Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying TLR4-mediated osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. The gene discussed is RUNX2; the disease is osteoporosis.