Oral Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

The effect of denosumab on post-fracture mortality risk in the 45 and Up study (#12)

Dunia Alarkawi 1 , Dana Bliuc 1 , Thach Tran 1 , Weiwen Chen 1 2 , Judy Simpson 3 , Lyn March 4 5 6 , Fiona M Blyth 7 , Jackie Center 1 2
  1. Bone Biology Division, Garvan Institute of Medical Research, University of New South Wales, Sydney, NSW, Australia
  2. Clinical School, Faculty of Medicine, St Vincent's Hospital, University of New South Wales, Sydney, NSW, Australia
  3. Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
  4. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  5. Institute of Bone and Joint Research, Kolling Institute, Sydney, NSW, Australia
  6. Clinical School, Royal North Shore Hospital, St Leonards, NSW, Australia
  7. Clinical School, Concord Repatriation General Hospital, Sydney, NSW, Australia

Bisphosphonates (BP), most commonly used antiresorptive agents, have been associated with mortality reduction possibly through reduction in bone loss and other extra-skeletal effects. However, the effect on mortality of Denosumab (DB), an increasingly used antiresorptive treatment has not been well explored.

This study determined the effect of DB, oral and intravenous BP (oBP and iBP) on post-fracture mortality. The 45 and Up Study is a prospective population-based cohort study with questionnaire data linked to i) mortality data, ii) hospital records by the Centre for Health Record Linkage (CHeReL) and, iii) the Pharmaceutical Benefits Scheme data provided by the Department of Human Services.

In this study 17,524 participants (15,604 not treated and 617 women and 154 men on DB, 615 women and 266 men on oBP and 176 women 90 men on iBP) aged 45+ years with an incident fracture were followed from 2006 to 2017. Propensity scores (PS) were calculated using pre-specified variables (age, comorbidities, socioeconomic status, lifestyle factors and comedications). DB, oBP and iBP users (treatment initiated after fracture) were matched 1:2 to non-users by PS, fracture type (hip and non-hip) and time to treatment initiation. Matching resulted in 90 -100% covariate balance except in iBP pairs in men (75%). Mortality risk was measured using pairwise multivariable Cox models, which accounted for any remaining imbalance post-matching.

DB in women but not in men was associated with 51% reduced mortality risk with the highest reduction observed in those who initiated treatment within a year post-fracture. oBP in women and men were also associated with 36-38% lower mortality risk while iBP’s association with mortality was not significant (Table).

DB in women was associated with lower post-fracture mortality, possibly driven by a reduction in bone loss as shown for oBP. Further studies exploring the mechanisms of antiresorptive treatment and mortality is warranted.

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