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. 2025 May 16:1-14.
doi: 10.1080/25785826.2025.2506870. Online ahead of print.

Ovariectomy-induced bone loss through inappropriate inflammatory response: an osteoimmunological perspective on postmenopausal osteoporosis

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Free article

Ovariectomy-induced bone loss through inappropriate inflammatory response: an osteoimmunological perspective on postmenopausal osteoporosis

Lilika Higuchi et al. Immunol Med. .
Free article

Abstract

Postmenopausal osteoporosis (PO) is a prevalent condition that significantly impairs the quality of life in elderly women. While traditionally attributed to estrogen deficiency, emerging evidence suggests that immune dysregulation plays a critical role in its pathogenesis. This study investigates the osteoimmunological mechanisms underlying PO using an ovariectomy (Ovx) mouse model. Our findings indicate that Ovx mice exhibit substantial reductions in bone mineral density and bone volume, accompanied by a marked suppression of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) production, particularly from natural killer T (NKT) cells. Lipidomic analysis of bone marrow further revealed an upregulation of omega-6 fatty acids, contributing to an inflammatory microenvironment that promotes excessive osteoclast activation. Notably, administration of the glycolipid OCH restored cytokine production and mitigated bone loss in Ovx mice, suggesting its therapeutic potential. These findings highlight the complex interplay between immune responses and lipid metabolism in PO and propose novel therapeutic strategies aimed at modulating immune function to prevent bone loss. This study offers valuable insights into the osteoimmunological mechanisms of PO and underscores the potential of immunomodulatory approaches for its management.

Keywords: Inflammation; osteoclast; osteoimmunology; postmenopausal osteoporosis.

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