According to a new study, nearly 78% of all Swedish women aged 55 years and older who sustained a thigh bone or femur fracture in 2008 had taken bisphosphonates for their osteoporosis. However the authors of the study published in the May 5 issue of the New England Journal of Medicine (NEJM) write that the absolute risk for such breaks is small enough to justify prescribing the drugs.
The study showed that risk of femur fracture was 47.3%. The incidence of the fractures was 0.09 per 10,000 patient-years among women who had never taken the drug compared with 5.5 among those who had ever taken it.
These results “should be reassuring for bisphosphonate users,” write lead author Jörg Schilcher, from the Department of Experimental and Clinical Medicine, Faculty of Health Science, Linköping University, Linköping, Sweden, and colleagues. “With a correct indication, the benefits of fracture prevention...will greatly outweigh the risk of atypical femoral fracture.” The study is also lauded because it involved 1.5 million women in Sweden who were aged 55 years or older in 2008 and reviewed the x-rays of nearly all those who had particular kinds of femur fractures.
“It's the largest and most comprehensive study of this issue that I've seen,” said Sundeep Khosla, president of the American Society for Bone and Mineral Research (ASBMR) and a professor of medicine and physiology at the Mayo Clinic in Rochester, Minnesota.
In October 2010, the US Food and Drug Administration (FDA) revised the labels of bisphosphonates to warn about the possible increased risk for femur fractures. Agency officials at the time said that patients taking bisphosphonates for osteoporosis should continue to do so because the drugs prevent far more fractures than they may trigger. The label revision applies only to bisphosphonates with FDA approval for osteoporosis, such as alendronate (Fosamax, Merck) and risedronate sodium (Actonel, Proctor & Gamble Pharmaceuticals). Bisphosphonates for the treatment of Paget's disease and high blood calcium levels caused by cancer are not affected.
Dr. Schilcher and co-authors combed the National Swedish Patient Register and found 12,777 women aged 55 years and older who broke their femur in 2008. Of these, 1271 had subtrochanteric or diaphyseal fractures just below the hip joints. The researchers were able to track down x-rays for 1234 women. A review of these x-rays revealed that 59 women in this group had atypical femur fractures or clean fractures. Of the subset of 59 women with atypical femur fractures, 46, or almost 78%, had used bisphosphonates. This figure compares with 83,311 Swedish women in all who had taken the medication, based on the Swedish Prescribed Drug Register.
Per Aspenberg, a professor of orthopedic surgery at Linköping University in Sweden and a co-author of the study, also added the findings indicated a patient's risk of fracture diminished by 70% after stopping the drugs for a year. Dr. Aspenberg said more research needed to be done. Elizabeth Shane, a professor of medicine at Columbia University who chaired a task force on the issue, said the study reinforced the idea that the drugs should continue to be used in people at high risk for fractures. Risk factors include low bone density, a family history of osteoporosis or fractures, and alcohol and tobacco use.
Dr. Shane, who wasn't involved in the study, said that researchers were trying to figure out why some people are at higher risk for uncommon fractures when taking the drugs. She said the American Society of Bone and Mineral Research, which convened the task force, was now working to set up a national registry of patients with these fractures in the hopes of getting answers.
Commenting on the findings, Dr. Nelson Watts, director of the University of Cincinnati's Bone Health and Osteoporosis Center, said that “nothing in life is risk-free. Balancing benefits with risks is important for any decision.” Watts added, “For patients with osteoporosis, the benefits of treatment for reducing the more common and disabling types of hip fracture outweigh the slight risks of atypical femur fractures.” Another expert, Dr. Robert R. Recker, director of the Osteoporosis Research Center at Creighton University School of Medicine in Omaha, Neb., and president of the National Osteoporosis Foundation, agreed. “My advice to patients is the risk of atypical fractures is extremely small; however, the benefit in terms of fracture prevention is huge and completely swamps it,” he said.