Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.

Osteoporosis is a disease characterized by increased bone turnover and decreased bone mass, closely associated with suppressed osteogenesis, enhanced osteoclastogenesis, and immune-metabolic dysregulation. Studies in osteoimmunology have shown that immune dysregulation can disrupt bone homeostasis through multiple signaling pathways and metabolic interactions between immune cells and bone cells. Macrophages, as key players in osteoimmunity, dynamically alter their metabolism in specific environments, integrating environmental signals to exhibit context-specific functions. Among the primary metabolic phenotypes, classically activated macrophages (M1) mainly promote bone resorption, while alternatively activated macrophages (M2) primarily facilitate osteogenesis. These effects are mainly achieved through inflammatory pathways, macrophage-driven osteoclastogenesis, and efferocytosis. Dysregulation of macrophage metabolic reprogramming in osteoimmunity can lead to diseases such as osteoporosis. The link between metabolic reprogramming and epigenetic modifications is a research hotspot in immune-metabolic diseases, and targeting macrophage metabolic reprogramming has shown potential therapeutic benefits for osteoporosis. This review discusses the impact of macrophage metabolic reprogramming-related osteoimmune pathways on osteoporosis.