Comparative Effectiveness and Safety of Denosumab Versus Bisphosphonates in Elderly Patients with Cancer Bone
Che-Wei Liu1,2,3, Shun-Neng Hsu4,5, Shao-Hsuan Chang6
1Department of Orthopaedics, Cathay General Hospital, Taipei 10630, Taiwan.
Abstract:
Objective: Bone-modifying agents (BMA) are central to the prevention of skeletal-related events (SREs) in patients with cancer bone metastases, yet evidence guiding agent selection in very old patients remains limited. This study aimed to compare the effectiveness and safety of Denosumab versus bisphosphonates in patients aged ≥75 years with solid tumour-related bone metastases using a target trial emulation framework. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network to emulate a hypothetical randomised trial. Patients aged ≥75 years with solid tumour-related bone metastases initiating Denosumab or bisphosphonates were included. After 1:1 propensity score matching (PSM), 10,662 patients were analysed in each treatment group. The primary outcome was time to first SRE. Secondary outcomes included individual SRE components, all-cause mortality, and safety events. Results: Among 21,324 matched patients (mean age, 75.6 years), bisphosphonate use was associated with a higher risk of SREs compared with Denosumab (hazard ratio [HR], 1.15; 95% CI, 1.06-1.25). The excess risk was driven by pathological fractures (HR, 1.28; 95% CI, 1.10-1.49), whereas other SRE components did not differ significantly. All-cause mortality was higher among bisphosphonate users (HR, 1.41; 95% CI, 1.33-1.49, p < 0.001). Hypocalcaemia occurred more frequently with Denosumab (5.7% vs. 2.4%), while risks of acute kidney injury and end-stage renal disease (ESRD) were similar. Findings were consistent across sensitivity and subgroup analyses. Conclusions: In patients aged ≥75 years with solid tumour-related bone metastases, Denosumab was associated with lower risks of skeletal-related events-particularly pathological fractures-and reduced all-cause mortality compared with bisphosphonates. These results extend randomised trial evidence to a clinically vulnerable population and support Denosumab as a preferred BMA in older adults.
Insights
In older adults (≥75 years) with cancer bone metastases, Denosumab reduced skeletal-related events (SREs), especially fractures, and all-cause mortality compared to bisphosphonates. This supports Denosumab as a preferred bone-modifying agent for this vulnerable population.
Area of Science:
- Oncology
- Pharmacology
- Geriatrics
Background:
- Bone-modifying agents (BMAs) are crucial for managing cancer bone metastases and preventing skeletal-related events (SREs).
- Limited evidence exists for optimal BMA selection in elderly patients (≥75 years), a population often excluded from clinical trials.
Purpose of the Study:
- To compare the effectiveness and safety of Denosumab versus bisphosphonates in patients aged ≥75 years with solid tumour-related bone metastases.
- To emulate a target trial using a retrospective cohort study to provide evidence for this vulnerable patient group.
Main Methods:
- Retrospective cohort study using the TriNetX Global Collaborative Network.
- 1:1 propensity score matching (PSM) of patients initiating Denosumab or bisphosphonates (n=10,662 per group).
- Primary outcome: time to first SRE. Secondary outcomes: SRE components, all-cause mortality, and safety events.
Main Results:
- Denosumab was associated with a lower risk of SREs (HR, 1.15) compared to bisphosphonates, primarily driven by fewer pathological fractures (HR, 1.28).
- All-cause mortality was significantly higher in the bisphosphonate group (HR, 1.41; p < 0.001).
- Hypocalcaemia was more frequent with Denosumab; risks of acute kidney injury and end-stage renal disease (ESRD) were similar between groups.
Conclusions:
- In elderly patients (≥75 years) with bone metastases from solid tumours, Denosumab demonstrated superior effectiveness in reducing SREs, particularly fractures, and all-cause mortality compared to bisphosphonates.
- These findings extend randomized trial evidence to a clinically vulnerable population, supporting Denosumab as a preferred BMA in older adults.
