The Role of Short-Chain Fatty Acids and Derived Metabolites in Osteoporosis.

PURPOSE OF REVIEW: To investigate the role of short-chain fatty acids (SCFAs) in the pathogenesis of osteoporosis and their potential value as therapeutic targets.

RECENT FINDINGS: Recent studies have shown that SCFAs, metabolic products of gut microbiota, play a crucial regulatory role in bone remodeling. SCFAs achieve this by activating G protein-coupled receptors (GPCRs), inhibiting histone deacetylases (HDACs), and regulating signaling pathways involved in bone metabolism. This effectively suppresses osteoclast activity, reduces bone resorption, enhances osteoblast function, and alleviates oxidative stress, thereby promoting bone formation. These findings not only reveal the key mechanisms by which SCFAs maintain bone metabolic homeostasis but also highlight their potential for treating osteoporosis in the elderly and postmenopausal women. Related clinical trials and drug research are currently underway. This review explores the potential value and theoretical basis of targeting SCFAs for the prevention and treatment of osteoporosis, summarizes existing clinical trials and related drug research, and provides new directions for developing future treatment strategies.