Drug linked to death of jawbone

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Drug linked to death of jawbone

By Rita Rubin, USA TODAY

Salvatore Ruggiero was puzzled.

Over a three-year period, the jaws of dozens of

patients who had undergone oral surgery at his

hospital had failed to heal properly. Part of the

jawbone had died and become exposed.

" We never saw this before in the jaw " except in

patients who had received radiation therapy to that

part of the face, says Ruggiero, chief of oral and

maxillofacial surgery at Long Island Jewish Medical

Center. " It just never existed. "

Further investigation revealed one common thread: All

of the patients had been treated with at least one of

a class of drugs called bisphosphonates.

Most were cancer patients who had received the

intravenous bisphosphonates Zometa or Aredia or both

for excessive calcium in their blood or bone tumors.

But about 10% were osteoporosis patients who had taken

an oral bisphosphonate, mainly Fosamax.

In May, Ruggiero co-wrote a report on 63 patients with

osteonecrosis — or bone death — of the jaw in the

Journal of Oral and Maxillofacial Surgery. Six had

taken Fosamax, and a seventh had taken Actonel,

another oral bisphosphonate for osteoporosis.

The problem doesn't appear to be as severe with oral

bisphosphonates as it is with the IV drugs, Ruggiero

notes. Patients who have been receiving IV

bisphosphonates should avoid having teeth pulled " at

all costs, " he says.

Based on his cases, a Food and Drug Administration

review posted last week on the agency's Web site

suggests that osteonecrosis of the jaw (ONJ) is a risk

of all bisphosphonates, not just the IV drugs.

Bisphosphonates remain in bone indefinitely. Ruggiero

speculates that their long-term use could upset the

delicate balance between cells that put calcium in

bone and cells that take calcium away.

The FDA review concluded that all bisphosphonate

labels should mention osteonecrosis.

Novartis, maker of Zometa and Aredia, added a

precaution about ONJ to their package inserts in

August, although the inserts note that cancer patients

have other osteonecrosis risk factors, such as their

malignancies.

Merck spokesman Tony Plohoros says his company is in

the process of adding information about the ONJ cases

to the Fosamax label. And Terri Pedone, spokeswoman

for Sanofi-Aventis, which markets Actonel with Procter

& Gamble, says, " We are currently addressing the FDA's

request to update the label " with information about

ONJ.

Rugierro says he has now seen a total of 12 or 13

cases of ONJ in patients treated with an oral

bisphosphonate. Marx, chairman of the division

of oral and maxillofacial surgery at Florida's

University of Miami, says he's aware of at least 40 or

50 cases of ONJ nationwide in patients who had taken

Fosamax.

That's a infinitely small fraction of the

approximately 3 million women in the USA who are

taking the drug, although most experts agree that only

1% to 10% of adverse events linked to drugs are

reported.

Interestingly, some doctors have prescribed IV

bisphosphonates " off label " for osteoporosis. And

Roche and GlaxoKline announced in December that

they are seeking FDA permission to market an IV form

of their oral bisphosphonate, Boniva, for

osteoporosis.

Drug linked to death of jawbone

By Rita Rubin, USA TODAY

Salvatore Ruggiero was puzzled.

Over a three-year period, the jaws of dozens of

patients who had undergone oral surgery at his

hospital had failed to heal properly. Part of the

jawbone had died and become exposed.

" We never saw this before in the jaw " except in

patients who had received radiation therapy to that

part of the face, says Ruggiero, chief of oral and

maxillofacial surgery at Long Island Jewish Medical

Center. " It just never existed. "

Further investigation revealed one common thread: All

of the patients had been treated with at least one of

a class of drugs called bisphosphonates.

Most were cancer patients who had received the

intravenous bisphosphonates Zometa or Aredia or both

for excessive calcium in their blood or bone tumors.

But about 10% were osteoporosis patients who had taken

an oral bisphosphonate, mainly Fosamax.

In May, Ruggiero co-wrote a report on 63 patients with

osteonecrosis — or bone death — of the jaw in the

Journal of Oral and Maxillofacial Surgery. Six had

taken Fosamax, and a seventh had taken Actonel,

another oral bisphosphonate for osteoporosis.

The problem doesn't appear to be as severe with oral

bisphosphonates as it is with the IV drugs, Ruggiero

notes. Patients who have been receiving IV

bisphosphonates should avoid having teeth pulled " at

all costs, " he says.

Based on his cases, a Food and Drug Administration

review posted last week on the agency's Web site

suggests that osteonecrosis of the jaw (ONJ) is a risk

of all bisphosphonates, not just the IV drugs.

Bisphosphonates remain in bone indefinitely. Ruggiero

speculates that their long-term use could upset the

delicate balance between cells that put calcium in

bone and cells that take calcium away.

The FDA review concluded that all bisphosphonate

labels should mention osteonecrosis.

Novartis, maker of Zometa and Aredia, added a

precaution about ONJ to their package inserts in

August, although the inserts note that cancer patients

have other osteonecrosis risk factors, such as their

malignancies.

Merck spokesman Tony Plohoros says his company is in

the process of adding information about the ONJ cases

to the Fosamax label. And Terri Pedone, spokeswoman

for Sanofi-Aventis, which markets Actonel with Procter

& Gamble, says, " We are currently addressing the FDA's

request to update the label " with information about

ONJ.

Rugierro says he has now seen a total of 12 or 13

cases of ONJ in patients treated with an oral

bisphosphonate. Marx, chairman of the division

of oral and maxillofacial surgery at Florida's

University of Miami, says he's aware of at least 40 or

50 cases of ONJ nationwide in patients who had taken

Fosamax.

That's a infinitely small fraction of the

approximately 3 million women in the USA who are

taking the drug, although most experts agree that only

1% to 10% of adverse events linked to drugs are

reported.

Interestingly, some doctors have prescribed IV

bisphosphonates " off label " for osteoporosis. And

Roche and GlaxoKline announced in December that

they are seeking FDA permission to market an IV form

of their oral bisphosphonate, Boniva, for

osteoporosis.