Atypical Fractures Rise With Bisphosphonate Use


From the Annual Meeting of the American Society For Bone And Mineral Research

Major Finding: The rate of atypical femur fractures in patients with osteoporosis who were treated with a bisphosphonate rose with increased duration of use. On average, 50 atypical fractures occurred for every 100,000 patients treated for 5 years, 100 atypical fractures occurred per 100,000 patients treated for 6 years, and almost 250 atypical fractures occurred per 100,000 patients treated for 12 years.

Data Source: Review of radiographs from 1,448 Kaiser California patients with a diaphyseal femur fracture during January 2007 through December 2009, including 135 that met the atypical criteria.

Disclosures: Dr. Ott and Dr. Wang had no disclosures. Dr. Shane has been a consultant to Amgen and has received research support from Merck, Novartis, and Eli Lilly.

TORONTO – Patients with osteoporosis who are on bisphosphonate therapy clearly face an increased treatment-linked risk for atypical femur fractures, but at a low rate that is dwarfed by the number of typical hip fractures the drugs prevent.

The risk for atypical fracture appears to rise substantially as time on the drug increases, but an atypical fracture can occur at any time, prompting experts to stress that a bisphosphonate should be given only to a patient who needs the treatment. And the prodromal thigh or groin pain that precedes a majority of atypical fractures should alert physicians to stop bisphosphonate treatment, although stopping the drug is no guarantee against a subsequent atypical fracture.

Above all, experts agreed, atypical fracture risk is no reason to deny bisphosphonate treatment to patients who need it, because these drugs improve bone mineral density and prevent typical hip fractures, and because in appropriate patients this benefit far exceeds the atypical fracture risk.

This consensus on how to view bisphosphonates and their risk for causing atypical fractures pervaded the meeting One multispeaker session during the meeting reviewed the data compiled by and the recommendations from an American Society for Bone and Mineral Research (ASBMR) task force that were published online late last year, while several other speakers reported some of the incidence data that task force members considered when writing their recommendations (J. Bone Miner. Res. 2010 [doi:10.1002/jbmr.253]).

“The message is that for patients with osteoporosis at high risk of having a fracture, treatment with a bisphosphonate will benefit far more than risk for an atypical fracture,” said Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York, and cochair of the task force. h

The largest and most comprehensive look at atypical fracture rates came from data compiled from the 2.6 million beneficiaries older than 45 years enrolled in Kaiser California. During January 2007 through December 2009, 15,819 people had femur fractures, excluding those from major trauma, those secondary to Paget's disease or metastatic lesions, or periprosthetic fractures. The researchers reviewed the radiographs for 1,448 of these fractures located in the diaphyseal region.

Of the reviewed fractures, the researchers identified 135 as atypical, based on their location in the diaphyseal portion of the femur, either in the shaft or subtrochanteric region, as well as other features: a transverse fracture, usually with lateral cortical thickening especially at the fracture site, and flaring of the lateral cortex, Dr. Susan Ott of the University of Washington, Seattle, reported at the meeting.

The 135 patients with atypical fractures were 98% women, with an average age of 71 years and an average body mass index of 26.6 kg/m

All but 4% of the atypical fracture patients received a bisphosphonate at the time of fracture, and were on their regimen for an average of 6 years. Two-thirds had prodromal thigh pain, and 26% had bilateral atypical fractures. In all, 60% of the fractures occurred in the femur shaft, and 40% were in the subtrochanteric region.

The most common age at fracture was 65–69 years, with a majority of atypical fracture patients aged 65 or older. The fracture rate rose steadily with increasing years of bisphosphonate use, with most fractures occurring in patients who had used the drugs for at least 5 years, even though these long-term users represented a small minority of all Kaiser patients who used a bisphosphonate during the 3 years studied. The number of fractures per 100,000 people exposed rose steadily with increasing years of use, reaching 50 per 100,000 when bisphosphonate use continued for 5 years and 100 fractures per 100,000 patients in those using the drug for 6 years, and then continuing to rise steadily with added years of use, reaching a high of nearly 250 fractures for every 100,000 patients exposed to a bisphosphonate for 12 years.

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