Friday, March 18, 2011

Oral Bisphosphonates Pose Low Risk of Osteonecrosis of the Jaw (ONJ)

For the past several years, we in dentistry have been concerned about the long term affects of the drug class of bisphosphonates.

While the bisphosphonates definitely have a place in medicine, they have shown the potential for side effects in dentistry. In a nutshell, bisphosphonates are used to help prevent bone changes that can cause and/or contribute to osteoporosis. They are absolutely necessary for some patients because osteoporosis can be a severely debilitating disease and can have a tremendous effect on the patient's quality of life.

However, as bisphosphonates became more commonly prescribed, we in dentistry began to see a situation develop that became referred to as "Osteonecrosis of the Jaw" or "ONJ" for short. Basically ONJ appeared to be bone injuries in the mouth that did not heal as expected. Patients that had been taking bisphosphonates & then had an mouth injury, extraction, etc were at risk for this debilitating condition.

Dentists & oral surgeons became concerned because there are 2 types of bisphosphonates, oral & IV. It seemed like the IV drugs were the ones causing the problems, but because of the so many people having been exposed to both types, it was hard to tell.


Today on WebMD comes news that the oral drugs may have a lower risk or ONJ. The WebMD page is here.

Here is the article:

Low Risk of Jaw Problems With Oral Osteoporosis Drugs

Study Shows Lower Risk of Jaw Osteonecrosis With Oral Bisphosphonates Than With IV Drugs
By Kathleen Doheny
WebMD Health News
jaw xray

March 17, 2011 -- Osteoporosis drugs and serious jaw problems have been linked in past studies, but new research presented at the International Association for Dental Research in San Diego finds a low risk with oral osteoporosis drugs, known as bisphosphonates.

Echoing the findings of previous studies, the researchers did find a higher increase in risk for intravenous bisphosphonates, taken by a minority of those with osteoporosis.

"The risk of intravenous bisphosphonates [and jaw problems] is increased by sixfold compared to oral bisphosphonates," says researcher Peter Tawil, DDS, a resident in postdoctoral periodontics at the University of Pennsylvania School of Dental Health.

The study was funded partially by an unrestricted grant from the Alliance for Better Bone Health, supported by Warner Chillchott, Sanofi-Aventis, and Procter & Gamble. Sanofi and Warner Chillchott manufacture oral bisphosphonates.

Osteoporosis Drugs and Jaw Osteonecrosis

Reports of bisphosphonates and a link with the jaw problem known as osteonecrosis of the jaw began to appear in about 2003, Tawil tells WebMD. Osteonecrosis of the jaw is rare but serious and involves death of the bone due to lack of blood flow.

Early case reports, says Tawil, mainly involved patients on intravenous bisphosphonates.

As the reports surfaced, ''there were some dentists advising patients, 'Don't get treated for osteoporosis,''' says study researcher Marjorie Jeffcoat, DMD, professor of periodontology at the University of Pennsylvania.

"We felt patients were really being put at risk by telling them not to have their osteoporosis treated," she says, so she requested support for the studies.

Oral Osteoporosis Drugs vs. IV Drugs

Jeffcoat and Tawil report on four studies in all. Three were clinical trials totaling 516 participants, all on oral bisphosphonates for at least two years. Some were on alendronatae (Fosamax), made by Merck; others were on risendronate (Actonel), made by Warner Chillcott.

They examined patients every three months to look for evidence of osteonecrosis of the jaw and compared them with 516 matched patients not on bisphosphonates.

No cases were found in either group.

Next, the researchers evaluated a data base of more than 55 million people enrolled in 700 health plans from 2000 to 2006. They focused in on those who took bisphosphonates.

"Some of them took IV bisphosphonates; others took the oral," Tawil says. Of those on the drugs, 213,364 were on oral and 2,321 were on IV.

Next, they compared these to a group of 423,845 patients who did not take any bisphosphonates.

"The incidence of having necrosis of the jaw was very low -- about one per 1,000 for those who took oral [bisphosphonates]," Tawil says.

In the intravenous group, six of every 1,000 developed osteonecrosis of the jaw.

The risk of the jaw problem while on oral bisphosphonates, Tawil says, was similar to those not on the drugs. In non-users, he says, the risk was about 0.9, or less than one in 1,000.

The findings echo those of some previous studies finding low risk with the oral drugs, Jeffcoat says, but their research population is larger.

"The benefit outweighs the risk in treating osteoporosis with oral drugs," she says. Jeffcoat reports receiving research funding from Merck in 2004. Merck makes the oral bisphosphonate Fosamax.

Second Opinion

John Kalmar, DMD, professor of oral and maxillofacial pathology at Ohio State University, Columbus, reviewed the study abstract for WebMD. He agrees with some findings but is highly skeptical of others.

''I agree that the risk of osteonecrosis of the jaw is less with oral than for IV [bisphosphonates]," he says. "At this point everyone would agree."

But, he says, to equate the risk of those on oral drugs with persons not taking them, "I take great exception to."

"All studies to date have shown that even though the risk is a small increase it is still a measurable increase," Kalmar says.

Another potential problem, Kalmar tells WebMD, involves coding. Recently, a more specific medical code has come into use for osteonecrosis of the jaw. But in a database as large as the one studied by Jeffcoat and Tawil, which goes back to 2000, he says it is likely some cases of osteonecrosis were coded incorrectly.

It's no surprise to Kalmar that the study involving 516 patients on the drugs revealed no cases, as that number of patients is probably too small.

"Most estimates to date [for the jaw problem] are in the range of one to 1,000 to 10,000 for oral bisphosphonate users," Kalmar says.

Kalmar reports serving as an adjucator for Novartis and is consulted on whether cases of osteonecrosis of the jaw are due to bisphosphonates or not.

Julie Masow, a spokeswoman for Novartis, which makes Reclast and Zometa, two IV bisphosphonates, says she was not aware of the new research. The company had no comment at this time, she says.

This study was presented at a medical conference. The findings should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.

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