Osteoporosis Drug Fosamax Linked to Two Serious Side Effects

Osteoporosis is a disease of progressive bone loss, which increases the risk of fracture. This debilitating disease affects nearly 10 million Americans and contributes to 1.5 million bone fractures each year. There is currently no cure for osteoporosis, but medications have proven effective in treating the disease. Bisphosphonates, such as Fosamax, are usually one of the first-line treatments for most osteoporosis patients, reducing the risk of fracture by increasing bone density. They are also used to slow bone “turnover” in people who have certain types of bone cancer. Unfortunately, these medications also carry a risk for serious side effects. Use of bisphosphonates has been associated with unusual bone fractures, severe bone, joint and muscle pain and an increased risk of atrial fibriliation (AF), a type of abnormal heart rhythm. Now, researchers have discovered that two other serious side effects associated with bisphosphonates may be more frequent than previously suggested: osteonecrosis of the jaw and esophogeal tumors.

The risk of developing osteonecrosis of the jaw (ONJ) was previously reported to be “negligible,” but when Dr. Parish Sedghizadeh, an assistant professor of clinical dentistry at the University of Southern California School of Dentistry in Los Angeles, saw the number of cases in his clinic rise from one a year to one to four a week, he decided to investigate the phenomenon and report his findings. ONJ, sometimes called jawbone death, occurs when bone in the jaw fails to heal after a minor trauma, resulting in pain, soft-tissue swelling and infection, loosening of teeth, drainage, and exposed bone. “This is more frequent than everybody would like to think it is,” said Sedghizadeh.

For the study, which appears in the January issue of the Journal of the American Dental Association, Sedghizadeh and colleagues searched the USC’s School of Dentistry’s electronic medical records looking for patients who had used alendronate (Fosamax), and among those, patients who were also having treatment for ONJ. The team found that nine of 208 patients taking Fosamax had active ONJ, a prevalence of about 4 percent. All nine patients had undergone some kind of dental procedure, such as having a tooth extracted. Among 4,384 tooth extraction patients not on Fosamax, none developed ONJ. “We’ve been told that the risk with oral bisphosphonates is negligible, but four percent is not negligible,” Sedghizadeh said in a press statement.

It is unclear why bisphosphonates have this effect only on jaw bones, but Sedghizadeh speculates that the drugs might make it easier for bacteria to adhere to exposed bone after a tooth extraction. The USC School of Dentistry now screens every patient for bisphosphonate use. “We put patients on anti-microbial, anti-fungal rinse one week pre-operatively or post-operatively,” Sedghizadeh said. “If they have been on bisphosphonates six months or a year or longer, then we have a prevention protocol which has been very, very effective.”

A USC statement said that most doctors who have prescribed bisphosphonates have not told their patients about the potential risks, even from short term use. The statement related the story of Lydia Macwilliams of Los Angeles who was on Fosamax for three years before she became Sedghizadeh’s patient. She said she was “surprised” that the doctor who prescribed Fosamax didn’t tell her “about any possible problems” with her teeth. 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.

According to a statement released by Merck and Co., makers of Fosamax, Sedghizadeh’s study “contains methodological flaws and scientific limitations, making it unreliable as a source for valid scientific conclusions regarding the prevalence of ONJ in patients taking alendronate.” The statement also said that in controlled trials involving more than 17,000 patients, there have been no reports of ONJ.

More worrisome news for the millions of Americans currently taking Fosamax comes from the Food and Drug Administration. A brief report, written by Diane Wysowski of the FDA’s division of drug risk assessment and published in the New England Journal of Medicine, reveals that since the initial marketing of Fosamax in October 1995, the agency has received 23 reports in which patients developed esophageal tumors. Of these patients, eight have died so far, Wysowski reported.

In her report, Wysowski also urges that physicians “avoid prescribing oral bisphosphonates to patients with Barrett’s esophagus (often a precursor to esophageal cancer),” and concludes that “studies should include oral bisphosphonates as possible risk factors for esophageal cancer.” However, Wysowski acknowledged to ABCNews.com that “it is uncertain if the drugs can cause esophageal cancer.” She says that, however, “use of oral bisphosphonates has been linked to inflammation of the esophagus, also called esophagitis, primarily in patients who have not used them according to directions.” Esophagitis, which is an inflammation of the lining of the tube carrying food to the stomach, is already know to be a side effect of the drugs, which is why patients are instructed to remain upright for at least a half hour after taking them.

While some experts believe this report warrants a change in doctors’ habits of prescribing oral bisphosphonates, most say that the incidence of esophageal cancer in patients taking Fosamax may not be high enough to be concerned about. “In this case we don’t know how real this risk is. We need more data,” said Dr. Ethel Siris, director of the Toni Stabile Osteoporosis Center at Columbia University Medical Center. Siris is also fearful that this will be another case where the media reports on this inconclusive link between Fosamax and esophageal cancer will scare patients into giving up on a medication that is protecting them from the effects of osteoporosis. “Every time the media report on some new possible side effect, a lot of patients for whom the benefits of therapy greatly outweigh a true risk stop their medication.” Siris said. “We need to inform, but we do not need to create major distress based on incomplete data.”

Merck and Co. also denied the possible link between Fosamax and esophageal cancer, citing data from controlled clinical trials. Fosamax is the most widely prescribed oral bisphosphonates and ranks as the 21st most prescribed drug in the United States since 2006.