Department of Research & Evaluation News

In a study published in the New England Journal of Medicine, Kaiser Permanente Southern California research scientists report that while atypical femur fracture risk is rare, it does increase with longer use of bisphosphonate to treat osteoporosis, especially after 5 years. Asian women had approximately 5 times the risk of these fractures with prolonged bisphosphonate use compared to white women.

“Atypical femur fractures with bisphosphonate use are extremely rare, particularly compared to the fractures that the bisphosphonates prevent,” said the study’s lead author Dennis M. Black, PhD, a professor of epidemiology and biostatistics with the University of California, San Francisco, and an adjunct investigator with Kaiser Permanente Southern California Department of Research & Evaluation. “However, this study found that atypical femur fracture risk does increase with length of bisphosphonate use, a risk that may be reduced by taking a break from using bisphosphonates, often referred to as a ‘drug holiday.’”

Bisphosphonates have been used since the 1990s as an effective medication to reduce the risk of hip, spine, and other fractures among aging women with osteoporosis. However, in 2006 reports began to emerge about women who were taking the bisphosphonates developing unusual fractures in their thigh bones. While some small studies on this condition have been conducted, they had mixed results. Researchers in this current study looked at the issue among a large, ethnically and racially diverse patient population. The study also provides important new insights into whether the risk of these fractures decreases once the drug is stopped.

Kaiser Permanente and UCSF researchers studied the electronic health records of nearly 200,000 bisphosphonate-treated women 50 years old and older from Kaiser Permanente in Southern California from Jan. 1, 2007, to Nov. 30, 2017. Among 196,129 women studied, 277 sustained atypical femur fractures.

Among the findings:

• The risk of atypical femur fracture was very low for women with 3 to 5 years of treatment: 1 to 2 cases for each 10,000 women.
• The benefits of treatment were overwhelmingly positive compared to atypical femur fracture risk: For 3 to 5 years of treatment, 100 to 200 osteoporotic fractures could be prevented for each atypical femur fracture associated with treatment.
• Beyond 5 years atypical fracture risk increased, suggesting that treatment duration should be limited in women at higher atypical femur fracture risk.
• Atypical femur fracture and other fracture risk could be predicted, which means treatment can be personalized based on risk factors such as age, bone density, weight, and race.
• Among all racial and ethnic groups, Asian women had the highest risk of atypical femur fractures with bisphosphonate use, approximately 5 times higher than other groups, suggesting that they may benefit more from shorter courses of therapy.
• Discontinuing bisphosphonate therapy is associated with a rapid decline in atypical femur fracture risk, going from 4.5 fractures per 10,000 women in current users to 1.8 per 10,000 one year after stopping the medication and 0.5 per 10,000 2 years after stopping.

“Despite these findings, the risk of atypical femur fracture remains very low compared with risk of hip and other fractures, which bisphosphonates are used to reduce,” said the senior author of the article, Annette L. Adams, PhD, of Kaiser Permanente Southern California. “We also found that the risk varies greatly between racial and ethnic groups, which tells us that the recommendations for treatment regimens and drug holidays to reduce atypical femur fracture risk should be tailored to each patient.”

The study shows physicians the importance of personalized treatment plans, said study co-author Richard Dell, MD, an orthopedic surgeon at Kaiser Permanente Downey Medical Center.

“This study shows that the personalization of treatment plans based on individual risk factors can dramatically reduce the already low risk of atypical femur fracture,” Dr. Dell said, “and enhance the fracture-reduction benefit of bisphosphonate treatment.”