For the study, Sedghizadeh and colleagues looked at the electronic medical records of patients attending USC's School of Dentistry to find out who had ever used alendronate (Fosomax) and of those who was also having treatment for osteonecrosis of the jaw.

After controlling for referral bias, they found that of 208 patients with a history of alendronate (Fosomax) use, nine were being treated for osteonecrosis of the jaw. This is about 4 per cent of the patient population (or 1 in 23 patients).

The researchers concluded that this was "the first large institutional study in the United States with respect to the epidemiology of ONJ [osteonecrosis of the jaw] and oral bisphosphonate use".

They wrote that more studies were now needed to "help delineate more clearly the relationship between oral BP [bisphosphonate] use and ONJ".

In a separate press statement, Sedghizadeh commented on the contrast between this study's findings and the drug maker's assertions that bisphosphonate-related ONJ risk is only noticeable with intravenous use of the drugs:

"We've been told that the risk with oral bisphosphonates is negligible, but four percent is not negligible," said Sedghizadeh.

The USC statement said that most doctors who have prescribed bisphosphonates have not told their patients about the potential risks, even from short term use, due to the drug taking a long time to leave bone tissue (after stopping use it takes 10 years for the drug's level to halve).

The statement related how Lydia Macwilliams of Los Angeles said no one had told her about the risk of Fosomax. She was on it for three years before she became Sedghizadeh's patient of at the USC School of Dentistry. She said she was "surprised" that her doctor who prescribed Fosomax "didn't tell me about any possible problems with my teeth."

Macwilliams was especially at risk for because she was to have three teeth removed, said Sedghizadeh, explaining that bisphosphonate use makes mouth and jaw tissue bacterial infection more aggressive because it sticks more firmly to the jaw. The type of infection that occurs here is often resistant to many antibiotic treatments because it is a "biofilm bacterial process" where the germs live in a slimy protective matrix. Procedures like tooth extractions that directly expose the jaw bone, raise the danger under these circumstances.

Two of Macwilliams' three tooth extractions had difficulty healing due to infection. But she said luckily they healed slowly but completely because of the treatment and USC's rigorous oral hygiene routine for patients with a history of bisphosphonate use.

"It took about a year to heal," said Macwilliams, "but it's doing just fine now."

Sedghizadeh said he hoped more studies would confirm their findings so that more doctors and dentists are encouraged to talk to their patients about the oral health risks of these widely used drugs.

"Here at the School of Dentistry we're getting two or three new patients a week that have bisphosphonate-related ONJ," said Sedghizadeh.

"I know we're not the only ones seeing it," he added.

Today, osteoporosis affects about 10 million people in the US and according to a 2007 report from IMS Health, Fosomax is the most widely prescribed oral bisphosphonate and ranks as the 21st most prescribed drug on the market since 2006.

"Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: An institutional inquiry."
Parish P. Sedghizadeh, Kyle Stanley, Matthew Caligiuri, Shawn Hofkes, Brad Lowry, and Charles F. Shuler.
J Am Dent Assoc 1 January 2009, Volume 140, Issue 1, pages 61-66.

Click here for Abstract.

Sources: Journal abstract, University of Southern California.

Written by: Catharine Paddock, PhD