Effect of Statin Use on the Risk of Osteoporotic Fracture in Patients With Metabolic Syndrome: A Nested Case-Control Study

Statins may have advantageous pleiotropic effects on bone metabolism, however, the clinical evidence about the association is still unclear. Although many studies have already evaluated this association, they have performed mostly in a general population with limitation of between-study heterogeneity. Statin may not be equally effective for bone metabolism to every patient, but it can give some benefits for some patients especially with metabolic syndrome (MetS). However, no recent study assessing this relationship, to best our knowledge, has evaluated specifically on patients with MetS. It is also unclear whether the association between statin and osteoporotic fracture differ by statin intensity, dose (cumulative defined daily dose), and duration. This study aimed to investigate the association of statin use with the risk of major osteoporotic fracture in MetS patients from a population-based cohort (NHIS-HEALS, 2002–2015). A nested case-control study was performed in patients with MetS (≥50 years) who had no history of previous osteoporotic fracture. This study included 17,041 cases diagnosed as new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratio (OR) and 95% confidence interval (CI). During the 4-year follow up period, statin users had a significantly lower risk of major osteoporotic fractures by 9% (OR, 0.91; 95% CI, 0.85 to 0.97) compared with non-users. Among subtypes of major osteoporotic fracture, a risk reduction of vertebral fracture was significant (OR, 0.86; 95% CI, 0.79 to 0.94), but not non-vertebral fracture (OR, 0.97; 95% CI, 0.88 to 1.06) with statin use. Longer duration (OR, 0.97 per 1 year) and cumulative dose (OR, 0.97 per 365 defined daily dose) of statin was negatively associated with the risk of major osteoporotic fracture. There was no difference in risk of major osteoporotic fractures among groups according to statin intensity. In conclusion, this study supports the hypothesis that statin treatment has a beneficial effect on major osteoporotic fracture, especially for vertebral fracture, in patients with MetS with a possibly dose-effect relationship.