Increased Atypical Fracture Rate Associated With Bisphosphonate Treatment in Postmenopausal Asian Women

Researchers examine the association between duration of bisphosphonate treatment and risk of atypical femur fracture in postmenopausal women.

Based on the findings of several epidemiologic studies, investigators examined racial disparities associated with the risk of atypical femur fracture (AFF) in women receiving bisphosphonate treatment.1

The National Osteoporosis Foundation (NOF) recommends pharmacologic therapy for postmenopausal women with a history of fragility fracture or with osteoporosis based upon bone mineral density (BMD) measurement (T-score ≤ -2.5).2 Pharmacologic therapy is also recommended for the treatment of high-risk postmenopausal women with T-scores between -1.0 and -2.5.  Fracture risk is typically calculated using the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and is determined by a combination of BMD and clinical risk factors. Particular attention should be paid to treating women with a recent fracture, including hip fracture, as they are at high risk for a second fracture.  For most postmenopausal women without contraindication, bisphosphonates are considered first-line therapy. 

In a study published in the journal Bone, Lo and colleagues describe a higher rate of atypical fractures in Asian woman compared with white women.  Using data from Kaiser Permanente Northern California, the investigators examined 48,390 women aged 50 years and older (65.3% white, 17.1% Asian).  Study subjects were started on oral bisphosphonate therapy with alendronate (96.6%), risedronate, or ibandronate from 2002 through 2007 and followed for a median of 7.7 years to determine diaphyseal femur fracture outcomes.  Diaphyseal fractures were classified as atypical (AFF) or non-atypical (non-AFF) using the 2013 American Society for Bone and Mineral Research Task Force criteria.

The investigators identified an atypical fracture rate of 18.7 per 100,000 person-years overall. The age-adjusted relative hazard for AFF in Asian women compared to white women was 8.5 (95% confidence interval, 4.9-14.9), modestly reduced to 6.6 (3.7-11.5) after adjusting for duration and current use of bisphosphonate).  The study was limited by a relatively narrow geographical area from which study participants were recruited (all participants were from a northern California registry).  Additionally, the study did not specifically address the risk of AFF associated with continued bisphosphonate therapy.  The researchers advised that further studies should be conducted to determine if there is a true reduction in AFF risk with cessation of bisphosphonate treatment in Asian women.

Summary and Clinical Applicability

The rate of AFF was found to be 8-fold higher among Asian women compared with white women (64.2 vs 7.6 per 100,000 person-years).  This finding is clinically relevant as physicians can use this information to risk stratify those patients who are at higher risk for AFF and to direct diagnostic examination, as needed.


1. Lo J, Hui R, Grimsrud C, et al. The association of race/ethnicity and risk of atypical femur fracture among older women receiving oral bisphosphonate therapy. Bone. 2016; Jan 6. pii: S8756-3282(16)00003-X. doi: 10.1016/j.bone.2016.01.002. [Epub ahead of print]

2. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis.  Washington, DC: National Osteoporosis Foundation; 2010.