The Fracture – Mortality Association and The Effect of Osteoporosis Treatment on Mortality: A Multinational Study

• Main Author: Al Arkawi, Dunia
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: UNSW, Sydney 2023
• Subjects: Osteoporosis; Fractures; Mortality; Antiresorptives; Chronic Kidney Disease; anzsrc-for: 42 HEALTH SCIENCES; Norway; Tromsø
• Online Access: http://hdl.handle.net/1959.4/101054; https://unsworks.unsw.edu.au/bitstreams/9452f159-5366-4bbf-bdf1-984cc0ce5eaa/download; https://doi.org/10.26190/unsworks/24761

Fractures, the main consequences of osteoporosis, are associated with subsequent fractures and mortality. However, limited evidence exists on the impact of non-hip non-vertebral (NHNV) fractures and subsequent fractures on mortality in ageing populations. Bisphosphonates (BPs), the most used osteoporosis treatment, have been associated with reduced mortality. Denosumab (Dmab), an increasingly prescribed osteoporosis treatment, is effective at reducing fractures, but unlike BPs, its effect on mortality has not been well-explored. Moreover, the safety of BPs is unclear in patients with moderate-severe chronic kidney disease (CKD) who have a high risk of fracture and are usually excluded from drug trials. Therefore, using data from Norway, UK, Spain and Australia, this thesis explores the impact of osteoporotic fracture types and subsequent fractures on mortality. It also examines the association between BPs and Dmab and mortality and investigates the effect of BPs on mortality in patients with moderate-severe (Grade 3B-5D) chronic kidney disease (CKD). Norway has one of the highest fracture rates in the world. Using data from the Tromsø Study, Norway, this research demonstrated two-fold increased mortality following hip fractures, and proximal NHNV fractures were associated with an increased mortality risk of 49% in women and 81% in men. A subsequent fracture following any initial fracture increased mortality risk by 89% in women and 77% in men. The Sax Institute’s 45 and Up Study, NSW, Australia, demonstrated that oBPs in both genders and Dmab in women were associated with 44% and 48% reduced mortality risk post-fracture, respectively. Furthermore, data from the UK and Spain demonstrated that oral BPs (oBPs) were not associated with increased mortality among patients with moderate-severe CKD. Instead, oBPs in the UK cohort were associated with a decreased risk of mortality by 8% in the whole cohort, 11% in women, 20% in those with prior history of fracture, and 30% in those with CKD Grade 4-5D. In summary, this ...