**1.1 Bone metastasis**

Bone is one of the most common sites of metastasis in cancer patients [1]. Bone tissue consists of living cells located in an extracellular matrix composed of minerals (**Figure 1**). This extracellular matrix is composed of organic matter, mainly type 1 collagen, and inorganic matter, including calcium and phosphate. Calcium and phosphate combine to form hydroxyapatite crystals in bone tissue [3]. Bone cells include three types of cells: osteoblasts, osteoclasts, and osteocytes. Osteoblasts, known as bone-forming cells, are located along the surface of the bone and play a role in bone formation. Osteoclasts, also known as bone-eating cells, contain multinucleated cells that are formed from hematopoietic stem cells under the influence of several factors and play the role of bone resorption. The location of these cells is also on the surface of the bone. Osteocytes contain 90–95% of bone cells derived from osteoblast cells that are surrounded by extracellular matrix and play a structural role [2, 4].

Bone metastasis occurs due to a complex pathophysiological process between cancer cells and bone cells that stimulates bone formation or resorption activity. Bone metastasis occurs in people with cancer that started outside the bone. In this case, the cancer cells are isolated from the original site and reach the peripheral areas mainly through venous blood flow, and if the conditions are provided for the growth and proliferation of these cells in the target tissue, they metastasize there [5].

Communication between tumor cells and hematopoietic stem cells is essential for the formation of bone metastases. Bone is the third most common tissue that hosts cancer cells from other tissues. Liver and lung metastases usually do not cause

**Figure 1.** *Cells located in the bone matrix (B): Osteoblast (Ob), osteoclast (Oc), and osteocyte (Ot) cells [2].*

symptoms until the patient is advanced. However, bone metastases in patients are very painful and are usually diagnosed earlier. The source of most bone metastases is breast, prostate, lung, thyroid, and kidney cancers [6–8].

The risk of bone metastasis varies in different cancers. For example, 70% of patients with breast and prostate cancer develop bone metastases, while the rate of bone metastases in patients with gastrointestinal cancer is between 3 and 15% [4]. Also, the most common sites of bone metastasis include the bones of the spine, pelvic, ribs, humerus, and femur [9].
