Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis.
BACKGROUND
Bisphosphonates are the mainstay of anti-osteoporotic treatment and are commonly used for a longer duration than in the placebo-controlled trials. A link to development of atypical subtrochanteric or diaphyseal fragility fractures of the femur has been proposed, and these fractures are currently the subject of a U.S. Food and Drug Administration review.


OBJECTIVE
Our objective was to examine the risk of subtrochanteric/diaphyseal femur fractures in long term users of alendronate.


METHODS
We conducted an age- and gender-matched cohort study using national healthcare data.


METHODS
Patients were alendronate users, without previous hip fracture, who began treatment between January 1, 1996, and December 31, 2005 (n=39,567) and untreated controls, (n=158,268).


METHODS
Subtrochanteric or diaphyseal femur fractures were evaluated.


RESULTS
Subtrochanteric and diaphyseal fractures occurred at a rate of 13 per 10,000 patient-years in untreated women and 31 per 10,000 patient-years in women receiving alendronate [adjusted hazard ratio (HR)=1.88; 95% confidence interval (CI)=1.62-2.17]. Rates for men were six and 31 per 10,000 patient-years, respectively (HR=3.98; 95% CI=2.62-6.05). The HR for hip fracture was 1.37 (95% CI=1.30-1.46)) in women and 2.47 (95% CI=2.07-2.95) in men. Risks of subtrochanteric/diaphyseal fracture were similar in patients who had received 9 yr of treatment (highest quartile) and patients who had stopped therapy after the equivalent of 3 months of treatment (lowest quartile).


CONCLUSIONS
Alendronate-treated patients are at higher risk of hip and subtrochanteric/diaphyseal fracture than matched control subjects. However, large cumulative doses of alendronate were not associated with a greater absolute risk of subtrochanteric/diaphyseal fractures than small cumulative doses, suggesting that these fractures could be due to osteoporosis rather than to alendronate.
Abrahamsen
Bo
B
Odense Patient Data Exploratory Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. b.abrahamsen@physician.dk
Eiken
Pia
P
Eastell
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced / Q000453:epidemiology*; D006620:Hip Fractures / Q000453:epidemiology; D006801:Humans; D006810:Humeral Fractures / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D016103:Spinal Fractures / Q000453:epidemiology; D014481:United States; D014486:United States Food and Drug Administration
D050071:Bone Density Conservation Agents; D019386:Alendronate