Progress of Programmed Cell Death in Steroid-Induced Osteonecrosis of the Femoral Head

Abstract

Steroid-induced osteonecrosis of the femoral head is a severe osteoarticular condition resulting from glucocorticoid overuse, characterized by femoral head bone structure collapse and cell death, now predominant among nontraumatic femoral head necroses. The increasing clinical use of glucocorticoids has led to a rise in the incidence of steroid-induced osteonecrosis of the femoral head, yet its precise molecular mechanisms remain incompletely understood, posing challenges for clinical management. This review proposes that the “GC-induced metabolic-inflammatory-oxidative stress vicious cycle” serves as the core driver propelling the activation of the SONFH multi-pathway PCD network. Centered on this thesis, the review systematically examines the synergistic and antagonistic interactions among PCD pathways—including pyroptosis, autophagy, and ferroptosis—in SONFH, emphasizing the pivotal role of mitochondrial dysfunction and ROS bursts. This framework not only integrates the independent functions of each PCD pathway but also reveals their interwoven molecular networks, offering novel perspectives for developing multi-target synergistic therapeutic strategies.

Keywords

autophagy / ferroptosis / necroptosis / programmed cell death / pyroptosis / steroid-induced osteonecrosis of the femoral head

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2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.