Race May Affect Atypical Femur Fracture Risk in Women Taking Bisphosphonates

Doctor checks patient's heartbeat
Doctor checks patient’s heartbeat
Asian women taking bisphosphonates may have a higher risk for atypical femur fracture than white women.

SEATTLE — New study results indicate that Asian women taking bisphosphonates may be at a much higher risk than their white counterparts for atypical femur fractures, leading researchers to suggest that clinicians should tailor their advice about atypical femur fracture risk to a patient’s race.

“We were not surprised by the findings,” said lead study researcher Joan Lo, MD, who is a research scientist at Kaiser Permanente Northern California Division of Research in Oakland.

Dr Lo, who presented the study results at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting, noted that previously published epidemiologic studies have shown that Asian women tend to have a greater propensity atypical femur fractures while taking a bisphosphonate compared with white women.  

To learn more, Dr Lo and colleagues examined the relative risk of atypical femur fracture following the initiation of a bisphosphonate for Asian women vs white women.

The researchers mined data from a large northern California healthcare delivery system for diaphyseal femur fractures among women aged 50 years or older who initiated oral bisphosphonate therapy between 2002 and 2007.

As part of their investigation, the researchers examined which patients were treated with glucocorticoids (1825 mg or more of a prednisone equivalent in the prior year), aromatase inhibitors, and pharmacologic proton pump inhibitors. They adjusted for demographic and clinical characteristics at baseline, including prior fracture history, diabetes, and rheumatoid arthritis.

After identifying all diaphyseal fractures, the researchers classified fractures as atypical femur fractures based on 2013 American Society of Bone and Mineral Research Task Force criteria.

A total of 48,390 women (mean age, 69.5 years) who initiated bisphosphonate therapy were identified. All women had at least 3 years of follow-up.

The researchers noted that the cohort was diverse. Of all women, 65.3% were white, 17.1% were Asian, 9.5% were Hispanic, 4.1% were black, and 4.1% were identified as other or unknown.

The researchers used Cox proportional hazard analyses adjusting for differences in bisphosphonate exposure and other potential risk factors.

In this cohort, 68 women experienced an atypical femur fracture over a median follow-up of 7.7 years.

Results indicated that Asian women had a dramatically higher risk for atypical femur fracture. The researchers found an 8-fold higher risk among Asian women (64.2 per 100,000 person-years) compared with white women (7.6 per 100,000 person-years).

“This is a rare complication, but we need to know who may be at more risk than others,” Dr Lo said in an interview with Endocrinology Advisor. “It is important to be aware of this difference.”

The researchers also conducted unadjusted analyses and found that prior fracture, diabetes, rheumatoid arthritis, and baseline glucocorticoid levels were not associated with atypical femur fracture. The same was true for aromatase inhibitor therapy and proton pump inhibitor therapy. 

Dr Lo said the analyses showed that race/ethnicity was strongly associated with risk for atypical femur fracture, with an age-adjusted relative hazard of 8.5 (95% CI, 4.9-14.9) for Asian women compared with white women. 

In addition, the researchers found that the age-adjusted relative hazard was only modestly reduced to 6.6 (95% CI, 3.7-11.5) after adjusting for bisphosphonate therapy duration and current use.

The median duration of bisphosphonate use was 2.7 years among white women and 3.8 years among Asian women.

These findings warrant further investigation, and studies should examine the mechanisms that may be responsible for this pronounced difference in race/ethnicity, according to Dr Lo.

In the meantime, the researchers believe clinicians should counsel Asian women that they may have a higher risk for experiencing an atypical femur fracture while on bisphosphonate therapy. 


  1. Lo J. Late-Breaking Abstract Presentations. The Association of Race Ethnicity and Risk of Atypical Femur Fracture in Women Treated with Oral Bisphosphonate Drugs. Presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.