Diphosphates are firmly bound to the mineral hydroxyapatite. These compounds bind specifically to mineral deposit tissues, especially bone tissue. The P-C-P bond of diphosphonates effectively resists hydrolytic enzymes and cannot be metabolized in the body, so they are only excreted as intact molecules by active secretion from the renal tubules. Early diphosphonates, represented by etidronate, inhibited osteoclast function only at high doses. The unique side chain structure of alendronate has greatly enhanced its ability to inhibit osteoclasts, and a very small dose is sufficient to work . 1. Cellular level: The ultimate target cells of diphosphonates are considered to be osteoclasts, and such drugs inhibit the osteoclastic activity of osteoclasts through the following three aspects. (1) Inhibition of osteoclast formation. Diphosphonates inhibit osteoclast differentiation in isolated osteoclasts. When osteoblasts are co-cultured with bone marrow cells, diphosphonates inhibit 1,25-(OH)2D3-induced osteoclast formation. Alendronate sufficiently inhibits the formation of multinucleated osteoclasts from mononuclear osteoclast precursors and inhibits the proliferation of macrophages. (2) Inhibition of osteoclast function. There is clear evidence that diphosphonates inhibit osteoclast function. Osteoclasts in isolated cultures and animals in vivo undergo cytoskeletal and cellular morphological changes associated with cell function in response to diphosphate, and the ruffled edges with osteoclastic capacity disappear. (3) Shortening the lifespan of osteoclasts. Diphosphate promotes apoptosis of osteoclasts. It is not clear whether diphosphonate promotes osteoclast apoptosis as a direct effect, and promoting osteoclast apoptosis may be its main mechanism for shortening the lifespan of osteoclasts. 2, molecular level: diphosphate can enter the cell through cell membrane surface receptors or by cellular phagocytosis, and interact with intracellular enzymes or molecules to affect cellular metabolism. From structural analysis, purine receptors are likely to be receptors for diphosphate as well. It is difficult for diphosphate to pass through the lipid bilayer of the cell membrane, and it can only enter the cell by phagocytosis; therefore, it is understandable that diphosphate can act selectively on osteoclasts and macrophages. It is known that diphosphate can inhibit three enzymes of osteoclasts: H+ -ATPase, squalene synthase and phosphorylase. 3, modification of bone minerals: diphosphonates can physically impede the dissolution of bone minerals. However, the pharmacological effect of diphosphate is strong and it is unlikely that low concentrations of diphosphate will inhibit bone resorption by physical action alone. The inhibitory effect on osteolysis is mainly accomplished by inhibiting the function of osteoclasts.