Immunometabolic reprogramming in osteoporosis-osteoarthritis comorbidity: from inflammaging to osteochondral unit degeneration.

Osteoporosis (OP) and osteoarthritis (OA) are common and highly co-occurring degenerative bone diseases in the elderly population, and their comorbidity mechanisms cannot be fully explained by traditional factors such as mechanical load, changes in bone mass, or hormonal imbalance. OP is primarily characterized by systemic decrease in bone mass and reduced bone strength, while OA is mainly manifested by cartilage degeneration within specific joints, synovial inflammation, and abnormal subchondral bone remodeling. Although both are influenced by aging, inflammation, and metabolic abnormalities, there are significant differences in their affected areas and pathological processes. In recent years, increasing evidence suggests that immunosenescence, chronic low-grade inflammation, and structural-functional imbalance of the osteochondral unit may constitute an important pathological basis for the progression of both diseases. Immunometabolic reprogramming is gradually being recognized as a potential mechanistic framework linking bone loss and joint degeneration, involving multiple processes such as enhanced glycolysis, impaired oxidative phosphorylation, lipid metabolism disorders, dysregulation of the NAD