Osteoporosis is a common chronic disorder whereby bones become weakened during aging and are easily broken (i.e. fractured), leading to increased morbidity and mortality. A commonly used medication in osteoporosis management is denosumab which has been shown to significantly reduce the risk of vertebral, non-vertebral and hip fractures. Although denosumab is an effective treatment for osteoporosis, there have been recent reports of denosumab causing atypical femoral fractures (AFF) which are fractures that differ from typical fractures whereby they have delayed healing and have a higher risk of non-union (i.e. failure to heal properly). To further address this concern, our study's objective will be to determine whether individuals with osteoporosis, treated with denosumab have a higher risk of AFF using a population-based cohort study.
The findings from our study will inform patients and the clinical community on whether denosumab increases the risk of AFF, which can lead to development of strategies to improve the treatment of osteoporosis with an aim of AFF risk reduction.
Overview: Denosumab is one of the antiresorptive agents frequently used to treat osteoporosis. Recently, case reports have emerged describing individuals who developed atypical femoral fracture (AFF) while being treated with denosumab. Given that denosumab is an anti-resorptive agent that can lead to AFF, there is need to study whether denosumab treatment for osteoporosis is associated with an increased risk of AFF.
Objective: To determine the risk of AFF among individuals treated with denosumab for osteoporosis using a population-based cohort study.
Methods: We will use data from the Clinical Practice Research Datalink (CPRD) Aurum, a large primary care database from the United Kingdom to conduct a population-based cohort study. We will also link CPRD with the Hospital Episode Statistics (HES) data and the HES Diagnostic Imaging Datasets (HES DID) to identify AFF, for our study. We will assemble a cohort of individuals with osteoporosis newly initiated on osteoporosis medications between 2010 and 2022, followed until June 2023. Time-dependent Cox proportional hazards models will be used to estimate the hazard ratio and corresponding 95% confidence interval of incident AFF among denosumab users versus individuals with osteoporosis receiving other non-bisphosphonate therapies for osteoporosis, adjusting for multiple covariates. We will also conduct several sensitivity analyses to confirm our findings.
Expected outcomes: Use of denosumab has increased over the years due to its efficacy in treating osteoporosis and reducing the risk of fractures. In light of reports of AFF among individuals treated with denosumab for osteoporosis, this study will determine whether denosumab use increases the risk of AFF in the real-world setting. The findings from this study will further inform patients and their physicians whether AFF is associated with denosumab use, which may lead to the development of strategies to mitigate this risk and allow patients with osteoporosis to continue to benefit from denosumab treatment.
Our primary outcome will be incident AFF.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
David Goltzman - Collaborator - McGill University
Kristian Filion - Collaborator - McGill University
Lisa Lix - Collaborator - University of Manitoba
Roland Grad - Collaborator - McGill University
Stephane Bergeron - Collaborator - McGill University
Suzanne Morin - Collaborator - McGill University
Ying Cui - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;HES Diagnostic Imaging Dataset;Practice Level Index of Multiple Deprivation