Insights into the Role of Macrophage Polarization in the Pathogenesis of Osteoporosis

Millions of people worldwide suffer from osteoporosis, which causes bone fragility and increases the risk of fractures. Osteoporosis is closely related to the inhibition of osteogenesis and the enhancement of osteoclastogenesis. In addition, chronic inflammation and macrophage polarization may contribute to osteoporosis as well. Macrophages, crucial to inflammatory responses, display different phenotypes under the control of microenvironment. There are two major phenotypes, classically activated macrophages (M1) and alternatively activated macrophages (M2). Generally, M1 macrophages mainly lead to bone resorption, while M2 macrophages result in osteogenesis. M1/M2 ratio reflects the "fluid" state of macrophage polarization, and the imbalance of M1/M2 ratio may cause disease such as osteoporosis. Additionally, antioxidant drugs, such as melatonin, are applied to change the state of macrophage polarization and to treat osteoporosis. In this review, we introduce the mechanisms of macrophage polarization-mediated bone resorption and bone formation and the contribution to the clinical strategies of osteoporosis treatment.