113 Background: Skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, and the need for palliative bone interventions are major complications in metastatic prostate cancer with bone involvement. Bone-targeted agents like RANKL inhibitors and bisphosphonates mitigate these risks but raise safety concerns, particularly regarding atypical fractures. We conducted a study to assess fracture risk and overall survival outcomes in patients receiving either RANKL inhibitors or bisphosphonates. Methods: Using the TriNetX Research Network database, we identified adults (≥18 years) diagnosed with prostate cancer and bone metastases between 2000 and 2024. Patients were stratified into two cohorts: those receiving RANKL inhibitors only and those receiving bisphosphonates only. Propensity score matching (1:1) was performed to adjust for baseline confounders. Kaplan–Meier survival analysis with log-rank testing was used to compare outcomes between groups. The primary outcome was fracture risk, while secondary outcomes included overall survival and incidence of cardiovascular events. Results: A total of 15,520 prostate cancer patients with bone metastases were identified. After 1:1 propensity score matching, each cohort included 5,282 patients. The 1-year fracture risk was significantly lower in the RANKL inhibitor group compared to the bisphosphonate group (−0.81% 95% CI, −1.40% to −0.21%; p = 0.0079), although this difference was not sustained at 5 years; however, Kaplan–Meier analysis continued to demonstrate a significant divergence (p = 0.023). Fracture sites for both groups were most frequently classified as “other specified sites” which includes the ribs, vertebrae, and skull (65% RANKL vs 69% bisphosphonates), followed by the pelvis and femur (26 vs 25%), then the humerus (both 5%), with the remaining few fractures in upper and lower limbs. Among patients who experienced fractures, 1-year overall survival favored RANKL inhibitors (59.2% vs 47.6%; HR 0.69 95% CI, 0.50–0.94; p = 0.0196), with a trend toward improved 5-year survival (p = 0.0585; median 15 months vs 10 months). There were no significant differences in the incidence of deep venous thrombosis or pulmonary embolism (1.85% 95% CI, −5.40% to 9.11%; p = 0.616). However, cardiac events were significantly more frequent in the bisphosphonates group (21.9% vs 10.7%; difference −11.8% 95% CI, −19.80% to −2.57%; p = 0.012). Conclusions: In prostate cancer patients with bone metastases, RANKL inhibitors were associated with a lower short-term fracture risk and improved early survival compared with bisphosphonates, without an increase in thromboembolic events. Cardiac events were more frequent with bisphosphonates, suggesting that RANKL inhibitors may offer a safer skeletal and cardiovascular profile in metastatic prostate cancer.
Javaid et al. (Sun,) studied this question.