Ferroptosis Mechanism in the “Secondary Injury” Phase of Osteoporotic Fractures: From Laboratory to Perioperative Intervention

¹ Department of Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Hubei Provincial Clinical Medical Research Center for Nephropathy, Minda Hospital of Hubei Minzu University, Hubei Minzu University, Enshi 445000, Hubei, China,

BAS 2025 , 3(6), 33–40; https://doi.org/10.26689/bas.v3i6.12809

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Delayed healing of osteoporotic fractures is a common and challenging clinical problem, traditionally attributed to insufficient local blood supply. However, recent years have seen increasing attention on the critical role of ferroptosis during the “secondary injury” phase of osteoporotic fractures. Ferroptosis damages chondrocytes through iron overload and lipid peroxidation, having a significant impact on bone repair. This article explores the molecular mechanisms of ferroptosis, focusing on the role of osteoclasts in secreting free iron and the impact of changes in GPX4 and FSP1 expression on ferroptosis regulation, highlighting the significance of ferroptosis chondrocyte subpopulations in fracture healing. It also evaluates the application potential and existing controversies of perioperative intervention strategies such as iron chelators and vitamin K2, discussing the development trends of bone-targeted iron chelating nanoparticles and rapid detection technologies for ferroptosis evaluation. This review aims to provide new theoretical bases and intervention ideas for the treatment of clinical osteoporotic fractures, promoting solutions to delayed fracture healing.

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