Medicine–food homologous bioactives in metabolic dysregulation-associated osteoporosis: a review of preclinical evidence and potential liver–bone and gut–bone actions

Abstract Background Osteoporosis is increasingly linked to metabolic dysregulation. Medicine–food homologous (MFH) materials contain diverse natural bioactives with reported osteoprotective effects, but their overall evidence landscape remains insufficiently integrated. Purpose To synthesize preclinical evidence on MFH-derived bioactives that improve osteoporosis-related phenotypes and to discuss their possible trans-organ actions under metabolic disturbance. Methods PubMed, Web of Science, Scopus, and CNKI were searched from January 2000 to September 2025. Original in vivo or in vitro studies were included when a defined MFH-derived constituent or standardized single-material extract was tested in an osteoporosis-relevant model and reported both bone-related and metabolism-related outcomes. Results A total of 38 bioactive components from 24 MFH materials were identified and regrouped into seven higher-level natural-product categories, including flavonoids, phenolic and polyphenolic compounds, polysaccharides, saponins, terpenoids, proteins/peptides, and other specialized metabolites. Across studies, osteoprotective effects were frequently accompanied by parallel improvements in lipid metabolism, inflammatory status, oxidative stress, gut microbiota, or related metabolites. These findings suggest that MFH bioactives may act beyond bone-local signaling alone. In the discussion, this pattern was further interpreted through liver-bone and gut-bone. Conclusion MFH-derived bioactives show potential to improve osteoporosis-related phenotypes and may exert broader systemic regulatory effects, although specific mediators and causal links still require validation.