Cellular mechanisms of osteoporosis: A comprehensive perspective on ferroptosis, cuproptosis and lipid metabolism abnormalities.

Abstract

Osteoporosis is a prevalent skeletal disorder characterised by reduced bone mineral density and compromised bone microarchitecture, leading to increased bone fragility and increased risk of fracture. Recent studies have implicated ferroptosis, cuproptosis, and dysregulated lipid metabolism as pivotal factors in the pathogenesis of osteoporosis. Ferroptosis is an iron-dependent form of cell death that disrupts the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption by promoting lipid peroxidation and inducing cellular injury. Cuproptosis, associated with disruptions in copper homeostasis, influences bone cell integrity through oxidative stress and inflammatory responses, thereby impacting bone density. Aberrant lipid metabolism may exacerbate osteoporosis by disrupting bone-fat homeostasis, oxidative stress, and inflammatory responses. This review synthesizes the interplay between cuproptosis, ferroptosis, and lipid metabolism, elucidates the cellular mechanisms underlying osteoporosis, and accordingly provides novel therapeutic targets and intervention strategies, potentially enhancing osteoporosis prevention and treatment.