A Systematic Review on the Molecular Mechanisms of Resveratrol in Protecting Against Osteoporosis

source extracted confidence: high 2026-04-09
#animals #humans #osteoblasts #osteogenesis #osteoporosis

A Systematic Review on the Molecular Mechanisms of Resveratrol in Protecting Against Osteoporosis

Shuid et al., 2025 | Int J Mol Sci | Systematic Review

Citation

Shuid Ahmad Nazrun, Abdul Nasir Nurul Alimah, ... Naina Mohamed Isa. A Systematic Review on the Molecular Mechanisms of Resveratrol in Protecting Against Osteoporosis. Int J Mol Sci. 2025-Mar-22;26(7). doi:10.3390/ijms26072893

Abstract

Osteoporosis is a prevalent metabolic bone disorder characterized by decreased bone mineral density and increased fracture risk, particularly among aging populations. While conventional pharmacological treatments exist, they often have adverse effects, necessitating the search for alternative therapies. Resveratrol, a naturally occurring polyphenol, has gained significant attention for its potential osteoprotective properties through various molecular mechanisms. This systematic review aims to comprehensively analyze the molecular pathways through which resveratrol protects against osteoporosis. Using an advanced search strategy in the Scopus, PubMed, and Web of Science databases, we identified 513 potentially relevant articles. After title and abstract screening, followed by full-text review, 28 studies met the inclusion criteria. The selected studies comprised 14 in vitro studies, 8 mixed in vitro and in vivo studies, 6 in vivo studies, and 1 cross-sectional study in postmenopausal women. Our findings indicate that resveratrol exerts its osteoprotective effects by enhancing osteoblast differentiation through the activation of the Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/Akt), Sirtuin 1 (SIRT1), AMP-Activated Protein Kinase (AMPK), and GATA Binding Protein 1 (GATA-1) pathways while simultaneously inhibiting osteoclastogenesis by suppressing Mitogen-Activated Protein Kinase (MAPK) and TNF Receptor-Associated Factor 6/Transforming Growth Factor-β-Activated Kinase 1 (TRAF6/TAK1). Additionally, resveratrol mitigates oxidative stress and inflammation-induced bone loss by activating the Hippo Signaling Pathway/Yes-Associated Protein (Hippo/YAP) and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathways and suppressing Reactive Oxygen Species/Hypoxia-Inducible Factor-1 Alpha (ROS/HIF-1α) and NADPH Oxidase 4/Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (Nox4/NF-κB). Despite promising preclinical findings, the low bioavailability of resveratrol remains a significant challenge, highlighting the need for novel delivery strategies to improve its therapeutic potential. This review provides critical insights into the molecular mechanisms of resveratrol in bone health, supporting its potential as a natural alternative for osteoporosis prevention and treatment. Further clinical studies are required to validate its efficacy and establish optimal dosing strategies.

Key Findings

Further clinical studies are required to validate its efficacy and establish optimal dosing strategies.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population postmenopausal women
Sample Size 28
Age Range See abstract
Condition stress

MeSH Terms

  • Animals
  • Humans
  • Osteoblasts
  • Osteogenesis
  • Osteoporosis
  • Resveratrol
  • Signal Transduction

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: resveratrol

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09