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Natural bioactive compounds in estrogen deficiency-induced osteoporosis: Classification and an integrated gut microbiota-metabolite-immune-bone framework
Long Luo, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China
Tao Zhang, Department of Medical Immunology, School of Basic Medicine and Forensic Medicine, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China
Wen-Sheng Xu, Department of Joint Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China
Author contributions: Luo L performed the literature search and data collection, conceived the study, and drafted the manuscript; Zhang T contributed to the critical revision of the manuscript and preparation of figures and tables; Xu WS supervised the study, provided critical intellectual input and revised the manuscript. All authors reviewed and approved the final manuscript.
AI contribution statement: The authors declare that no AI tools or generative AI technologies were used in the preparation of this manuscript.
Supported by Graduate Research and Innovation Project of Baotou Medical College, No. BYKYCX202606 and Natural Science Foundation of Inner Mongolia, No. 2022MS08039.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.
Corresponding author: Wen-Sheng Xu, PhD, Department of Joint Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, No. 41 Linyin Road, Kundulun District, Baotou 014000, Inner Mongolia Autonomous Region, China. xwsoye@126.com
Received: September 11, 2026
Revised: October 16, 2026
Accepted: November 2, 2026
Published online: November 18, 2026
Processing time: 60 Days and 19.5 Hours
Revised: October 16, 2026
Accepted: November 2, 2026
Published online: November 18, 2026
Processing time: 60 Days and 19.5 Hours
Core Tip
Core Tip: This minireview introduces a microbiota-dependent classification of natural bioactive compounds for estrogen deficiency-induced osteoporosis and proposes an integrated gut-metabolite-immune-bone framework. Rather than acting solely on bone cells, these interventions may reshape microbial metabolites, intestinal barrier function, estrogen availability, immune balance, and post-transcriptional regulation. This framework highlights priorities for causal multi-omics studies, microbiota-stratified trials, and the clinical evaluation of individualized nutrition-based interventions as potential adjunctive strategies.