Risk of Osteoporosis Associated with HMG-CoA Reductase Inhibitors in Patients with Dyslipidemia: A Retrospective Cohort Study in Korea

Objective: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (i.e., statins) are widely used to treat dyslipidemia.Several studies indicate that statin users have greater bone mineral density and a lower risk of fractures than non-users.However, a recent study indicated that high-dose statin use increased the risk of osteoporosis.Thus, we assessed the risk of osteoporosis of statin users compared with nonusers.Methods: This was a retrospective cohort study using the National Health Insurance Service database in Korea from 2011 to 2019.Patients aged 40 years and diagnosed with dyslipidemia (ICD-10, E78) between January 1, 2014 and December 31, 2015 were enrolled.Statin users were defined as patients with at least one statin prescription.The outcome was osteoporosis.Primary analysis was performed using Cox's proportional hazard model after 1:1 exact matching and 1:1 propensity score (PS) matching (462,900 patients per group) to calculate the hazard ratio (HR) and 95% confidence interval (CI).Results: Statin users had a lower risk of osteoporosis versus non-users (HR: 0.92, 95% CI: 0.91-0.93); the subgroup analyses were consistent.In the subgroup analysis, the risk of osteoporosis in statin users versus non-users was 0.96 (95% CI: 0.95-0.97),0.88 (95% CI: 0.87-0.89),and 0.75 (95% CI: 0.72-0.79) in the low, moderate, and high dose groups, respectively; the results were statistically significant at all doses.Conclusion: Statin use is significantly associated with a lower risk of osteoporosis compared to non-use of statins.In particular, as the dose increased, the risk of osteoporosis decreased, confirming a dose-response relationship.(