Immune-related osteitis mimicking femoral head osteonecrosis during dual checkpoint blockade: a case report

Enrica Teresa Tanda1,2, Agostina Lagodin D'Amato2, Giovanni Rossi1

  • 1U.O.C. Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Frontiers in Oncology
|November 13, 2025
PubMed

Immune checkpoint inhibitors (ICIs) have dramatically reshaped the therapeutic landscape of oncology, offering long-term survival benefits across multiple tumor types. However, ICIs are associated with a broad range of immune-related adverse events (irAEs), most of which are now well characterized and manageable. A subset of irAEs, however, remains rare, unpredictable, and poorly understood, both in terms of clinical presentation and pathogenesis. Here, we describe the case of a patient with advanced melanoma treated with combined anti-CTLA-4 and anti-PD-1 therapy who developed severe left hip pain during treatment. Imaging findings were initially suggestive of osteonecrosis of the femoral head. However, histopathological analysis of the resected femoral head revealed a dense lymphoplasmacytic infiltrate with fibrosis and vascular congestion, without evidence of bone necrosis, consistent with an immune-mediated osteitis. To our knowledge, this represents the first documented case of direct immune-related inflammation selectively affecting bone tissue during ICI therapy. Recognition of such atypical skeletal irAEs may be critical for improving diagnosis and management strategies in the expanding field of immuno-oncology.

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