Icariin prevents ovariectomy-induced osteoporosis by modulating marrow fatty acid metabolism.

Ping Luo, Mengxiang Guo, Liang-duo Jiang, Ze-Hong Miao, H H Chen, Lan Lu, Xue-Lan Zuo, Hua Nian, George Q Li

J Endocrinol Invest

May 21, 2026

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Abstract

PURPOSE: To investigate icariin's regulation of marrow fatty acid metabolism and stearoyl-CoA desaturase (SCD) indices in preventing ovariectomy-induced osteoporosis. METHODS: Thirty-six female Sprague-Dawley rats underwent sham surgery or ovariectomy and were treated with either icariin (125 mg/kg/day) or vehicle via oral gavage for 12 weeks, 6 days per week. Bone marrow was collected from tibias for fatty acid profiling via gas chromatography-mass spectrometry. Serum levels of bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were measured using Enzyme-Linked Immunosorbent Assay. Tibial trabecular microstructure was assessed by micro-CT. RESULTS: Ovariectomy significantly altered marrow fatty acid composition, marked by increased palmitic acid (C16:00) and palmitoleic acid (C16:1 n-7), decreased stearic acid (C18:00) and arachidonic acid (C20:4 n-6), and elevated SCD indices. These changes were associated with deteriorated bone microarchitecture and impaired bone turnover. Icariin treatment effectively normalized marrow fatty acid levels, suppressed SCD indices, and consequently attenuated bone loss by improving bone volume fraction, trabecular number, and thickness, while reducing trabecular separation. Additionally, icariin restored the balance of bone turnover markers, increasing BALP and decreasing TRACP-5b. Significant correlations were identified between specific fatty acids and both bone structural parameters and remodeling markers. CONCLUSIONS: Icariin attenuates osteoporotic bone loss by preventing ovariectomy-induced disturbances in marrow fatty acid metabolism, particularly through the suppression of SCD indices and normalization of C16:00, C16:1 n-7, and C18:00 levels. This study highlights the critical role of lipid homeostasis in bone integrity and identifies icariin as a promising lipid-modulating candidate for postmenopausal osteoporosis.