As with many cohort studies, this report has several limitations (8–10). First, patients were not randomly assigned. Physicians, and therefore clinical circumstances, determined who received which drug. Second, the authors had no access to the factors that led physicians to choose one drug and not another. Third, 1 group—those who received calcitonin—were more ill, based on the number of comorbid conditions, medications listed, and recent hospitalizations. Fourth, fewer patients receiving calcitonin or raloxifene had an osteoporosis diagnosis. All these factors could influence fracture rates independent of the effectiveness of the drug these patients received, and even the most sophisticated multivariate analysis cannot overcome these limitations. To the authors' credit, they acknowledge several situations in which they cannot exclude confounding by indication—whereby a clinical finding that determines whether a person receives a drug is causally related to the study outcome—as a possible explanation for some results. Randomly assigned treatment would negate most of these concerns, which is why we have come to rely on randomized trials for evidence about drug treatments.