Comparative Safety and Effectiveness of Denosumab Versus Zoledronic Acid in Patients With Osteoporosis: A Cohort Study.

Limited head-to-head comparative safety and effectiveness data exist between denosumab and zoledronic acid in real-world healthcare. We aimed to examine the safety and effectiveness of denosumab compared to zoledronic acid with regard to risk of serious infection and cardiovascular disease (CVD) and osteoporotic fracture. We conducted a cohort study using claims data (2009-2013) from a US commercial insurance plan database. We included patients aged ≥50 years who were newly initiated on denosumab or zoledronic acid. The primary outcomes were (1) hospitalization for serious infection; (2) composite CVD endpoint including myocardial infarction, stroke, coronary revascularization, and heart failure; and (3) nonvertebral osteoporotic fracture including hip, wrist, forearm, and pelvic fracture. To control for potential confounders, we used 1:1 propensity score (PS) matching. Cox proportional hazards models compared the risk of serious infection, CVD, and osteoporotic fracture within 365 days after initiation of denosumab versus zoledronic acid. After PS matching, a total of 2467 pairs of denosumab and zoledronic acid initiators were selected with a mean age of 63 years and 96% were female. When compared with zoledronic acid, denosumab was not associated with an increased risk of serious infection (HR 0.81; 95% confidence interval [CI], 0.55 to 1.21) or CVD (HR 1.11; 95% CI, 0.60 to 2.03). Similar results were obtained for each component of CVD. The risk of osteoporotic fracture was also similar between groups (HR 1.21; 95% CI, 0.84 to 1.73). This large population-based cohort study shows that denosumab and zoledronic acid have comparable clinical safety and effectiveness with regard to the risk of serious infection, CVD, and osteoporosis fracture within 365 days after initiation of medications. © 2016 American Society for Bone and Mineral Research.