Jaw Decay Linked to Fosamax

Source: By Linda Marsa, Special to The LA Times

Sue Piervin never suspected the pills she took to strengthen her bones
could severely damage her jaw. Twelve years ago, a routine X-ray
revealed her bones were thinning, so her doctor prescribed a drug to
help stop the erosion of bone density. Then, in 1999, Piervin developed
a painful bone spur in her jaw that had decayed to such an extent that
it had to be surgically removed.

At
the time, doctors were puzzled. But when she had a recurrence last
year, they had a pretty good idea what was causing the trouble:
Fosamax, the medication she was taking to prevent bone loss.

Since
2001, more than 2,400 patients taking Fosamax and other bone-building
medications like it have reported bone death in their jaws, mostly
after a minor trauma such as getting a tooth extracted. Most were
taking especially potent, intravenously delivered versions of these
drugs, which are known as bisphosphonates.

An additional 120
people who were taking bisphosphonates in pill form to prevent bone
thinning have been stricken with such incapacitating bone, joint or
muscle pain that some were bedridden and others required walkers,
crutches or wheelchairs.

The incidence of both these
complications is minuscule in comparison with the millions of people
taking these medications. More than 36 million prescriptions for oral
bisphosphonates, such as Actonel, Fosamax and Boniva, were dispensed in
2005, according to IMS Health, a pharmaceutical information and
consulting company. Nearly 3 million cancer patients have been treated
with intravenous versions of the medications.

But because at
least 90% of drug side effects aren’t reported to the Food and Drug
Administration, the real number of people stricken with jaw necrosis
and other side effects could be higher.

"We’ve uncovered about
1,000 patients [with jaw necrosis] in the past six to nine months
alone, so the magnitude of the problem is just starting to be
recognized," says Kenneth M. Hargreaves, chair of the endodontics
department at the University of Texas Health Science Center in San
Antonio.

With concern growing over the possible side effect, the
American Assn. of Endodontists last week released a position statement
on the problem. "Until further information is available, it would
appear prudent to consider all patients taking bisphosphonates to be at
some risk," the group said.

Unreported cases of the pain
syndrome may be "considerable," says Diane K. Wysowski of the FDA’s
Office of Drug Safety, "because physicians may attribute the pain to
osteoporosis."

The issue is especially worrisome, says Dr. Susan
M. Ott, an osteoporosis expert at the University of Washington in
Seattle, because the number of women taking bisphosphonates stands to
increase now that women are more reluctant to preserve their bones by
taking estrogen after menopause.

In 2002, when a landmark study
revealed that hormone replacement therapy carried slight but measurable
heart and breast cancer risks, prescriptions for oral bisphosphonates
shot up 32%, according to IMS Health.

Bisphosphonate drugs
have been used since 1995 to strengthen bone in women who are losing
bone density and for nearly 15 years in men and women who have cancer.
The medicines act by altering the dynamics of bone, which is constantly
being turned over.

Cells called osteoclasts break bone down.
Others called osteoblasts build it up. Osteoporosis occurs when
formation of new bone does not keep pace with bone destruction.

Debate over risks

Bisphosphonates
thwart the action of the osteoclasts, thickening bones and making them
less likely to break. Physicians aren’t sure why these drugs sometimes
do seemingly the opposite and cause jaw death. But they know that
osteoclasts are also involved in prompting osteoblasts to form.
Consequently, over time, these medications may actually impede rather
than promote the creation of new bone.

Christopher Loder, a
spokesman for Fosamax maker Merck, points out that osteonecrosis of the
jaw with Fosamax is "exceedingly rare." "In all of our controlled
clinical trials with Fosamax, which involved more than 17,000 patients,
including some that were 10 years in duration, we had no reports" of
it, he says.

The risk appears to vary according to the strength
of the bisphosphonate being used. Recent studies show that about 80% to
90% of jaw decay occurs in cancer patients who take potent intravenous
bisphosphonates (Aredia, Zometa). The drugs replenish bone tissue that
is lost when cancer spreads to the bone and can reduce pain and the
risk of debilitating fractures.

The rare side effect, called
osteonecrosis of the jaw, causes severe infections, swelling and the
loosening of teeth. Patients often require long-term antibiotic therapy
or surgery to remove the dying bone tissue.

"I’ve taken off
several jaws because of this problem," says Dr. Salvatore Ruggiero, an
oral surgeon at Long Island Jewish Medical Center in New York who was
among the first to observe this phenomenon in 2001. "Because bone death
can’t be reversed, there’s nothing we can do for these patients except
ease their pain and prevent it from spreading."

Patients who
have cancer-related bone weakening and pain have few options but to
take bisphosphonates. More worrisome for experts are the millions of
women such as Piervin who take the weaker bisphosphonate pills to treat
osteoporosis, and for many more years than do cancer patients. "Even
though the chances of getting this are small, considering there are 23
million women taking this drug, we could be talking about a significant
number of people," Ruggiero says. "Risks increase the longer you’re on
the drugs, and it can take years for the complication to manifest
itself."

It’s not uncommon for rare side effects to come to
light only after a drug has been approved, says Dr. Eric Colman of the
FDA’s Division of Endocrine and Metabolic Drugs in Silver Spring, Md.
Serious adverse reactions that weren’t apparent in premarket tests
emerge in half of all prescription medications.

"People need to realize there are unknown side effects with every drug, and these medications are no exception," he says**.**

What patients can do

In
the last two years, drug makers have added warnings about bone death to
some of the medications’ labels and about the pain syndrome to all of
them.

But despite an alert sent to physicians by the FDA in
2004, "it’s been a battle getting people educated," Ruggiero says.
Dentists and oncologists know about the problem, but gynecologists and
family doctors, who write many of the prescriptions for oral
bisphosphonates, aren’t as informed.

Patients
need to be vigilant. "Women taking these drugs for osteoporosis should
tell their doctor if they develop severe pain," says Dr. Theresa Kehoe,
an endocrinologist with the FDA’s Division of Endocrine and Metabolic
Drugs.

In addition, anyone who uses oral or intravenous
bisphosphonates should alert their dentist and oral surgeon if they
need an invasive dental procedure. Better yet, says Hargreaves, get
dental work done before going on these drugs, although avoiding jaw
trauma is no guarantee of protection.

The drugs greatly reduce
risks of incapacitating fractures for older women with osteoporosis.
Women who don’t have osteoporosis but have other risk factors, such as
usage of bone-depleting steroids, previous fractures or a family
history of the condition can also benefit, says Dr. Charles H. Chestnut
III, who heads osteoporosis research at the University of Washington.

But
they should be considered far more cautiously by younger women who have
less bone thinning and are taking oral bisphosphonates simply to
prevent further deterioration. These meds become incorporated into the
bone’s matrix, where they can linger for five years or more. Their
effects are cumulative. And women are expected to take them for the
rest of their lives.

"These drugs are still relatively new and problems sometimes take years to show up," says Ott of the University of Washington.

"We’re
not quite sure what we’re dealing with over the long haul. Side effects
like this should make ordinary, healthy women think twice."

Piervin
still takes calcium and Miacalcin, a nasal spray that helps preserve
bone density but isn’t nearly as potent as the bisphosphonates. She
also walks every day and does weight-bearing exercise three times
weekly to help her bones stay stronger — even parks her car eight to 10
blocks from work to fit more walking into her schedule.

She’d take hormones, but she’s worried about the risk. She’d exercise more, but she doesn’t have the time.

"I’m off Fosamax," she says, "but I’m in limbo regarding future treatment."

6 Comments on Jaw Decay Linked to Fosamax

New comments are currently closed for this post.
Anon
4/19/2006
ONJ is quite conditional, a possible cross interaction of a drug with dental procedurs. If Merke is being targeted, how about the dentists who conducted the implants? The case is way more complicated than the story described above.
estelle lynch
4/25/2006
So far, my interniost and gynecologist say to continue Fosamax, my friend's dr. says to stop. At this moment I am not sure what I will do.
Joseph Margarone III DDS
5/9/2006
I'm a practicing oral surgeon, and this problem of oral bisphosphonates is certainly in its infancy. Please refer to my article titled, Bisphosphonate-associated Osteonecrosis of the Jaws in the December 2005 issue of the Journal of the American Dental Association pages 1669-1674 along with two other articles on this subject in this issue.
Anon
11/8/2006
I have just begun to take Actonel after a bone density scan indicated a decrease in density. I also need to replace a bridge with an implant and have just learned from my dentist about the risk discussed above. I think I will stop the medication and proceed with the dental work before I decide on the actonel. I wish I knew what the effects of this short term (8 weeks) of 35mg doses may have done!
W.Bohannan DDS, MD
11/9/2006
Actonel or risedronate is an oral drug that can be used for Paget's disease of bone (osteitis deformans) and to treat or prevent osteoporosis. It is also used to prevent and treat osteoporosis that is caused by cortisone-related medications (glucocorticoid-induced osteoporosis). It is a nitrogen containing drug which makes it more potent as to non nitrogen containing drugs like Etidronate (Didronel). Without getting into the physiology of bone and the pharmacology of the drug, the risks of complications of BRON (Bisphosphonate related osteonecrosis) is time dependent. It take time for the drug to concentrate in the bone. From several months to several years. Additionally, the oral drugs have a much lower incidence of BRON than the IV forms. The information being brought forth by the University of Miami docs clearly show a time/complication association. Sound recommendations for patients taking oral bisphosphonates that are based on strong clinical research designs are lacking. Most treatment recommendations are based on clinical experience of clinicians involved in caring for these patients, in which it appears that the risk of developing BRON associated with oral bisphosphonates increased when duration of therapy exceeded three years. As more data become available, these guidelines will change. For individuals who have taken an oral bisphosphonate for less than three years and have no clinical risk factors, no alteration or delay in the planned surgery is necessary. This includes any and all surgeries common to oral and maxillofacial surgeons, periodontists, and other dental providers. However, it is suggested that if dental implants are placed, informed consent should be provided related to possible future implant failure and possible osteonecrosis of the jaws if the patient continues to take an oral bisphosphonate. Such patients should be placed on a regular recall schedule. It is also advisable to contact the provider who originally prescribed the oral bisphosphonate and suggest monitoring such patients and considering either alternate dosing of the bisphosphonate, drug holidays, or an alternative to the bisphosphonates. For those patients who have taken an oral bisphosphonate for less than three years and have also taken corticosteroids concomitantly, the prescribing provider should be contacted to consider discontinuation of the oral bisphosphonate (drug holiday) for at least three months prior to oral surgery, if systemic conditions permit. The bisphosphonate should not be restarted until osseous healing has occurred. These strategies are based on the hypothesis that concomitant treatment with corticosteroids may increase the risk of developing BRON and that a “drug holiday” may mitigate this risk. As it has been shown, despite the long term bio-availability, BRON does appear to improve after the drug is stopped. For those patients who have taken an oral bisphosphonate for more than three years with or without any concomitant prednisone or other steroid medication, the prescribing provider should be contacted to consider discontinuation of the oral bisphosphonate for three months prior to oral surgery, if systemic conditions permit. The bisphosphonate should not be restarted until osseous healing has occurred. Again, this type of treatment modalities have been put forth by AAOMS based on the clinical observations of various clinicians treating many patients. This discussion could go on forever, but based on the time and type of drug used elicits a risk factor for the patient. If an exposure occurs, the clinical findings then places the patient in a class and that dictates treatment. So based on the time you’ve been on the drug, your risk of developing problem is very low and only slightly higher than a patient who is not on the drug. It will be up to you and your doctor and surgeon to determine what is the best course of action for you. Of note, there is a study going on to determine if hyperbaric oxygen is helpful in patient with BRON. I hope it will be of help, but understanding the pathophysiology of the disease, I don’t think it will be as helpful as HBO is with osteoradionecrosis. Sorry for the long winded answer, I'm now seeing about 15 patients with various stages of BRON and have been trying to talking to many different practioners and reading all I can. I also wish to thank Vishtasb Broumand, DMD, MD for all of his help and pointers.
Rand Redfern DDS
3/18/2007
Over the past two years I have had over sixty suspected cases of BON referred to me. Of these only two are on IV medications and due to cancer. The remaining cases are taking an oral bisphosphonate. Interestingly a different area of the jaw seems to be affected. I use cbct and mri in diagnosis and treament of TMD. I am seeing various symtoms including "compression fracture" of the condyle(s) and severe erosive degeneration of the fossae in some cases. Has anyone else investigated the TMJs in the effected cases?

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