Adherence to oral bisphosphonates and the risk of subtrochanteric and femoral shaft fractures among female medicare beneficiaries
Previous studies have shown an association between duration of bisphosphonate use and atypical femur fractures. This cohort study showed an increasingly higher risk of subtrochanteric and femoral shaft fractures among those who were more adherent to oral bisphosphonates.
Long-term use of oral bisphosphonates has been implicated in an increased risk of atypical femur fractures located in subtrochanteric and femoral shaft regions. Another measure of drug exposure, medication adherence, however, has not been investigated.
Among all Medicare fee-for-service female beneficiaries from 2006–2010, we followed 522,287 new bisphosphonate users from their index prescription until being censored or having a primary diagnosis of closed subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures. Data about radiographs of fracture site and features were not available. Adherence was classified according to the medication possession ratio (MPR) as the following: MPR < 1/3 as less compliant, MPR ≥ 1/3– < 2/3 as compliant, and MPR ≥ 2/3 as highly compliant. Alternative cutoff points at 50 and 80 % were also used. Survival analysis was used to determine the cumulative incidence and hazard of subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures.
There was a graded increase in incidence of subtrochanteric/femoral shaft fractures as the level of adherence increased (Gray’s test, P < 0.001). The adjusted hazard ratio (HR) for the highly compliant vs. the less compliant was 1.23 (95 % Confidence Interval [CI] 1.06–1.43) overall, became significant after 2 years of follow-up (HR = 1.51, 95 % CI 1.06–2.15) and reached the highest risk in the fifth year (HR = 4.06, 95 % CI 1.47–11.19). However, age-adjusted incidence rates of intertrochanteric/femoral neck fractures were significantly lower among highly compliant beneficiaries, compared to less compliant users (HR = 0.69, 95 % CI 0.66–0.73). Similar results were obtained when the cutoff points for being compliant and highly compliant were set at 50 and 80 %, respectively.
Subtrochanteric/femoral shaft fractures, unlike intertrochanteric/femoral neck fractures, are positively associated with higher adherence to long-term (≥3 years) oral bisphosphonates in the elderly female Medicare population.
KeywordsBisphosphonates Fracture Osteoporosis Atypical femur fracture
This study was funded by the Intramural Research Program at NIAMS/NIH. We want to thank Shannon Pietzsch from General Dynamic Information Technology, Inc., Drs. Elizabeth Rasch and Alex Constantin from Department of Rehabilitation Medicine of NIH Clinical Center, and Dr. Seo Young Kim from Brigham and Woman’s hospital for their supports.
Author’s roles: ZW, MW, and TB had full access to the study details and output but limited access to the data due to the CMS ENCLAVE data user agreement, and will take responsibility for the integrity of the data and the accuracy of data analysis. Conception and design: ZW, MW, TB and LC. Data acquisition: ZW and LC. Analysis and interpretation: ZW, MW, and TB. Drafting of manuscript: ZW. Critical revision of the manuscript: ZW, MW, LC, and TB. Statistical analysis: ZW and MW.
Conflicts of interest
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