Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients: a population-based cohort study

A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study indicated that PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients. The risk tends to increase as the cumulative doses of PPIs increase. A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study investigated the association between PPI use and the risk of osteoporosis and fracture among stroke survivors. A population-based propensity-matched retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients diagnosed with a new stroke between 2000 and 2012 were identified. After propensity score matching, 10,596 patients were enrolled, and 5298 patients were each assigned to the PPI user and non-user groups. Hazard ratios (HRs) were calculated for the risk of osteoporosis, hip fracture, and vertebral fractures according to PPI use or non-use. Sensitivity analyses were conducted to evaluate the dose effects of PPI. PPI use after stroke was associated with an increased risk of osteoporosis, hip fracture, or vertebral fracture, with an adjusted HR (aHR) of 1.28 (P < 0.001). The aHRs were also significant for each outcome: osteoporosis, 1.26 (P < 0.001); hip fracture, 1.18 (P = 0.048); vertebral fracture, 1.33 (P < 0.001). A pattern of dose effect was identified. For any event (osteoporosis/hip fracture/vertebral fracture), the aHR for PPI use of 1-90, 91-365, and > 365 cDDDs was 1.22 (P < 0.001), 1.27 (P < 0.001), and 1.66 (P < 0.001), respectively. For each outcome, the highest dose was associated with the highest risk, with aHR of 1.79 (P < 0.001), 1.41 (P = 0.039), and 1.82 (P < 0.001) for osteoporosis, hip fracture, and vertebral fracture, respectively. Age- and sex-stratified analyses revealed similar patterns. PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients.