Osteoporosis or fracture risk associated with thiazolidinedione and proton pump inhibitor co‐administration in patients with type 2 diabetes mellitus

Thiazolidinedione (TZD) and proton pump inhibitor (PPI) belong to classes of drugs that affect bone metabolism; however, few studies have investigated the effects of these drugs on bone metabolism. The aim of this study was to assess the risk of osteoporosis or fracture in patients with type 2 diabetes mellitus (T2DM) co-administered TZD and PPIs.This retrospective cohort study was conducted using the National Sample Cohort database from 2003 to 2013. We included adult patients with T2DM who were prescribed TZD and PPIs together for the first time. The Cox proportional hazard model was used to determine the risk ratio of fracture or osteoporosis in the co-administration cohort (TZD + PPI) compared with the TZD-only group (TZD). We adjusted for age, sex, use of other medications and other diseases that affect the bone.Of 9073 patients administered TZD, the number of eligible patients was 7240 (545 TZD + PPI, 6695 TZD-only). After 1:3 propensity score matching, 545 patients remained in the TZD + PPI group and 1635 in the TZD-only group. The risk of osteoporosis or fracture was significantly higher in the TZD + PPI cohort than in the TZD-only cohort. The adjusted hazard ratio (HR) for fracture or osteoporosis was 1.47 (95% CI 1.05-2.07). TZD and PPI use in women were associated with an increased risk of skeletal outcomes.TZD and PPI use were associated with an increased risk of osteoporosis or fracture in patients with T2DM.