Synergistic Effect of Statins and Postmenopausal Hormone Therapy in the Prevention of Skeletal Fractures in Elderly Women

Study Objective. To examine the role of concurrent 3–hydroxy‐3–methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis‐related fractures. Design. Case‐control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. Measurements and Main Results. Postmenopausal hormone therapy use was classified as “current” (12 mo before index date) or “never or past.” The risk of fractures was ascertained among continuous (≥80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid‐lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53–1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04–0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. Conclusion. Concurrent statin use and hormone therapy may have a synergistic protective effect on skeletal fractures beyond the additive effect of each individual therapy.