Denosumab and Mortality in a real-world setting - A Comparative Study.

Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well-explored. This study examined the association between Dmab and all-cause mortality compared to no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from The Sax Institute's 45 and Up Study (n= 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions 1 , medication records 2 and stored securely 3 . The new-user cohort design with propensity-score (PS) matching was implemented. In the Fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men, and oral BPs: 615 women, 266 men). In the No-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs - 479 men, 1534 women and Dmab:Zol - 280 men, 625 women). Mortality risk was measured using gender-specific pairwise multivariable Cox models. In the Fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (HR 0.52; 95% CI, 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR 0.56; 95% CI, 0.42-0.77 and men HR 0.56; 95% CI, 0.40-0.78). In the No-fracture cohort, compared with BPs, Dmab was associated with 1.5 to 2.5-fold higher mortality than oral BPs (women HR 1.49; 95% CI, 1.13-1.98 and men HR 2.74; 95% CI, 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. This article is protected by copyright. All rights reserved.