Abstract: Osteoporosis is an age-related degenerative disease characterized by reduced bone mineral density and deterioration of bone microarchitecture,which markedly increases the risk of fractures.With the rising field of osteoimmunology,increasing attention has been given to the role of the immune system—particularly macrophages—in maintaining bone metabolic homeostasis and in the pathogenesis of osteoporosis.As aging progresses,macrophages exhibit a pro-inflammatory tendency,characterized by elevated expression of inflammatory cytokines,alterations in metabolic and signaling pathways,and a phenotypic shift toward the M1 subtype.Concurrently,changes in the extracellular environment further reinforce these senescent features.Such macrophage senescence not only impairs their intrinsic functions but also exerts profound effects on systemic immune responses and tissue repair capacity.In bone metabolism,macrophages exert dual roles:they can promote bone loss through the secretion of pro-inflammatory cytokines and chemokines,while also supporting bone regeneration by enhancing osteoblast activity and regulating the clearance of apoptotic cells.Macrophages are essential for maintaining the hematopoietic stem cell niche,and their senescence can disrupt this microenvironment.Moreover,macrophage senescence influences the bone microenvironment and osteogenesis through multiple mechanisms,including altered secretion profiles,metabolic signaling,inflammatory pathways,mitochondrial homeostasis,and extracellular vesicles.This review systematically summarizes recent advances in understanding the role of macrophages in skeletal aging,aiming to provide a more comprehensive immunological perspective for the precise intervention of osteoporosis.

Key words: macrophage senescence, osteoporosis, osteoimmunology, inflammaging