(P 114) DENOSUMAB THERAPY AND MIRELS ADJUSTED ODDS OF PATHOLOGIC FRACTURE OR PROPHYLACTIC STABILIZATION IN APPENDICULAR SKELETAL METASTASES

Objective: In metastatic disease to the skeleton, pathologic fracture is debilitating, and prophylactic fixation carries its own morbidity and cost. Denosumab may avert both events, yet evidence that accounts for lesion biomechanics is scarce. We analyzed whether denosumab lowers the combined risk of pathologic fracture or prophylactic fixation in the context of Mirels’ score.

Methods: We performed a retrospective analysis of 535 radiographically confirmed long-bone metastases arising from five primary histologies (breast, lung, renal, thyroid, prostate) treated between 2015 2024 at a tertiary cancer center. Patients were categorized by denosumab exposure, and the primary composite endpoint was occurrence of pathologic fracture or prophylactic stabilization. Associations were examined with logistic regression, unadjusted and adjusted for Mirels’ total score and reported as odds ratios (ORs) with 95% confidence intervals (CI).

Results: Among 535 patients, 202 (37.8%) received denosumab. Pathologic fracture or prophylactic surgery occurred in 24.8% of denosumab-treated versus 34.2% of untreated patients (p = 0.026). Unadjusted analysis showed a 37% reduction in odds of fracture or surgery with denosumab therapy (OR 0.63, 95% CI 0.43-0.93). After controlling for Mirels’ score, this association lost statistical significance (OR 0.83, 0.52-1.33). Mirels’ score remained the dominant predictor of event occurrence even after accounting for denosumab therapy, with each point increase more than tripling event odds (OR 3.13, 2.55-3.93).

Conclusion: Denosumab was associated with a reduction in the odds of fracturing or requiring prophylactic surgery. However, lesion severity remains the key driver of outcomes, highlighting the importance of Mirels’ score for guiding treatment decisions.