Exposure: Postmenopausal women exposed to bisphosphonates
Outcome: Atypical femur fracture (AFF) over the course of treatment (radiographically confirmed).
Hypothesis: Greater exposure to BPs is independently associated with AFF risk, particularly among those with other risk factors.
Model: The accumulation model would be the most appropriate in this example. Longer bisphosphonate use is expected to be independently associated with increased risk of AFF. Conversely, after adjustment for other risk factors and BMD, it is expected that the risk of fracture will be reduced (either minimal or moderate) or not associated with bisphosphonate use.
Regression Model: To determine whether other factors are associated with AFF, Cox models for time to AFF will be derived using a set of candidate predictors. For the proposed analysis, duration and timing of BP use will be fixed covariates, evaluated at the time the prediction is made. The analysis will also estimate the independent effect of BP use on AFF in the population age≥50, both overall and in the subset with pre-treatment BMD measurements. Longer bisphosphonate use is expected to be independently associated with increased risk of AFF.
Data sets: It would be difficult to find a dataset that may answer the above questions due to the rare outcome (AFF). However, one could use the Kaiser California data. The information would be available via electronic medical records, with standing linkage to cause of death and fact of death, laboratory data both inpatient and outpatient readily accessible, geocoding (census blocks – race, income, education), drug utilization, and radiological testing and results, demographic and enrollment data, and hospital discharge data.