Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment

Osteoporosis is a systemic metabolic bone disorder characterized by reduced bone mass and impaired microarchitecture, with its core pathological mechanism being an imbalance between bone formation and resorption. Traditional therapies targeting osteoblast/osteoclast function have limited efficacy and safety concerns. Recent osteoimmunology advances reveal that the innate immune system regulates bone homeostasis via intercellular interactions, cytokine networks, and metabolic reprogramming. This systematic review examines the roles of innate immune cells (macrophages, neutrophils, NK cells, DCs), complement system, and emerging pathways (trained immunity, mitochondrial symbiosis disruption) in osteoporosis. It summarizes therapeutic strategies (immunometabolic modulators, complement antagonists, cytokine-targeted drugs, TCM components) and outlines challenges (target specificity, clinical translation) and future directions, providing theoretical foundations for novel OP treatments.