Fosamax causing Jaw Necrosis

[Guest guest]

the Los Angeles Times

 

Bone drugs' reverse danger

Rare instances of jaw decay are being linked to

medicines used to prevent bone loss.

 

By Linda Marsa

Special to The Times

 

April 3, 2006

 

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.

 

" I had three oral surgeries to remove all the dead

bone, " says the 56-year-old Los Angeles resident. " It

was not a fun summer. "

 

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. "

 

 

 

 

 

 

Copyright 2006 Los Angeles Times | Privacy Policy |

Terms of Service