Evelyn Pringle October 12, 2006
An article in the October 2006, "Current Opinions in Orthopaedics," by Dr Catherine Van Poznak, assistant professor of internal medicine at the University of Michigan Medical School, reports that 10% of cancer patients taking Fosamax, or other drugs known as bisphosphonates, have developed osteonecrosis of the jaw (ONJ).
An April 4, 2006 United Press International poll found that more than 2,400 patients who were taking the injected form of bisphosphonate had suffered bone damage to their jaws since 2001. Other bisphosphonates include Aredia, Zometa, Actonel and Bondronat.
ONJ, also called jawbone death, is a disfiguring, debilitating and non-reversible condition marked by exposed and deteriorating jawbone. The disease kills tissue within the jawbone causing pain, swelling, loose teeth, and inflammation. The condition may take years to develop and usually becomes known following a dental extraction, implant or other procedure when the wound does not heal properly.
Fosamax is the world's top selling bisphosphonate, and is prescribed to prevent osteoporosis, but experts now say that the ONJ side effect directly contradicts its intended purpose.
In the name of profits, critics say Fosamax was over promoted by the pharmaceutical giant Merck, as a life-long treatment for osteoporosis with individuals, especially women, too young to be at risk of developing bone problems.
"The pharmaceutical industry has every desire that a patient who starts on a bisphosphonate would take it for life," said Dr Robert Gagel, of the Anderson Cancer Center in Houston, to Gina Kolata of the New York Times. "The bone community, of which I am a member," he noted, "has always been a bit suspicious of that viewpoint."
The injuries showing up now, critics say, are the result the massive marketing of a class of drug to relatively young persons, who in the majority of cases, did not need them to begin with.
In addition to the tens of millions of dollars spent on public advertising campaigns, Merck relied heavily on industry backed front groups to promote Fosamax and the National Osteoporosis Foundation (NOF), proved most helpful in first promoting the disease in younger women, followed by the promotion of the "cure."
Merck is a major donor to this organization and is listed in its Annual Report, albeit minus the amount of money that the company donates each and every year.
NOF serves as a major funnel when it comes to promotional campaigns. In 2004 alone, the group's Annual Report listed revenues of more than $6 million.
The NOF's web site promotes Fosamax but does not warn about ONJ. Consumer who look to these types of organizations for unbiased information about pharmaceutical products are unaware of their financial support from the drug companies that manufacture the drugs they promote.
Critics say that needs to change now that front groups are playing a much larger role in the drug approval process. For instance, when a drug is up for review before the FDA's Drug Safety and Risk Management Advisory Committee, members of these groups sign up to testify to praise the safety and efficacy of a drug without disclosing their financial support from the sponsoring drug company.
Wake Forest University health sciences researcher, Dr Curt Furberg, sat on the FDA Advisory Committee for 2 terms and says he frequently heard testimony from members of these groups.
Unlike other speakers, he told the Washington Post on February 7, 2006, spokesmen for the groups do not identify their potential conflicts of interest at the Committee meetings and often sound like they represent drug companies.
Typically, he told the Post, the groups will present a patient to testify about how a drug with emerging safety problems changed his life for the better.
"I don't doubt that," Dr Furberg said. "But it is interesting that there was no widow at the hearing who says, 'My husband took these drugs and he had a heart attack and died and it changed my life.'
"It's not balanced," he says. "My sense it that one point of view is missing - the bad news."
Merck's marketing tactics for Fosamax have been extremely successful. The company recorded sales of $3.2 billion from Fosamax in 2005, when more 22 million prescriptions were written in the US alone, according to the pharmaceutical tracking firm IMS Health.
These high sales figures peaked during the same year that the FDA asked Merck to warn patients about the risk of developing ONJ.
But the warnings apparently had little impact. On May 15, 2006, Business Week Online, reported that the "global osteoporosis market is at $6 billion in annual sales today, and with a rapidly graying population, it's growing 25% a year."
There is no treatment for ONJ and therefore, according to Dr Van Poznak, the focus of medical professionals must be on preventing the condition or alleviating the symptoms.
"We don't know how to predict who will develop ONJ or who is most at risk," she said.
Critics say Merck knew about ONJ and failed to warn medical professionals and consumers for years. "Merck became aware of this problem in early 2001 when the first reports starting coming in," says Attorney Cory Rosenbaum, a partner in the Rosenbaum Faria law firm.
"They waited until September 2004 to issue a warning to health care professionals, and they didn't post any warnings on their labels until 2005," he said in a September 24, 2006 press release.
Dr Gregory Lutcavage, an oral and facial reconstructive surgeon with Eastern Carolina Oral and Maxillofacial Surgery Associates, told the Goldsboro News Argus on July 24, 2006, that the warning process has been very frustrating, especially witnessing patients suffering and drug companies delaying going public about the risks and ramification.
"One drug company did not come out with the update to their circular until about three or four months ago," he said. "We were seeing this three years ago.
"I said to my partners several years ago," Dr Lucavage told News Argus, "this is a class action suit waiting to happen."
And the inevitable event he mentioned is indeed happening. One of several class action lawsuits was filed in Florida in April 2006, accusing Merck of failing to warn medial professionals and patients about the risk of ONJ associated with Fosamax.
"We're getting people calling every day," Attorney, Gary Wilson, in Minneapolis told the LA Times on July 11, 2006. Mr Wilson said his firm will probably file about 20 cases in the coming months.
Florida attorney, Timothy O'Brien, told the Times that he has filed 30 Fosamax lawsuits and expects to file at least 300 more over the next few months involving Fosamax and Actonel.
The lawsuits claim that Merck aggressively marketed Fosamax as safe and effective, despite knowing about the drug's potential to cause a disease in which a patient's jawbone rots and dies.
Although experts agree that there is no cure for ONJ, for the purpose of prevention, the American Dental Association recommends that patients be sure to inform their dentist if they are taking a bisphosphonate before any dental work is performed.
In a warning to professionals, the American Association of Endodontists, a group representative of dental care providers who specialize in root canal surgery, issued a position statement in March 2006 that said, "until further information becomes available, the AAE recommends that all patients taking bisphosphonates be considered at some risk."
"While bisphosphonates support the buildup of bone in areas weakened by disease," the AAE told its members, "as a side effect of treatment, patients may experience the opposite in their lower and upper jawbones."
Fosamax is a relatively new drug, FDA approved in 1995, so the long-term risk of ONJ is unknown, experts say. Unreported cases may be higher than expected, according to Diane Wysowski of the FDA's Office of Drug Safety, because doctors may attribute the pain caused by ONJ to osteoporosis.
Kenneth Hargreaves, chair of the endodontics department at the University of Texas, noted the rapidly increasing cases in the April 3, 2006 LA Times. "We've uncovered about 1,000 patients in the past six to nine months alone," he said, "so the magnitude of the problem is just starting to be recognized."
However, because only between 1% and 10% of adverse events are ever reported to the FDA, experts say the number of cases of ONJ is bound to be much higher.
Dr Salvatore Ruggiero, an oral surgeon at Long Island Jewish Medical Center, was one of the first medical professionals to notice the rise in ONJ patients in 2001. "We never saw this before in the jaw" except in patients who had received radiation therapy to that part of the face, Dr Ruggiero told USA Today on May 13, 2005. "It just never existed."
On April 14, 2006, he told the Wall Street Journal that of the 155 cases of ONJ that he has come across, 22 involve patients who were taking Fosamax and other oral bisphosphonates and some of the patients took Fosamax for seven or eight years. "With the oral drugs like Fosamax, exposure time is the key," Dr Ruggiero told the WSJ.
He is concerned about the millions of women taking bisphosphonates to treat osteoporosis long term. "Risks increase," he explained, "the longer you're on the drugs, and it can take years for the complication to manifest itself."
"Even though the chances of getting this are small," he told the Times on April 3, 2006, "considering there are 23 million women taking this drug, we could be talking about a significant number of people."
Experts agree that stopping the use of Fosamax will not necessarily be helpful for persons who have already been on the drug for several years because the build-up of Fosamax in the body is cumulative and the drug can remain in the bones indefinitely.
There are signs that medical professionals are becoming more aware of ONJ. A study quoted in the September 14, 2006, Star Ledger, by health care marketing research group, Manhattan Research, found that in the first half of 2006, an increasing number of doctors were visiting brand name drug web sites seeking information about dosages and side effects of drugs, and the top 10 sites visited included Fosamax.
Experts recommend that anyone who has been on Fosamax for three or more years should get a thorough examination of the jaw from an oral surgeon before having any extractions or implant work done.