Responses to AFP Journal Club on Hip Fracture and PPI Use/IN REPLY

The "AFP Journal Club" concerning hip fracture risk in patients on long-term proton pump inhibitor (PPI) therapy highlighted an important association which, if causal, could have important public health implications given the common use of PPIs. The study by Yang and colleagues was a cohort study rather than a case-control study.1 The authors may have been confused because the study researchers1 used a nested case-control analysis, which is a common approach when the cohort contains a large number of participants.2 Although both study methods are prone to uncontrolled confounding (as the authors point out), cohort studies are generally less prone to bias than case-control studies and can be used to calculate incidence,2 as was done in the study by Yang and associates.1 A meta-analysis of randomized controlled trials of PPI therapy would be the most valid proof that this association is causal, but will probably not be practical because trials of PPIs have not had follow-up long enough to detect differences in hip fracture incidence. [...] it would be unethical to conduct a randomized trial of smoking, but we can do a cohort study: watch patients who smoke or do not smoke and see if there are any differences in lung cancer over time.