Long-Term Persistence with Denosumab and Bisphosphonates after Fracture and Its Association with Clinical Outcomes: A Population-Based Linked Cohort Study — ASN Events
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Long-Term Persistence with Denosumab and Bisphosphonates after Fracture and Its Association with Clinical Outcomes: A Population-Based Linked Cohort Study (#191)

Mike Lin 1 2 3 , Huy Nguyen 1 4 , Thach Tran 1 4 , Robert D Blank 1 , Dana Bliuc 1 5 , Jacqueline R Center 1 3 6
  1. Bone Epidemiology, Clinical and Translation Science Lab, Garvan Institute of Research, Sydney, NSW, Australia
  2. Endocrinology & Metabolism Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  3. School of Clinical Medicine St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health UNSW , Sydney, NSW, Australia
  4. School of Biomedical Engineering, University of Technology, Sydney, NSW, Australia
  5. North Wales Medical School, Bangor University, Bangor, Gwynedd LL57 2DG, United Kingdom
  6. Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW , Australia

Aim: Osteoporosis is a common chronic endocrine disorder causing low-trauma fractures. Sustained antiresorptive therapy is required for antifracture efficacy [1–3], yet long-term persistence after fracture remains poorly characterised. We examined 5-year persistence with oral bisphosphonates, zoledronic acid and denosumab; predictors of early non-persistence; and associations of first-year non-persistence with refracture and mortality.

Methods: From a population-based linked cohort of 2.3 million adults aged ≥50 years in New South Wales, Australia, we identified adults with an incident hospitalised low-trauma fracture during 2005–2018, no osteoporosis medication use in the prior 5 years, and initiation of an oral bisphosphonate, zoledronic acid or denosumab within 12 months. Grace periods were 60 days for oral bisphosphonates and denosumab and 6 months for zoledronic acid. Aalen–Johansen analyses estimated non-persistence, death before non-persistence, and remaining alive and persistent. Fine–Gray models examined predictors of non-persistence within 24 months; 12-month landmark analyses assessed 3-year refracture and mortality.

Results: The cohort included 25,570 women (mean age 77.1 years) and 7,485 men (79.1 years). At 1 year, the proportion alive and persistent was highest with zoledronic acid (women 91.2%; men 85.1%), followed by denosumab (69.4%; 56.5%) and oral bisphosphonates (54.0%; 48.2%). By 5 years, this had fallen to 5.9%–25.3%. Five-year non-persistence ranged from 63.9%–83.1% in women and 65.3%–76.5% in men; death before non-persistence was more frequent in men. First-year non-persistence was associated with 18–27% higher refracture risk and 15–20% higher mortality in women, and 23–24% and 20–32% higher risks, respectively, in men. Specialist rather than primary care prescribing predicted greater non-persistence, whereas dementia predicted lower non-persistence.

Conclusion: Long-term persistence after low-trauma fracture was poor across all therapies, and early advantages of longer-acting agents were not sustained. Early non-persistence identified patients at higher risk of refracture and death, highlighting the need to strengthen treatment continuity for secondary fracture prevention.

 

  1. [1] Ross S, Samuels E, Gairy K, Iqbal S, Badamgarav E, Siris E. A meta-analysis of osteoporotic fracture risk with medication nonadherence. Value Health. 2011 Jun;14(4):571-81. doi: 10.1016/j.jval.2010.11.010. Epub 2011 Apr 30. PMID: 21669382.
  2. [2] Imaz I, Zegarra P, González-Enríquez J, Rubio B, Alcazar R, Amate JM. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int. 2010 Nov;21(11):1943-51. doi: 10.1007/s00198-009-1134-4. Epub 2009 Dec 5. PMID: 19967338.
  3. [3] Lyu H, Yoshida K, Zhao SS, Wei J, Zeng C, Tedeschi SK, Leder BZ, Lei G, Tang P, Solomon DH. Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis : A Population-Based Cohort Study. Ann Intern Med. 2020 Oct 6;173(7):516-526. doi: 10.7326/M20-0882. Epub 2020 Jul 28. PMID: 32716706.