Plants used in medicines and foods in osteoporosis: mechanistic insights into bone-remodeling homeostasis and clinical evidence.

Osteoporosis (OP) arises from the progressive uncoupling of bone remodeling, in which osteoclastic resorption exceeds osteoblastic formation under the combined influence of estrogen deficiency, nutrient insufficiency, oxidative stress, chronic inflammation, and age-related stem-cell decline. Although current antiresorptive and anabolic drugs improve bone mineral density (BMD), their long-term use is constrained by adverse effects, limited impact on bone microarchitecture, and suboptimal patient adherence. Plants used in medicines and foods (PMF), characterized by their dietary origin, multi-metabolite composition, and favorable safety profile, have emerged as promising candidates for sustained OP management. Accumulating evidence indicates that PMF metabolites, including flavonoids, polysaccharides, glycosides, and coumarins, exert coordinated osteoprotective effects by enhancing osteogenic pathways (Wnt/β-catenin, BMP/SMAD), suppressing osteoclastogenic signaling (RANKL/NFATc1/NF-κB), modulating endocrine axes, reshaping the gut-bone and immune microenvironment, and improving aging-related bone marrow-derived mesenchymal stem cell (BMSC) dysfunction. This review synthesizes current mechanistic and clinical evidence supporting PMF-based interventions and highlights critical challenges and the need for large-scale randomized controlled trials (RCTs). These advances will be essential for translating PMF into evidence-based, globally applicable strategies for OP prevention and adjunctive therapy.