| Toll-like receptor 4 (TLR4), as a pattern recognition receptor (PRR), is a key molecule involved in the intrinsic immune response. When activated, it can release large amounts of inflammatory factors and promote inflammatory responses through multiple downstream signaling pathways. Due to its close association with low-grade inflammation and oxidative stress injury, it is now found to be extensively involved in the pathophysiological process of diabetic osteoporosis (DOP). On the one hand, TLR4 drives the onset and progression of diabetes and its related complications through its involvement in oxidative stress, insulin resistance signaling, and accumulation of advanced glycosylation end products. On the other hand, TLR4 is involved in the development and progression of osteoporosis by regulating osteoclast differentiation, inhibiting osteoblast production, and disrupting bone reconstruction through the NF-κB signaling pathway. Interestingly, TLR4 also targets NF-κB and Wnt/β-catenin signaling involved in the fracture healing process in DOP patients. However, the current studies related to TLR4 in DOP are mainly focused on the animal and cellular levels, and few relevant clinical studies have been reported. Therefore, this paper reviews the field of TLR4 in diabetes and osteoporosis-related signaling pathways, aiming to provide a new direction for the prevention and treatment of DOP. |