Musculoskeletal Complications of Radiation Therapy and Immunotherapy

Radiation therapy (RT) and immunotherapy are widely used in modern oncologic care and are both associated with a broad spectrum of musculoskeletal complications. These adverse effects can be acute or delayed and include bone fragility, insufficiency fractures, osteoradionecrosis, cartilage degeneration, inflammatory arthritis, myositis, and tendinopathy. Many of these complications can closely mimic metastatic disease or infection, creating diagnostic challenges. RT-induced musculoskeletal injuries are influenced by factors such as total dose, fractionation, and technique, with newer modalities such as stereotactic body RT and proton beam therapy associated with specific imaging appearances and complication profiles. Immunotherapy, particularly immune checkpoint inhibitor medication, has introduced a distinct set of immune-related adverse events affecting the musculoskeletal system, including inflammatory arthropathy, myositis, and enthesitis, often occurring in seronegative patterns and overlapping with other systemic toxicities. The authors provide an in-depth overview of the radiobiologic principles underlying RT, the evolving landscape of immunotherapy, and the diverse musculoskeletal complications that arise from both therapies. Emphasis is placed on the clinical context and imaging features that aid in recognizing and differentiating these conditions from neoplastic or infectious processes. A thorough understanding of these complications is essential for accurate diagnosis, timely management, and improved patient outcomes. ^©RSNA, 2025 Supplemental material is available for this article.