Materiały źródłowe

• #1 Bone metastasis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bone-metastasis/symptoms-causes/syc-20370191

  Bone metastasis occurs when cancer cells spread from their original site to a bone. […] Nearly all types of cancer can spread (metastasize) to the bones. But some types of cancer are particularly likely to spread to bone, including breast cancer and prostate cancer. […] Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver. […] Virtually any type of cancer can spread to the bones, but the cancers most likely to cause bone metastasis include: breast cancer, kidney cancer, lung cancer, lymphoma, multiple myeloma, prostate cancer, and thyroid cancer.

• #2 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  Apoorva Jayarangaiah; Alysia K. Kemp; Pramod Theetha Kariyanna. […] The skeleton is the third most common site of metastatic disease after lung and liver. Most bone metastases originate from the breast, prostate or lung although kidney and thyroid tumors can metastasize to bone as well. […] Carcinoma is the most common cause of secondary bone cancer. Many bone metastases originate from disseminated breast, lung, and prostate cancer. Although, increasingly renal cell and thyroid cancer can metastasize to bone. […] Hematologic malignancies such as multiple myeloma and lymphoma involve bone. Similarly, mesenchymal tumors such as sarcomas, can exhibit late metastases to the bone as well. […] Bone metastases affect survival rates ranging from 6 to 7 months in lung cancer to several years in the breast (19 to 25 months) or prostate cancer (12 to 53 months).

• #2 Bone Metastasis (Cancer Spread to Bone): Signs & Treatment

  https://my.clevelandclinic.org/health/diseases/bone-metastasis

  Bone metastasis is when cancer spreads to your bones from another part of your body. It often affects people with breast, lung and prostate cancer. […] Bone metastasis is a symptom of metastatic cancer that happens when cancer from one place in your body spreads to your bones. It typically affects people with breast cancer, lung cancer and prostate cancer, but other types of cancer can also cause bone metastasis. […] This condition happens when cells from cancerous tumors enter your blood and travel to your bones. Once there, the cancerous cells set off what experts call the vicious cycle of bone metastasis. […] Research shows links between bone cell types and specific types of metastatic cancer. For example, 70% to 85% of bone metastasis from prostate cancer is osteogenic, meaning it happens when osteoblasts make too many bone cells. But 75% of metastatic breast cancer is osteolytic from bone cells that break down too fast.

• #3 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  Bone metastasis is a relatively common complication of cancer, often developing as they advance, especially in prostate cancer and breast cancer. […] Bone is the most common and preferred site for metastatic involvement of cancer. Advanced cancers frequently develop metastases to the bone during the later phases of cancer progression. At least 100,000 patients develop bone metastases every year, although the exact number of bone metastases is not known. Multiple myeloma (MM), breast cancer, and prostate cancer are responsible for up to 70% of bone metastases cases. […] Prostate and breast cancers are the most common primary cancers of bone metastases. […] Regardless of their survival expectancy, however, most patients with bone metastasis need immediate medical attention and active palliative therapy to prevent devastating complications related to bone metastasis, such as pathologic bone fractures and severe bone pain.

• #3 Bone metastases | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/metastatic/bone-metastases

  Cancer that starts in one part of the body and spreads to the bone is called bone metastases. It’s sometimes called secondary bone cancer or metastatic bone disease. Cancer that starts in the bone is called primary bone cancer. Bone metastases are much more common than primary bone cancer. […] Some kinds of cancer are more likely to spread to the bones than others. The most common types of cancer that spread to the bones are: breast, prostate, lung, kidney, thyroid, uterus. […] Osteoblastic metastases develop when cancer cells invade the bone and cause too many bone cells to form. The bone becomes very dense (sclerotic). Osteoblastic metastases often happen when prostate cancer spreads to the bone. […] Osteolytic metastases develop when metastatic cancer cells break down too much of the bone, making it very weak. Holes may develop in the bones as the bone is destroyed. Osteolytic metastases often happen when breast cancer spreads to the bone. […] Osteolytic metastases are more common than osteoblastic metastases. And both can happen together in the same area of bone, such as with metastatic breast cancer.

• #4 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  Bone metastasis is a relatively common complication of cancer, often developing as they advance, especially in prostate cancer and breast cancer. […] Bone is the most common and preferred site for metastatic involvement of cancer. Advanced cancers frequently develop metastases to the bone during the later phases of cancer progression. At least 100,000 patients develop bone metastases every year, although the exact number of bone metastases is not known. Multiple myeloma (MM), breast cancer, and prostate cancer are responsible for up to 70% of bone metastases cases. […] Prostate and breast cancers are the most common primary cancers of bone metastases. […] Regardless of their survival expectancy, however, most patients with bone metastasis need immediate medical attention and active palliative therapy to prevent devastating complications related to bone metastasis, such as pathologic bone fractures and severe bone pain.

• #5 Bone metastases | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/bone-metastases-1?lang=us

  Bone metastases account for 70% of all malignant bone tumors, and are seen in a vast number of primary cancers. This is due to not only the propensity of these tumors to metastasize to bone but also the fact that these are some of the most common tumors. […] Primary tumors that commonly metastasize to bone include prostate cancer (most common in males), breast cancer (most common in females), non-small cell lung cancer, hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer. […] Lung cancer, breast cancer, renal cell carcinoma, and prostate cancer account for ~80% of all bone metastases.

• #6 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  The prognosis of bone metastases is generally poor, although it partly depends on the primary site of the original cancer and on the presence of any additional metastases to visceral organs. […] Major morbidities associated with bone metastases include severe pain, hypercalcemia, bone fractures, spinal compression fractures, and cord or nerve root compression. […] Bisphosphonates are drugs commonly used to treat bone metastases. The benefits of bisphosphonate therapy are bone pain relief, the reduction of bone destruction, and the prevention of hypercalcemia and bone fractures. […] Zoledronic acid is currently one of the most potent bisphosphonates and is effective in most types of metastatic bone lesions. […] Metastatic cancer with bone metastases occurs as cancer advances and spreads to the bone from the primary site of the original solid cancer. Nearly 70% of patients with prostate and breast cancers and about 30% to 40% of patients with lung cancer develop bone metastases. In addition, up to 95% of MMs involve bone. […] The most frequent and important symptom of bone metastasis is pain. In addition, bone metastasis causes bone fractures, hypercalcemia, and spinal cord and nerve compression. Imaging studies, such as bone scans and PET studies, are useful tools in diagnosing bone metastases.

• #7 Incidence of patients with bone metastases at diagnosis of solid tumors in adults: a large population-based study

  https://atm.amegroups.org/article/view/39755/html

  Bones are one of the most common metastatic sites for solid malignancies. […] Bone metastases can significantly increase mortality and decrease the quality of life of cancer patients. […] In the United States, around 350,000 people die each year from bone metastases. […] Several patients with bone metastasis and SREs are affected by breast or prostate cancer, while lower rates are observed in patients with lung, kidney, thyroid, or other cancers. […] The incidence rate of bone metastases in the United States is still unknown, and estimates have varied from 21,000-400,000 per annum. […] Previous studies have shown that the prevalence of bone metastases is more than 70% in patients with metastatic breast and prostate cancer, and approximately 30% in metastatic renal cell carcinoma.

• #8 Bone metastasis | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/bone-metastasis?content_id=CON-20370177

  Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver. […] Nearly all types of cancer can spread (metastasize) to the bones. But some types of cancer are particularly likely to spread to bone, including breast cancer and prostate cancer.

• #9 Understanding Bone Metastasis | Saint Luke’s Health System

  https://www.saintlukeskc.org/health-library/understanding-bone-metastasis

  Bone metastasis is when cancer that started in another part of the body spreads to the bone. […] Certain types of cancer are more likely to spread to the bone than others. These include cancers of the breast, prostate, lung, bladder, kidneys, and thyroid. […] Experts dont know exactly why cancer spreads to the bones. It’s thought that bones have proteins, hormones, or other substances that attract cancer cells. The structure and makeup of the bones may also make it easier for cancer cells to attach and grow. […] Bone metastasis is a complication of the underlying cancer in the body. If the cancer continues to spread, it can keep causing symptoms. Over time, it can lead to death.

• #10 Bone Metastases | OncoLink

  https://www.oncolink.org/cancers/bone/bone-metastases/bone-metastases

  When cancer cells spread from one area of the body to another, it is called metastasis. When the cancer spreads (metastasizes) to your bones, it is called bone metastasis (or bone mets). Cancer that metastasizes to your bone is not bone cancer. It is cancer of where the primary (original) tumor is. Cancer cells from the primary tumor can travel through the bloodstream or lymph system to a part of a bone. […] The most common cancers to metastasize to the bone are breast, prostate, lung, thyroid, and kidney cancer. […] There are three reasons cancer spreads to the bone: Blood Flow: There is a lot of blood flow to your bone and bone marrow. Once cancer cells get into blood vessels, they can travel all over your body. They often go where there is the most blood flow. Adhesive (sticky) Molecules: Tumor cells put out adhesive molecules that can stick to your bone marrow and bone. These molecules tell the tumor to destroy more bone and to grow more cancer cells inside the bone. Growth Factors: The bone has a lot of growth factors that tell cells to divide, grow, and mature. As the cancer attacks the bone, these growth factors are released and cause tumor cells to grow. […] Cancers can lead to osteolytic or osteoblastic bony changes, or both.

• #11 What Is Metastasis? (Stage IV, Metastatic or Secondary Cancer)

  https://my.clevelandclinic.org/health/diseases/22213-metastasis-metastatic-cancer

  Metastasis happens when cancer cells break off from the original tumor, enter your bloodstream or lymphatic system, and then spread to other areas of your body. […] Metastasis is when cancer spreads beyond the place where it started to other areas of your body. Nearly all cancers have the potential to metastasize. […] Metastasis happens when cancer cells break off from the original tumor and spread to other parts of your body. These cancer cells can travel through your bloodstream or lymph vessels. […] Many factors can trigger metastasis, like: A weakened immune system. Hypoxia (a lack of oxygen in your tissues). Lactic acidosis (a buildup of lactic acid in your blood). Autophagy (a type of cell death). […] Some metastases may require local targeted therapy to manage symptoms. For instance, if you have breast cancer that spreads to the bone and causes pain or fractures, your provider can treat and ease those symptoms with surgery or radiation to the bone.

• #12 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #13 Bone Metastases | OncoLink

  https://www.oncolink.org/cancers/bone/bone-metastases/bone-metastases

  When cancer cells spread from one area of the body to another, it is called metastasis. When the cancer spreads (metastasizes) to your bones, it is called bone metastasis (or bone mets). Cancer that metastasizes to your bone is not bone cancer. It is cancer of where the primary (original) tumor is. Cancer cells from the primary tumor can travel through the bloodstream or lymph system to a part of a bone. […] The most common cancers to metastasize to the bone are breast, prostate, lung, thyroid, and kidney cancer. […] There are three reasons cancer spreads to the bone: Blood Flow: There is a lot of blood flow to your bone and bone marrow. Once cancer cells get into blood vessels, they can travel all over your body. They often go where there is the most blood flow. Adhesive (sticky) Molecules: Tumor cells put out adhesive molecules that can stick to your bone marrow and bone. These molecules tell the tumor to destroy more bone and to grow more cancer cells inside the bone. Growth Factors: The bone has a lot of growth factors that tell cells to divide, grow, and mature. As the cancer attacks the bone, these growth factors are released and cause tumor cells to grow. […] Cancers can lead to osteolytic or osteoblastic bony changes, or both.

• #14

  https://www.orthobullets.com/pathology/8045/metastatic-disease-of-extremity

  Metastatic Disease of the Extremity is a malignant pathologic process that is the most common cause of destructive bone lesions in the extremities of adult patients. […] bone is the third most common site for metastatic disease (behind lung and liver) […] solitary bone lesions are 500 times more likely to be metastatic carcinoma than a primary bone tumor in patients 40 years old. […] carcinomas that commonly spread to bone include breast (most common in females), lung, thyroid, kidney, prostate (most common in males). […] tumor cell intravasation […] E cadherin cell adhesion molecule (CAM) on tumor cells modulates release from primary tumor focus into bloodstream. […] PDGF promotes tumor migration. […] chemokine ligand 12 (CXCL12) in the stromal cells bone marrow acts as homing chemokine to certain tumor cells and promotes targeting of bone.

• #15 Understanding Bone Metastasis | UMass Memorial Health

  https://www.ummhealth.org/health-library/understanding-bone-metastasis

  Bone metastasis is when an area of bone has cancer that spread there from another part of the body. Breast, prostate, lung, kidneys, and thyroid cancers are more likely to spread to the bone. […] Experts dont know exactly why cancer spreads to the bones. It’s thought that bones have proteins, hormones, or other substances that attract cancer cells. The structure and makeup of the bones may also make it easier for cancer cells to attach and grow. […] Certain types of cancer are more likely to spread to the bones than others. These include cancers of the breast, prostate, lung, bladder, kidneys, and thyroid. Sometimes with metastatic cancer, health care providers can’t tell where it started. This type of cancer is called cancer of unknown primary origin.

• #16

  https://www.ttsh.com.sg/About-TTSH/TTSH-News/Pages/bone%20metastasis.aspx

  The bone is the third most common site of cancer spread from other organs and a major cause of morbidity in cancer patients. […] In some cancer types, such as advanced breast and prostate cancer, the incidence of bone metastasis may be up to 80%. […] The most frequent cancers that metastasise to the bone arise from paired organs. Breast, prostate, lung, renal and thyroid cancers all frequently spread to the bone. […] Cancer spreads to the bone by the haematogenous (blood vessel) route. […] According to this hypothesis, the bone is the soil and cancer cells circulating in the bloodstream lodge or seed into the bone. […] The mechanisms and signalling molecules involved in this process are similar to those involved in osteoporosis, meaning that many anti-osteoporotic drugs are also useful for treating bone metastases.

• #17 Metastatic Bone Disease: Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1253331-overview

  Metastatic bone disease occurs when cancer spreads from a primary organ site to bone. The spine is the most common location of metastatic disease. In females, the breasts and lungs are the most common primary disease sites; approximately 80% of cancers that spread to bone arise in these locations. […] In males, cancers of the prostate and lungs make up 80% of the carcinomas that metastasize to bone. The remaining 20% of primary disease sites in patients of both sexes are the kidney, gut, and thyroid, as well as sites of unknown origin. […] Previously, the two main theories of how tumor cells metastasize and grow in bones were Paget’s fertile soil hypothesis and Ewing’s circulation theory. Subsequently, a substantial amount of work more clearly defined the metastatic process to bone. Bone metastases occur in a predictable distribution. In order of frequency, the most common locations include the following: Spine, Pelvis, Ribs, Proximal limb girdles.

• #18 Bone metastasis – Wikipedia

  https://en.wikipedia.org/wiki/Bone_metastasis

  Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. […] Bone metastases can be classified as osteolytic, osteoblastic, or both. […] Dysregulation of these processes by tumor cells leads to either osteoblastic or osteolytic lesions, reflective of the underlying mechanism of development. […] Bone is the third most common location for metastasis, after the lung and liver. […] While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment of the marrow tends to favor particular types of cancer, including prostate, breast, and lung cancers. […] The pathogenesis of bone metastasis via the vasculature is hypothesized to be related to the Batson vertebral vein plexus, a longitudinal valveless system connected to the breast, lung, kidney, thyroid, and prostate gland that extends from the sacrum to the skull.

• #19 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #20 Bone metastases | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/metastatic/bone-metastases

  Cancer that starts in one part of the body and spreads to the bone is called bone metastases. It’s sometimes called secondary bone cancer or metastatic bone disease. Cancer that starts in the bone is called primary bone cancer. Bone metastases are much more common than primary bone cancer. […] Some kinds of cancer are more likely to spread to the bones than others. The most common types of cancer that spread to the bones are: breast, prostate, lung, kidney, thyroid, uterus. […] Osteoblastic metastases develop when cancer cells invade the bone and cause too many bone cells to form. The bone becomes very dense (sclerotic). Osteoblastic metastases often happen when prostate cancer spreads to the bone. […] Osteolytic metastases develop when metastatic cancer cells break down too much of the bone, making it very weak. Holes may develop in the bones as the bone is destroyed. Osteolytic metastases often happen when breast cancer spreads to the bone. […] Osteolytic metastases are more common than osteoblastic metastases. And both can happen together in the same area of bone, such as with metastatic breast cancer.

• #21 Metastatic Bone Disease – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/metastatic-bone-disease/

  Sometimes, the tumor will lead to destruction of the bone in a particular area. This process is called osteolytic bone destruction, and it is common in cancers that have spread to bone from the lung, thyroid, kidney, and colon. […] Alternatively, new bone can form in response to the cancer spread. […] Osteolytic and osteoblastic metastatic bone disease occur because the different cancer cells secrete factors that interact with the naturally occurring cells in the bone and cause bone destruction, new bone formation, or both. […] Because MBD weakens the affected bones, people with this disease are at risk for fractures. […] A diagnosis of metastatic bone disease should not be assumed unless a patient has a known primary cancer that has previously spread to bone. […] If you are over the age of 45 with no personal history of cancer, and an X-ray detects a bone tumor, you should schedule a consultation with an orthopaedic oncologist.

• #22 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #23 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  An important consideration in understanding bone metastases is the unique composition of the soil or the bone microenvironment. […] Osteolytic metastasis is the most common form of bone metastasis in all cancer patients. […] Most in vivo studies indicate that osteolysis is caused by osteoclast stimulation, not by the direct effects of cancer cells on bone. […] Osteolytic metastases are associated with increased osteoclast activity and reduced osteoblast activity that is uncoupled from bone resorption. […] Tumor cells produce factors that stimulate osteoclastic bone resorption directly or indirectly. […] PTHrP is one of the major mediators of breast cancer related osteolytic bone metastasis. […] The bone microenvironment is rich in growth factors. […] Recently, there has been considerable improvement in our understanding of the successive steps by which tumor cells affect the bone.

• #24 Metastatic Bone Disease: Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1253331-overview

  The red marrow theory, combined with knowledge about the cytokine stimulation of metastases, provides an excellent explanation of how this distribution occurs. […] Cells from the primary site must, through the process of neovascularization or through migration to the nearest blood vessel, attach to the basement membrane of the vessel wall and produce proteolytic enzymes that disrupt the basement membrane. […] Producing chemotactic factors, as well as RANK ligand (RANKL; a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts), these cells stimulate osteoclast activity, causing bone resorption and leading to the formation of pockets or holes in the bone in which the tumor cells grow. […] Another important substance that stimulates bone resorption is parathyroid hormone related peptide (PTHrP). This substance is expressed by breast carcinoma cells, as well as by oat cell tumors of the lung, and is a potent stimulant of osteoclasts. […] Mundy and Yoneda also reported that myeloma cells are especially adapted to producing bone destruction through direct stimulation of osteoclasts.

• #25 Metastasis to bone: causes, consequences and therapeutic opportunities | Nature Reviews Cancer

  https://www.nature.com/articles/nrc867

  Common tumours, such as those of the breast, lung and prostate, frequently metastasize to bone, and in many patients with advanced disease the skeleton is the site of the most significant tumour burden. […] In the case of breast-cancer-causing osteolysis, the main mediator is parathyroid-hormone-related peptide (PTHrP), whereas, in osteoblastic lesions, known mediators include endothelin-1 and platelet-derived growth factor. […] In osteolytic metastasis, there is a 'vicious cycle’ in the bone microenvironment, whereby bi-directional interactions between tumour cells and osteoclasts lead to both osteolysis and tumour growth. […] The molecular mechanisms that are responsible for this vicious cycle are now being clarified and involve tumour-cell production of PTHrP and bone-derived growth factors that are released as a consequence of increased bone resorption.

• #26 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  For patients, the occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The process by which breast cancer cells metastasize to the bone is frequently referred to as a “vicious cycle.” It begins when metastatic breast cancer cells produce parathyroid hormone-releasing peptide (PTHrP), which binds to the same receptors as parathyroid hormone and stimulates osteoblasts to secrete increased amounts of RANK-L. […] The occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The evolution of solid tumor metastasis is a complex process. Metastatic dissemination of tumor cells involves pre-metastatic niche formation, tumor cell dissemination through the circulation and chemotactic attraction and homing of tumor cells to the metastatic site of a target organ, as well as reciprocal interactions with local stromal cells and immune cells within the new microenvironment.

• #27 Bone metastases | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/metastatic/bone-metastases

  Cancer that starts in one part of the body and spreads to the bone is called bone metastases. It’s sometimes called secondary bone cancer or metastatic bone disease. Cancer that starts in the bone is called primary bone cancer. Bone metastases are much more common than primary bone cancer. […] Some kinds of cancer are more likely to spread to the bones than others. The most common types of cancer that spread to the bones are: breast, prostate, lung, kidney, thyroid, uterus. […] Osteoblastic metastases develop when cancer cells invade the bone and cause too many bone cells to form. The bone becomes very dense (sclerotic). Osteoblastic metastases often happen when prostate cancer spreads to the bone. […] Osteolytic metastases develop when metastatic cancer cells break down too much of the bone, making it very weak. Holes may develop in the bones as the bone is destroyed. Osteolytic metastases often happen when breast cancer spreads to the bone. […] Osteolytic metastases are more common than osteoblastic metastases. And both can happen together in the same area of bone, such as with metastatic breast cancer.

• #28 Sclerotic bone metastases | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/sclerotic-bone-metastases?lang=us

  Sclerotic bone metastases can arise from several different primary malignancies, including 1-3: […] prostate cancer (most common) […] breast carcinoma (may be mixed) […] transitional cell carcinoma (TCC) […] neuroendocrine tumor […] medullary thyroid carcinoma […] medulloblastoma […] neuroblastoma […] mucinous adenocarcinoma of the gastrointestinal tract (e.g. colon carcinoma, gastric carcinoma) […] Hodgkin lymphoma (e.g. ivory vertebra) […] small cell lung cancer […] pulmonary adenocarcinoma. […] Osteoblastic bone metastases are characterized by increased bone formation. However, the exact mechanism that leads to osteoblastic formation is not entirely elucidated. Several tumor-derived growth factors are assumed to increase osteoblast activity while osteoclast activity is restricted.

• #29 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  Some neoplasia produce bone metastases which are predominantly osteoblastic, most notably prostate cancer and approximately 15-20% breast cancers. […] During osteoblastic bone metastases, the balance between bone resorption and bone formation is tipped in favor of the latter. […] There is an accumulating body of evidence implicating Endothelin-1 (ET-1) as a central mediator of osteoblastic metastasis. […] Proteases such as urokinase-type plasminogen receptor (uPA) and Prostate Specific Antigen (PSA) are also implicated in osteoblastic bone metastasis. […] There is evidence that osteoblastic metastasis also involves considerable osteolysis. […] Bone metastases are common in patients with advanced cancers, and their presence usually signifies serious morbidity and a grave prognosis.

• #30

  https://www.orthobullets.com/pathology/8045/metastatic-disease-of-extremity

  tumor cells secrete PTHrP which stimulates the release of RANKL from osteoblasts. […] RANKL then binds to the RANK receptor on osteoclast precursor cells. […] differentiation to active osteoclasts occurs, which causes bony destruction. […] the tumor continues to grow through the release of growth factors, proinflammatory cytokines (IL-6 and IL-8), and VEGF. […] osteoblastic lesions due to tumor-secreted endothelin-1(ET-1) bind to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts. […] ET-1 decreases WNT suppressor DKK-1, activating WNT pathway, increasing osteoblast activity.

• #31 Metastasis to bone: causes, consequences and therapeutic opportunities | Nature Reviews Cancer

  https://www.nature.com/articles/nrc867

  Common tumours, such as those of the breast, lung and prostate, frequently metastasize to bone, and in many patients with advanced disease the skeleton is the site of the most significant tumour burden. […] In the case of breast-cancer-causing osteolysis, the main mediator is parathyroid-hormone-related peptide (PTHrP), whereas, in osteoblastic lesions, known mediators include endothelin-1 and platelet-derived growth factor. […] In osteolytic metastasis, there is a 'vicious cycle’ in the bone microenvironment, whereby bi-directional interactions between tumour cells and osteoclasts lead to both osteolysis and tumour growth. […] The molecular mechanisms that are responsible for this vicious cycle are now being clarified and involve tumour-cell production of PTHrP and bone-derived growth factors that are released as a consequence of increased bone resorption.

• #32 Bone metastases | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/metastatic/bone-metastases

  Cancer that starts in one part of the body and spreads to the bone is called bone metastases. It’s sometimes called secondary bone cancer or metastatic bone disease. Cancer that starts in the bone is called primary bone cancer. Bone metastases are much more common than primary bone cancer. […] Some kinds of cancer are more likely to spread to the bones than others. The most common types of cancer that spread to the bones are: breast, prostate, lung, kidney, thyroid, uterus. […] Osteoblastic metastases develop when cancer cells invade the bone and cause too many bone cells to form. The bone becomes very dense (sclerotic). Osteoblastic metastases often happen when prostate cancer spreads to the bone. […] Osteolytic metastases develop when metastatic cancer cells break down too much of the bone, making it very weak. Holes may develop in the bones as the bone is destroyed. Osteolytic metastases often happen when breast cancer spreads to the bone. […] Osteolytic metastases are more common than osteoblastic metastases. And both can happen together in the same area of bone, such as with metastatic breast cancer.

• #33 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  Some neoplasia produce bone metastases which are predominantly osteoblastic, most notably prostate cancer and approximately 15-20% breast cancers. […] During osteoblastic bone metastases, the balance between bone resorption and bone formation is tipped in favor of the latter. […] There is an accumulating body of evidence implicating Endothelin-1 (ET-1) as a central mediator of osteoblastic metastasis. […] Proteases such as urokinase-type plasminogen receptor (uPA) and Prostate Specific Antigen (PSA) are also implicated in osteoblastic bone metastasis. […] There is evidence that osteoblastic metastasis also involves considerable osteolysis. […] Bone metastases are common in patients with advanced cancers, and their presence usually signifies serious morbidity and a grave prognosis.

• #34 Bone Metastasis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/18450

  Carcinoma is the most common cause of secondary bone cancer. Many bone metastases originate from disseminated breast, lung, and prostate cancer. Although, increasingly renal cell and thyroid cancer can metastasize to bone. Carcinomas are of epithelial tissue origin and go on to form the covering over solid organs and glands throughout the body. Non-epithelial cell lines produce cancers that spread to the bone. Hematologic malignancies such as multiple myeloma and lymphoma involve bone. Similarly, mesenchymal tumors such as sarcomas, can exhibit late metastases to the bone as well. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer).

• #35 Bone Metastasis (Cancer Spread to Bone): Signs & Treatment

  https://my.clevelandclinic.org/health/diseases/bone-metastasis

  Bone metastasis is when cancer spreads to your bones from another part of your body. It often affects people with breast, lung and prostate cancer. […] Bone metastasis is a symptom of metastatic cancer that happens when cancer from one place in your body spreads to your bones. It typically affects people with breast cancer, lung cancer and prostate cancer, but other types of cancer can also cause bone metastasis. […] This condition happens when cells from cancerous tumors enter your blood and travel to your bones. Once there, the cancerous cells set off what experts call the vicious cycle of bone metastasis. […] Research shows links between bone cell types and specific types of metastatic cancer. For example, 70% to 85% of bone metastasis from prostate cancer is osteogenic, meaning it happens when osteoblasts make too many bone cells. But 75% of metastatic breast cancer is osteolytic from bone cells that break down too fast.

• #36 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Bone is the single most frequent site for bone metastasis in breast cancer patients. […] In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. […] Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. […] Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials. […] Several factors seem to affect the metastatic pattern, including demographic, clinical, pathological, and genetic factors. […] In BC, BM present a radiographic pattern that can be lytic, blastic, or mixed.

• #37 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Given the lack of information in this field, we performed a literature review on risk factors for BM in BC patients. […] There are conflicting results when analysing the effect of age in the development of BM. […] Menopausal status might also be related to the development of BM in BC patients since oestrogens are essential regulators of bone remodelling, potentially contributing to a fertile microenvironment that might promote BM. […] The mechanisms explaining this association are not completely clear but seem to relate with higher levels of oestradiol, higher levels of insulin or even other non-biologic mechanisms such as chemotherapy under-dosing or obesity-related complications. […] Different invasive BC histological types, namely ductal, lobular, medullar, tubular, and mucinous BC are widely known to show different metastatic patterns.

• #38 Metastatic Bone Disease Causes, Symptoms, and Treatments

  https://www.upmc.com/services/orthopaedics/conditions/metastatic-bone-disease

  Doctors define metastatic bone disease as cancer that spreads from one part of the body into a bone. The tumor may begin in an organ, gland, or connective tissue, and the cancer cells move through the blood or lymph system into the skeleton. […] Doctors arent sure what causes cancer to spread from one part of the body to a bone. […] The main risk factor for metastatic bone disease is having cancer in another organ. About half of the cancers that start in other organs can spread to a bone, according to the American Academy of Orthopaedic Surgeons. […] Some types of cancers are more likely to spread to the skeleton, including: Breast, Kidney, Lung, Melanoma, Ovarian, Prostate, Thyroid.

• #39 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Given the lack of information in this field, we performed a literature review on risk factors for BM in BC patients. […] There are conflicting results when analysing the effect of age in the development of BM. […] Menopausal status might also be related to the development of BM in BC patients since oestrogens are essential regulators of bone remodelling, potentially contributing to a fertile microenvironment that might promote BM. […] The mechanisms explaining this association are not completely clear but seem to relate with higher levels of oestradiol, higher levels of insulin or even other non-biologic mechanisms such as chemotherapy under-dosing or obesity-related complications. […] Different invasive BC histological types, namely ductal, lobular, medullar, tubular, and mucinous BC are widely known to show different metastatic patterns.

• #40 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies relate grade to the risk of developing BC metastasis, regardless of the site. […] When analysing which risk factors are associated with BM, those that indicate a less aggressive disease are generally referred. […] Several authors have reported an effect of tumour size in the risk of developing BM, with bigger tumours showing a higher risk. […] Lymph node involvement is a known risk factor for metastasis in BC patients. […] Recent access to large datasets of genetic information linked to clinicopathological and outcomes data, as well as the thriving study of cancer biomarkers, enabled the study of genetic associations with the pattern of metastases. […] It has long been known that BC is a heterogeneous disease which is susceptible to multiple classifications. […] Another classification system, using prognostic multigene classifiers, classifies BC in five intrinsic subtypes (luminal A, luminal B, HER-2-enriched, basal-like, and normal-like), associated with distinct morphologies and clinical implications.

• #41 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Bone is the single most frequent site for bone metastasis in breast cancer patients. […] In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. […] Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. […] Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials. […] Several factors seem to affect the metastatic pattern, including demographic, clinical, pathological, and genetic factors. […] In BC, BM present a radiographic pattern that can be lytic, blastic, or mixed.

• #42 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies relate grade to the risk of developing BC metastasis, regardless of the site. […] When analysing which risk factors are associated with BM, those that indicate a less aggressive disease are generally referred. […] Several authors have reported an effect of tumour size in the risk of developing BM, with bigger tumours showing a higher risk. […] Lymph node involvement is a known risk factor for metastasis in BC patients. […] Recent access to large datasets of genetic information linked to clinicopathological and outcomes data, as well as the thriving study of cancer biomarkers, enabled the study of genetic associations with the pattern of metastases. […] It has long been known that BC is a heterogeneous disease which is susceptible to multiple classifications. […] Another classification system, using prognostic multigene classifiers, classifies BC in five intrinsic subtypes (luminal A, luminal B, HER-2-enriched, basal-like, and normal-like), associated with distinct morphologies and clinical implications.

• #43 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Bone is, actually, the least common metastatic site for basal-like tumours. […] Even in studies using HER-2 overexpression, ER and PR status, and Ki67 as surrogate markers for intrinsic subtypes, this results hold true, with bone being the predominant site of metastasis in luminal A-like tumours, luminal B-like tumours, and luminal/HER2-like groups. […] In 2003, Kang et al published a study in which BC cell populations with high affinity to bone in mouse models showed a distinct transcriptional signature. […] This BM-specific genetic profile would be superimposed to a poor prognosis gene signature. […] A recent study described v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) as a mediator of BC BM. […] PTHrP is expressed in 73-100% BC BM, a clearly higher frequency to that found in visceral metastases and primary tumours.

• #44 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies relate grade to the risk of developing BC metastasis, regardless of the site. […] When analysing which risk factors are associated with BM, those that indicate a less aggressive disease are generally referred. […] Several authors have reported an effect of tumour size in the risk of developing BM, with bigger tumours showing a higher risk. […] Lymph node involvement is a known risk factor for metastasis in BC patients. […] Recent access to large datasets of genetic information linked to clinicopathological and outcomes data, as well as the thriving study of cancer biomarkers, enabled the study of genetic associations with the pattern of metastases. […] It has long been known that BC is a heterogeneous disease which is susceptible to multiple classifications. […] Another classification system, using prognostic multigene classifiers, classifies BC in five intrinsic subtypes (luminal A, luminal B, HER-2-enriched, basal-like, and normal-like), associated with distinct morphologies and clinical implications.

• #45 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Bone is, actually, the least common metastatic site for basal-like tumours. […] Even in studies using HER-2 overexpression, ER and PR status, and Ki67 as surrogate markers for intrinsic subtypes, this results hold true, with bone being the predominant site of metastasis in luminal A-like tumours, luminal B-like tumours, and luminal/HER2-like groups. […] In 2003, Kang et al published a study in which BC cell populations with high affinity to bone in mouse models showed a distinct transcriptional signature. […] This BM-specific genetic profile would be superimposed to a poor prognosis gene signature. […] A recent study described v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) as a mediator of BC BM. […] PTHrP is expressed in 73-100% BC BM, a clearly higher frequency to that found in visceral metastases and primary tumours.

• #46 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies have associated PTHrP expression to the development of BM in BC patients. […] The relationship between MAF and the risk of BM is thought to result from the control that this protein might exert on PTHrP. […] There seems to be a correlation between serum BSP levels and the risk of BM in BC patients. […] BMP7 expression in primary tumour seems to correlate with the risk for accelerated BM formation in BC patients. […] This study concluded that a biomarker including CAPG and GIPC1 in primary BC tissue is associated with BM development. […] There is a profound effect of adjuvant therapy in the pattern of metastasis. […] Nevertheless, intrinsic subtype is widely accepted as a major risk factor for BM development. […] Other factors such as BMP7 expression, higher level of bone sialoprotein or elevation of B-CTx prior to treatment may also indicate a higher risk for BM. […] Further research on this topic is, therefore, mandatory.

• #47 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies have associated PTHrP expression to the development of BM in BC patients. […] The relationship between MAF and the risk of BM is thought to result from the control that this protein might exert on PTHrP. […] There seems to be a correlation between serum BSP levels and the risk of BM in BC patients. […] BMP7 expression in primary tumour seems to correlate with the risk for accelerated BM formation in BC patients. […] This study concluded that a biomarker including CAPG and GIPC1 in primary BC tissue is associated with BM development. […] There is a profound effect of adjuvant therapy in the pattern of metastasis. […] Nevertheless, intrinsic subtype is widely accepted as a major risk factor for BM development. […] Other factors such as BMP7 expression, higher level of bone sialoprotein or elevation of B-CTx prior to treatment may also indicate a higher risk for BM. […] Further research on this topic is, therefore, mandatory.

• #48 Primary Bone Cancer – NCI

  https://www.cancer.gov/types/bone/bone-fact-sheet

  What are the possible causes of bone cancer? […] Although primary bone cancer does not have a clearly defined cause, researchers have identified several factors that increase the likelihood of developing these tumors. […] Previous cancer treatment with radiation, chemotherapy, or stem cell transplantation. Osteosarcoma occurs more frequently in people who have had high-dose external radiation therapy (particularly at the location in the body where the radiation was given) or treatment with certain anticancer drugs, particularly alkylating agents; those treated during childhood are at particular risk. […] Certain inherited conditions. A small number of bone cancers are due to hereditary conditions. […] Certain benign bone conditions. People over age 40 who have Paget disease of bone (a benign condition characterized by abnormal development of new bone cells) are at increased risk of developing osteosarcoma.

• #49

  https://www.nhs.uk/conditions/bone-cancer/

  In most cases, it’s not known why a person develops bone cancer. […] You’re more at risk of developing it if you: […] have had previous exposure to radiation during radiotherapy […] have a condition known as Paget’s disease of the bone however, only a very small number of people with Paget’s disease will actually develop bone cancer […] have a rare genetic condition called Li-Fraumeni syndrome people with this condition have a faulty version of a gene that normally helps stop the growth of cancerous cells.

• #50

  https://www.mountelizabeth.com.sg/conditions-diseases/bone-metastasis/symptoms-causes

  Bone metastasis refers to cancer in a different organ that has spread to the bone. Also known as secondary bone cancer, it occurs when cancer cells break away and spread from the original (primary) tumour to the bone. This is different from a primary bone tumour, which starts in the bone. […] While all types of cancer have the possibility to spread to the bones, there are cancers that are more likely to lead to bone metastasis, such as: Breast cancer, Kidney cancer, Lung cancer, Lymphoma, Multiple myeloma, Prostate cancer, Thyroid cancer. […] Cancer cells are different from normal cells in various ways. Unlike normal cells, cancer cells keep growing and doubling, forming a tumour that grows in size. It is not clear what causes these cells to divide out of control. […] Some factors that are associated with an increased risk of developing bone cancer include: Inherited genetic syndromes, Certain rare genetic syndromes such as Li-Fraumeni syndrome and hereditary retinoblastoma can increase the risk of bone cancer, Radiation therapy, People who have had exposure to radiation (e.g. receiving radiation therapy for cancer) are at a higher risk, Chemotherapy, Some drugs involved in chemotherapy may increase ones risk for developing bone cancer, Secondary cancer, When a cancer starts in one place in the body and spreads elsewhere, this is a secondary cancer or a metastasis. Some cancer types are particularly likely to spread to the bone, including breast cancer and prostate cancer, Other bone conditions, Benign tumours in the bone and other non-cancerous bone diseases may increase ones risk for bone cancer. Rarely, people with Paget’s disease of the bone, which disrupts the bodys process of gradually replacing old bone tissue with new ones, can develop bone cancer.

• #51 Primary Bone Cancer – NCI

  https://www.cancer.gov/types/bone/bone-fact-sheet

  What are the possible causes of bone cancer? […] Although primary bone cancer does not have a clearly defined cause, researchers have identified several factors that increase the likelihood of developing these tumors. […] Previous cancer treatment with radiation, chemotherapy, or stem cell transplantation. Osteosarcoma occurs more frequently in people who have had high-dose external radiation therapy (particularly at the location in the body where the radiation was given) or treatment with certain anticancer drugs, particularly alkylating agents; those treated during childhood are at particular risk. […] Certain inherited conditions. A small number of bone cancers are due to hereditary conditions. […] Certain benign bone conditions. People over age 40 who have Paget disease of bone (a benign condition characterized by abnormal development of new bone cells) are at increased risk of developing osteosarcoma.

• #52 Metastatic Bone Disease: Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1253331-overview

  The red marrow theory, combined with knowledge about the cytokine stimulation of metastases, provides an excellent explanation of how this distribution occurs. […] Cells from the primary site must, through the process of neovascularization or through migration to the nearest blood vessel, attach to the basement membrane of the vessel wall and produce proteolytic enzymes that disrupt the basement membrane. […] Producing chemotactic factors, as well as RANK ligand (RANKL; a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts), these cells stimulate osteoclast activity, causing bone resorption and leading to the formation of pockets or holes in the bone in which the tumor cells grow. […] Another important substance that stimulates bone resorption is parathyroid hormone related peptide (PTHrP). This substance is expressed by breast carcinoma cells, as well as by oat cell tumors of the lung, and is a potent stimulant of osteoclasts. […] Mundy and Yoneda also reported that myeloma cells are especially adapted to producing bone destruction through direct stimulation of osteoclasts.

• #53 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. […] Skeletal metastases are most frequently observed in multiple myeloma (up to 95%), breast and prostate cancer patients (65–80%), while lower rates are observed in patients with lung, kidney, thyroid or other cancers. In pediatric cancers, bone metastasis is frequent in children suffering from neuroblastoma, osteosarcoma and Ewing sarcoma. […] The main compartment affected by bone metastasis is the red bone marrow, found mainly in the central skeleton, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and to a variable extent in the proximal ends of long bones such as the femur and humerus. Its rich vascularization and unique cellular makeup support the homing of circulating tumor cells and the development of secondary deposits in the bone. Metastases therefore occur predominantly in the axial skeleton (>80% of patients with bone metastases), of which the majority affects the thoracic spine (70%), the lumbosacral region (20%) and cervical vertebrae (10%).

• #54 Metastatic Bone Disease: Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1253331-overview

  Metastatic bone disease occurs when cancer spreads from a primary organ site to bone. The spine is the most common location of metastatic disease. In females, the breasts and lungs are the most common primary disease sites; approximately 80% of cancers that spread to bone arise in these locations. […] In males, cancers of the prostate and lungs make up 80% of the carcinomas that metastasize to bone. The remaining 20% of primary disease sites in patients of both sexes are the kidney, gut, and thyroid, as well as sites of unknown origin. […] Previously, the two main theories of how tumor cells metastasize and grow in bones were Paget’s fertile soil hypothesis and Ewing’s circulation theory. Subsequently, a substantial amount of work more clearly defined the metastatic process to bone. Bone metastases occur in a predictable distribution. In order of frequency, the most common locations include the following: Spine, Pelvis, Ribs, Proximal limb girdles.

• #55 Bone Metastasis: Which Cancers Cause It?

  https://www.webmd.com/cancer/common-cancers-that-metastasize-to-the-bones

  The type of cancer may have something to do with why tumors form in bones. Certain cancers may release proteins that affect how a tumor forms. […] Bones provide fertile ground for the growth of tumor cells, because they are areas of constant cell turnover and growth. And bone cells release substances that may prompt faster cancer growth. […] Cancer cells can go anywhere, but they often go to the bones with the greatest blood supply. This includes bones in the spine, pelvis, ribs, upper arms, and thighs. […] In many cases of cancer such as breast cancer, either – or both — bone destruction and new bone formation may occur. […] Bone metastasis symptoms include: Bone pain is the most common symptom, and many patients with bone metastasis experience significant pain at some point in the course of their disease.

• #56 Bone Metastases | Loma Linda University Health

  https://lluh.org/conditions/bone-metastases

  Cancer that has started in one place can spread to and invade other parts of the body. This spread is called metastasis. If a tumor spreads to the bone, it’s called bone metastasis. […] Different types of cancer tend to spread to certain parts of the body. These cancers commonly spread to the bones: Breast, Kidney, Lung, Prostate, Thyroid, Bladder, Ovary, Melanoma. […] A tumor that has metastasized to bone is not made of bone cells. Bone metastases are made up of abnormal cancer cells that started from the original (primary) tumor site. […] In adults, metastatic bone cancer is much more common than primary bone cancer. […] Cancer cells that spread to the bone often affect these places: Limbs (upper arm and upper leg bones), Pelvis (hipbones), Rib cage, Skull, Spine. […] Bone metastases can cause these symptoms: Pain is the most common symptom of bone metastasis.

• #57 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. […] Skeletal metastases are most frequently observed in multiple myeloma (up to 95%), breast and prostate cancer patients (65–80%), while lower rates are observed in patients with lung, kidney, thyroid or other cancers. In pediatric cancers, bone metastasis is frequent in children suffering from neuroblastoma, osteosarcoma and Ewing sarcoma. […] The main compartment affected by bone metastasis is the red bone marrow, found mainly in the central skeleton, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and to a variable extent in the proximal ends of long bones such as the femur and humerus. Its rich vascularization and unique cellular makeup support the homing of circulating tumor cells and the development of secondary deposits in the bone. Metastases therefore occur predominantly in the axial skeleton (>80% of patients with bone metastases), of which the majority affects the thoracic spine (70%), the lumbosacral region (20%) and cervical vertebrae (10%).

• #58 Metastatic Bone Tumors – Bone, Joint, and Muscle Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/bone-joint-and-muscle-disorders/bone-and-joint-tumors/metastatic-bone-tumors

  Cancers that begin elsewhere in the body may spread (metastasize) to the bones. […] In particular, cancers of the breast, lung, prostate gland, kidney, thyroid gland, and colon may metastasize to the bones. […] Breast cancer is the most common cancer to spread to bone. However, any cancer may eventually spread to bone. […] Cancer may spread to any bone, although cancers do not commonly spread to bone below the mid forearm or mid calf. When cancer does metastasize to these sites, it is most often from cancer in the lung or kidney. […] The cancerous marrow cells secrete substances that cause loss of bone. Bone loss may be widespread or, more often, appear as punched-out areas in bones. […] If multiple myeloma is suggested by the bone biopsy results or if multiple myeloma is suspected for other reasons, the diagnosis is confirmed by removing and examining bone marrow cells.

• #59 Bone Metastasis: Which Cancers Cause It?

  https://www.webmd.com/cancer/common-cancers-that-metastasize-to-the-bones

  The type of cancer may have something to do with why tumors form in bones. Certain cancers may release proteins that affect how a tumor forms. […] Bones provide fertile ground for the growth of tumor cells, because they are areas of constant cell turnover and growth. And bone cells release substances that may prompt faster cancer growth. […] Cancer cells can go anywhere, but they often go to the bones with the greatest blood supply. This includes bones in the spine, pelvis, ribs, upper arms, and thighs. […] In many cases of cancer such as breast cancer, either – or both — bone destruction and new bone formation may occur. […] Bone metastasis symptoms include: Bone pain is the most common symptom, and many patients with bone metastasis experience significant pain at some point in the course of their disease.

• #60 Bone metastasis – Wikipedia

  https://en.wikipedia.org/wiki/Bone_metastasis

  Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. […] Bone metastases can be classified as osteolytic, osteoblastic, or both. […] Dysregulation of these processes by tumor cells leads to either osteoblastic or osteolytic lesions, reflective of the underlying mechanism of development. […] Bone is the third most common location for metastasis, after the lung and liver. […] While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment of the marrow tends to favor particular types of cancer, including prostate, breast, and lung cancers. […] The pathogenesis of bone metastasis via the vasculature is hypothesized to be related to the Batson vertebral vein plexus, a longitudinal valveless system connected to the breast, lung, kidney, thyroid, and prostate gland that extends from the sacrum to the skull.

• #61 Bone Metastasis | Yeditepe Üniversitesi Hastanesi

  https://yeditepehastaneleri.com/en/health-guide/diseases-treatments/bone-metastasis

  Although bone metastases can be seen in any bone, they are most common in the spine, pelvis, and thigh bone close to the hip. The main reason for the more frequent occurrence of bone metastases in these regions is that these are regions where the bone marrow is more active and the extensive venous networks around the spine. […] There are quite complex mechanisms in the formation of bone metastases. The main factor is the microenvironment of the tumor. Cancer cells that come to the bone by leaving main cancer as a result of various mechanisms and signals try to adapt to this new microenvironment. Cancer cells that come to the bone plant the seeds of bone metastasis by premetastatic niche, a process called osteomimicry, in which they imitate bone cells. Interestingly, these cancer cells that settle in the bone may be in a low-proliferation or dormant state until a signal is received that triggers activation. When they start to proliferate, they first form micrometastases that cannot be detected, and then bone metastases that can be clinically revealed.

• #62 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  For patients, the occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The process by which breast cancer cells metastasize to the bone is frequently referred to as a “vicious cycle.” It begins when metastatic breast cancer cells produce parathyroid hormone-releasing peptide (PTHrP), which binds to the same receptors as parathyroid hormone and stimulates osteoblasts to secrete increased amounts of RANK-L. […] The occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The evolution of solid tumor metastasis is a complex process. Metastatic dissemination of tumor cells involves pre-metastatic niche formation, tumor cell dissemination through the circulation and chemotactic attraction and homing of tumor cells to the metastatic site of a target organ, as well as reciprocal interactions with local stromal cells and immune cells within the new microenvironment.

• #63 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  The time at which potentially metastatic cells are released from the primary tumor and move to the secondary site may depend on the tumor type. […] Several genetic studies and mutational profiling of primary and metastatic tumors suggest that additional genetic events have to occur to enable metastases formation. […] However, dissemination of certain tumor cells, including Her2-dependent breast cancer, may occur very early, potentially already in the pre-malignant phase of the disease. […] Experimental studies show that while up to 80% of tumor cells released from the primary tumor successfully pass the first steps into extravasation, only about 2–4% initiate the growth of micrometastases, and less than 0.01% survive in the new metastatic niche environment and give rise to macrometastases. […] The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

• #64 Bone Metastasis | Yeditepe Üniversitesi Hastanesi

  https://yeditepehastaneleri.com/en/health-guide/diseases-treatments/bone-metastasis

  Although bone metastases can be seen in any bone, they are most common in the spine, pelvis, and thigh bone close to the hip. The main reason for the more frequent occurrence of bone metastases in these regions is that these are regions where the bone marrow is more active and the extensive venous networks around the spine. […] There are quite complex mechanisms in the formation of bone metastases. The main factor is the microenvironment of the tumor. Cancer cells that come to the bone by leaving main cancer as a result of various mechanisms and signals try to adapt to this new microenvironment. Cancer cells that come to the bone plant the seeds of bone metastasis by premetastatic niche, a process called osteomimicry, in which they imitate bone cells. Interestingly, these cancer cells that settle in the bone may be in a low-proliferation or dormant state until a signal is received that triggers activation. When they start to proliferate, they first form micrometastases that cannot be detected, and then bone metastases that can be clinically revealed.

• #65 Bone Metastasis | Yeditepe Üniversitesi Hastanesi

  https://yeditepehastaneleri.com/en/health-guide/diseases-treatments/bone-metastasis

  Although bone metastases can be seen in any bone, they are most common in the spine, pelvis, and thigh bone close to the hip. The main reason for the more frequent occurrence of bone metastases in these regions is that these are regions where the bone marrow is more active and the extensive venous networks around the spine. […] There are quite complex mechanisms in the formation of bone metastases. The main factor is the microenvironment of the tumor. Cancer cells that come to the bone by leaving main cancer as a result of various mechanisms and signals try to adapt to this new microenvironment. Cancer cells that come to the bone plant the seeds of bone metastasis by premetastatic niche, a process called osteomimicry, in which they imitate bone cells. Interestingly, these cancer cells that settle in the bone may be in a low-proliferation or dormant state until a signal is received that triggers activation. When they start to proliferate, they first form micrometastases that cannot be detected, and then bone metastases that can be clinically revealed.

• #66 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  The time at which potentially metastatic cells are released from the primary tumor and move to the secondary site may depend on the tumor type. […] Several genetic studies and mutational profiling of primary and metastatic tumors suggest that additional genetic events have to occur to enable metastases formation. […] However, dissemination of certain tumor cells, including Her2-dependent breast cancer, may occur very early, potentially already in the pre-malignant phase of the disease. […] Experimental studies show that while up to 80% of tumor cells released from the primary tumor successfully pass the first steps into extravasation, only about 2–4% initiate the growth of micrometastases, and less than 0.01% survive in the new metastatic niche environment and give rise to macrometastases. […] The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

• #67 Bone metastasis – Wikipedia

  https://en.wikipedia.org/wiki/Bone_metastasis

  Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. […] Bone metastases can be classified as osteolytic, osteoblastic, or both. […] Dysregulation of these processes by tumor cells leads to either osteoblastic or osteolytic lesions, reflective of the underlying mechanism of development. […] Bone is the third most common location for metastasis, after the lung and liver. […] While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment of the marrow tends to favor particular types of cancer, including prostate, breast, and lung cancers. […] The pathogenesis of bone metastasis via the vasculature is hypothesized to be related to the Batson vertebral vein plexus, a longitudinal valveless system connected to the breast, lung, kidney, thyroid, and prostate gland that extends from the sacrum to the skull.

• #68 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #69 Metastatic Bone Disease: Practice Essentials, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/1253331-overview

  The red marrow theory, combined with knowledge about the cytokine stimulation of metastases, provides an excellent explanation of how this distribution occurs. […] Cells from the primary site must, through the process of neovascularization or through migration to the nearest blood vessel, attach to the basement membrane of the vessel wall and produce proteolytic enzymes that disrupt the basement membrane. […] Producing chemotactic factors, as well as RANK ligand (RANKL; a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts), these cells stimulate osteoclast activity, causing bone resorption and leading to the formation of pockets or holes in the bone in which the tumor cells grow. […] Another important substance that stimulates bone resorption is parathyroid hormone related peptide (PTHrP). This substance is expressed by breast carcinoma cells, as well as by oat cell tumors of the lung, and is a potent stimulant of osteoclasts. […] Mundy and Yoneda also reported that myeloma cells are especially adapted to producing bone destruction through direct stimulation of osteoclasts.

• #70

  https://www.orthobullets.com/pathology/8045/metastatic-disease-of-extremity

  tumor cells secrete PTHrP which stimulates the release of RANKL from osteoblasts. […] RANKL then binds to the RANK receptor on osteoclast precursor cells. […] differentiation to active osteoclasts occurs, which causes bony destruction. […] the tumor continues to grow through the release of growth factors, proinflammatory cytokines (IL-6 and IL-8), and VEGF. […] osteoblastic lesions due to tumor-secreted endothelin-1(ET-1) bind to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts. […] ET-1 decreases WNT suppressor DKK-1, activating WNT pathway, increasing osteoblast activity.

• #71 Metastasis to bone: causes, consequences and therapeutic opportunities | Nature Reviews Cancer

  https://www.nature.com/articles/nrc867

  Common tumours, such as those of the breast, lung and prostate, frequently metastasize to bone, and in many patients with advanced disease the skeleton is the site of the most significant tumour burden. […] In the case of breast-cancer-causing osteolysis, the main mediator is parathyroid-hormone-related peptide (PTHrP), whereas, in osteoblastic lesions, known mediators include endothelin-1 and platelet-derived growth factor. […] In osteolytic metastasis, there is a 'vicious cycle’ in the bone microenvironment, whereby bi-directional interactions between tumour cells and osteoclasts lead to both osteolysis and tumour growth. […] The molecular mechanisms that are responsible for this vicious cycle are now being clarified and involve tumour-cell production of PTHrP and bone-derived growth factors that are released as a consequence of increased bone resorption.

• #72 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  For patients, the occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The process by which breast cancer cells metastasize to the bone is frequently referred to as a “vicious cycle.” It begins when metastatic breast cancer cells produce parathyroid hormone-releasing peptide (PTHrP), which binds to the same receptors as parathyroid hormone and stimulates osteoblasts to secrete increased amounts of RANK-L. […] The occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The evolution of solid tumor metastasis is a complex process. Metastatic dissemination of tumor cells involves pre-metastatic niche formation, tumor cell dissemination through the circulation and chemotactic attraction and homing of tumor cells to the metastatic site of a target organ, as well as reciprocal interactions with local stromal cells and immune cells within the new microenvironment.

• #73

  https://www.orthobullets.com/pathology/8045/metastatic-disease-of-extremity

  tumor cells secrete PTHrP which stimulates the release of RANKL from osteoblasts. […] RANKL then binds to the RANK receptor on osteoclast precursor cells. […] differentiation to active osteoclasts occurs, which causes bony destruction. […] the tumor continues to grow through the release of growth factors, proinflammatory cytokines (IL-6 and IL-8), and VEGF. […] osteoblastic lesions due to tumor-secreted endothelin-1(ET-1) bind to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts. […] ET-1 decreases WNT suppressor DKK-1, activating WNT pathway, increasing osteoblast activity.

• #74 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  Some neoplasia produce bone metastases which are predominantly osteoblastic, most notably prostate cancer and approximately 15-20% breast cancers. […] During osteoblastic bone metastases, the balance between bone resorption and bone formation is tipped in favor of the latter. […] There is an accumulating body of evidence implicating Endothelin-1 (ET-1) as a central mediator of osteoblastic metastasis. […] Proteases such as urokinase-type plasminogen receptor (uPA) and Prostate Specific Antigen (PSA) are also implicated in osteoblastic bone metastasis. […] There is evidence that osteoblastic metastasis also involves considerable osteolysis. […] Bone metastases are common in patients with advanced cancers, and their presence usually signifies serious morbidity and a grave prognosis.

• #75 Prostate cancer bone metastases thwart immunotherapy by producing TGF-β | MD Anderson Cancer Center

  https://www.mdanderson.org/newsroom/prostate-cancer-bone-metastases-thwart-immunotherapy-by-producing-transformational-growth-factor-beta.h00-159307779.html

  Prostate cancer that spreads to the bone triggers the destruction of bone tissue that, in turn, thwarts the effectiveness of immune checkpoint inhibitors by blocking the development of T cells that are crucial to successful treatment, researchers from The University of Texas MD Anderson Cancer Center report in Cell. […] The team found that the bone destruction caused by tumors leads to massive production of transforming growth factor-beta (TGF-), a protein that causes helper T cells to polarize into Th17 CD4 cells instead of the Th1 CD4 effector cells required to trigger an anti-tumor immune response. […] Lack of Th1 cells in the bone marrow suggested a distinct cytokine profile in the bone microenvironment. […] They found significant elevation of TGF-, known to restrain Th1 lineage and drive both Th17 and Treg development.

• #76 Prostate cancer bone metastases thwart immunotherapy by producing TGF-β | MD Anderson Cancer Center

  https://www.mdanderson.org/newsroom/prostate-cancer-bone-metastases-thwart-immunotherapy-by-producing-transformational-growth-factor-beta.h00-159307779.html

  Bone metastasis triggers abnormal bone remodeling, and bone components are known as a major reservoir of TGF-. […] The team hypothesized that bone matrix remodeling causes the high TGF- levels in prostate bone metastases. […] Their experiments confirmed that osteoclasts cells that degrade bone activated by tumors release excessive amounts of TGF- while they erode bone surfaces. […] There was no difference in TGF- levels between healthy controls and patients without bone metastases, while patients with bone tumors had aberrantly high levels of TGF- in their bones. […] Treating mice with bone metastases with the ipilimumab and nivolumab combination failed to stop tumor growth. But adding anti- TGF- to the immunotherapy combination halted tumor growth.

• #77 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  The prognosis of bone metastases is generally poor, although it partly depends on the primary site of the original cancer and on the presence of any additional metastases to visceral organs. […] Major morbidities associated with bone metastases include severe pain, hypercalcemia, bone fractures, spinal compression fractures, and cord or nerve root compression. […] Bisphosphonates are drugs commonly used to treat bone metastases. The benefits of bisphosphonate therapy are bone pain relief, the reduction of bone destruction, and the prevention of hypercalcemia and bone fractures. […] Zoledronic acid is currently one of the most potent bisphosphonates and is effective in most types of metastatic bone lesions. […] Metastatic cancer with bone metastases occurs as cancer advances and spreads to the bone from the primary site of the original solid cancer. Nearly 70% of patients with prostate and breast cancers and about 30% to 40% of patients with lung cancer develop bone metastases. In addition, up to 95% of MMs involve bone. […] The most frequent and important symptom of bone metastasis is pain. In addition, bone metastasis causes bone fractures, hypercalcemia, and spinal cord and nerve compression. Imaging studies, such as bone scans and PET studies, are useful tools in diagnosing bone metastases.

• #78 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  Some neoplasia produce bone metastases which are predominantly osteoblastic, most notably prostate cancer and approximately 15-20% breast cancers. […] During osteoblastic bone metastases, the balance between bone resorption and bone formation is tipped in favor of the latter. […] There is an accumulating body of evidence implicating Endothelin-1 (ET-1) as a central mediator of osteoblastic metastasis. […] Proteases such as urokinase-type plasminogen receptor (uPA) and Prostate Specific Antigen (PSA) are also implicated in osteoblastic bone metastasis. […] There is evidence that osteoblastic metastasis also involves considerable osteolysis. […] Bone metastases are common in patients with advanced cancers, and their presence usually signifies serious morbidity and a grave prognosis.

• #79 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  The prognosis of bone metastases is generally poor, although it partly depends on the primary site of the original cancer and on the presence of any additional metastases to visceral organs. […] Major morbidities associated with bone metastases include severe pain, hypercalcemia, bone fractures, spinal compression fractures, and cord or nerve root compression. […] Bisphosphonates are drugs commonly used to treat bone metastases. The benefits of bisphosphonate therapy are bone pain relief, the reduction of bone destruction, and the prevention of hypercalcemia and bone fractures. […] Zoledronic acid is currently one of the most potent bisphosphonates and is effective in most types of metastatic bone lesions. […] Metastatic cancer with bone metastases occurs as cancer advances and spreads to the bone from the primary site of the original solid cancer. Nearly 70% of patients with prostate and breast cancers and about 30% to 40% of patients with lung cancer develop bone metastases. In addition, up to 95% of MMs involve bone. […] The most frequent and important symptom of bone metastasis is pain. In addition, bone metastasis causes bone fractures, hypercalcemia, and spinal cord and nerve compression. Imaging studies, such as bone scans and PET studies, are useful tools in diagnosing bone metastases.

• #80 What Does Bone Metastases Feel Like? Your FAQs

  https://www.healthline.com/health/cancer/what-does-bone-metastases-feel-like

  When cancer spreads from a primary site to the bones, the bone tumors are called bone metastases, or bone mets. This can happen with any type of cancer but it occurs more frequently in breast, lung, or prostate cancer. […] Bone cancer pain can be caused by: inflammation from the cancer cells, changes in bone structure, a bone fracture. […] The telltale symptom of bone mets is bone pain. The cancer can also weaken bones and lead to an increased risk of fractures or bone breaks. […] In many cases, bone pain is the first sign that cancer has spread to the bones. […] Low red blood cell count or high blood calcium levels can be early signs of bone metastases.

• #81 What Does Bone Metastases Feel Like? Your FAQs

  https://www.healthline.com/health/cancer/what-does-bone-metastases-feel-like

  When cancer spreads from a primary site to the bones, the bone tumors are called bone metastases, or bone mets. This can happen with any type of cancer but it occurs more frequently in breast, lung, or prostate cancer. […] Bone cancer pain can be caused by: inflammation from the cancer cells, changes in bone structure, a bone fracture. […] The telltale symptom of bone mets is bone pain. The cancer can also weaken bones and lead to an increased risk of fractures or bone breaks. […] In many cases, bone pain is the first sign that cancer has spread to the bones. […] Low red blood cell count or high blood calcium levels can be early signs of bone metastases.

• #82

  https://www.virtualhospice.ca/en_US/Main+Site+Navigation/Home/Support/Support/Asked+and+Answered/Symptoms+of+Illness/Pain/What+causes+pain+associated+with+bone+metastasis_.aspx

  What causes pain associated with bone metastasis? […] When a cancer has spread to a bone, it causes the structure of the bone to break down or to become abnormal. […] Because of the damaged bone structure, a person with bone metastasis is prone to bone breaks. […] There are unique issues when the metastasis is in the bones of the spine. […] Neuropathic pain is very different from bone pain, but it also can be a result of bone metastasis.

• #83 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  The prognosis of bone metastases is generally poor, although it partly depends on the primary site of the original cancer and on the presence of any additional metastases to visceral organs. […] Major morbidities associated with bone metastases include severe pain, hypercalcemia, bone fractures, spinal compression fractures, and cord or nerve root compression. […] Bisphosphonates are drugs commonly used to treat bone metastases. The benefits of bisphosphonate therapy are bone pain relief, the reduction of bone destruction, and the prevention of hypercalcemia and bone fractures. […] Zoledronic acid is currently one of the most potent bisphosphonates and is effective in most types of metastatic bone lesions. […] Metastatic cancer with bone metastases occurs as cancer advances and spreads to the bone from the primary site of the original solid cancer. Nearly 70% of patients with prostate and breast cancers and about 30% to 40% of patients with lung cancer develop bone metastases. In addition, up to 95% of MMs involve bone. […] The most frequent and important symptom of bone metastasis is pain. In addition, bone metastasis causes bone fractures, hypercalcemia, and spinal cord and nerve compression. Imaging studies, such as bone scans and PET studies, are useful tools in diagnosing bone metastases.

• #84 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  For patients, the occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The process by which breast cancer cells metastasize to the bone is frequently referred to as a “vicious cycle.” It begins when metastatic breast cancer cells produce parathyroid hormone-releasing peptide (PTHrP), which binds to the same receptors as parathyroid hormone and stimulates osteoblasts to secrete increased amounts of RANK-L. […] The occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The evolution of solid tumor metastasis is a complex process. Metastatic dissemination of tumor cells involves pre-metastatic niche formation, tumor cell dissemination through the circulation and chemotactic attraction and homing of tumor cells to the metastatic site of a target organ, as well as reciprocal interactions with local stromal cells and immune cells within the new microenvironment.

• #85 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  Apoorva Jayarangaiah; Alysia K. Kemp; Pramod Theetha Kariyanna. […] The skeleton is the third most common site of metastatic disease after lung and liver. Most bone metastases originate from the breast, prostate or lung although kidney and thyroid tumors can metastasize to bone as well. […] Carcinoma is the most common cause of secondary bone cancer. Many bone metastases originate from disseminated breast, lung, and prostate cancer. Although, increasingly renal cell and thyroid cancer can metastasize to bone. […] Hematologic malignancies such as multiple myeloma and lymphoma involve bone. Similarly, mesenchymal tumors such as sarcomas, can exhibit late metastases to the bone as well. […] Bone metastases affect survival rates ranging from 6 to 7 months in lung cancer to several years in the breast (19 to 25 months) or prostate cancer (12 to 53 months).

• #86 Mechanisms, Diagnosis and Treatment of Bone Metastases

  https://www.mdpi.com/2073-4409/10/11/2944

  For patients, the occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The process by which breast cancer cells metastasize to the bone is frequently referred to as a “vicious cycle.” It begins when metastatic breast cancer cells produce parathyroid hormone-releasing peptide (PTHrP), which binds to the same receptors as parathyroid hormone and stimulates osteoblasts to secrete increased amounts of RANK-L. […] The occurrence of bone metastases is an unfavorable prognostic factor. It worsens their quality of life and increases morbidity and mortality. […] The evolution of solid tumor metastasis is a complex process. Metastatic dissemination of tumor cells involves pre-metastatic niche formation, tumor cell dissemination through the circulation and chemotactic attraction and homing of tumor cells to the metastatic site of a target organ, as well as reciprocal interactions with local stromal cells and immune cells within the new microenvironment.

• #87 Metastasis to bone: causes, consequences and therapeutic opportunities | Nature Reviews Cancer

  https://www.nature.com/articles/nrc867

  Common tumours, such as those of the breast, lung and prostate, frequently metastasize to bone, and in many patients with advanced disease the skeleton is the site of the most significant tumour burden. […] In the case of breast-cancer-causing osteolysis, the main mediator is parathyroid-hormone-related peptide (PTHrP), whereas, in osteoblastic lesions, known mediators include endothelin-1 and platelet-derived growth factor. […] In osteolytic metastasis, there is a 'vicious cycle’ in the bone microenvironment, whereby bi-directional interactions between tumour cells and osteoclasts lead to both osteolysis and tumour growth. […] The molecular mechanisms that are responsible for this vicious cycle are now being clarified and involve tumour-cell production of PTHrP and bone-derived growth factors that are released as a consequence of increased bone resorption.

• #88 Mechanisms of cancer metastasis to the bone | Cell Research

  https://www.nature.com/articles/7290266

  Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. […] Greater than 50% of patients with advanced breast or prostate cancer show bone metastases. […] Bone metastases can lead to pain, pathological fractures, nerve compression syndromes, and hypercalcemia. […] Why do certain cancers metastasize so readily to bone? Osteotropic cancers are a specific example of the more general observation that primary tumors show organ-specific patterns of metastasis. […] The ability of cells to survive, clonally expand, and recruit a blood supply is expected to determine successful metastasis. […] Other factors thought to play a role in site-specific metastasis are anatomic considerations such as blood flow patterns from the primary tumor and the homing ability of cancer cells for certain tissues.

• #89 What Happens When Lung Cancer Spreads to Bone?

  https://www.verywellhealth.com/lung-cancer-with-bone-metastases-2249357

  Lung cancer with bone metastases refers to the spread of cancer from the primary (original) tumor to the bone. The spread of cancer cells occurs either through the bloodstream or lymphatic system (a system of fluids, vessels, and organs that protect the body against foreign invaders). […] Bone metastases from lung cancer affect between 30% and 40% of people with advanced lung cancer. The bones are the third most common site for metastases, after the liver and adrenal glands, among people with lung cancer. […] Although lung cancer that has spread to bone is not curable, there are treatments that can lengthen survival times and improve quality of life. […] Bone metastases from lung cancer can cause severe complications as the malignancy progresses. These complications undermine the spine and the integrity of the bones and cause metabolic changes that can compromise a person’s ability to function.

• #90

  https://link.springer.com/article/10.1007/s11916-006-0034-y

  Painful metastatic bone disease remains a challenge for physicians. […] Advances in understanding the intricate pathway responsible for pain generation and the addition of agents such as bisphosphonates to the physicians armamentarium further assist in the management of painful bone metastases. […] This significant finding has the potential of preventing metastases by blocking events at a molecular level. […] The data presented in this paper provide proof that osteoblastic metastases are facilitated by tumor production of ET-1.

• #91 10 ways to manage bone pain caused by cancer

  https://www.cancercenter.com/community/blog/2020/08/cancer-and-bone-pain

  Bone pain is a common symptom or side effect of cancer and may significantly affect patients quality of life. […] Patients diagnosed with cancer, especially advanced-stage or metastatic disease, often experience bone pain at some point in their cancer journey. Cancer-related bone pain may have many causes, but its not likely caused by primary bone cancer, which is very rare. Many cancers found in the bone are diagnosed as metastatic disease, which occurs when cancer cells break away from a primary tumor and spread to other parts of the body. Bones are a common location to which cancer metastasizes. Some cancers that commonly spread to the bones include breast cancer, lung cancer, prostate cancer, thyroid cancer and kidney cancer. […] Cancer cells that spread to the bone disrupt the balance of normal cellular activity of the bones structure, damaging bone tissue, which may cause pain.

• #92 10 ways to manage bone pain caused by cancer

  https://www.cancercenter.com/community/blog/2020/08/cancer-and-bone-pain

  Other causes of cancer-related bone pain include pressure from a tumor pressing on the bone or nerves, cancer treatments that may damage or weaken bones, infection or inflammation, and fractures. […] Some treatments may help to reduce pain by shrinking the tumor. Others aim to reduce the risk of bone fractures and complications from bone metastases. […] Radiation therapy that targets bone metastasis and destroys cancer cells that have settled in the bones.

• #93 Management of Lung Cancer Presenting with Solitary Bone Metastasis

  https://www.mdpi.com/1648-9144/58/10/1463

  Lung neoplasm is the main cause of cancer-related mortality, and bone metastasis is among the most common secondary tumors. […] Bone metastases are associated with increased morbidity, loss of function, and decreased quality of life. […] The main locations of metastases secondary to non-small-cell lung cancers (NSCLC) are the spine in 50% of cases, the ribs in 27.1%, the iliac bone in 10%, the sacrum in 7.1%, and the femur in 5.7% of cases, followed by the humerus, scapula, and sternum at 2.9%. […] Bone metastases are often asymptomatic and represent the first symptom in only 2.5% of lung neoplasm cases. […] The best course of action for a resectable lung tumor that also has a solitary, resectable bone metastasis is still up for debate. […] Bone neoplastic development results from an alteration in the perfectly balanced bone-remodeling cycle between bone resorption by osteoclasts and bone tissue production mediated by osteoblasts.

• #94 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #95 Bone metastasis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bone-metastasis/symptoms-causes/syc-20370191

  Bone metastasis occurs when cancer cells spread from their original site to a bone. […] Nearly all types of cancer can spread (metastasize) to the bones. But some types of cancer are particularly likely to spread to bone, including breast cancer and prostate cancer. […] Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver. […] Virtually any type of cancer can spread to the bones, but the cancers most likely to cause bone metastasis include: breast cancer, kidney cancer, lung cancer, lymphoma, multiple myeloma, prostate cancer, and thyroid cancer.

• #96 Bone Metastasis (Cancer Spread to Bone): Signs & Treatment

  https://my.clevelandclinic.org/health/diseases/bone-metastasis

  Bone metastasis is when cancer spreads to your bones from another part of your body. It often affects people with breast, lung and prostate cancer. […] Bone metastasis is a symptom of metastatic cancer that happens when cancer from one place in your body spreads to your bones. It typically affects people with breast cancer, lung cancer and prostate cancer, but other types of cancer can also cause bone metastasis. […] This condition happens when cells from cancerous tumors enter your blood and travel to your bones. Once there, the cancerous cells set off what experts call the vicious cycle of bone metastasis. […] Research shows links between bone cell types and specific types of metastatic cancer. For example, 70% to 85% of bone metastasis from prostate cancer is osteogenic, meaning it happens when osteoblasts make too many bone cells. But 75% of metastatic breast cancer is osteolytic from bone cells that break down too fast.

• #97 Bone metastasis | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/bone-metastasis?content_id=CON-20370177

  Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver. […] Nearly all types of cancer can spread (metastasize) to the bones. But some types of cancer are particularly likely to spread to bone, including breast cancer and prostate cancer.

• #98 Mayo Clinic Health Library – Bone metastasis | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20370177

  Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver.

• #99 Bone metastasis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bone-metastasis/symptoms-causes/syc-20370191

  Bone metastasis occurs when cancer cells spread from their original site to a bone. […] Nearly all types of cancer can spread (metastasize) to the bones. But some types of cancer are particularly likely to spread to bone, including breast cancer and prostate cancer. […] Bone metastasis occurs when cancer cells break away from the original tumor and spread to the bones, where they begin to multiply. […] Doctors aren’t sure what causes some cancers to spread. And it’s not clear why some cancers travel to the bones rather than to other common sites for metastasis, such as the liver. […] Virtually any type of cancer can spread to the bones, but the cancers most likely to cause bone metastasis include: breast cancer, kidney cancer, lung cancer, lymphoma, multiple myeloma, prostate cancer, and thyroid cancer.

• #100 Bone Metastasis: Concise Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6363326/

  Bone metastasis is a relatively common complication of cancer, often developing as they advance, especially in prostate cancer and breast cancer. […] Bone is the most common and preferred site for metastatic involvement of cancer. Advanced cancers frequently develop metastases to the bone during the later phases of cancer progression. At least 100,000 patients develop bone metastases every year, although the exact number of bone metastases is not known. Multiple myeloma (MM), breast cancer, and prostate cancer are responsible for up to 70% of bone metastases cases. […] Prostate and breast cancers are the most common primary cancers of bone metastases. […] Regardless of their survival expectancy, however, most patients with bone metastasis need immediate medical attention and active palliative therapy to prevent devastating complications related to bone metastasis, such as pathologic bone fractures and severe bone pain.

• #101 Bone Metastasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507911/

  A pivotal occurrence in the pathogenesis of bone metastases involves the cellular interaction between the receptors on the tumor cells (e.g., CXCR4, RANKL) and the stromal cells of the bone marrow and bone matrix. […] Secondary bony involvement can be largely classified as osteoblastic (prostate cancer) and osteolytic (breast, lung, renal cancers) or mixed (breast cancer). […] The therapeutic approach to bone metastases should be a multidisciplinary approach targeted at preserving the quality of life, including pain control, minimizing SREs, and achieving local tumor control when possible. […] Osteoclast inhibitors (bisphosphonates and denosumab) decrease morbidity and mortality associated with bone metastases as they reduce skeletal-related events and can be used to help reduce bone pain.

• #102

  https://www.orthobullets.com/pathology/8045/metastatic-disease-of-extremity

  tumor cells secrete PTHrP which stimulates the release of RANKL from osteoblasts. […] RANKL then binds to the RANK receptor on osteoclast precursor cells. […] differentiation to active osteoclasts occurs, which causes bony destruction. […] the tumor continues to grow through the release of growth factors, proinflammatory cytokines (IL-6 and IL-8), and VEGF. […] osteoblastic lesions due to tumor-secreted endothelin-1(ET-1) bind to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts. […] ET-1 decreases WNT suppressor DKK-1, activating WNT pathway, increasing osteoblast activity.

• #103 Cancer Spread to Bones: Life Expectancy, Treatment, Types

  https://www.healthline.com/health/cancer-spread-to-bones-life-expectancy

  When a cancer spreads to the bones, its called bone metastasis. Its also called metastatic bone disease or secondary bone cancer, because the cancer didnt start in the bones. […] Bone metastasis usually occurs in people who have been previously diagnosed with cancer or who have advanced cancer. But sometimes the pain of bone metastasis may be the first sign of cancer. […] The exact mechanism of how cancer cells metastasize to the bones isnt fully known. Its a very active area of scientific research. New understanding of how metastasis works is continuing to lead to new methods of treatment. […] Cancer cells upset the normal process of bone remodeling, causing bones to become weak or too dense, depending on the type of bone cells affected. […] The research on cancer metastasis is rapidly growing. As researchers better understand the mechanisms of bone metastasis, new drugs and other treatments are being developed. These target particular processes in cells involved in how the cancer cells invade and grow in bones. […] As we learn more about the mechanisms of how cancer cells invade and disrupt bones, scientists develop new ways of targeting and slowing these cancer cells.

• #104 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Bone is the single most frequent site for bone metastasis in breast cancer patients. […] In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. […] Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. […] Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials. […] Several factors seem to affect the metastatic pattern, including demographic, clinical, pathological, and genetic factors. […] In BC, BM present a radiographic pattern that can be lytic, blastic, or mixed.

• #105 Bone metastasis risk factors in breast cancer – ecancer

  https://ecancer.org/en/journal/article/715-bone-metastasis-risk-factors-in-breast-cancer

  Several studies have associated PTHrP expression to the development of BM in BC patients. […] The relationship between MAF and the risk of BM is thought to result from the control that this protein might exert on PTHrP. […] There seems to be a correlation between serum BSP levels and the risk of BM in BC patients. […] BMP7 expression in primary tumour seems to correlate with the risk for accelerated BM formation in BC patients. […] This study concluded that a biomarker including CAPG and GIPC1 in primary BC tissue is associated with BM development. […] There is a profound effect of adjuvant therapy in the pattern of metastasis. […] Nevertheless, intrinsic subtype is widely accepted as a major risk factor for BM development. […] Other factors such as BMP7 expression, higher level of bone sialoprotein or elevation of B-CTx prior to treatment may also indicate a higher risk for BM. […] Further research on this topic is, therefore, mandatory.

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