These results were obtained from the Nurses' Health Study, which began in 1976 by enrolling 121,700 US nurses who have been followed up every 2 years ever since. Since 2000, the participants have been asked, along with many other questions, whether they regularly used a PPI. Response rates for this study are consistently at least 90%. Compared with nonusers, the risk of hip fracture among women who regularly used a PPI for at least 2 years was 35% higher than nonusers (age-adjusted hazard ratio = 1.35; 95% CI, 1.1 - 1.6). Duration of use was associated with increased likelihood of fracture. Women who smoked were at higher risk (age-adjusted hazard ratio = 1.51; 1.2- 1.9). Conversely, women who never smoked had no increased risk. The effect was the same when investigators controlled for reasons for using chronic therapy, such as heartburn.