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.


BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Intramural Research Program, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced* / Q000453:epidemiology; D005265:Femoral Neck Fractures / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006620:Hip Fractures / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D006278:Medicare; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D016903:Drug Monitoring
D050071:Bone Density Conservation Agents; D004164:Diphosphonates