Yourlawyer.com (Osteonecrosis of the Jaw (ONJ) News)

Dentists concerned about cases of decaying jaw bones

Tue, 19 Dec 2006 00:00:00 -0800

Dentists in Terre Haute are among those in the profession who are becoming more concerned about increasing cases of decaying jaw bones apparently linked to osteoporosis drugs such as Fosamax.

The technical name for dying jaw bone is osteonecrosis of the jaw , known as ONJ. Symptoms, which may take weeks or months to appear, include pain, loose teeth, exposed jaw bone in the mouth and drainage, according to the American Dental Association Web site.

The drugs being linked to the condition are known as bisphosphonates. They include Fosamax, Actonel and Boniva, which come in pill form, as well as other bone-strengthening medications given through IVs. The oral drugs are often prescribed for osteoporosis patients. The IV versions are more commonly prescribed for patients dealing with cancers that may attack their bones.

“This is a big topic with us right now,” said Terre Haute dentist Dr. Aaron Luttrell, president of the Western Indiana Dental Society.

The ADA is warning dentists to avoid “invasive dental procedures” in patients on IV bisphosphonates and is recommending a “conservative” approach to dental procedures for any patients using oral bisphosphonates. The organization also recommends anyone planning to begin taking bisphosphonate therapy have any dental procedures done before taking the drugs.

Some cases of ONJ have appeared after someone using bisphosphonates has had a tooth pulled or some other dental procedure, but other cases have appeared “spontaneously,” according to a recent article in Dental Economics.

“We’ve seen about five or six patients” with ONJ, said Dr. Michael Deady, a Terre Haute-based oral surgeon. All his patients were on oral bisphosphonates, mostly Fosamax, he said. Some of the cases appeared linked to previous dental procedures, others appeared “spontaneously,” he said.

“Experimental data is a little bit lacking,” on how exactly bisphosphonates are linked to ONJ, said Dr. Don-John Summerlin, a professor of oral and maxillofacial pathology at the IU Medical Center in Indianapolis. “There’s a lot we don’t know yet,” he said.

One prominent theory, however, holds that because bisphosphonates impede cells in the body that remove old bone tissue while allowing cells that add new bone tissue to continue to function as usual, a patient’s bones “become denser and denser,” Summerlin said.

And while this makes bones tougher to break, it may also make it more difficult for them to heal or naturally rebuild themselves, especially after a dental procedure such as a tooth extraction, according to James H. Foulkes, a Terre Haute dentist and former president of the Academy of General Dentistry.

Why the problem affects jaw bones and not so much other bones may be because of the “unique” quality of that bone, according to Luttrell. The jaw bone breaks down and rebuilds itself more than other bones, he said.

“As far as the dental profession is concerned, there is a definite link [between ONJ and bisphosphonates] and there is no question about that,” Foulkes said. “Our controversy is how to deal with it.”

Lawyers are seizing on the data linking Fosamax a best selling osteoporosis drug and other bisphosphonates to ONJ and are advertising to represent ONJ patients who have taken bisphosphonate drugs, whether orally or through an IV. Locally, at least one firm is advertising for such clients.

As of May of this year, Merck and Co. Inc., the pharmaceutical company that makes Fosamax, reported 15 ONJ-related lawsuits had been filed against it, according to CNNMoney.com. In one case, “seven figures” are being sought in damages, CNN reported.

Of the more than 20 million Americans using oral bisphosphonates, the number of reported cases of ONJ seems still to be in the hundreds or few thousands. As of May 2005, just 800 cases had been reported to the FDA, according to Medscape Medical News.

ONJ is “extremely rare,” said Merck spokesman Skip Irvine. “Merck estimates the worldwide cumulative reporting rate … is less than one [case] in 100,000 patient treatment years,” he said.

Merck did a 10-year clinical trial of Fosamax before winning FDA approval in 1995. In that trial, involving 17,000 patients, no cases of ONJ were reported, Irvine said.

But this does not have area dentists sleeping any easier.

“I don’t know how many people really know what’s going on,” Deady said when asked about the low number of reported cases. “If I’ve seen six cases. It’s pretty scary,” he said.

“We’re afraid it may be the tip of the iceberg,” Foulkes said. The fact that the population is aging and more and more people are using bisphosphonates to not only treat but sometimes to try and prevent osteoporosis, means it’s possible more cases may be just over the horizon, he said.

“Intuitively,” IU’s Summerlin said, he believes the risk of ONJ is increasing, but, he adds, he has no data to say that “factually.”

“I would say ‘don’t panic,’” Summerlin said. And, in the case of cancer patients using IV bisphosphonates, he believes the risk of some bone loss is probably greatly outweighed by the benefits of the drugs.

“I don’t think anyone can produce absolute data saying how significant the problem is. I think it is a minority of the patients that have this problem,” but even a small percentage of the millions using bisphosphonates “could be a large number of people,” he said.

BONE-DENSITY DRUGS CAN KILL JAWS

Wed, 05 Jul 2006 00:00:00 -0700

Across the country, dentists have begun asking patients a pointed question before deciding on treatment:

Do you take a bone-building medication such as Fosamax?

These widely used drugs, called bisphosphonates, have recently been linked to a rare side effect that causes parts of the jawbone to deteriorate and die.

The bulk of the 3,000 published cases of jaw osteonecrosis meaning "dead bone" have occurred after dental procedures, mostly in cancer patients on intravenous bisphosphonates. But the problem has also developed out of the blue in otherwise healthy people taking bisphosphonate pills to boost bone density.

"If you're going to be on this drug, make sure you really need it," said Alan Meltzer, a Voorhees, Pa., periodontist.

Since 2003, when the first 36 cases were described in a medical journal, the Food and Drug Administration has required all bisphosphonate labels to include a precaution, hundreds of lawsuits have been filed against drug makers, and expert dental groups have issued advice for managing the tens of millions of people now on the drugs.

Still, there are no good treatments for what specialists have begun calling "bisphossy jaw." Nor is it clear that quitting the drugs reduces the risk because bisphosphonates can persist for years in the bone. The incidence, variation and progression of the jaw disease are also unclear.

"What we have seen and heard from health-care givers is that more and more people are showing up with milder forms, so the true incidence rate now is anybody's guess," said John R. Kalmar, an Ohio State University oral pathologist and author of a May review article in Annals of Internal Medicine. "We're telling people to be cautious."

The advent of bisphosphonates about a decade ago was a boon for people whose bones were riddled by cancer treatment, osteoporosis or a disorder called Paget's disease. Since 1995, 191 million prescriptions have been filled for oral Fosamax, Actonel and Boniva, plus millions more for intravenous Zometa, Aredia and generic Pamidronate.

For healthy people seeking to boost bone density, the risk of jawbone death appears to be remote; the estimate from Fosamax maker Merck & Co. is less than one out of 100,000 patients per year.

On the other hand, many postmenopausal women taking the pills may not really need them. Low bone density does not automatically progress to osteoporosis, and even when it does, a debilitating fracture is not inevitable.

Crystal Baxter, a former University of Pittsburgh professor of prosthodontics who now practices in Arizona, said she is very leery of doing elective dental implants in patients who have taken oral bisphosphonates.

"The scary thing," she said, "is that these drugs are being marketed to practically every aging woman in the world."

It has become clear through trial and terrible error that trying to fix bisphossy jaw with invasive dental procedures only makes it worse.

Ruth Ann Dutton, 66, for example, went to her regular dentist after a shard of bone spontaneously broke through her gum. Although she had taken Aredia and Zometa for advanced breast cancer, the splintering of her jaw was not triggered by a dental procedure.

"He did a root canal, but it never got better," she said.

A year ago, she was referred to Meltzer, who prescribed antibiotics and antiseptic rinses.

"Right now, it's doing pretty decent," she said. "The hole is mostly closed up."

Barry Levin, an Elkins Park periodontist, said one of his elderly patients has not been as fortunate. She quit Fosamax after tooth extractions led to a diagnosis of osteonecrosis, but bone grafted to her damaged jaw has not healed properly.

"It's been a nightmare," Levin said.

Bisphosphonates build bone by tamping down the normal turnover of bone cells. Kalmar and other experts speculate that osteonecrosis develops when the drugs are too effective at suppressing bone regeneration.

Why hasn't the problem shown up after, say, hip replacement surgery? Experts say the jaws are particularly vulnerable because cells turn over faster there than in other bones. Jaws are also constantly exposed to minor trauma from chewing, and to bacteria from the mouth.

Another Merck Drug Is Under Legal Attack

Wed, 05 Jul 2006 00:00:00 -0700

As Merck & Co. defends itself against a deluge of litigation involving its pain reliever Vioxx, the pharmaceutical giant also is fielding the first of what could be another wave of lawsuits involving Fosamax, its second-biggest seller.

The emerging litigation targeting the osteoporosis drug, still in its early stages, illustrates how quickly lawyers can organize themselves and assemble prospective plaintiffs after reports of adverse drug effects even when those problems appear to be relatively rare.

Reports in the last few years have linked Fosamax and similar drugs, known as bisphosphonates, to a serious side effect in which the jawbone partially crumbles and dies. Researchers agree that the incidence of this problem, called osteonecrosis, is quite small.

But trial lawyers are advertising on the Internet and in newspapers for patients who have taken Fosamax or the other drugs, and they are finding potential clients.

"We're getting people calling every day," said a lawyer in Minneapolis.

This attorney said his firm had enlisted medical and dental experts to thoroughly review the records of potential plaintiffs who have taken one of the drugs, adding that he would probably file about 20 cases in the coming months.

"It's too early to tell whether these cases will be successful," said a San Francisco defense lawyer who represents drug makers. "But as soon as there is publicity about any kind of possible problems with a medication, the plaintiffs get geared up."

Merck spokesman Skip Irvine says that Fosamax is safe and effective in treating osteoporosis and that the company "will vigorously defend ourselves against these suits."

"Osteonecrosis is very rare and not well understood," Irvine said, noting that in controlled clinical trials involving more than 17,000 patients, there had been no reports of the malady.

Ethel Siris, a professor of medicine at Columbia University College of Physicians and Surgeons who has also consulted for Merck, said new research studies were underway to understand what triggers the onset of this jaw problem.

In the meantime, she said, she tells her osteoporosis patients that the benefits of the bisphosphonate drugs greatly outweigh their risks.

Fosamax is probably the best-known brand-name drug for preventing hip fractures and deteriorating bones that often destroy the quality of life for older women.

Millions of women have taken the drug since it was first marketed in 1995. Fosamax generated $3.2 billion in sales last year, outstripping the other major oral osteoporosis remedies, Actonel, produced by Procter & Gamble Co. and Sanofi-Aventis, and Boniva, made by Roche Laboratories.

Scientific reports of jaw problems have generated a wave of newspaper articles that in turn have sown panic among users of the drugs.

Many have turned to their doctors or dentists for advice on how to prevent jaw decay and the best treatment options. Last month, the American Dental Assn. released a set of treatment guidelines.

Some users have turned to lawyers as well.

One Florida attorney, has filed 30 damage suits involving Fosamax and expects to file at least 300 more over the next few months involving that drug as well as Actonel.

One of his clients is Rochelle Kenig, who took Fosamax for nine years until she woke up one morning in 2004 with "excruciating, excruciating" pain in her jaw.

"This has been a living nightmare, and nobody knew anything about it," the Boynton Beach, Fla., resident recalled.

Kenig, 67, said she underwent multiple courses of potent antibiotics, repeated surgeries, treatment in a hyperbaric chamber and acupuncture. Yet the pain and bone deterioration continued, she said.

She finally got some relief in April after a new group of surgeons replaced part of her jaw with a titanium plate secured with metal hinges. But, Kenig said, the decay and infections had caused a permanent loss of sensation on the right side of her lip and face, as well as the loss of several teeth.

Merck's Irvine declined to comment on Kenig's claim, adding, "We don't want to argue cases in the newspapers."

The attorney in Florida has asked a Florida federal court to certify a class action for the Fosamax suits. He estimated that he and other lawyers had filed a total of 50 lawsuits with possibly hundreds more to come.

Two bisphosphonates produced by Novartis Pharmaceuticals Corp., Aredia and Zometa, are given intravenously in treating some forms of bone cancer. The drugs have also been targeted in lawsuits from about 100 claimants to date.

Some experts see the relatively slow pace of lawsuit filings against Fosamax and its related drugs compared with the flood of Vioxx suits that followed Merck's decision to pull the drug in 2004 as evidence that plaintiffs' lawyers have become more cautious in recent years.

Litigation involving silicone gel breast implants and Bayer's cholesterol-lowering drug Baycol proved less successful than lawyers initially expected, said Francis McGovern, a Duke University law professor.

"Now, you might take a particularly good case and see how good it is before you take lots of others and invest a lot of money," McGovern said.

Drug makers are also taking more precautions. Merck added language about the potential problem to Fosamax's label in July after a request from the Food and Drug Administration, which had reviewed reports of osteonecrosis, Irvine said.

The revised label "communicates the issue clearly to physicians," Irvine said.

Fosamax risk weighed

Mon, 19 Jun 2006 00:00:00 -0700

Graphic designer Patricia Korch settled into her oral surgeon’s chair, ready to have a troublesome tooth extracted as part of orthodontia she’d delayed for many years.

“You take Fosamax,” he said, studying her medical history form.

“Yes, I do,” she replied.

He walked around the chair, as if he was going to break bad news to her, she recalled.

Then he did.

He told her that Fosamax, which she took to stave off the bone-weakening disease osteoporosis, was one of a class of drugs called bisphosphonates implicated in a serious bone disease. In a small number of cases, after tooth extraction or implant placement, the bone failed to heal, remained exposed or became infected.

Called osteonecrosis of the jaw, or ONJ, it was first linked to bisphosphonates by a Miami dentist in 2003. No cases were reported in any of the clinical trials done before the drugs went on the market, but Dr. Robert E. Marx noticed ONJ among 36 cancer patients who were taking intravenous versions of the drugs. The medications were prescribed to prevent fractures and ease pain caused by cancer that had spread to their bones.

Case reports continued to crop up, including 15 patients who were taking oral forms of the drug to prevent osteoporosis. A May article in the Annals of Internal Medicine reviewing previously published reports said 94 percent of patients who developed ONJ were being treated for metastatic cancer with IV bisphosphonates. Sixty percent of patients had a dental procedure done before ONJ was diagnosed.

The risk for people undergoing oral surgery while taking oral bisphosphonates, such as Fosamax, Boniva and Actonel, is unknown, the article’s authors said, but for people like Ms. Korch contemplating elective oral surgery, any risk was too high.

“It was very shocking,” she said. “You can’t really minimize it because there’s no cure for this.”

Her orthodontist and dentist devised a plan to perform a root canal, after which the tooth, no longer connected to the bone, will come out like a baby tooth. In that way the bone would not be affected and her orthodontia to correct severe crowding could continue.

That will solve her immediate problem, but she still decided to stop taking Fosamax.

Medical experts, including the National Institutes of Health, haven’t gone that far. The National Institute of Arthritis and Musculoskeletal and Skin Diseases calls cases linking these oral drugs to ONJ rare. Its Center for Clinical Research is planning research into the question.

The Food and Drug Administration has ordered the makers of bisphosphonates to list ONJ in its precautions on package inserts.

Dr. Meryl S. Leboff, director of the skeletal health and osteoporosis program at Brigham & Women’s Hospital in Boston, also calls the risk low.

“We really don’t know the true incidence of this problem worldwide, but the risk in patients who are treated with oral bisphosphonates is very, very low. Low, but not zero,” she said. “It’s important for physicians to work with dentists and oral surgeons and that patients really try to optimize their dental hygiene.”

Osteoporosis the disease the drugs target affects 10 million Americans, leading to fractures for one out of two women and one out of four men over 50 in this group, according to NIAMSD.

About 34 million Americans, both men and women, have low bone mass, putting them at risk for osteoporosis. Being older, female, Caucasian or Asian, and having a family history of osteoporosis puts people at higher risk. Other factors estrogen and testosterone levels, physical activity, diet, medications, alcohol, cigarettes also come into play.

Low bone mass occurs when the process of old bone being renewed (resorption) and new bone being formed (formation) changes. Up until about age 30, formation outpaces resorption. After that the ratio shifts. Bone loss can eventually lead to osteoporosis.

Bisphosphonates prevent bone loss by inhibiting resorption of old bone and interfering with the bone formation. Scientists theorize that ONJ may occur after oral surgery in patients taking bisphosphonates because the drugs thwart the bone resorption needed for healing. Another possible explanation is that the drugs prevent formation of new blood vessels, causing the bone tissue to die.

Whatever the mechanism, there is no cure for ONJ. And bisphosphonates do stay in the body for years after a person stops taking them. In a position paper published last year, the American Academy of Oral Medicine said prevention was the best approach.

“The message needs to be that anyone considering Fosamax should really get their dentistry straightened out because of the risk of osteonecrosis,” said Dr. Stanley M. Levenson of Worcester, who is Ms. Korch’s dentist and agreed when her oral surgeon would not extract her impacted tooth. “She was lucky that wasn’t something she had to do.”

Some 23 million Americans take oral bisphosphonates for osteoporosis, according to the American Dental Association. And some of them need to have infected teeth extracted.

Dr. Shay Shen, a Worcester oral surgeon, said he looks at whether a patient is taking oral or intravenous bisphosphonates and at how high a dose.

“But if the tooth really needs to be removed and there’s no other way of doing it, we still go ahead and remove the tooth,” he said. “It’s not an absolute contraindication that you cannot take a tooth out if a patient is taking Fosamax.”

Patients are put on antibiotics to prevent infection after oral surgery.

Ms. Korch, who gives her age as “45-plus,” attributes her low bone mass to her small stature, European heritage and family history.

“I am in good health other than issues with bone density. If you had the option of the possibility of developing an irreversible, excruciatingly painful, disfiguring disease, would you take that chance?” she asked in a chat room on www.archwired.com, a site for adults wearing braces.

Dropping a medication is not new to her. She was on hormone replacement therapy until the Women’s Health Initiative clinical trial was halted in 2002 because of an increased risk of heart attacks and stroke that outweighed the benefit of bone strength. She said she is frustrated by the lack of information on Fosamax at this point, but plans to stay off the drug at least until her alternative to tooth extraction is completed.

“It’s everybody out of the pool again,” she said.

Bone-building drugs linked to bone-rotting side effect

Tue, 13 Jun 2006 00:00:00 -0700

Michael Erlichman walked into his dental office last week and encountered a patient with an unusual but growing problem.

An elderly woman was complaining about soreness caused by her dentures, but there was nothing Erlichman could do to relieve her pain. That's because she suffers from a rare jawbone disease that is increasingly being linked to a group of drugs for osteoporosis and cancer. And he noted she'd been taking one of those drugs for several years.

"There's more concern about this all the time now," said Erlichman, an oral surgeon in Little Falls. "The drugs are known to truly help people, but they can also cause the jawbone to become inert to the point where you can't drill a cavity or perform an implant.

"You can't do anything with these patients. And I worry about others developing the problem."

Each year, millions of Americans seeking to ward off brittle bones take pills that belong to a class of medicines called bisphosphonates. By far, the most popular pill is Merck's osteoporosis drug, Fosamax, which has been available for a decade. A much smaller number of patients receive an intravenous version of the medication as part of their chemotherapy.

To date, the incidence of drug-induced jawbone disease remains rare. Researchers report fewer than 400 cases of the disease, known as osteonecrosis, a painful and debilitating condition that essentially rots the jawbone. And the vast majority of these cases 94 percent are associated with a pair of intravenous medicines sold by Novartis, according to an article last month in the Annals of Internal Medicine.

Nonetheless, oral surgeons and dentists are increasingly worried the number of cases will multiply, and warnings have been posted on Web sites run by their professional groups. The problem, they say, is that bisphosphonates remain in the bones for years. Given that more prescriptions are written each year for the pills, which include Actonel and Boniva, experts suggest the rate at which osteonecrosis will be diagnosed is likely to increase.

"The concentration in the bones begins to build up by the third year. So it's not surprising that we're starting to see more cases among people who take the pills," said Robert Marx, who chairs the oral and maxillofacial surgery department at the University of Miami medical school, and who first sounded the alarm about the problem three years ago.

Although Fosamax has been prescribed since 1995, usage grew dramatically about five years ago, which Marx said would explain why cases linked to that pill are only now being diagnosed. Actonel has been available since 2000, and Boniva was launched last year. Marx said he doesn't expect to see as many cases associated with those pills right now.

Marx believes Merck researchers didn't anticipate the extent to which bisphosphonates can effect the jaw compared with other bones. In his view, the Fosamax clinical trials should have looked for the problem. If they had, Marx said, "they could've predicted this might have occurred."

A Merck spokesman responded that Fosamax is linked to a very small number of cases compared with the millions of people who have taken the pill. In 1997, for instance, 1.5 million new prescriptions were written for Fosamax; that figure jumped to 4.5 million by 2002, but slid to 4.2 million last year, according to Verispan, a market-research firm.

The idea that greater use will result in an increased risk of osteonecrosis "isn't substantiated by the current data," Merck spokesman Chris Loder wrote in an e-mail. "To suggest so would be misleading and incorrect." But at the request of regulators, Merck last year changed Fosamax labeling to mention osteonecrosis has been reported among patients taking bisphosphonates.

Two studies about to be published are expected to substantiate that view, according to the lead author, Marjorie Jeffcoat of the University of Pennsylvania dental school. One study traced 320 Fosamax patients for two years and the other tracked 80 Fosamax and Actonel patients for five years.

"The data didn't show a cause and effect," said Jeffcoat. However, she noted the data didn't provide a definitive answer about whether a bisphosphonate pill could cause osteonecrosis if taken for a lengthy period of time.

The Merck spokesman added that no cases of osteonecrosis were found among 17,000 patients in its clinical trials, although he acknowledged the company has received side-effect reports. However, he argued these reports "do not necessarily indicate causality," declined to provide the number of side-effect reports received.

An FDA spokeswoman, Laura Alvey, said she could not immediately provide the number of side-effect reports the agency has received involving bisphosphonates and osteonecrosis.

Paula Koenigs, a spokeswoman for Procter & Gamble, which markets Actonel with Sanofi-Aventis, said there is no scientific study that concludes bisphosphonates cause osteonecrosis, and the jawbone disease wasn't seen in clinical trials.

Maureen Byrne, a spokeswoman for Roche, which jointly markets Boniva with Glaxo, said osteonecrosis wasn't seen in trials.

Nonetheless, the growing concerns about osteonecrosis are prompting lawsuits against the drugmakers. So far, Merck faces at least 15 lawsuits over Fosamax, while two have been filed against Procter & Gamble and Sanofi-Aventis.

One Florida lawyer, who is in the process of filing additional lawsuits against Merck, argued the company has failed to properly warn patients. He maintained that despite a 2004 report by the FDA's Office of Drug Safety, Merck hasn't added meaningful language in the Fosamax label to specifically indicate the risk of osteonecrosis.

"They never come out and say it's a risk factor," said Tim O'Brien, who noted that Novartis is so far the only company to have sent letters to doctors about the risk. "You have to read between the lines (of the product labeling) and read the medical literature to understand what they actually are saying. It's very misleading."

He added the FDA has cited Merck for being too aggressive in promoting Fosamax. The agency sent four letters between 1997 and 2001 for making unbalanced or misleading claims in promotional brochures or consumer advertising.

Lawsuits alleging damaging side effects caused by prescription drugs are increasingly common. The Vioxx scandal has generated more than 11,500 lawsuits against Merck. By comparison, the number of Fosamax lawsuits is minuscule, but the specter of more bad publicity doesn't thrill Wall Street.

"This is definitely a headache that the big drugmakers, especially Merck, don't need," said David Moskowitz, an industry analyst at Friedman Billings Ramsey, who noted Fosamax generated $3.2 billion in sales last year. "Merck has few growth drivers, and they can't afford for Fosamax to sustain too much damage."

One solution might crimp Fosamax sales. Hillel Ephros, who chairs the dentistry department at St. Joseph's Regional Medical Center in Paterson, wants doctors to consider alternatives before writing prescriptions for the pills.

"Everyone needs to know that osteonecrosis can't be fixed," said Ephros, who has seen seven cases of the disease. "The problem makes me feel shackled and frustrated. We have to defer and postpone procedures for patients on oral bisphosphonates, and the day may come when I will decline altogether. Maybe that can be prevented."

The drugmakers are advertising their pills widely. Last year, they spent $174.3 million, up from $54.8 million in 2003, according to TNS Media Intelligence, a market-research firm. That's because Boniva was launched last year with a big promotional effort, prompting Procter & Gamble and Sanofi-Aventis to spend more on Actonel.

One doctor suggests ads should explicitly and prominently mention the possibility the pills can cause osteonecrosis. Salvatore Ruggiero, chief of oral and maxillofacial surgery at Long Island Jewish Medical Center in New Hyde Park, N.Y., believes the risk of developing osteonecrosis is "very small," but few know it exists.

"The problem has taken a long time to manifest itself, and so I think it'd be unfair to say these drug companies expected this to happen. That'd be a real stretch. The lawyers are creating a perception that it's a big problem," he said. "But we need to realize that there is this side effect. And it needs to be better known."

For Mary Kyle, the debate is taking place too late.

A retired elementary school teacher who lives in Mount Laurel, Kyle said she was prescribed Fosamax four years ago to prevent osteoporosis, but recently was diagnosed with osteonecrosis after complaining of jaw pain. Last week, she filed a lawsuit against Merck.

"I was told I'll have this problem for the rest of my life," said Kyle, 58. "My oral surgeon couldn't give me much hope there's anything he can do. Now, I want to educate others. There are a lot of people on this drug and this problem may happen to them, but they may not know the drug is causing the problem."

Bone drug may hold hazards

Sat, 20 May 2006 00:00:00 -0700

Millions of midlife and older Americans rely on the medication Fosamax to stave off osteoporosis, a crippling disease that turns bones so brittle that someone can break a hip just by walking around inside the house.

But a growing number of physicians and oral surgeons have raised concerns that the long-term use of Fosamax, and similar so-called "bisphosphonates," can lead to "dead jaw" syndrome, a painful condition that causes ulcers, tooth loss and exposed bone.

Researchers say cases are rare and seem most common among patients receiving intravenous bisphosphonates such as Zometa or Aredia in conjunction with chemotherapy or radiation for breast cancer and multiple myelomas. Incidents also appear more likely to follow serious dental surgery, such as a tooth extraction.

But while cancer patients appear more at risk, Dr. Bruce Pihlstrom of the National Institutes of Health said some patients taking standard oral doses of bisphosphonates for osteoporosis also developed the condition technically called "osteonecrosis," a word that literally means "dead bone."

"Patients need to be aware of the risk," said Pihlstrom, a clinical research director specializing in dental and cranial-facial work. "If I was taking these drugs, I would make sure I had the best dental health care I could get."

Pihlstrom said NIH plans to fund new research to quantify the potential risks of bisphosphonates.

The American Association of Endodontists, which deals with conditions inside the tooth, issued a statement several months ago, advising precautions for patients on such drugs and urging dentists to report all cases to the Food and Drug Administration. Pihlstrom said he so far knew of 368 reported cases.

About 44 million Americans, almost 70 percent of them women, have low bone density or osteoporosis. Fosamax, manufactured by Merck & Co., is the world's best-selling osteoporosis medication. More than 22 million prescriptions were written for Fosamax in this country last year, according to pharmaceutical research firm IMS Health, and the drug has about $3 billion annually in sales.

Rochelle Kenig, who lives west of Boynton Beach, had no second thoughts about starting on Fosamax 10 years ago when a bone-density test showed she was in the early stages of osteoporosis.

In September 2004, Kenig began having excruciating pain in her right lower jaw. Her jaw swelled, and she developed an infection that required intravenous antibiotics. A maxillofacial surgeon finally told her in May 2005 that she had osteonecrosis.

Kenig's doctor told her to stop the Fosamax immediately.

Earlier this year, Kenig had a portion of her jaw removed, followed by a graft to fill a hole in her rotting jaw bone.

"I don't want this to happen to anyone else. And I'm angry it happened to me," said Kenig, 67.

Kenig is part of a class action lawsuit filed in U.S. District Court in Fort Myers last month. The suit represents about 300 people nationwide. All were formerly on Fosamax and none were cancer patients.

The suit will ask the court to set up medical monitoring and pay for treatments and surgery for osteonecrosis patients.

In a statement released last month, Merck stated that "in all of our controlled clinical trials which have included more than 17,000 patients, we have not had reports of osteonecrosis of the jaw occurring in patients taking Fosamax." The company said it complied with FDA requests last year and includes updates about osteonecrosis risk both in packaging inserts and product information sent to physicians.

But Dr. Michelle Fiorillo, a family physician with the Holy Cross Medical Group in Fort Lauderdale, doesn't remember seeing any such warnings and said the representative promoting Fosamax never mentioned them.

Now she says she's carefully monitoring her patients who have been on the medication for years. Diagnosing a woman with osteoporosis this week, Fiorillo placed her on a low-dose estrogen patch instead of Fosamax when she learned the woman had dental problems.

The connection between jawbone death and bisphosphonate use is difficult to track, Fiorillo said, because it's physicians who prescribe the drug but dentists who treat the result. And switching patients off bisphosphonates will do little good immediately, Fiorillo said, as the drug has a long half-life it can continue to effect the body's bone-building properties for six to 12 years, researchers think.

"This definitely is changing the way I prescribe for my patients with osteoporosis," Fiorillo said.

Painful jaw decay tied to osteoporosis drugs

Fri, 05 May 2006 00:00:00 -0700

Some drugs commonly used to prevent and treat osteoporosis can cause a painful and irreversible decay in the jaw in rare cases.

Health Canada is adding new warnings to the medications, called bisphosphonates, which are taken to protect and strengthen bone.

In rare cases, first described three years ago, bisphosphonates can cause jaw bones to rot and die.

Jaw necrosis affects up to 10 per cent of people who take bisphosphonate drugs, experts. say. Most have metastatic cancer and have been injected with potent drugs to protect their bones.

Gwen Davis-Wells, 62, who has multiple myeloma and takes the bisphosphonate drug Aredia to protect her bones, said she was shocked when doctors told her they thought the drug was causing the problem with her jaw bone.

Doctors have since prescribed a liquid diet for her, saying her jaw is very thin and getting worse.

"When I'm at church and we're giving the peace sign, I can't let people give me a kiss on the jaw, hug me too tight, because these little things could cause it to break," said Davis-Wells.

About 10 per cent of cases are caused by oral bisphosphonates such as Fosamax or Actonel. Women may take the drugs to prevent or treat osteoporosis, a bigger market for medications.

Last year, doctors in Canada wrote five million prescriptions for oral bisphosphonates.

"Worldwide, to our knowledge, there are only 35 reported cases in millions and millions of individuals who've received these drugs for the management of osteoporosis," said Dr. Gillian Hawker, a rheumatologist at Women's College Hospital in Toronto.

The risk of jaw necrosis seems to be linked to the dose, and how long people take it, said Dr. Maico Melo, an oral surgeon at Washington Center Hospital who is treating Davis-Wells.

Osteoporosis is expected to become more common among Canada's aging population. The concern is, as more people are prescribed bisphosphonates at an earlier age, more cases of jaw necrosis will surface, Melo said.

People who are on the drugs are advised against having invasive dental surgery, as it seems to increase the risk, doctors say.

Merck sued over Fosamax

Thu, 13 Apr 2006 00:00:00 -0700

Merck & Co, which is already facing a raft of cases over its pain reliever Vioxx, may need to hire additional attorneys to fight a recently filed lawsuit alleging the company was negligent in promoting its osteoporosis drug Fosamax.

According to a lawsuit filed Monday in U.S. District Court in Fort Myers, Fla., Fosamax is a defective product because it can cause osteonecrosis of the jaw, or a rotting of the jaw bone. The suit, which seeks class action status, alleges that Merck concealed and continues to hide Fosamax's potentially dangerous side effects from patients and doctors.

Fosamax is Merck's second best-selling drug with last year's revenue essentially flat at $3.2 billion.

In a statement, Merck said that in all of its clinical trials of Fosamax, which have included more than 17,000 patients, it has not had any reports of osteonecrosis of the jaw. Merck said that there have been reports of patients taking Fosamax developing the condition but that doesn't necessarily mean the drug caused it.

The lawsuit alleges that the U.S. Food and Drug Administration asked Merck to add a warning to Fosamax's label in August of 2004 and that it has yet to comply with that request.

Merck counters that it received a request from the FDA to update the label with information about the condition in January 2005. It says that by July 2005 information regarding the problem was on the label.

But Tim O'Brien, who filed the suit, said the information in the label isn't an adequate warning.

Clinton woman suing Merck over problem with Fosamax

Wed, 12 Apr 2006 00:00:00 -0700

A Clinton woman is suing the drug maker Merck, claiming a drug it makes resulted in a side-effect she never imagined.

As many people know, Merck is already facing a flood of lawsuits over its drug Vioxx. But another problem with a different drug seems to be emerging.

The osteoporosis drug Fosamax is under fire, with reports linking its long term use to a condition causing patients' jawbones to rot and die. That disease is called osteonecrosis (ONJ) and it caused problems for Gwendolyn Wolfe.

"A substantial portion of her jawbone had to be removed and Dr. Carlson did that in surgery," says Wolfe's attorney. "She's still having significant pain and will for the rest of her life."

Her attorney has filed a lawsuit seeking class action certification claiming Fosamax has injured countless patients around America and. The suit also claims Merck knew about the problems but failed to report them.

Jaw Complications May Be Linked to Bone-Saving Drugs

Wed, 22 Jun 2005 00:00:00 -0700

Three months after Betty Beckman had a broken tooth pulled, her jaw still hasn't healed.

So the Nebraska City woman travels each weekday to Omaha, where doctors put her in a pressure chamber in which she breathes pure oxygen, in hopes of helping her jaw heal.

What left her with a sharp, exposed piece of jawbone isn't clear. But after a friend gave her an article about puzzling cases in which patients had patches of jawbone die after similar procedures, Beckman suspects that it may have something to do with a drug she's taking. And she wants to warn others who might be at risk.

The patients in the article, like Beckman, took drugs called bisphosphonates. Most, like Beckman, were cancer patients receiving high intravenous doses to lower elevated blood calcium or prevent cancer from invading bone. A few were osteoporosis patients taking oral versions marketed under names like Fosamax and Actonel to strengthen bone.

"After I read it, I thought, 'Oh, dear,'" said Beckman, 65.

Although some doctors are beginning to share Beckman's suspicions, it's unclear whether the normally bone-saving drugs play a role in jawbone death. Some don't think there's a connection to osteoporosis drugs. The anecdotal cases and the roughly 875 reports that the IV drugs' maker had received by February from among millions of users point to a small risk among users.

The concern arises because use of the drugs, particularly for osteoporosis, is growing. Doctors don't know as much as they would like about the jaw condition and have few tools to treat it. The best way to prevent it, at least among cancer patients, may be to do a dental exam and repair any problems before treatment begins with the drugs.

"It's more of a public awareness and medical awareness issue," said Dr. Michael Miloro, chief of oral and maxillofacial surgery at the Nebraska Medical Center, who is treating Beckman.

Oral surgeons were among the first to notice the problem. In May 2004, a New York doctor reported seeing 63 patients with the jaw condition from February 2001 to November 2003.

Of those cases, 56 had received the IV drugs Zometa or Aredia; seven had been taking oral medications.

After a tooth is pulled, the bone typically remolds itself and fills in the gap. But the drugs inhibit cells that take away dead bone and clear the way for other cells to finish the rebuilding job.

An estimated 90 percent to 95 percent of the 875 cases have been in cancer patients taking the intravenous versions, said Dr. John Hellstein, clinical professor of oral and maxillofacial pathology at the University of Iowa.

A smaller number have shown up in osteoporosis patients, he said. He based his estimates on published reports, the cases he has seen and those he has discussed with other doctors.

But Dr. Robert Recker, director of Creighton University's Osteoporosis Research Center, said he isn't convinced that there's a risk associated with the osteoporosis drugs.

Recker has treated several thousand patients with oral bisphosphonates in clinical trials and in practice. He also has seen clinical trial data on the drugs as a member of scientific advisory boards for Merck and Procter & Gamble Pharmaceuticals, the respective makers of Fosamax and Actonel.

"I don't think there's any significant risk in patients who have osteoporosis," he said. "The risk is in patients who are taking giant doses for cancer."

No one is advising patients to stop taking the drugs, which produce clear benefits, Hellstein said. "You don't want to scare people not to take their osteoporosis medicine, because that would be a lot worse."

Novartis, which makes the intravenous drugs, has added inserts to package labels noting that it has received reports of the condition among patients taking the drug. The company sent a letter to dentists in May and has produced a brochure for cancer patients.

Merck, maker of Fosamax, is in discussions with the Food and Drug Administration about the matter. Procter & Gamble Pharmaceuticals plans to add precautions about the condition to Actonel's labels at the FDA's request.

Miloro said it's unclear whether the pressure chamber treatments will work for Beckman.

"I can't blame anyone," she said. "I just wish I'd known."

Zometa (zoledronic acid) & Aredia (pamidronate disodium) Associated with Osteonecrosis of Jaw

Wed, 18 May 2005 00:00:00 -0700

Novartis and FDA notified dental healthcare professionals of revisions to the prescribing information to describe the occurence of osteonecrosis of the jaw (ONJ) observed in cancer patients receiving treatment with intravenous bisphosphonates, Aredia (pamidronate disodium) and Zometa (zoledronic acid).

The prescribing information recommends that cancer patients receive a dental examination prior to initiating therapy with intravenous bisphosphonates (Aredia and Zometa), and avoid invasive dental procedures while receiving bisphosphonate treatment. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition.

Read the Novartis Dear Healthcare Professional letter below. The and revised labels for Zometa and Aredia are attached.

Novartis Pharmaceuticals Corporation One Health Plaza East Hanover, NJ 07936

IMPORTANT DRUG PRECAUTION FOR DENTAL HEALTH PROFESSIONALS WITH PATIENTS BEING TREATED FOR CANCER

May 05, 2005

Dear Doctor:

We are writing to inform you of an adverse event Osteonecrosis of the Jaw (ONJ) observed in cancer patients receiving treatment with intravenous bisphosphonates, Aredia and Zometa, which may have an impact on the dental care of patients within your practice. While on treatment, invasive dental procedures should be avoided, if possible.

The prescribing information recommends that cancer patients:

receive a dental examination prior to initiating therapy with intravenous bisphosphonates (Aredia and Zometa); and

avoid invasive dental procedures while receiving bisphosphonate treatment. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. Clinical judgment by the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Aredia is used in the treatment of hypercalcemia of malignancy, Pagets disease, osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. Zometa is used in the treatment of hypercalcemia of malignancy, the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy.

In the U.S. Package Insert for both Aredia and Zometa, the following information on osteonecrosis of the jaw has been added under the Precautions Section.

Precautions

Osteonecrosis of the jaw

Osteonecrosis of the jaw (ONJ) has been reported in patients with cancer receiving treatment regimens including bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. Many had signs of local infection including osteomyelitis.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

ONJ is a complex problem with multiple risk factors. Typical signs and symptoms of ONJ include, but are not limited to: pain, swelling, or infection of the gums; loosening of the teeth; poor healing of the gums; numbness or a feeling of heaviness in the jaw; drainage and exposed bone. The seriousness of ONJ ranges from patient being asymptomatic to requiring sections of the jaw to be removed.

Dentists, oral surgeons, periodontists, prosthodontists, dental hygienists, and other dental health professionals can play a vital role in identifying ONJ and other oral complications of cancer and cancer therapy.

Jaw Disease Found in Patients Using Cancer Drug

Fri, 04 Mar 2005 00:00:00 -0800

A a common chemotherapy drug may cause a serious bone disease called "osteonecrosis of the jaw" (ONJ), according to doctors at Long Island Jewish (LIJ) Medical Center.

The discovery, published in the Journal of Oral and Maxillofacial Surgeons, prompted both the US Food and Drug Administration (FDA) and Novartis, the manufacturer of bisphosphonates used in cancer chemotherapy, to issue warnings earlier this fall to physicians and dentists about the risk for this potential adverse effect.

ONJ is a condition in which the bone tissue in the jaw fails to heal after minor trauma, such as a tooth extraction, causing the bone to be exposed. The exposure eventually can lead to infection and fracture, and may require long-term antibiotic therapy or surgery to remove the dying bone tissue.

Prolonged Use of Bisphosphonates Causes ONJ

The chief of the Division of Oral and Maxillofacial Surgery at LIJ, Salvatore Ruggiero, DMD, MD, and his staff reported that they were struck by the appearance of a cluster of cancer patients with necrotic lesions in the jaw, a condition they previously saw only rarely in one to two patients a year. When they launched a study of patients charts, they found that 63 patients diagnosed with this condition over a three-year period shared only one common clinical feature: They had all received long-term bisphosphonate therapy.

Bisphosphonates commonly are used in tablet form to prevent and treat osteoporosis in post-menopausal women. Stronger forms are used widely in the management of advanced cancers that have metastasized to the bone, where the disease often causes bone pain and possibly even fractures.

Several cancers can involve or metastasize to the bone, including lung, breast, prostate, multiple myeloma and others. In cancer chemotherapy, the drugs are given intravenously, and usually for long periods of time.

Disease Causes Traumatized Bone to Die Off

In their study, Dr. Ruggiero and his staff teamed up with Bhoomi Mehrotra, MD, in the Division of Hematology-Oncology at LIJ, and doctors in the Oral-Maxillofacial Surgery Division at the University of Maryland Medical Center.

Of the 63 patients diagnosed with ONJ between February 2001 and November 2003 at their centers, 56 were cancer patients who had received infusions of bisphosphonates for at least a year, and seven were non-cancer patients who had been receiving long-term oral therapy for osteoporosis.

The patients developed ONJ after normal bone trauma, such as a tooth extraction, while receiving bisphosphonate therapy. Rather than healing, the bone began to die, and the majority of patients required surgery to remove the diseased bone.

Early Diagnosis Key to Preserving Jaw Bone

In the FDA MedWatch and Novartis alerts issued in late September, oncologists and dentists were advised of the addition of osteonecrosis of the jaw to the "Precautions" and "Adverse Reactions" sections on the labeling of injectable bisphosphonates, describing the spontaneous reports of the condition being found mostly in cancer patients.

The alerts also recommend a dental examination with appropriate preventive dentistry in patients with risk factors such as cancer, chemotherapy, corticosteroids and poor oral hygiene prior to initiating treatment with bisphosphonates.

"Monitoring the dental health of patients on bisphosphonates is key, because an early diagnosis may reduce the complications resulting from advanced destruction of the jaw bone," said Dr. Ruggiero. "Since our paper was published and dentists became aware of the connection, many more patients with the condition have been identified, even in our own center. Prevention and early detection are so important to preserving the jaw bone in these individuals."

Individuals should attempt to avoid tooth extractions and other major dental work while on the drugs.

Osteoclasts Inhibit Bone Regeneration

Bisphosphonates block the work of bone cells called "osteoclasts," one of two important types of bone cells that are involved in the continuous process of bone remodeling in a delicate balancing act. During this process, osteoblasts "the good guys" put calcium in the matrix of the bone and make bone stronger. Osteoclasts "the bad guys" take calcium away, diminishing the internal strength of the bone.

Bone remodeling is like a necessary game of tug-of-war between the goods guys and the bad. Bone mass and mineral content constantly adjust throughout the life cycle to support the places on the skeleton where the most outside force occurs.

Novartiss Aredia (pamidronate disodium) and Zometa (zoledronic acid) injections are the two intravenous bisphophosphonates used in chemotherapy regimens. Novartis changed their labeling in August.

Mercks Fosamax (alendronate) and Procter and Gamble Pharmaceuticalss Actonel (risedronate sodium) are the most commonly used oral bisphosphonates, which are only indicated for osteoporosis. Labeling for the oral forms has not been changed.

"The oral form is much less potent than the intravenous form and appears to be substantially less likely to cause the problem," said Dr. Ruggiero.

Aredia Fosamax Osteonecrosis of the Jaw Injury Lawyer

Fri, 04 Mar 2005 00:00:00 -0800

Osteonecrosis of the Jaw (ONJ)

Osteonecrosis of the jaw (ONJ) has been reported in patients with cancer receiving treatment regimens including Fosamax, a bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. Many had signs of local infection including osteomyelitis.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Cases of osteonecrosis (primarily involving the jaws) have been reported in patients treated with bisphosphonates. The majority of the reported cases are in cancer patients attendant to a dental procedure. Osteonecrosis of the jaw has multiple well documented risk factors including a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g., anemia, coagulopathies, infection, pre-existing oral disease).

Although causality cannot be determined, it is prudent to avoid dental surgery as recovery may be prolonged.

If you or a loved one has taken Bisphosphonates drugs and have been diagnosed with Osteonecrosis of the Jaw (ONJ), please fill out the form at the right for a free case evaluation by a qualified defective drug attorney.