Association Between the Use of Proton Pump Inhibitors and Osteoporosis/Fracture: Nested Case—Control Studies Using a National Health Screening Cohort

Abstract Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders. However, PPI use may be associated with an increased risk of osteoporosis and fractures. Therefore, this study aimed to investigate the association between PPI use and the risk of osteoporosis and fractures using national data. Two nested case-control studies were conducted using nationwide population cohort data. The first study included patients with osteoporosis and controls while the second included patients with fractures and controls. Associations between PPI use and the risk of osteoporosis and fractures were analyzed using propensity score overlap-weighted odds ratios (ORs). The results showed that current PPI use was associated with a higher risk of osteoporosis than non-use (overlap-weighted OR = 37.4, 95% confidence interval: 33.3–42.1, P < 0.001). This association was stronger with a longer duration of PPI use. Similar associations were observed for distal radius, hip, and spinal fractures in the patient group. However, no significant associations were observed between PPI use and fractures in the PPI-treated group. Here, PPI use was associated with a higher risk of osteoporosis and fractures, particularly with a longer duration of use. Therefore, clinicians should consider the potential risks associated with PPIs when prescribing them to patients with acid-related disorders.