Yourlawyer.com (Actonel News)

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.

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."

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.

Actonel Osteonecrosis Side Effects Lawsuit ONJ Lawyer

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

Injured by Actonel?

Actonel (generic: risedronate sodium), manufactured by Procter & Gamble, was granted FDA approval on March 27, 1998. Actonel is prescribed to treat postmenopausal osteoporosis. Actonel is a type of drug known as bisphosphonates, the same family of drugs as Fosamax, Aredia, and Zometa. Individuals using Actonel or other bisphosphonates should avoid tooth extractions and other major dental work while on the drugs.

A connection between Actonel (and other bisphosphonates) and a serious bone disease called Osteonecrosis of the Jaw (ONJ) was found. Osteonecrosis of the Jaw (ONJ) is also known as Dead Jaw. This finding was published in the Journal of Oral and Maxillofacial Surgeons, and it prompted the US Food and Drug Administration (FDA) and the manufacturer of Actonel to issue a warning to health care professionals on September 24, 2004.

Bisphosphonates are commonly used in tablet form to prevent and treat osteoporosis in post-menopausal women. Stronger forms of bisphosphonates are commonly used 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 cancer, breast cancer, prostate cancer, multiple myeloma, and others. When bisphosphonates are given in cancer chemotherapy, the drugs are given intravenously and usually for longer periods of time.

Osteonecrosis of the Jaw (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 can eventually lead to infection and fracture and may require long-term antibiotic therapy or surgery to remove the dying bone tissue. Experts say that prevention and early treatment of patients using bisphosphonates such as Actonel is extremely important in preserving the jawbone.

If you or a loved one took Actonel and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.