Asian ethnicity associated with atypical femur fracture risk
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A cohort of Asian adults were 3.4 times more likely to experience an atypical femur fracture compared with non-Asian adults, although the incidence was still low, according to findings published in Bone.
“Although rare, the effect of a painful, spontaneous atypical femur fracture is devastating,” Hanh H. Nguyen, MBBS, BMedSci, FRACP, of the department of medicine at Monash University School of Clinical Sciences in Victoria, Australia, and colleagues wrote in the study background. “Prodromal thigh pain occurs in 70%, 40% are bilateral, and delayed healing is common, resulting in prolonged immobilization. The incidence is low, at 0.3 to 0.8 cases per 100,000 person-years in bisphosphonate-naive individuals, rising to 50 cases per 100,000 person-years in bisphosphonate-users, and increasing with longer duration of bisphosphonate therapy (113 per 100,000 person-years after 7 to 8 years).”
Nguyen and colleagues analyzed data from 71 adults aged at least 50 years who sustained 97 atypical femur fractures (82 complete, 15 incomplete), admitted to Monash Health between 2009 and 2017 (mean age, 74 years; 88.7% women), as well as a cohort of adults who sustained typical femur fractures (n = 3,330; mean age, 83 years; 69.1% women).
“As subject-level data linkage between the Monash Health study population and national pharmaceutical data registry was not possible, a nested case-control substudy was conducted in order to assess differences in medication use and comorbidities,” the researchers wrote. “Radiologically adjudicated typical subtrochanteric/femoral shaft fracture cases were selected from the study cohort to form an age- and sex-matched control group.”
The cumulative incidence rate of atypical femur fracture was 4.2 per 100,000 person-years, or 2.1% of the incidence of coded femur fractures in the total cohort, far lower than for any ICD-10-AM coded “typical” femur fracture (202.9 per 100,000 person-years).
Researchers found that Asian adults were 3.4 times more likely to sustain an atypical femur fracture vs. non-Asian adults (95% CI, 2.1-5.6), with the highest incidence observed among Southeast Asian adults (16.6 per 100,000 person years), suggesting differences in risk between Asian countries.
In a nested case-control study comparing atypical femur fracture cases to typical femur fractures, history of antiresorptive therapy was much higher among atypical cases vs. controls (93.9% vs. 13%). The most common bisphosphonate used was alendronate (n = 49), followed by risedronate (n = 24); 10 patients were prescribed sequential therapy. There were too few atypical femur fracture cases with a history of zoledronic acid or denosumab (Prolia, Amgen) therapy to determine whether higher risk for atypical femur fracture is associated with oral bisphosphonates compared with IV or denosumab therapy, according to the researchers.
“Our findings are reassuring to clinicians as the risk-benefit ratio is in favor of initiating antiresorptive therapy in osteoporosis populations given the burden of typical femur fractures in this study, particularly neck of femur fractures, far outweighs the incidence of atypical femur fractures, and the known efficacy of bisphosphonates in reducing fragility fracture risk by up to 70%,” the researchers wrote.
The researchers noted that mechanisms to explain the association between Asian ethnicity and atypical femur fractures remain unknown but possibly relate to femoral geometry or bone microarchitecture.
“Femoral geometric parameters more common in Asians may predispose to atypical femur fractures, such as shorter femoral neck length, smaller neck-shaft angles, and shorter limbs with increased femoral bowing,” the researchers wrote. – by Regina Schaffer
Disclosures: Nguyen reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Robert Blank, MD, PhD
This is an observational study from the Monash Health System in Melbourne, Australia, that includes 25% Asian-origin patients, comprising multiple Asian regions. The primary data were administrative and were supplemented by review of radiographs. Two studies were performed. First, there was a retrospective cohort study to examine factors associated with atypical femur fracture. Second, there was a nested case-control study comparing atypical femur fracture to other subtrochanteric femoral fractures, with the degree of trauma not knowable per data structure.
The main finding of greatest interest to me was that excess risk of atypical femur fracture was among those of Southeast Asian ethnicity, with little if any excess risk evident among those of Chinese, Korean, Japanese, Indian, Pakistani, Sri Lankan or central Asian origin. This should not be surprising. Asia is the world’s largest and most highly populated continent. It should be expected that its inhabitants are diverse.
This study also confirmed prior findings that antiresorptive drug therapy increases atypical femur fracture risk, but that the frequency of atypical femur fracture is very low compared with typical osteoporotic fractures.
This work did not collect any data that helps to identify the specific determinants of atypical femur fracture risk, a limitation that the authors stressed in their discussion.
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