Bone mineral density changes in patients treated with anti-PD-1 immune checkpoint inhibitors.

12107 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment (tx), with almost half of all cancer patients (pts) today eligible for ICI tx. However, these agents frequently cause immune-related adverse events (irAEs). While many irAEs are well-documented, emerging reports suggest that skeletal toxicity may represent an underrecognized complication of ICI tx, particularly with agents that target PD-1. Preclinical models show that global deletion of the PD-1 gene ( Pdcd1 ) or anti-PD-1 tx increases bone resorption, decreases bone formation, and weakens bones. However, skeletal effects remain poorly characterized in humans. We performed a retrospective analysis to assess bone mineral density (BMD) changes via dual-energy X-ray absorptiometry (DXA) results in pts treated with anti-PD-1 ICIs. Methods: We retrospectively analyzed adult pts from a single institution who received at least one dose of an anti-PD-1 agent with or without chemotherapy from 2014 to 2025 and who had pre- and post-tx DXA scans available. We collected demographics, cancer and treatment history, DXA data (including BMD, T-scores, and Z-scores), and scan timing relative to ICI tx. Descriptive statistics and paired t-tests (p<0.05) were used for data analysis. Results: Of 382 pts who received anti-PD-1 tx, 103 had only post-tx DXA scans, and 28 had both pre- and post-tx DXA scans. Of these 28 pts, 93% were female with a median age of 70 at the time of tx (range 58-88). Pts had statistically significant decreases in femur BMD and T-scores pre- vs. post-tx: mean BMD 0.85 vs. 0.81 g/cm 2 (p=0.04) and mean T-score -0.95 vs. -1.66 (p=0.02). Mean Z-scores decreased but were not statistically significant: 0.05 vs. -0.24 (p=0.09). In contrast, there was a trend toward increases in lumbar spine BMD, T-scores, and Z-scores, but none of these changes were statistically significant: mean BMD 1.16 vs. 1.15 g/cm 2 (p=0.93), mean T-score -0.19 vs. -0.06 (p=0.73), and mean Z-score 0.96 vs. 0.99 (p=0.72). Conclusions: This is the largest reported study to date examining BMD changes after anti-PD-1 ICI tx. Although this sample size is small and consists of mostly female pts, these results show significant decreases in femur BMD and femur T-scores after anti-PD-1 ICI tx, resulting in potentially increased fracture risk. T-scores in particular are more accurate in this older pt population than Z-scores. The site-specific changes seen in this dataset align with preclinical studies showing that in female PD-1 knockout mice of all ages, spinal bone mass does not change, but femoral bone mass is reduced. This could reflect differences in cortical vs. trabecular bone or mechanical loading. These findings underscore the importance of skeletal monitoring and indicate that prospective studies are needed to validate the observed bone changes and better characterize fracture risk in patients receiving anti-PD-1 therapy.