Jan. 2, 2009 -- After having teeth pulled, 4% of patients in a study who were taking Fosamax developed a dangerous condition called osteonecrosis of the jaw, USC researchers report. None of the tooth extraction patients not taking Fosamax developed osteonecrosis.
The condition, sometimes called jawbone death, occurs when bone in the jaw fails to heal after a minor trauma. It results in pain, swelling, infection, and exposed bone.
Merck says the study has numerous flaws. But study researchers Parish P. Sedghizadeh, DDS, and colleagues say Fosamax and other bisphosphonate drugs may be riskier than previously thought.
"Here at the USC School of Dentistry, we're getting two or three new patients a week that have bisphosphonate-related osteonecrosis of the jaw -- and I know we're not the only ones seeing it," Sedghizadeh says in a news release.
Just last month, an expert panel for the American Dental Association concluded that the risk of jaw osteonecrosis "apparently remains low" for people taking bisphosphonates. In addition to Fosamax, other oral bisphosphonate drugs include Zometa, Aredia, and Actonel, and Boniva.
Even so, it's not the first time questions have been raised about bisphosphonates and jawbone death. A 2005 paper in the Journal of the American Dental Association reviewed the risk, as did a 2005 study in the Journal of Endodontics and a 2006 editorial in the New England Journal of Medicine.
Injection versions of the drugs appear to carry a higher risk. The risk of osteonecrosis is generally thought to be quite low for oral bisphosphonates.
"We've been told that the risk with oral bisphosphonates is negligible, but 4% is not negligible," Sedghizadeh says.
The Fosamax label and the labels of other bisphosphonate drugs note that jaw osteonecrosis has been reported in patients taking bisphosphonates, including some patients taking the drugs for postmenopausal osteoporosis. But jaw osteonecrosis patient Lydia Macwilliams says nobody warned her during her three years of Fosamax use.
"My doctor who prescribed Fosamax didn't tell me about any possible problems with my teeth," Macwilliams, one of Sedghizadeh's patients, says in a USC news release.
In their study, Sedghizadeh and colleagues combed through their records and identified 208 patients who took Fosamax. Sixty-six of these patients had teeth extracted; nine of these patients developed jaw osteonecrosis -- four at the site of the extraction and five after denture-related ulceration.
Among 4,384 tooth extraction patients not on Fosamax, none developed jaw osteonecrosis.
However, patients who developed osteonecrosis had other factors, including chemotherapy, type 2 diabetes, high blood pressure, high cholesterol, and steroid therapy. Some of these conditions are risk factors for osteonecrosis.
Nevertheless, Sedghizadeh notes that USC now warns all dental patients taking Fosamax and other bisphosphonates that "you may be at risk of developing osteonecrosis (bone death) of the jaw, and certain dental treatments may increase that risk."
Merck notes in a statement that the Sedghizadeh study contains methodological flaws and that the findings cannot be used to reach "valid scientific conclusions regarding the prevalence of osteonecrosis of the jaw" in patients taking Fosamax.
"Data from randomized, prospective clinical trials are the gold standard and are more reliable than data from studies like the [Sedghizadeh study]," the statement reads. "In controlled clinical trials involving more than 17,000 patients, contributing as much as 10 years' data with [Fosamax], there have been no reports of osteonecrosis of the jaw. This includes approximately 3,000 osteoporosis patients taking [Fosamax] for three to five years and approximately 800 patients taking [Fosamax] for eight to 10 years."
Sedghizadeh and colleagues call for other institutions to go through their own records to establish whether patients on Fosamax and other bisphosphonates have a higher risk of jawbone death after dental procedures.
The Sedghizadeh study appears in the January issue of the Journal of the American Dental Association.