The Iron–Ferroptosis Axis in Bone Homeostasis: A Potential Complementary Pathway for Osteoporosis in Endometriosis Publisher Pubmed



Motafeghi F ; Ramezani Tehrani F ; Ghassemi Barghi N
Source: European Journal of Medical Research Published:2026

Abstract

Endometriosis, a chronic gynecological disorder, is clinically associated with an increased risk of osteoporosis. While this link has been primarily attributed to hypoestrogenism resulting from the disease process or its treatment, this paradigm may not fully capture the underlying pathophysiology. This review proposes a complementary hypothesis centered on the iron–ferroptosis axis. We posit that the chronic pelvic inflammation and significant localized iron overload inherent to endometriosis may establish a systemic pro-oxidative state. This state, we propose, could sensitize bone tissue to ferroptosis—an iron-dependent form of regulated cell death driven by lipid peroxidation—thereby acting as a synergistic factor that exacerbates hormonally driven bone loss. This conceptual framework synthesizes evidence from bone metabolism, reproductive endocrinology, and cell death biology to suggest that systemic iron dysregulation may serve as a mechanistic bridge between localized pelvic pathology and systemic skeletal fragility. By framing the iron–ferroptosis axis as a theoretical potential amplifier of established hormonal mechanisms, this manuscript aims to stimulate new research into the non-hormonal drivers of osteoporosis in women with endometriosis and to identify novel avenues for therapeutic investigation. © The Author(s) 2026.