Red flag raised on Fosamax


Two recent reports have linked the osteoporosis drug alendronate (Fosamax) with rare but serious side effects.

In a letter to the New England Journal of Medicine published Jan. 1, a Food and Drug Administration official reported that since Fosamax was first marketed in 1995, 23 cases of esophageal cancer in patients taking the drug -- including eight deaths -- have been reported to the agency. And a USC study published in the January issue of the Journal of the American Dental Assn. reported that nine patients who were taking Fosamax suffered osteonecrosis of the jaw -- a bone-killing infection -- after having teeth extracted at USC dental clinics.

The number of cases in these reports is too small to determine the extent of risk for someone taking the drug, but doctors and dentists are likely to take more precautions with patients taking or considering taking Fosamax or similar drugs, say Dr. Robert Rude, a professor of medicine at USC, and Parish Sedghizadeh, the dentist who led the USC study.


And though concern is warranted, the risk can be managed, they say.


Who takes Fosamax or related drugs?

An estimated 30 million Americans take Fosamax or some other oral bisphosphonate: ibandronate (Boniva), risedronate (Actonel) and Reclast (zoledronic acid). These drugs have dominated the osteoporosis market based on their effectiveness at slowing bone loss, their convenience (available in pill forms) and the movement away from hormone replacement therapy.

A typical patient is a postmenopausal woman with bone density T-scores of negative 2.5 or lower (the definition for osteoporosis). Men also experience bone loss with age and are prescribed oral bisphosphonates.


What is the cancer risk?

Dr. Aurelia Nattiv, director of the Santa Monica-UCLA Osteoporosis Center, says that the true prevalence of esophageal cancer in individuals taking Fosamax cannot be determined yet.

“Further study is warranted -- with a large population base -- to determine if esophageal cancer in those taking Fosamax [and other oral bisphosphonates] is higher than in the general population,” she says, where the prevalence of esophageal cancer is 5 per 100,000. She advises caution until such data are available.


Can the cancer risk be minimized?

One of the more common side effects of oral bisphosphonates is irritation of the esophagus, which patients may experience as mild indigestion or more problematic pain, Rude says. That’s why people are advised to take their pill first thing in the morning on an empty stomach with a full glass of water and stay upright for at least a half-hour after that.

It’s a long way from heartburn to cancer, and yet Rude says that anything that inflames the esophagus -- including acid reflux -- raises the risk for Barrett’s esophagus, a change in the lining of the esophagus. And Barrett’s raises the risk for esophageal cancer. Rude says doctors should discuss the risk with all their patients, even though the cancer is rare. Oral bisphosphonates should be avoided in people with Barrett’s esophagus, Nattiv says.


What is the risk of jaw deterioration?

Sedghizadeh, now director of the USC dentistry school’s Center for Biofilms, says he and his colleagues had been seeing many more patients with osteonecrosis of the jaw, an extremely rare condition, in the last two years. In this condition, poor healing, infection or both blocks the nutrient supply to the jawbone and it dies. “With advanced disease, patients may lose a section of their jaw,” he says.

Suspecting oral bisphosphonates, the USC researchers mined their electronic medical records. Osteonecrosis of the jaw was seen in 4% of people taking Fosamax who had tooth extractions. No cases were seen in people not taking the drug.

The study was small -- just 208 patients, of whom nine developed osteonecrosis of the jaw -- but it’s a step toward finding a link, Sedghizadeh says. Since 30 other dental schools in North America use the same electronic medical records system, it should be possible to quickly expand the numbers, he says.


Can the risk of osteonecrosis be minimized?

USC dental clinics have changed protocols as a result of their findings. “We do more conservative procedures if we can,” Sedghizadeh says, such as a root canal to save the tooth instead of an extraction. But if the tooth must be pulled, patients use an antifungal and antimicrobial rinse and are more carefully followed. “It’s wound management,” Sedghizadeh says. “The bone is exposed and because of the drug, it’s susceptible to infection.” The American Dental Assn. has guidelines similar to USC’s.

Rude says doctors prescribing bisphosphonates should caution their patients about the potential risks of dental work while on the medication. He suggests patients get their dental work done before starting bisphosphonate treatment.


How can patients weigh the risks and benefits?

The benefits of treating osteoporosis are clear. One in 2 women over age 50 will break a bone in her lifetime and some 2 million fractures per year are related to osteoporosis, according to the National Osteoporosis Foundation. “That’s a pretty big risk for not addressing the issue,” Rude says.

But if the recent reports hold true, doctors may shy away from prescribing bisphosphonates as much as they now do for women who have osteopenia -- a less severe low bone density (T-score between negative 1 and negative 2.5).

“Nobody wants to be bent over when they’re older,” Nattiv says. “A lot of patients want to do whatever it takes to prevent that from happening.” She thinks that bisphosphonates and other medications may be overprescribed in patients with osteopenia -- and that more care is needed. “Doctors need to individualize treatment based on a patient’s risk factors, bone density values and potential adverse effects of the treatment,” she says.