The risk of fracture seems to “start at about 3 years and peaks between 5 and 6 years,” Dr. Forouzesh said. To be ahead of the game, he advises not waiting until the risk peaks. “Back off ahead of time. I do a drug holiday in 3 or 4 years,” he said.
It's not clear at this point if the phenomenon—if it is truly real—is limited to alendronate or a bisphosphonate class effect.
Alendronate has been on the market the longest and has been the most widely used agent, Dr. Lane noted. “I am sure over time” it will emerge with other members of the class, as well, she said.
Meanwhile, there are efforts to raise awareness of the issue. The American College of Rheumatology issued a bulletin on the matter in March (“Atypical Femoral Fractures With Long-Term Bisphosphonate Use,” which can be accessed online at
www.rheumatology.org/publications/hotline/2010_03_22_bisphosphonate.asp
At Cedars-Sinai, “we are trying to have [a conference] to make rheumatologists and others aware of how to deal with the problem,” Dr. Robinson said.
A New Finding Unraveled, Slowly
Doctors first became aware of the issue a few years ago.
“First, there were a lot of reports in Singapore of unusual hip fractures before the lesser trochanter, [with] unusual x-ray changes,” Dr. Silverman said.
Reports started to be seen in the United States, and physicians across the country began sharing their stories.
Only by reexamining medical records did doctors realize that the patients shared a common history of bisphosphonate use, Dr. Bengs said.
At the present, it's a “slow-rolling snowball. It might be huge, but there still are doctors who do not believe it. I only converted recently because I researched it,” he said.
Many of the physicians who were interviewed for this story said they are concerned that women will go off the drugs because of press reports.
They point out that in a recent bisphosphonate manufacturer–sponsored study, investigators couldn't disprove a connection, but did conclude that the fractures are rare, and that the benefit of taking the drugs still outweighs the risks (N. Engl. J. Med. 2010;362:1761-71).
Another manufacturer-sponsored study showed that subtrochanteric femur fractures have occurred in people who have not used bisphosphonates (Osteoporos. Int. 2010;21[suppl. 1]:s7-24).
“We have a new radiologic finding, but no data that the incidence of the fractures has gone up,” Dr. Silverman said.
The Food and Drug Administration said that it is staying on top of the issue. The agency continues “to evaluate the issue of the use of bisphosphonates and atypical femur fracture,” a press person wrote in response to an e-mail inquiry.
The agency has no plans at present for an advisory committee meeting regarding the issue.
Concerned Women
As the issue continues to be examined, doctors are fielding questions from concerned women.
“My answer [to them] is that it's an unknown and unconfirmed [phenomenon], and that the data are not out there to answer the questions,” said Dr. Eric M. Ruderman of the division of rheumatology at Northwestern University in Chicago.
At present, Dr. Ruderman doesn't stop bisphosphonate use because of fracture concerns, but he does have his patients take a drug holiday after 7 years because evidence is lacking for benefit after that point, he said.
He continues monitoring bone density thereafter to assess the need for further treatment.
Disclosures: Dr. Motamedi, Dr. Robinson, and Dr. Forouzesh said that they had no conflicts to disclose. Dr. Bengs disclosed he is a paid consultant for Amgen Inc. Dr. Lane disclosed research grants, royalties, consulting fees from and positions of influence and ownership interests in Amgen, Eli Lilly & Co. and Pfizer Inc. Dr. Ruderman disclosed that he is a consultant for Amgen and Pfizer. Dr. Silverman disclosed he has served as a speaker, member of a speakers bureau, advisor for Eli Lilly, Novartis Pharmaceuticals Corp., Procter & Gamble, and Roche Inc., and that he has received research support from Eli Lilly, Procter & Gamble, Roche, and Novartis.
This femur fractured 2 days after the image revealed cortical thickening and a beaklike stress fracture, perhaps from bisphosphonates.
Source Courtesy UCLA