Metabolic reprogramming in macrophages: the central role of lipid metabolism in bone homeostasis

Abstract Macrophage lipid metabolism is a pivotal regulator of bone homeostasis. Macrophages orchestrate the balance between bone resorption and formation primarily through their M1/M2 polarization states, with M1 macrophages promoting resorption and M2 macrophages supporting formation. This review comprehensively describes how key lipid metabolic pathways, such as fatty acid oxidation (FAO) and cholesterol metabolism, govern this polarization and subsequent bone remodeling. It integrates the core mechanisms by which lipid metabolism drives M1 and M2 polarization, and highlights that targeting macrophage lipid metabolism represents a promising therapeutic strategy for bone diseases. Finally, we identify emerging frontiers, including the “gut-bone axis” and epigenetic regulation, as critical directions for future research.