Front Immunol. 2026 May 20;17:1738143. doi: 10.3389/fimmu.2026.1738143. eCollection 2026.
ABSTRACT
Osteoporosis (OP) is a chronic metabolic bone disease characterised by low bone mass and deterioration of bone microarchitecture as its core pathological features, which predominantly affects the elderly population and postmenopausal women. Macrophages, as key components of the immune system, function in regulating inflammatory responses, tissue repair and immune modulation, and play a pivotal role in the pathogenesis and progression of osteoporosis: their distinct polarisation states can directly influence osteoblast differentiation and bone resorption activity, and the regulation of bone metabolic homeostasis mediated by macrophages has become one of the current research hotspots. Under specific stimuli, macrophages can polarise into the classically activated M1 phenotype with pro-inflammatory activity and the alternatively activated M2 phenotype with anti-inflammatory and reparative functions, and the imbalance in the M1/M2 polarisation ratio is one of the pathological factors contributing to the development and progression of osteoporosis (Figure 1); accumulating evidence indicates that abnormal shifts in macrophage polarisation phenotypes may disrupt the normal bone remodeling process and break the homeostatic balance of bone metabolism, therefore modulating the M1/M2 polarisation balance holds great significance for the treatment and prevention of osteoporosis, and the dynamic balance of M1/M2 macrophage polarisation also exerts a critical effect in various pathological conditions including tumours, cardiovascular diseases and immune disorders. This article systematically reviews the molecular mechanisms underlying the regulation of bone metabolism by macrophage polarisation, with a focus on summarising the advances in macrophage-targeted therapeutic strategies for osteoporosis, including the polarisation-regulating effects of conventional anti-osteoporotic drugs and the applications of emerging technologies such as nano delivery and cellular intervention, aiming to facilitate the development of more targeted and efficacious therapeutic strategies for osteoporosis based on macrophage polarisation and provide theoretical support and practical directions for addressing the public health challenge of osteoporosis against the backdrop of global ageing.
PMID:42245645 | PMC:PMC13229837 | DOI:10.3389/fimmu.2026.1738143