Osteoporosis is a systemic metabolic disease with the defective coupling of bone resorption and bone reconstruction, resulting in imbalance of calcium and phosphorus metabolism and gradual reduction of bone density. Purinergic ligand-gated ion channel 7 receptor (P2X7R) are highly expressed in osteocyte, regulating continuous absorption and remodeling of the skeletal system. P2X7R activation is associated with osteoclast formation and reabsorption and with osteoblast differentiation. P2X7R can also influence bone loss by stimulating immune cells during inflammatory response. This article reviews the research progress of P2X7R in osteoporosis in recent years, providing evidence for the pathogenesis of osteoporosis and the development of new drugs.