Affiliation:
1. Skeletal Diseases Program, Garvan Institute of Medical Research University of New South Wales Sydney Australia
2. Clinical School, Faculty of Medicine, St Vincent's Hospital University of New South Wales Sydney Australia
3. Institute of Bone and Joint Research Kolling Institute Sydney Australia
4. Clinical School Royal North Shore Hospital St Leonards Australia
5. Clinical School, Concord Repatriation General Hospital Sydney Australia
6. School of Population Health, Faculty of Medicine and Health University of New South Wales Sydney Sydney Australia
Abstract
ABSTRACTDenosumab (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 with 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 (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). 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; 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; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex‐specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [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; 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; 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. © 2023 American Society for Bone and Mineral Research (ASBMR).
Publisher
Oxford University Press (OUP)
Subject
Orthopedics and Sports Medicine,Endocrinology, Diabetes and Metabolism