Tumor bone metastases can be divided into three major categories: osteolytic metastases, osteogenic metastases and mixed metastases. Among clinical patients, only myeloma is purely osteolytic. In contrast, prostate cancer is basically an osteogenic metastasis. The majority of breast cancer patients have osteolytic metastases, but at least 15-20% of patients have osteogenic features as well. Mixed metastases are the most common type of metastases in clinical practice. 1.Osteolytic metastasis. In osteolytic metastasis of tumor, the destruction of bone is mainly caused by osteoclasts. The main role of tumor cells is to secrete a series of factors to activate osteoclasts. In myeloma, osteoclasts accumulate and activate only on the bone resorbing surface of the neighboring myeloma cells. Several pro-osteolytic factors may be involved in the activation of osteoclasts in myeloma, including interleukin 1, interleukin 6, macrophage inflammatory protein (MIPIα) and RANKL. Some studies have shown that myeloma cells can secrete RANKL, which inhibits the programmed osteoclast regulation. It is unclear whether RANKL produced by myeloma is sufficient to induce osteoclast formation. Another factor that may be involved in osteolysis in myeloma is MIPIα, which may regulate osteolysis by enhancing the activation of osteoclasts induced by RANKL or interleukin 6. Clinical data suggest that approximately 70% of myeloma patients express MIPIα, and inhibition of RANKL or MIPIα signaling significantly reduces osteolysis in a mouse model of myeloma. The numerous factors produced by breast cancer cells directly or indirectly induce the formation of osteoclasts, and conversely, the activation of osteoclasts and the guidance of the osteolytic process can release a large amount of growth factors from bone tissue, thus stimulating tumor growth and continued bone destruction. This vicious cycle of “tumor growth-osteolysis-tumor growth” promotes both the osteolysis process and the expansion of tumor margins. Some of the growth factors that may participate in this vicious cycle include parathyroid hormone-related peptide, TGF-β, interleukin 1, interleukin 6, prostaglandin E2, macrophage clone-stimulating factor, and tumor necrosis factor α, which can mostly activate osteoclasts by inducing the expression of RANKL. 2. Osteogenic metastasis. Evidence has been found that insulin-like growth factors (ICFI and II) or TGFβ may be involved in the vicious cycle that induces osteogenic metastasis. Prostate cancer is usually considered to be the prototypical case of osteogenic metastasis, and in addition, bone metastases from bladder cancer, some breast cancers and some lung cancers are also predominantly osteogenic. Prostate cancer cells produce large amounts of TGF-β, which has a strong stimulatory effect on osteogenesis.BMP, a peptide growth factor, belongs to the TGF-β superfamily and is the most potent stimulator of bone formation in vivo.Recent studies have shown that endothelin-1 (Endothelin-1) mediates the osteogenic response of prostate cancer cells by activating alkaline phosphatase. Inhibition of endothelin receptor A leads to a decrease in the number of tumor bone metastases and tumor reduction. The clinical significance of various types of metastases is that after osteolytic metastases occur, patients often have different degrees of symptoms such as pain, hypercalcemia, decreased weight-bearing capacity of bones, pathological fractures, etc. If the fractures occur in the bones of the limbs and clavicle, they may lead to decreased or lost limb function; if they occur in the spine, they may lead to spinal cord compression and paralysis; if they occur in other areas, they may also cause corresponding functional deficits. Osteogenic metastases Although osteogenic metastases can form new bone, this new bone is fragile and has a weak weight-bearing capacity. When osteogenic metastases occur, the patient may experience pain, but the pain is less severe than that of osteolytic metastases. In the absence of hypercalcemia, pathologic fractures do not usually occur. Purely osteogenic metastases are rare. The vast majority of bone metastases seen clinically are mixed metastases, except that some are thought to be osteolytic metastases and some are thought to be osteogenic metastases. Regardless of the type of bone metastasis, the patient’s quality of life will be reduced.