Higher cumulative dose of topical corticosteroids is associated with osteoporosis and major osteoporotic fracture: A nationwide case–control study

Background: Connections between long-term use of topical corticosteroids (TCSs) of varying potency and osteoporosis and major osteoporotic fracture (MOF) are unclear. Susceptibility to adverse bone effects of TCSs in different sex, age and ethnic groups is unknown too. Objectives: To demonstrate the association between cumulative dose of TCSs of varying potency and osteoporosis and MOF in Taiwanese population, with stratified analysis of sex and age. Methods: We conducted a nationwide case–control study and obtained data from Taiwan National Health Insurance Research Database. Cumulative TCS doses in different exposure periods were calculated, and the potency of TCSs was converted to prednisolone equivalent. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for osteoporosis and MOF associated with TCS use. Results: From 2017 to 2020, 129,682 osteoporosis cases and 34,999 MOF cases were selected and randomly matched with 518,728 and 139,996 controls by sex and age. We found clear dose–response relationships between long-term TCS exposure and osteoporosis and MOF. For example, compared to no TCS use, adjusted ORs of osteoporosis were 1.216 (95% CI 1.189–1.243), 1.260 (95% CI, 1.241–1.280) and 1.341 (95% CI, 1.314–1.369) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Adjusted ORs of MOF were 1.118 (95% CI 1.069–1.170), 1.191 (95% CI, 1.156–1.227) and 1.288 (95% CI, 1.238–1.340) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Stratified analysis showed women had higher ORs of osteoporosis and MOF compared to men. Younger people (<50 years) had highest OR of osteoporosis compared to other age groups. Conclusions: Higher cumulative TCS dose was associated with increased risk of osteoporosis and MOF. Long-term use of TCSs should be cautious, especially in susceptible populations such as women and young people.