Bone Adverse Events in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy: A Comprehensive Review of the Literature from the Clinical Action Group of the European Calcified Tissue Society.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management, leading to unprecedented improvements in clinical outcomes. Several adverse events from ICIs have been documented, but the risk and clinical relevance of bone adverse events (BAEs) remain uncertain. Sporadic reports describe inflammatory cytokine upregulation, osteoporosis onset during ICI treatment, and increased risk of fragility fractures. In this review, original articles written in English and published up to June 2025, were identified in PubMed, Scopus, and WOS databases by using pre-selected keywords. Based on pre-defined inclusion/exclusion criteria, 23 articles were included in the final analysis. As BAEs, we considered the following conditions: fractures, osteoporosis, osteopenia, bone pain, altered bone metabolism markers. Overall, we found 1610 cancer patients developing at least one BAE, whose percentage was highly variable among studies (range 0.3-88.9%), reflecting the differences in study design, patient enrollment, and BAE recording. Median age was > 55 years, and BAEs were reported in patients with various primary solid tumors, most commonly lung cancer patients (10/23 studies), mainly treated with programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors. However, several limitations of the studies emerged from the analysis and are highlighted in the manuscript. In conclusion, BAEs may occur more frequently among patients treated with ICIs but are likely to be underreported in most studies. Further investigation is needed to estimate and mitigate the risk of such events, since diagnostic techniques and anti-osteoporotic drugs are widely available in the clinical practice. A research agenda focusing on higher-quality reporting of BAEs from ICIs is warranted.