The latest findings regarding the risk for atypical femur fracture (AFF) with use of bisphosphonates for osteoporosis show a significant increase in risk when treatment extends beyond 5 years. The risk is notably higher risk among Asian women, compared with White women. However, the benefits in fracture reduction still appear to far outweigh the risk for AFF.
The research, published in the New England Journal of Medicine, importantly adds to findings from smaller studies by showing effects in a population of nearly 200,000 women in a diverse cohort, said Angela M. Cheung, MD, PhD.
“This study answers some important questions – Kaiser Permanente Southern California is a large health maintenance organization with a diverse racial population,” said Dr. Cheung, director of the Center of Excellence in Skeletal Health Assessment and osteoporosis program at the University of Toronto.
“This is the first study that included a diverse population to definitively show that Asians are at a much higher risk of atypical femur fractures than Caucasians,” she emphasized.
Although AFFs are rare, concerns about them remain pressing in the treatment of osteoporosis, Dr. Cheung noted. “This is a big concern for clinicians – they want to do no harm.”
Risk for AFF increases with longer duration of bisphosphonate use
For the study, Dennis M. Black, PhD, of the departments of epidemiology and biostatistics and orthopedic surgery at the University of California, San Francisco, and colleagues identified women aged 50 years or older enrolled in the Kaiser Permanente Southern California system who were treated with bisphosphonates and were followed from January 2007 to November 2017.
Among the 196,129 women identified in the study, 277 AFFs occurred.
After multivariate adjustment, compared with those treated for less than 3 months, for women who were treated for 3-5 years, the hazard ratio for experiencing an AFF was 8.86. For therapy of 5-8 years, the HR increased to 19.88, and for those treated with bisphosphonates for 8 years or longer, the HR was 43.51.
The risk for AFF declined quickly upon bisphosphonate discontinuation; compared with current users, the HR dropped to 0.52 within 3-15 months after the last bisphosphonate use. It declined to 0.26 at more than 4 years after discontinuation.
The risk for AFF with bisphosphonate use was higher for Asian women than for White women (HR, 4.84); this did not apply to any other ethnic groups (HR, 0.99).
Other risk factors for AFF included shorter height (HR, 1.28 per 5-cm decrement), greater weight (HR, 1.15 per 5-kg increment), and glucocorticoid use (HR, 2.28 for glucocorticoid use of 1 or more years).
Among White women, the number of fractures prevented with bisphosphonate use far outweighed the risk for bisphosphonate-associated AFFs.
For example, among White women, during a 3-year treatment period, there were two bisphosphonate-associated AFFs, whereas 149 hip fractures and 541 clinical fractures were prevented, the authors wrote.
After 5 years, there were eight AFFs, but 286 hip fractures and 859 clinical fractures were prevented.
Although the risk-benefit ratio among Asian women still favored prevention of fractures, the difference was less pronounced – eight bisphosphonate-associated AFFs had occurred at 3 years, whereas 91 hip fractures and 330 clinical fractures were prevented.
The authors noted that previous studies have also shown Asian women to be at a disproportionately higher risk for AFF.
An earlier Kaiser Permanente Southern California case series showed that 49% of 142 AFFs occurred in Asian patients, despite the fact that those patients made up only 10% of the study population.