Decoding oxidative stress-driven metabolic reprogramming in skeletal degenerative diseases: Natural phytochemicals as precision metabolic modulators

Skeletal degenerative diseases are prevalent chronic disorders associated with aging. Oxidative stress promotes metabolic reprogramming in bone, cartilage, and intervertebral disc cells; however, the underlying mechanisms remain incompletely understood. Plant-derived phytochemicals may suppress oxidative stress and regulate metabolic reprogramming, thereby offering potential therapeutic benefits. In this review, we summarize oxidative stress-induced alterations in mitochondrial function and glucose, lipid, and amino acid metabolism across major skeletal degenerative diseases and discuss the therapeutic effects of natural phytochemicals that attenuate oxidative stress and modulate these metabolic changes. Clinical translation remains limited by three major challenges: the lack of validated biomarkers, inadequate patient stratification, and inefficient delivery systems. Potential strategies to address these challenges include biomarker-guided patient selection, the development of more physiologically relevant experimental models, and dynamic study protocols, which may facilitate the translation of basic research findings into clinical practice.