Polyphenols and Bone Health: A Comprehensive Review of Their Role in Osteoporosis Prevention and Treatment.

Osteoporosis is a progressive bone disorder characterized by decreased bone mineral density and structural deterioration, leading to increased fracture risk. Conventional treatments, although effective, are limited by adverse effects and low long-term adherence. In recent years, polyphenols, plant-derived bioactive compounds, have emerged as promising candidates for bone health promotion due to their antioxidant, anti-inflammatory, and osteo-regulatory properties. This review synthesizes the current preclinical and clinical evidence on the potential of polyphenols, including quercetin, resveratrol, curcumin, isoflavones, and epigallocatechin gallate, to modulate bone metabolism and prevent or mitigate osteoporosis. Mechanistically, polyphenols enhance osteoblastogenesis, inhibit osteoclast differentiation, regulate the RANKL/OPG axis, and activate key osteogenic pathways such as Wnt/β-catenin and MAPKs. Additionally, their estrogen-like activity and ability to modulate gut microbiota offer further therapeutic potential. Preclinical models consistently demonstrate improvements in bone mass, architecture, and turnover markers, while clinical trials, although limited, support their role in preserving bone density, particularly in postmenopausal women. Despite promising outcomes, variability in bioavailability, dosage, and study design limits current translational application. Further large-scale clinical studies and standardized formulations are needed. Polyphenols represent a compelling adjunct or alternative approach in the integrated management of osteoporosis.