In this issue of JBMR, Curtis colleagues (1) use data from the placebo group of a randomized, controlled osteoporosis trial to argue for a possible healthy adherer effect. Our understanding of this effect began when some randomized, controlled clinical trials in cardiovascular disease had cardiovascular outcomes that contradicted findings in prior observational studies. These findings highlighted the fact that several sources of bias can occur in observational studies. These biases can be related to patient behaviors, including both healthy user and healthy adherer effects. The best known examples of these biases have appeared in studies of cardiovascular disease. For example, a large observational study, the Nurses’ Health Study, showed decreased coronary heart disease in women taking hormonereplacement therapy (HRT) in 1985, a finding that was confirmed by other observational studies. However, more than 10 years later, two randomized, controlled clinical trials contradicted the observational findings: The Heart and Estrogen/ Progestin Replacement Study (HERS) showed no cardiovascular benefit from estrogen supplementation, and the Women’s Health Initiative showed increased incidence of cardiovascular events in women taking estrogen. How can we explain this divergence of results? First, we must identify and understand this divergence by understanding sources of bias. The first potential bias, the healthy user effect, occurs when patients who choose to receive one preventive service such as estrogen or a lipid-lowering agent also choose to receive other preventive services such as immunizations and screening tests. For example, patients who adhere to statins more frequently receive vaccinations and screening services. These same patients also may have less comorbidity and better functional status, increasing the likelihood of other healthy behaviors These patients also may be involved in fewer accidents, suggesting possible risk aversion. A second potential bias—the healthy adherer bias—was first demonstrated in 1980 when decreased mortality and fewer cardiovascular events were found in good adherers of placebo in a