Materiały źródłowe

• #1 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #2 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. […] Bone metastases can be divided into two broad categories; (i) osteolytic metastases that are associated with bone destruction and (ii) osteosclerotic metastases that are characterized by new bone formation. […] Although precise molecular mechanisms underlying preferential cancer metastasis to bone need to be elucidated, it seems likely that bone provides an attractive environment that allows circulating cancer cells to home, survive and proliferate. […] The binding of cancer cells at the metastatic site involves cell-to-cell interactions, or interactions between cells and the extracellular matrix, and these processes involves cell adhesion molecules like integrins.

• #3 Bone Pain and Lung Cancer Metastasis Symptoms

  https://www.lungcancercenter.com/lung-cancer/symptoms/bone-pain/

  Lung cancer can metastasize to different areas of the body, and one of the most common sites is in the bones. […] Bone pain can actually be one of the most overlooked symptoms of late-stage lung cancer and if you ignore it, you could be putting your life at risk. […] Bone pain occurs in a lung cancer patient if the disease spreads to the bones from a primary tumor, known as bone metastases. […] About 30-40% of people living with advanced lung cancer experience bone metastasis. […] Lung cancer patients experiencing bone metastases often feel bone pain before noticing other symptoms. […] Bone pain is the most common symptom of metastatic lung cancer. […] Patients often describe bone metastasis as deep, aching pains. […] Bone pain can also be accompanied by other symptoms like fatigue, weight loss, and depression.

• #4 Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST

  https://www.jcancer.org/v01p0080.htm

  Response criteria represent the standard by which the efficacy of therapeutic agents is determined in cancer trials. […] Because bone metastases are typically located in irregularly shaped bones and are difficult to measure with rulers, they have been previously considered unmeasurable disease. New developments in cancer response criteria have increased awareness of the importance of the response of bone metastases to therapy. […] Bone metastases are a common manifestation of advanced disease with autopsy studies showing an incidence of 33-36% in patients with lung cancer, 68% in prostate cancer, and 73% in breast cancer. […] The absence of measurable tumors can significantly affect patient disease management. […] RECIST 1.1 specifies that up to 5 target lesions, representing all affected organ systems but with no more than 2 target lesions per organ, be selected for measurement throughout the course of a therapeutic trial.

• #5 Breast Cancer Metastasis to Bone | Susan G. Komen®

  https://www.komen.org/breast-cancer/metastatic/bones/

  Bone metastases may be present when metastatic breast cancer is first diagnosed, or the cancer may spread to the bones later. […] The bones are the first site of metastases for almost half of women diagnosed with metastatic breast cancer. For many of these women, the bones will be the only site of metastases. […] People with bone metastases are at risk of serious bone complications such as bone fractures (breaks), spinal cord compression and bone pain. […] Bone complications are a concern for people with bone metastases. They can cause pain and may lead to loss of mobility, impacting quality of life. Bone complications can also decrease survival. […] For people with bone metastases, the use of bisphosphonates or denosumab can lower the risk of fractures related to bone metastases, help reduce pain caused by bone metastases, prevent complications of cancer in the bones such as hypercalcemia, reduce the need for surgery to repair bone fractures related to bone metastases, reduce the need for radiation therapy to treat bone pain, and prevent progression of bone metastases that could lead to a fracture.

• #6 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 metastasis can profoundly affect patients daily activities and quality of life (QOL) due to severe pain and associated major complications. […] The most common clinical symptom of bone metastasis is bone pain, which is usually localized and progresses slowly. Patients may experience worsening of pain at night or while ambulating, depending on the site of bone metastasis. Pain may radiate to the lower extremities; however, radiating pain may not always correlate with nerve impingement. […] 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.

• #7 Bone Metastasis: Concise Overview

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

  Major morbidities associated with bone metastases include severe pain, hypercalcemia, bone fractures, spinal compression fractures, and cord or nerve root compression. […] 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.

• #8 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  The most common symptom of bone metastasis is pain. Other symptoms are bone fractures, spinal cord compression and anemia. […] Pain is usually the first symptom patients notice. It’s most often felt at the site of the metastasis, which is referred to as localized pain. There are also cases where patients experience pain in areas surrounding the metastasis. […] Depending upon the location of the metastasis, the pain may vary. Bone metastasis patients often describe the pain as gradually increasing over a period of time and becoming more severe. Patients with metastases to the spinal cord often have pain or discomfort that is worse at night or with bed rest. However, those patients with lesions involving the long bones, such as the arms and legs, have pain with activity or movement. In this case, some relief is usually achieved with rest.

• #9 Bone Metastases: When Cancer Spreads to the Bones

  https://healthlibrary.uwmedicine.org/yourfamily/Women/34,25952-1

  Bone metastases can cause these symptoms: […] Pain is the most common symptom of bone metastasis. It’s often the first symptom you notice. At first, the pain may come and go. It’s usually worse at night or with rest. Over time, the pain may become severe. […] Bone metastasis can weaken bones. This puts your bones at risk for breaking. In some cases, a break (fracture) is the first sign of bone metastasis. […] Numbness or weakness in the legs, trouble urinating or having a bowel movement, or numbness in the belly are all signs that the spinal cord may be compressed. […] These are all signs that you may have high levels of calcium in your blood. Bone metastases can cause a release of calcium into the bloodstream. […] If bone metastasis affects your bone marrow, you may have other symptoms that are caused by lower blood cell counts. Your red blood cell levels may drop, causing anemia. Signs of anemia are tiredness, weakness, and shortness of breath. […] It’s important for you to discuss any of these symptoms with your healthcare provider right away. Finding and treating bone metastasis early can help reduce complications.

• #10 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. Bone metastases can also cause the following cancer-related emergencies. The most common symptom of bone metastases, and usually the first to happen, is pain in the bone. Bone pain can come and go, or it can be constant. It is often worse at night. The pain may be only in one area or it may spread throughout the body. It may be a dull ache or a sharp pain. There may also be swelling along with bone pain. Other signs and symptoms of bone metastases include broken bones (fractures), most often the ribs, vertebrae and long bones of the legs. […] The symptoms of bone metastases vary depending on which bones are affected and how many bones are affected. Other health conditions can cause the same symptoms as bone metastases. […] 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.

• #11 Bone Metastases | Cancer Spread to Bones | American Cancer Society

  https://www.cancer.org/cancer/managing-cancer/advanced-cancer/bone-metastases.html

  When cancer cells spread to the bones (bone metastases), they can cause many problems such as pain, broken bones, or more serious problems. […] Bone pain is often the first symptom of cancer that has spread to the bone. The pain may come and go at first. It tends to be worse at night and may get better with movement. Later on, it can become constant and may be worse during activity. The bone might be so weak that it will break. This can often be prevented if the bone metastasis is found early. […] Breaks might happen with a fall or injury, but a weak bone can also break during normal activities. These breaks often cause sudden, severe pain. Fractures most often happen in the long bones of the arms and legs and the bones of the spine. Sudden pain in the middle of the back, for instance, may mean a bone in the spine has broken.

• #12 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  The most common symptom of bone metastasis is pain. Other symptoms are bone fractures, spinal cord compression and anemia. […] Pain is usually the first symptom patients notice. It’s most often felt at the site of the metastasis, which is referred to as localized pain. There are also cases where patients experience pain in areas surrounding the metastasis. […] Depending upon the location of the metastasis, the pain may vary. Bone metastasis patients often describe the pain as gradually increasing over a period of time and becoming more severe. Patients with metastases to the spinal cord often have pain or discomfort that is worse at night or with bed rest. However, those patients with lesions involving the long bones, such as the arms and legs, have pain with activity or movement. In this case, some relief is usually achieved with rest.

• #13 Lung cancer and bone metastases – roycastle.org

  https://roycastle.org/about-lung-cancer/advanced-lung-cancer/lung-cancer-and-bone-metastases/

  You may become aware of pain in a specific part of your body. There are many reasons for pain, particularly following lung cancer treatment, so it is important to know that not all pain means metastases. […] People with bone metastases describe the pain as gradually increasing over a period of time and becoming more severe. […] On rare occasions, pain and weakness in the legs, along with loss of bowel and bladder function, may indicate tumours impacting on the lower spine. These symptoms are considered a medical emergency. Take immediate action and contact the emergency services. […] Symptoms can also vary depending on where in the bones the cancer has spread to: […] People who have metastases to the spinal cord often have pain that is worse at night, or with bed rest. They may also experience tingling in the legs and pain when walking. […] If you have a tumour in your arms or legs, you may have pain with activity or movement, and less pain when you are resting.

• #14 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 metastases can be very painful. The pain is from structural damage to the bones and inflammation caused by cancer cells. Sometimes the pain is related to a bone fracture. […] Bone pain is the most common symptom of metastatic bone cancer. It may be the first sign of metastases. Bone metastases are most likely to occur in the spine, ribs, hips, upper leg, upper arm, and skull. […] In earlier stages, the pain is more likely to come and go. As cancer grows, pain may become more constant. Depending on the site of the bone cancer, movement can increase the pain. Sometimes the pain persists no matter what you’re doing or what position you’re in.

• #15 Secondary (metastatic) breast cancer in the bone | Breast Cancer Now

  https://breastcancernow.org/about-breast-cancer/secondary-breast-cancer/secondary-breast-cancer-treatment/secondary-metastatic-breast-cancer-in-the-bone/

  When cancer that started in the breast has spread to the bones, its called secondary or metastatic breast cancer in the bone. […] The main symptoms of breast cancer that has spread to bone are: Pain particularly in the back, arms or legs, often described as gnawing which occurs when resting or sleeping, and may get worse when lying down especially at night. […] Other possible effects include: Spinal cord compression. […] Spinal cord compression is a risk for people with secondary breast cancer that has spread to the spine. […] Severe or unexplained back pain, which may also be felt around the front of the chest and belly. […] Spinal cord compression is usually treated with radiotherapy and steroids. […] Too much calcium in the blood (hypercalcaemia) can cause symptoms such as: Fatigue, Nausea and vomiting, Loss of appetite, Constipation, Loss of concentration, Drowsiness, Being very thirsty, Passing large amounts of urine, Weakness, Confusion. […] Cancer-related fatigue is one of the most common symptoms of secondary breast cancer.

• #16 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 pain is the most common symptom, but bone fracture also often happens. Bone metastasis typically affects your spine, but can also affect arms and legs. Easing symptoms is the most common treatment. […] The most common symptom is bone pain, which can feel like a dull ache that gets worse at night or a sudden sharp pain. Bone metastasis can cause complications with specific symptoms: Bone fractures: Bone metastasis makes your bones more fragile and likely to break even if you dont fall. The condition can affect any bone in your body, but often affects your spine and ribs, pelvis, upper arm bone (humerus), upper leg bone (femur) and skull. Bone fractures cause sharp, severe pain. If you break your leg or arm, you wont be able to move it.

• #17 Metastatic bone cancer – Harvard Health

  https://www.health.harvard.edu/cancer/metastatic-bone-cancer-overview

  The growth of cancer cells in bones can cause pain or broken bones. Pain that occurs without physical activity is especially worrisome. […] The most common symptom of metastatic bone cancer is pain. The most common sites of spread spine, pelvis, ribs, skull, upper arm, and long bones of the leg tend to be where metastatic bone pain occurs. […] Other symptoms include: broken bone. Bones weakened by cancer break more easily. A broken bone from a minor injury, or no injury at all, should be thoroughly checked out. Anemia. Bones make red blood cells. Cancer in bones can slow or halt red cell production.

• #18 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  The most common symptom of bone metastasis is pain. Other symptoms are bone fractures, spinal cord compression and anemia. […] Pain is usually the first symptom patients notice. It’s most often felt at the site of the metastasis, which is referred to as localized pain. There are also cases where patients experience pain in areas surrounding the metastasis. […] Depending upon the location of the metastasis, the pain may vary. Bone metastasis patients often describe the pain as gradually increasing over a period of time and becoming more severe. Patients with metastases to the spinal cord often have pain or discomfort that is worse at night or with bed rest. However, those patients with lesions involving the long bones, such as the arms and legs, have pain with activity or movement. In this case, some relief is usually achieved with rest.

• #19

  https://link.springer.com/article/10.1007/s00520-016-3154-x

  Women with breast cancer frequently develop painful bone metastases. […] Worsening of symptoms, particularly fatigue and pain, occurred in the months leading up to the diagnosis of bone metastases. […] Symptom burden, especially pain and fatigue, increased both before and after the diagnosis of bone metastases, highlighting the need for proactive monitoring and management of symptoms in breast cancer patients. […] Bone pain is usually the first symptom of bone metastases, leading to their diagnosis and subsequent management. […] Pain, fatigue, depression, distress, anxiety, disturbed sleep, dry mouth, numbness/tingling, and gastrointestinal symptoms have been identified as key problems in this population. […] The estimated increase in risk per month that patients would develop moderate to severe symptoms leading up to diagnosis was 9 % for both fatigue and pain and 19 % for numbness/tingling.

• #20

  https://link.springer.com/article/10.1007/s00520-016-3154-x

  Pain and fatigue were the earliest symptoms to reach their median time to moderate/severe intensity, which occurred within 1 month or less after the onset of bone metastases. […] Moderate to severe trouble sleeping and numbness/tingling commenced later, at a median 2.9 and 7.7 months, respectively. […] The cumulative proportion of patients with moderate to severe symptoms increased over time for most symptoms, particularly for pain and fatigue which affected a majority of patients within 3 months of the onset of bone metastases. […] We observed increasing symptom burden, particularly for pain and fatigue, both before and after the diagnosis of bone metastases in women with breast cancer.

• #21 Bone Metastases | Cancer Spread to Bones | American Cancer Society

  https://www.cancer.org/cancer/managing-cancer/advanced-cancer/bone-metastases.html

  When cancer cells spread to the bones (bone metastases), they can cause many problems such as pain, broken bones, or more serious problems. […] Bone pain is often the first symptom of cancer that has spread to the bone. The pain may come and go at first. It tends to be worse at night and may get better with movement. Later on, it can become constant and may be worse during activity. The bone might be so weak that it will break. This can often be prevented if the bone metastasis is found early. […] Breaks might happen with a fall or injury, but a weak bone can also break during normal activities. These breaks often cause sudden, severe pain. Fractures most often happen in the long bones of the arms and legs and the bones of the spine. Sudden pain in the middle of the back, for instance, may mean a bone in the spine has broken.

• #22 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). Bone mets can be called lesions, can be part of advanced cancer and can happen in any bone in the body. The most common signs of bone metastases are: Bone pain: This is often the first symptom. The pain often comes and goes, is worse at night, and can be relieved with movement. It may worsen and become constant. Fracture (broken bone): Bone may weaken and fracture (break). Fractures from bone metastases are called „pathologic” fractures. The fractures could be caused by trauma, but if the bone is weak enough, it can break just by doing an everyday activity. Spinal cord compression: Cancer that has spread to the spine can cause pressure on the spinal cord called spinal cord compression. Signs can be new or worsening pain in the back or neck, numbness and weakness in the body below the tumor, and trouble walking. Spinal cord compression can cause nerve damage and even paralysis (losing the ability to move). High calcium levels: Some bone metastases can cause calcium to leak from your bones into the bloodstream. This can cause high calcium levels (hypercalcemia) in the blood. Hypercalcemia can cause constipation, nausea, loss of appetite, extreme thirst, frequent urination, dehydration, fatigue, and in very serious cases, confusion and even coma. […] Your provider will watch you closely during the treatment of your primary cancer for these signs and symptoms. You should tell your provider if you start to have any symptoms of bone metastases.

• #23 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 pain is the most common symptom, but bone fracture also often happens. Bone metastasis typically affects your spine, but can also affect arms and legs. Easing symptoms is the most common treatment. […] The most common symptom is bone pain, which can feel like a dull ache that gets worse at night or a sudden sharp pain. Bone metastasis can cause complications with specific symptoms: Bone fractures: Bone metastasis makes your bones more fragile and likely to break even if you dont fall. The condition can affect any bone in your body, but often affects your spine and ribs, pelvis, upper arm bone (humerus), upper leg bone (femur) and skull. Bone fractures cause sharp, severe pain. If you break your leg or arm, you wont be able to move it.

• #24 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 pain is the most common symptom, but bone fracture also often happens. Bone metastasis typically affects your spine, but can also affect arms and legs. Easing symptoms is the most common treatment. […] The most common symptom is bone pain, which can feel like a dull ache that gets worse at night or a sudden sharp pain. Bone metastasis can cause complications with specific symptoms: Bone fractures: Bone metastasis makes your bones more fragile and likely to break even if you dont fall. The condition can affect any bone in your body, but often affects your spine and ribs, pelvis, upper arm bone (humerus), upper leg bone (femur) and skull. Bone fractures cause sharp, severe pain. If you break your leg or arm, you wont be able to move it.

• #25 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 pain is the most common symptom, but bone fracture also often happens. Bone metastasis typically affects your spine, but can also affect arms and legs. Easing symptoms is the most common treatment. […] The most common symptom is bone pain, which can feel like a dull ache that gets worse at night or a sudden sharp pain. Bone metastasis can cause complications with specific symptoms: Bone fractures: Bone metastasis makes your bones more fragile and likely to break even if you dont fall. The condition can affect any bone in your body, but often affects your spine and ribs, pelvis, upper arm bone (humerus), upper leg bone (femur) and skull. Bone fractures cause sharp, severe pain. If you break your leg or arm, you wont be able to move it.

• #26 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 pain is the most common symptom, but bone fracture also often happens. Bone metastasis typically affects your spine, but can also affect arms and legs. Easing symptoms is the most common treatment. […] The most common symptom is bone pain, which can feel like a dull ache that gets worse at night or a sudden sharp pain. Bone metastasis can cause complications with specific symptoms: Bone fractures: Bone metastasis makes your bones more fragile and likely to break even if you dont fall. The condition can affect any bone in your body, but often affects your spine and ribs, pelvis, upper arm bone (humerus), upper leg bone (femur) and skull. Bone fractures cause sharp, severe pain. If you break your leg or arm, you wont be able to move it.

• #27 Metastatic bone disease: Early referral for multidisciplinary care | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/89/7/393

  Patients with known cancer involving the skeleton or those who have had previous radiotherapy to skeletal metastatic deposits are at particular risk of pathologic fracture. […] A sudden change to more intense or severe pain usually indicates a pathologic fracture, particularly in the context of minimal trauma. […] Patients who receive radiotherapy for bony metastasis should be assessed by an appropriate specialist to determine the need for further stabilization or surgical treatment. […] Pathologic fractures caused by metastatic bone disease will not heal, even with radiotherapy. […] Current research favors early diagnosis and a prophylactic surgical approach in managing bony metastases in patients with impending pathologic fractures.

• #28 Metastatic bone disease: Early referral for multidisciplinary care | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/89/7/393

  Patients with known cancer involving the skeleton or those who have had previous radiotherapy to skeletal metastatic deposits are at particular risk of pathologic fracture. […] A sudden change to more intense or severe pain usually indicates a pathologic fracture, particularly in the context of minimal trauma. […] Patients who receive radiotherapy for bony metastasis should be assessed by an appropriate specialist to determine the need for further stabilization or surgical treatment. […] Pathologic fractures caused by metastatic bone disease will not heal, even with radiotherapy. […] Current research favors early diagnosis and a prophylactic surgical approach in managing bony metastases in patients with impending pathologic fractures.

• #29 Metastatic bone disease: Early referral for multidisciplinary care | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/89/7/393

  It is estimated that more than half of all cancers develop bony metastases, exacting a substantial cost in terms of patient quality of life and healthcare expenses. […] Most patients with metastatic bone disease present to an orthopedic team after a pathologic fracture has already occurred, increasing the likelihood of discomfort and morbidity. […] The quality of life in patients with skeletal metastases is compromised by skeletal-related events, ie, intractable pain, forced immobilization, hypercalcemia, spinal cord compression, and pathologic fractures. Bony metastasis is often the most symptomatic and disabling manifestation of secondary cancer. Approximately 68% of patients with skeletal metastasis have pain, and 10% to 20% of those with long-bone metastases eventually sustain pathologic fractures.

• #30 Bone Metastases: When Cancer Spreads to the Bones

  https://healthlibrary.uwmedicine.org/yourfamily/Women/34,25952-1

  Bone metastases can cause these symptoms: […] Pain is the most common symptom of bone metastasis. It’s often the first symptom you notice. At first, the pain may come and go. It’s usually worse at night or with rest. Over time, the pain may become severe. […] Bone metastasis can weaken bones. This puts your bones at risk for breaking. In some cases, a break (fracture) is the first sign of bone metastasis. […] Numbness or weakness in the legs, trouble urinating or having a bowel movement, or numbness in the belly are all signs that the spinal cord may be compressed. […] These are all signs that you may have high levels of calcium in your blood. Bone metastases can cause a release of calcium into the bloodstream. […] If bone metastasis affects your bone marrow, you may have other symptoms that are caused by lower blood cell counts. Your red blood cell levels may drop, causing anemia. Signs of anemia are tiredness, weakness, and shortness of breath. […] It’s important for you to discuss any of these symptoms with your healthcare provider right away. Finding and treating bone metastasis early can help reduce complications.

• #31 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  It is important for you to know that not all pain means metastasis. Your doctor may be able to help you to tell the difference between bone metastasis pain and normal aches and pains or pains from other sources. It is important to talk with your doctor about any pain or discomfort that you may be having. […] Bone metastases can weaken your bones and put you at risk for fractures. Not all patients will fracture bones, but it is important to be aware of that possibility. Impending fractures describe those bones that are about to break. If found early, your doctor may be able to treat the bone to keep it from breaking. […] If the secondary tumor is located in the spinal area, it can result in spinal cord compression. Spinal cord compression occurs when the tumor squeezes the spinal cord. This can lead to back pain or make walking painful and difficult. Other symptoms might include numbness and weakness in the legs, problems with the bowels or bladder, or numbness in the abdominal area.

• #32 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  This fact sheet is for women who have been diagnosed with breast cancer that has been found in the bones. Deposits of cancer in bones are called bone metastases or bone secondaries. […] If your breast cancer spreads to the bones, you may experience some of the symptoms described below. Symptoms may vary depending on the location and size of the cancerous deposit. […] Pain is the most common symptom of bone metastases. It tends be a constant, aching pain that may be worse during activity and can cause sleeping difficulties. […] Cancer deposits can weaken a bone and this can cause the bone to break (fracture). […] Cancer in the bones of the spine (called the vertebrae) can cause pressure on the nerves that travel through the spinal cord. Symptoms of spinal cord compression can include persistent pain in the back that may be worse with coughing, sneezing or straining, numbness or weakness in the legs, causing difficulty with walking, difficulty controlling the bladder or the bowel, paralysis (rarely).

• #33 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  This fact sheet is for women who have been diagnosed with breast cancer that has been found in the bones. Deposits of cancer in bones are called bone metastases or bone secondaries. […] If your breast cancer spreads to the bones, you may experience some of the symptoms described below. Symptoms may vary depending on the location and size of the cancerous deposit. […] Pain is the most common symptom of bone metastases. It tends be a constant, aching pain that may be worse during activity and can cause sleeping difficulties. […] Cancer deposits can weaken a bone and this can cause the bone to break (fracture). […] Cancer in the bones of the spine (called the vertebrae) can cause pressure on the nerves that travel through the spinal cord. Symptoms of spinal cord compression can include persistent pain in the back that may be worse with coughing, sneezing or straining, numbness or weakness in the legs, causing difficulty with walking, difficulty controlling the bladder or the bowel, paralysis (rarely).

• #34 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  This fact sheet is for women who have been diagnosed with breast cancer that has been found in the bones. Deposits of cancer in bones are called bone metastases or bone secondaries. […] If your breast cancer spreads to the bones, you may experience some of the symptoms described below. Symptoms may vary depending on the location and size of the cancerous deposit. […] Pain is the most common symptom of bone metastases. It tends be a constant, aching pain that may be worse during activity and can cause sleeping difficulties. […] Cancer deposits can weaken a bone and this can cause the bone to break (fracture). […] Cancer in the bones of the spine (called the vertebrae) can cause pressure on the nerves that travel through the spinal cord. Symptoms of spinal cord compression can include persistent pain in the back that may be worse with coughing, sneezing or straining, numbness or weakness in the legs, causing difficulty with walking, difficulty controlling the bladder or the bowel, paralysis (rarely).

• #35 Spinal Metastasis: When Cancer Spreads to the Spine

  https://my.clevelandclinic.org/health/diseases/21173-metastatic-spinal-tumors

  Symptoms include severe neck and back pain and weakness in your arms and legs. […] A cancerous tumor in your spine may cause bone pain, compression fractures or affect how your spinal cord works. […] Symptoms vary depending on whether the tumor is in your spine or spinal cord: Back or neck pain: Cancer in your spine may damage small bones (vertebrae) that make up your spine and house your spinal cord and nerves. Damage to your vertebrae causes pain. This pain may feel like a dull ache or a sudden sharp pain. It often gets worse at night. […] Numbness, weakness or tingling sensations: A tumor pressing on your spinal cord may make your arms or legs feel numb or weak. You may have tingling (like pins-and-needles) feelings in your chest. […] Difficulty controlling how and when you pee or poop: Your spinal cord controls how your bladder and bowels work. You may have urinary incontinence or fecal incontinence if there’s a tumor pressing on your spinal cord.

• #36 Spinal Metastasis: When Cancer Spreads to the Spine

  https://my.clevelandclinic.org/health/diseases/21173-metastatic-spinal-tumors

  Symptoms include severe neck and back pain and weakness in your arms and legs. […] A cancerous tumor in your spine may cause bone pain, compression fractures or affect how your spinal cord works. […] Symptoms vary depending on whether the tumor is in your spine or spinal cord: Back or neck pain: Cancer in your spine may damage small bones (vertebrae) that make up your spine and house your spinal cord and nerves. Damage to your vertebrae causes pain. This pain may feel like a dull ache or a sudden sharp pain. It often gets worse at night. […] Numbness, weakness or tingling sensations: A tumor pressing on your spinal cord may make your arms or legs feel numb or weak. You may have tingling (like pins-and-needles) feelings in your chest. […] Difficulty controlling how and when you pee or poop: Your spinal cord controls how your bladder and bowels work. You may have urinary incontinence or fecal incontinence if there’s a tumor pressing on your spinal cord.

• #37 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  This fact sheet is for women who have been diagnosed with breast cancer that has been found in the bones. Deposits of cancer in bones are called bone metastases or bone secondaries. […] If your breast cancer spreads to the bones, you may experience some of the symptoms described below. Symptoms may vary depending on the location and size of the cancerous deposit. […] Pain is the most common symptom of bone metastases. It tends be a constant, aching pain that may be worse during activity and can cause sleeping difficulties. […] Cancer deposits can weaken a bone and this can cause the bone to break (fracture). […] Cancer in the bones of the spine (called the vertebrae) can cause pressure on the nerves that travel through the spinal cord. Symptoms of spinal cord compression can include persistent pain in the back that may be worse with coughing, sneezing or straining, numbness or weakness in the legs, causing difficulty with walking, difficulty controlling the bladder or the bowel, paralysis (rarely).

• #38 Spinal Metastasis: When Cancer Spreads to the Spine

  https://my.clevelandclinic.org/health/diseases/21173-metastatic-spinal-tumors

  Paralysis: Spinal metastasis that damages your spinal nerves can lead to paralysis. That’s because your spinal nerves send electrical signals between your brain, spinal cord and the rest of your body. These electrical nerve signals help you feel sensations and move your body (motor nerves). […] Spinal metastasis is advanced cancer, meaning there’s cancer in your spine and at least one other area of your body. Everyones situation is a bit different, but in general, people with spinal metastasis will need ongoing treatment that focuses on slowing down cancer and managing symptoms.

• #39 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). Bone mets can be called lesions, can be part of advanced cancer and can happen in any bone in the body. The most common signs of bone metastases are: Bone pain: This is often the first symptom. The pain often comes and goes, is worse at night, and can be relieved with movement. It may worsen and become constant. Fracture (broken bone): Bone may weaken and fracture (break). Fractures from bone metastases are called „pathologic” fractures. The fractures could be caused by trauma, but if the bone is weak enough, it can break just by doing an everyday activity. Spinal cord compression: Cancer that has spread to the spine can cause pressure on the spinal cord called spinal cord compression. Signs can be new or worsening pain in the back or neck, numbness and weakness in the body below the tumor, and trouble walking. Spinal cord compression can cause nerve damage and even paralysis (losing the ability to move). High calcium levels: Some bone metastases can cause calcium to leak from your bones into the bloodstream. This can cause high calcium levels (hypercalcemia) in the blood. Hypercalcemia can cause constipation, nausea, loss of appetite, extreme thirst, frequent urination, dehydration, fatigue, and in very serious cases, confusion and even coma. […] Your provider will watch you closely during the treatment of your primary cancer for these signs and symptoms. You should tell your provider if you start to have any symptoms of bone metastases.

• #40 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  A full 80% of patients with bone metastases have cancer-induced bone pain (CIBP), and it often presents as their first symptom. […] CIBP significantly impairs the quality of life (QOL) of cancer patients with bone metastases and has been suggested to be a negative indicator of survival. […] Together, these studies provide evidence supporting CIBP’s negative impact on bone metastatic cancer patient prognosis. […] CIBP involves sensory nerve sprouting and the synthesis of neuropeptides. […] Importantly, levels of CGRP are increased in the serum of patients with advanced prostate cancer, including patients with bone metastasis compared to those with low-grade prostate cancer. […] These findings suggest that cancer-associated nerves stimulate bone metastatic progression. […] In this study, we found that (i) sensory nerves expressing CGRP are enriched in the periosteum of mice with bone metastasis; (ii) cancer patients with bone metastatic disease have elevated CGRP serum levels; (iii) tumor samples from patients with bone metastases express higher levels of a CGRP receptor, calcitonin receptor-like receptor (CRLR); (iv) CGRP induces proliferation of cancer cells through the CRLR/p38/HSP27 pathway; and (v) blocking CGRP, derived from sensory nerves, by monoclonal antibody against CGRP can reduce bone metastatic progression in vivo.

• #41 Bone Metastases | Cancer Spread to Bones | American Cancer Society

  https://www.cancer.org/cancer/managing-cancer/advanced-cancer/bone-metastases.html

  Cancer growing in the bones of the back can press on the spinal cord. One of the earliest symptoms of spinal cord compression is pain in the back or neck. […] When cancer spreads to the bones, too much calcium from the bones can be released into the bloodstream. This is called hypercalcemia. High blood calcium levels can cause problems such as constipation, passing urine often, feeling sluggish or sleepy, feeling thirsty all the time and drinking lots of liquids, muscle weakness, muscle and joint aches, confusion, coma, and kidney failure.

• #42 Overview of Metastatic Cancer in Bones

  https://www.webmd.com/cancer/features/bone-metastasis-what-happens

  „Numbness, paralysis, or trouble urinating.” Pressure on the spinal cord from bone metastases in the spine can cause this. […] „Loss of appetite, nausea, extreme thirst, confusion, or tiredness.” These symptoms may be due to high levels of calcium in the blood. As metastasis develops in the bone, there is release of calcium into the bloodstream. […] Treatment for bone metastasis can prolong life and relieve symptoms. Much depends upon the type of cancer you have, how old you are, and how much time has elapsed since you first were diagnosed. „But many people can do really well for a long period of time,” Fasano says.

• #43 Secondary (metastatic) breast cancer in the bone | Breast Cancer Now

  https://breastcancernow.org/about-breast-cancer/secondary-breast-cancer/secondary-breast-cancer-treatment/secondary-metastatic-breast-cancer-in-the-bone/

  When cancer that started in the breast has spread to the bones, its called secondary or metastatic breast cancer in the bone. […] The main symptoms of breast cancer that has spread to bone are: Pain particularly in the back, arms or legs, often described as gnawing which occurs when resting or sleeping, and may get worse when lying down especially at night. […] Other possible effects include: Spinal cord compression. […] Spinal cord compression is a risk for people with secondary breast cancer that has spread to the spine. […] Severe or unexplained back pain, which may also be felt around the front of the chest and belly. […] Spinal cord compression is usually treated with radiotherapy and steroids. […] Too much calcium in the blood (hypercalcaemia) can cause symptoms such as: Fatigue, Nausea and vomiting, Loss of appetite, Constipation, Loss of concentration, Drowsiness, Being very thirsty, Passing large amounts of urine, Weakness, Confusion. […] Cancer-related fatigue is one of the most common symptoms of secondary breast cancer.

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

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

  Bone metastasis can cause pain and broken bones. With rare exceptions, cancer that has spread to the bones can’t be cured. Treatments can help reduce pain and other symptoms of bone metastases. […] Sometimes, bone metastasis causes no signs and symptoms. […] When it does occur, signs and symptoms of bone metastasis include: Bone pain, Broken bones, Urinary incontinence, Bowel incontinence, Weakness in the legs or arms, High levels of calcium in the blood (hypercalcemia), which can cause nausea, vomiting, constipation and confusion.

• #45 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  Cancer in the bone can increase the levels of calcium in the blood. This can sometimes cause symptoms such as thirst, passing urine more often, vomiting, constipation or confusion. […] Although current treatments for bone metastases are unable to completely remove all cancer cells, many women with bone metastases can live for many years with extremely good quality of life. […] The effect of bone metastasis on your prognosis is individual and depends on what type of cancer you have, where it has spread to and how you respond to various treatments. The main aim of any treatment is to control pain and other symptoms so you can enjoy your day-to-day activities as much as possible.

• #46 Bone Metastases | Cancer Spread to Bones | American Cancer Society

  https://www.cancer.org/cancer/managing-cancer/advanced-cancer/bone-metastases.html

  Cancer growing in the bones of the back can press on the spinal cord. One of the earliest symptoms of spinal cord compression is pain in the back or neck. […] When cancer spreads to the bones, too much calcium from the bones can be released into the bloodstream. This is called hypercalcemia. High blood calcium levels can cause problems such as constipation, passing urine often, feeling sluggish or sleepy, feeling thirsty all the time and drinking lots of liquids, muscle weakness, muscle and joint aches, confusion, coma, and kidney failure.

• #47 Secondary (metastatic) breast cancer in the bone | Breast Cancer Now

  https://breastcancernow.org/about-breast-cancer/secondary-breast-cancer/secondary-breast-cancer-treatment/secondary-metastatic-breast-cancer-in-the-bone/

  When cancer that started in the breast has spread to the bones, its called secondary or metastatic breast cancer in the bone. […] The main symptoms of breast cancer that has spread to bone are: Pain particularly in the back, arms or legs, often described as gnawing which occurs when resting or sleeping, and may get worse when lying down especially at night. […] Other possible effects include: Spinal cord compression. […] Spinal cord compression is a risk for people with secondary breast cancer that has spread to the spine. […] Severe or unexplained back pain, which may also be felt around the front of the chest and belly. […] Spinal cord compression is usually treated with radiotherapy and steroids. […] Too much calcium in the blood (hypercalcaemia) can cause symptoms such as: Fatigue, Nausea and vomiting, Loss of appetite, Constipation, Loss of concentration, Drowsiness, Being very thirsty, Passing large amounts of urine, Weakness, Confusion. […] Cancer-related fatigue is one of the most common symptoms of secondary breast cancer.

• #48 Secondary (metastatic) breast cancer in the bone | Breast Cancer Now

  https://breastcancernow.org/about-breast-cancer/secondary-breast-cancer/secondary-breast-cancer-treatment/secondary-metastatic-breast-cancer-in-the-bone/

  When cancer that started in the breast has spread to the bones, its called secondary or metastatic breast cancer in the bone. […] The main symptoms of breast cancer that has spread to bone are: Pain particularly in the back, arms or legs, often described as gnawing which occurs when resting or sleeping, and may get worse when lying down especially at night. […] Other possible effects include: Spinal cord compression. […] Spinal cord compression is a risk for people with secondary breast cancer that has spread to the spine. […] Severe or unexplained back pain, which may also be felt around the front of the chest and belly. […] Spinal cord compression is usually treated with radiotherapy and steroids. […] Too much calcium in the blood (hypercalcaemia) can cause symptoms such as: Fatigue, Nausea and vomiting, Loss of appetite, Constipation, Loss of concentration, Drowsiness, Being very thirsty, Passing large amounts of urine, Weakness, Confusion. […] Cancer-related fatigue is one of the most common symptoms of secondary breast cancer.

• #49 Bone cancer (Secondary)

  https://www.cancervic.org.au/cancer-information/types-of-cancer/secondary-bone-cancer/secondary-bone-cancer-overview.html

  Bone pain This is often the first and most common symptom. The pain may be a dull, persistent ache. It can get worse with movement and is often worse at night. […] Fractures Cancer cells can weaken the bones and cause them to break more easily, often with little or no force (this is known as a pathological fracture). […] High calcium levels in the blood (hypercalcaemia) As the bone breaks down, calcium is released into the bloodstream. When calcium builds up in the blood, it may cause severe tiredness (fatigue), a feeling of sickness (nausea), vomiting, thirst, constipation or confusion. […] Pressure on the nerves in the spine (spinal cord compression) Abnormal bone growth or fractures can press on the nerves in the spine. This may cause back pain, muscle and limb weakness, tingling or numbness of the limbs, difficulty walking, or loss of bowel or bladder control.

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

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

  Bone metastasis causes complications like hypercalcemia, which can lead to coma if you dont receive treatment. Without treatment, you may have bone fractures that affect your ability to walk or take care of yourself. You may have severe bone pain that can affect your quality of life. You also run the risk of having spine compression which may lead to paralysis. […] If you have bone metastasis, it means you have cancer somewhere else in your body thats spread to your bones. Bone metastasis is a sign of advanced cancer. If this is your situation, youll need medical care and support for the primary cancer and bone metastasis. […] Survival rates range from six to seven months to more than four years, and vary based on factors like: Cancer type: One analysis states the survival rate for lung cancer to bone is six to seven months, compared to 53 months for prostate cancer to bone.

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

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

  Metastatic bone disease is cancer that starts in one part of the body and moves to your skeleton. The disease can lead to pain, broken bones, and serious health problems. […] The signs and symptoms of metastatic bone disease include: Anemia. Metastatic tumors often grow in the large bones that produce many of the body’s red blood cells, which carry oxygen to the rest of the body. Anemia or not enough red blood cells can lead to fatigue, weakness, and shortness of breath. […] Bone pain. The most common symptom of metastatic bone disease, bone pain may get worse at night. […] Fractures. Minor injuries or normal activities can cause fractures when you have metastatic bone disease. […] Hypercalcemia (high calcium levels). Tumors can cause too much calcium to be released into the bloodstream. High calcium levels can lead to muscle aches, weakness, constipation, and kidney failure.

• #52 Bone cancer (Secondary)

  https://www.cancervic.org.au/cancer-information/types-of-cancer/secondary-bone-cancer/secondary-bone-cancer-overview.html

  Low levels of blood cells Secondary bone cancer can affect the bone marrow, particularly if there is a large amount of spread to the bones. The bone marrow makes blood cells, so the cancer can lead to low levels of blood cells. Symptoms depend on the type of blood cells affected. You may feel tired and breathless, have an increased risk of infections, or bruise and bleed more easily. […] Secondary bone cancer cant always be cured, but treatment can reduce symptoms and improve quality of life. In some cases, treatment can keep secondary bone cancer under control for many years.

• #53 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  Patients can experience a number of other symptoms if bone metastases affect the bone marrow, which usually occurs in those who have received extensive chemotherapy or radiation therapy. If your level of red blood cells drops, you might become anemic and have symptoms of fatigue, weakness, and shortness of breath. Patients whose white blood cells are affected may be more likely to have infections, which could cause fevers, chills, fatigue, or pain. Lastly, if your platelet count is low, you may have abnormal bleeding. The symptoms vary depending upon the type of blood cell affected.

• #54 Secondary bone cancer | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/bone-cancer-secondary

  Secondary cancer in the bone may cause increased amounts of calcium to be released from the bone into your blood. A high level of calcium in the blood is called hypercalcaemia. […] Symptoms of spinal cord compression include: back or neck pain, which may be mild at first but becomes severe, weakness in your arms or legs, numbness or pins and needles in your legs, hands, around your buttocks or anywhere else in your body, problems controlling pee or peeing, constipation or problems controlling your bowels. […] Sometimes secondary cancer in the bone can affect the way the bone marrow works. […] If the bone marrow does not produce enough red blood cells, you may become anaemic. This means the tissues and organs in your body might not get enough oxygen. This can make you feel tired and breathless. […] If you have too few white blood cells, you will be more prone to infection. […] And if you have a low platelet count, you may have bruising or bleeding.

• #55 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  Patients can experience a number of other symptoms if bone metastases affect the bone marrow, which usually occurs in those who have received extensive chemotherapy or radiation therapy. If your level of red blood cells drops, you might become anemic and have symptoms of fatigue, weakness, and shortness of breath. Patients whose white blood cells are affected may be more likely to have infections, which could cause fevers, chills, fatigue, or pain. Lastly, if your platelet count is low, you may have abnormal bleeding. The symptoms vary depending upon the type of blood cell affected.

• #56 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  Patients can experience a number of other symptoms if bone metastases affect the bone marrow, which usually occurs in those who have received extensive chemotherapy or radiation therapy. If your level of red blood cells drops, you might become anemic and have symptoms of fatigue, weakness, and shortness of breath. Patients whose white blood cells are affected may be more likely to have infections, which could cause fevers, chills, fatigue, or pain. Lastly, if your platelet count is low, you may have abnormal bleeding. The symptoms vary depending upon the type of blood cell affected.

• #57 Metastatic Bone Disease – OrthoInfo – AAOS

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

  Metastatic Bone Disease (MBD) may cause pain in the area of spread, and it may lead to damage and weakness in the bone. […] The most common symptom of MBD is pain. Patients may have pain in the spine, pelvis, or extremities because the bone has been weakened by the tumor. […] Weakened bones break more easily. A fracture from a minor injury is another possible sign of MBD. […] Anemia (decreased red blood cell production) is, therefore, a common blood abnormality in patients with MBD. […] A cancer patient who experiences any pain, especially in the back, legs, and arms, should notify their doctor immediately. Pain that occurs without heavy activity (i.e., walking or lifting an object) is particularly concerning. […] Because MBD weakens the affected bones, people with this disease are at risk for fractures. Broken bones caused by MBD are called pathological fractures.

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

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

  Metastatic bone disease is cancer that starts in one part of the body and moves to your skeleton. The disease can lead to pain, broken bones, and serious health problems. […] The signs and symptoms of metastatic bone disease include: Anemia. Metastatic tumors often grow in the large bones that produce many of the body’s red blood cells, which carry oxygen to the rest of the body. Anemia or not enough red blood cells can lead to fatigue, weakness, and shortness of breath. […] Bone pain. The most common symptom of metastatic bone disease, bone pain may get worse at night. […] Fractures. Minor injuries or normal activities can cause fractures when you have metastatic bone disease. […] Hypercalcemia (high calcium levels). Tumors can cause too much calcium to be released into the bloodstream. High calcium levels can lead to muscle aches, weakness, constipation, and kidney failure.

• #59 Bone Metastasis Treatment Market | Emerging Therapies and Companies

  https://www.delveinsight.com/blog/bone-metastasis-market

  In advanced cancer patients, the most common site for the occurrence of metastasis is considered to be the bone. Bone Metastasis symptoms include bone pain, broken bones, urinary, and bowel incontinence, weakness in the legs or arms, and high levels of calcium in the blood (hypercalcemia), which can cause nausea, vomiting, constipation, and confusion. […] The development and progression of Bone Metastasis can be considered in several stages: colonization, quiescence, and progression, which can occur locally or regionally, leading to overt Bone Metastasis or dissemination to another location. The most prevalent symptom is pain. Bone Metastasis causes increased bone resorption, which increases the risk of several skeletal-related events (SREs) defined as pathological fracture, spinal cord compression, the need for bone irradiation or need for bone surgery, and hypercalcemia.

• #60 Bone Metastasis Treatment Market | Emerging Therapies and Companies

  https://www.delveinsight.com/blog/bone-metastasis-market

  In advanced cancer patients, the most common site for the occurrence of metastasis is considered to be the bone. Bone Metastasis symptoms include bone pain, broken bones, urinary, and bowel incontinence, weakness in the legs or arms, and high levels of calcium in the blood (hypercalcemia), which can cause nausea, vomiting, constipation, and confusion. […] The development and progression of Bone Metastasis can be considered in several stages: colonization, quiescence, and progression, which can occur locally or regionally, leading to overt Bone Metastasis or dissemination to another location. The most prevalent symptom is pain. Bone Metastasis causes increased bone resorption, which increases the risk of several skeletal-related events (SREs) defined as pathological fracture, spinal cord compression, the need for bone irradiation or need for bone surgery, and hypercalcemia.

• #61 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. […] Bone metastases can be divided into two broad categories; (i) osteolytic metastases that are associated with bone destruction and (ii) osteosclerotic metastases that are characterized by new bone formation. […] Although precise molecular mechanisms underlying preferential cancer metastasis to bone need to be elucidated, it seems likely that bone provides an attractive environment that allows circulating cancer cells to home, survive and proliferate. […] The binding of cancer cells at the metastatic site involves cell-to-cell interactions, or interactions between cells and the extracellular matrix, and these processes involves cell adhesion molecules like integrins.

• #62 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. […] Bone metastases can be divided into two broad categories; (i) osteolytic metastases that are associated with bone destruction and (ii) osteosclerotic metastases that are characterized by new bone formation. […] Although precise molecular mechanisms underlying preferential cancer metastasis to bone need to be elucidated, it seems likely that bone provides an attractive environment that allows circulating cancer cells to home, survive and proliferate. […] The binding of cancer cells at the metastatic site involves cell-to-cell interactions, or interactions between cells and the extracellular matrix, and these processes involves cell adhesion molecules like integrins.

• #63 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  The role played by this seed and soil interaction mechanism is clearly demonstrated by the inconsistency of metastasis formation throughout the skeleton. […] Osteolytic lesions arise when osteoclast-mediated bone resorption overcomes bone formation by osteoblasts, resulting in weakened structures that compromise bone integrity. […] Various factors including cytokines and hormones control the bone remodelling equilibrium, and a vicious cycle involving osteoclasts and tumour cells progressively leads to the development of osteolytic lesions. […] Patients bearing bone metastases often suffer from many complications including pain, decreased mobility, neurologic compromise and pathologic fractures. […] Despite numerous studies attempting to better understand bone metastasis pathophysiology, there are as yet no established and efficient clinical methods for their cure and/or their prevention.

• #64 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. […] Bone metastases can be divided into two broad categories; (i) osteolytic metastases that are associated with bone destruction and (ii) osteosclerotic metastases that are characterized by new bone formation. […] Although precise molecular mechanisms underlying preferential cancer metastasis to bone need to be elucidated, it seems likely that bone provides an attractive environment that allows circulating cancer cells to home, survive and proliferate. […] The binding of cancer cells at the metastatic site involves cell-to-cell interactions, or interactions between cells and the extracellular matrix, and these processes involves cell adhesion molecules like integrins.

• #65 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  The role played by this seed and soil interaction mechanism is clearly demonstrated by the inconsistency of metastasis formation throughout the skeleton. […] Osteolytic lesions arise when osteoclast-mediated bone resorption overcomes bone formation by osteoblasts, resulting in weakened structures that compromise bone integrity. […] Various factors including cytokines and hormones control the bone remodelling equilibrium, and a vicious cycle involving osteoclasts and tumour cells progressively leads to the development of osteolytic lesions. […] Patients bearing bone metastases often suffer from many complications including pain, decreased mobility, neurologic compromise and pathologic fractures. […] Despite numerous studies attempting to better understand bone metastasis pathophysiology, there are as yet no established and efficient clinical methods for their cure and/or their prevention.

• #66 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. Bone metastases can also cause the following cancer-related emergencies. The most common symptom of bone metastases, and usually the first to happen, is pain in the bone. Bone pain can come and go, or it can be constant. It is often worse at night. The pain may be only in one area or it may spread throughout the body. It may be a dull ache or a sharp pain. There may also be swelling along with bone pain. Other signs and symptoms of bone metastases include broken bones (fractures), most often the ribs, vertebrae and long bones of the legs. […] The symptoms of bone metastases vary depending on which bones are affected and how many bones are affected. Other health conditions can cause the same symptoms as bone metastases. […] 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.

• #67 Bone metastases: what is it, symptoms and treatment | Top Doctors

  https://www.topdoctors.co.uk/medical-dictionary/bone-metastases

  Bone metastases can cause bone to either form or be destroyed, or in some cases, both. […] Symptoms of metastasis in the bone include broken bones as the bones weaken, pain felt in the bones, and symptoms related to excess of calcium (feeling very thirsty, nausea, loss of appetite) which is released into the bloodstream as the bone is destroyed. […] Once cancer has started spreading, it is difficult to then control it and treat it. Bone metastases, in most cases, cannot be cured or reversed.

• #68 Bone Metastasis: When cancer spreads to the bones | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis

  Bone metastases are common among cancer patients. It is important to be informed of some of the common symptoms, how bone metastasis is diagnosed, and what treatment options are currently available. Be aware of your own body and share any concerns that you may have with your doctor. […] When cancer cells metastasize to the bone, they can cause changes to the bone. The process by which portions of the bone are damaged is called osteolysis. Oftentimes, small holes result from osteolysis. These holes in the bone are referred to as osteolytic lesions or lytic lesions. Lytic lesions can weaken the bones and increase the risk of breakage or other problems. It is also common for bone metastasis patients to experience pain with lesions. […] For the majority of bone metastasis patients, it is still possible to maintain a good quality of life. Depending upon where the bone metastasis is located, certain activities may be more difficult or even unsafe. You may need to make some changes in your daily routine to lower your risk of bone fracture or to decrease pain. However, most patients find that there are still many things that they can do on their own.

• #69 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #70 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  The role played by this seed and soil interaction mechanism is clearly demonstrated by the inconsistency of metastasis formation throughout the skeleton. […] Osteolytic lesions arise when osteoclast-mediated bone resorption overcomes bone formation by osteoblasts, resulting in weakened structures that compromise bone integrity. […] Various factors including cytokines and hormones control the bone remodelling equilibrium, and a vicious cycle involving osteoclasts and tumour cells progressively leads to the development of osteolytic lesions. […] Patients bearing bone metastases often suffer from many complications including pain, decreased mobility, neurologic compromise and pathologic fractures. […] Despite numerous studies attempting to better understand bone metastasis pathophysiology, there are as yet no established and efficient clinical methods for their cure and/or their prevention.

• #71 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. […] We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory nerve-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo.

• #72 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. […] We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory nerve-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo.

• #73 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. […] We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory nerve-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo.

• #74 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. […] We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory nerve-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo.

• #75 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  A full 80% of patients with bone metastases have cancer-induced bone pain (CIBP), and it often presents as their first symptom. […] CIBP significantly impairs the quality of life (QOL) of cancer patients with bone metastases and has been suggested to be a negative indicator of survival. […] Together, these studies provide evidence supporting CIBP’s negative impact on bone metastatic cancer patient prognosis. […] CIBP involves sensory nerve sprouting and the synthesis of neuropeptides. […] Importantly, levels of CGRP are increased in the serum of patients with advanced prostate cancer, including patients with bone metastasis compared to those with low-grade prostate cancer. […] These findings suggest that cancer-associated nerves stimulate bone metastatic progression. […] In this study, we found that (i) sensory nerves expressing CGRP are enriched in the periosteum of mice with bone metastasis; (ii) cancer patients with bone metastatic disease have elevated CGRP serum levels; (iii) tumor samples from patients with bone metastases express higher levels of a CGRP receptor, calcitonin receptor-like receptor (CRLR); (iv) CGRP induces proliferation of cancer cells through the CRLR/p38/HSP27 pathway; and (v) blocking CGRP, derived from sensory nerves, by monoclonal antibody against CGRP can reduce bone metastatic progression in vivo.

• #76 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  Our data suggest that CGRP-expressing sensory nerves induce bone metastatic progression through CRLR (a component of CGRP receptors) expressed on bone metastatic cancer cells, by activating the p38/HSP27 pathway. […] Importantly, we also observed that anti-CGRP Ab treatments reduced bone metastatic progression in vivo and cancer cell proliferation in vitro by blocking CGRP derived from sensory nerves.

• #77 Bone Metastases | Cancer Spread to Bones | American Cancer Society

  https://www.cancer.org/cancer/managing-cancer/advanced-cancer/bone-metastases.html

  When cancer cells spread to the bones (bone metastases), they can cause many problems such as pain, broken bones, or more serious problems. […] Bone pain is often the first symptom of cancer that has spread to the bone. The pain may come and go at first. It tends to be worse at night and may get better with movement. Later on, it can become constant and may be worse during activity. The bone might be so weak that it will break. This can often be prevented if the bone metastasis is found early. […] Breaks might happen with a fall or injury, but a weak bone can also break during normal activities. These breaks often cause sudden, severe pain. Fractures most often happen in the long bones of the arms and legs and the bones of the spine. Sudden pain in the middle of the back, for instance, may mean a bone in the spine has broken.

• #78

  https://link.springer.com/article/10.1007/s00520-016-3154-x

  Pain and fatigue were the earliest symptoms to reach their median time to moderate/severe intensity, which occurred within 1 month or less after the onset of bone metastases. […] Moderate to severe trouble sleeping and numbness/tingling commenced later, at a median 2.9 and 7.7 months, respectively. […] The cumulative proportion of patients with moderate to severe symptoms increased over time for most symptoms, particularly for pain and fatigue which affected a majority of patients within 3 months of the onset of bone metastases. […] We observed increasing symptom burden, particularly for pain and fatigue, both before and after the diagnosis of bone metastases in women with breast cancer.

• #79

  https://link.springer.com/article/10.1007/s00520-016-3154-x

  Pain and fatigue were the earliest symptoms to reach their median time to moderate/severe intensity, which occurred within 1 month or less after the onset of bone metastases. […] Moderate to severe trouble sleeping and numbness/tingling commenced later, at a median 2.9 and 7.7 months, respectively. […] The cumulative proportion of patients with moderate to severe symptoms increased over time for most symptoms, particularly for pain and fatigue which affected a majority of patients within 3 months of the onset of bone metastases. […] We observed increasing symptom burden, particularly for pain and fatigue, both before and after the diagnosis of bone metastases in women with breast cancer.

• #80 Bone metastasis – Wikipedia

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

  Bone metastases can cause severe pain, bone fractures, spinal cord compression, hypercalcemia, anemia, spinal instability, decreased mobility, and rapid degradation in the quality of life for patients. […] Patients have described the pain as a dull ache that grows worse over time, with intermittent periods of sharp, jagged pain. […] Even under controlled pain management, periods of breakthrough pain can occur rapidly, without warning, several times a day. […] Pain may be worse at night and partially relieved by activity. […] Metastases to weightbearing bones may become symptomatic early in the course of disease, as compared to metastases to the flat bones of the rib or sternum.

• #81 Bone metastasis – Wikipedia

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

  Bone metastases can cause severe pain, bone fractures, spinal cord compression, hypercalcemia, anemia, spinal instability, decreased mobility, and rapid degradation in the quality of life for patients. […] Patients have described the pain as a dull ache that grows worse over time, with intermittent periods of sharp, jagged pain. […] Even under controlled pain management, periods of breakthrough pain can occur rapidly, without warning, several times a day. […] Pain may be worse at night and partially relieved by activity. […] Metastases to weightbearing bones may become symptomatic early in the course of disease, as compared to metastases to the flat bones of the rib or sternum.

• #82 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #83 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #84 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #85 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #86 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #87 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Because bone involvement is the main source of cancer-related pain and is the major cause of severe pain for patients with advanced malignancies, SREs not only greatly increase morbidity and mortality, but also diminish quality of life for patients, which further impacts survival. […] In addition to SREs, a significant proportion of patients with bone metastases have systemic muscle weakness that results from cancer-related bone destruction, which increases the risk of falls, which can result in fractures, and negatively impacts performance status, survival, and quality of life.

• #88 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Bone is the third most frequent site of tumor metastasis; it is estimated that in the United States approximately 350,000 people die each year from bone metastases. […] The incidence of bone metastases varies based on age, sex, and the primary tumor site. […] Normal bone remodeling is markedly disturbed in bone metastasis, with imbalances in both osteoclast and osteoblast numbers and activity. […] These disturbances in the bone remodeling process can result in debilitating skeletal-related events (SREs), which are common complications (31 to 47 percent of patients with breast or prostate cancer or myeloma) that have catastrophic sequelae for patients. SREs include severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and derangements of calcium and phosphate homeostasis that can result in life-threatening hypercalcemia.

• #89 Mechanisms of bone metastases – UpToDate

  https://www.uptodate.com/contents/mechanisms-of-bone-metastases

  Because bone involvement is the main source of cancer-related pain and is the major cause of severe pain for patients with advanced malignancies, SREs not only greatly increase morbidity and mortality, but also diminish quality of life for patients, which further impacts survival. […] In addition to SREs, a significant proportion of patients with bone metastases have systemic muscle weakness that results from cancer-related bone destruction, which increases the risk of falls, which can result in fractures, and negatively impacts performance status, survival, and quality of life.

• #90 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 metastasis can profoundly affect patients daily activities and quality of life (QOL) due to severe pain and associated major complications. […] The most common clinical symptom of bone metastasis is bone pain, which is usually localized and progresses slowly. Patients may experience worsening of pain at night or while ambulating, depending on the site of bone metastasis. Pain may radiate to the lower extremities; however, radiating pain may not always correlate with nerve impingement. […] 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.

• #91 Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5796097/

  Local treatments of bone metastases have a dual role: (i) mechanical stabilization to prevent pathological fractures; (ii) tumour destruction to block or slow tumour and, for example, to fight against neurological complications in case of spinal metastases. […] Bone pain is very difficult to treat and tends to be resistant to opioids.

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

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

  Bone metastasis causes complications like hypercalcemia, which can lead to coma if you dont receive treatment. Without treatment, you may have bone fractures that affect your ability to walk or take care of yourself. You may have severe bone pain that can affect your quality of life. You also run the risk of having spine compression which may lead to paralysis. […] If you have bone metastasis, it means you have cancer somewhere else in your body thats spread to your bones. Bone metastasis is a sign of advanced cancer. If this is your situation, youll need medical care and support for the primary cancer and bone metastasis. […] Survival rates range from six to seven months to more than four years, and vary based on factors like: Cancer type: One analysis states the survival rate for lung cancer to bone is six to seven months, compared to 53 months for prostate cancer to bone.

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

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

  Bone metastasis causes complications like hypercalcemia, which can lead to coma if you dont receive treatment. Without treatment, you may have bone fractures that affect your ability to walk or take care of yourself. You may have severe bone pain that can affect your quality of life. You also run the risk of having spine compression which may lead to paralysis. […] If you have bone metastasis, it means you have cancer somewhere else in your body thats spread to your bones. Bone metastasis is a sign of advanced cancer. If this is your situation, youll need medical care and support for the primary cancer and bone metastasis. […] Survival rates range from six to seven months to more than four years, and vary based on factors like: Cancer type: One analysis states the survival rate for lung cancer to bone is six to seven months, compared to 53 months for prostate cancer to bone.

• #94 Bone Metastasis Treatment Market | Emerging Therapies and Companies

  https://www.delveinsight.com/blog/bone-metastasis-market

  The Bone Metastasis survival rate varies from patient to patient depending on the type of cancer and in which stage it is present currently. On top of that, the general health condition and type of Bone Metastasis treatment one has received are considered additional factors. Bone Metastasis survival rate is data gathered over a long period of time from a large number of people affected. […] The most common question related to Bone Metastasis is how to treat Bone Metastasis. Similar to DNA fingerprinting, Bone Metastasis treatment is exclusive to patients, highly individualized and requires a multidisciplinary approach. The treatment is different for different persons affected and it shall include the type of primary cancer observed, its current stage, which kind of bones are involved, prior cancer treatments taken and the overall health of a patient.

• #95 Bone Metastasis Treatment Market | Emerging Therapies and Companies

  https://www.delveinsight.com/blog/bone-metastasis-market

  The Bone Metastasis survival rate varies from patient to patient depending on the type of cancer and in which stage it is present currently. On top of that, the general health condition and type of Bone Metastasis treatment one has received are considered additional factors. Bone Metastasis survival rate is data gathered over a long period of time from a large number of people affected. […] The most common question related to Bone Metastasis is how to treat Bone Metastasis. Similar to DNA fingerprinting, Bone Metastasis treatment is exclusive to patients, highly individualized and requires a multidisciplinary approach. The treatment is different for different persons affected and it shall include the type of primary cancer observed, its current stage, which kind of bones are involved, prior cancer treatments taken and the overall health of a patient.

• #96 Bone Metastasis Treatment Market | Emerging Therapies and Companies

  https://www.delveinsight.com/blog/bone-metastasis-market

  The Bone Metastasis survival rate varies from patient to patient depending on the type of cancer and in which stage it is present currently. On top of that, the general health condition and type of Bone Metastasis treatment one has received are considered additional factors. Bone Metastasis survival rate is data gathered over a long period of time from a large number of people affected. […] The most common question related to Bone Metastasis is how to treat Bone Metastasis. Similar to DNA fingerprinting, Bone Metastasis treatment is exclusive to patients, highly individualized and requires a multidisciplinary approach. The treatment is different for different persons affected and it shall include the type of primary cancer observed, its current stage, which kind of bones are involved, prior cancer treatments taken and the overall health of a patient.

• #97 Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression | Life Science Alliance

  https://www.life-science-alliance.org/content/7/12/e202302041

  A full 80% of patients with bone metastases have cancer-induced bone pain (CIBP), and it often presents as their first symptom. […] CIBP significantly impairs the quality of life (QOL) of cancer patients with bone metastases and has been suggested to be a negative indicator of survival. […] Together, these studies provide evidence supporting CIBP’s negative impact on bone metastatic cancer patient prognosis. […] CIBP involves sensory nerve sprouting and the synthesis of neuropeptides. […] Importantly, levels of CGRP are increased in the serum of patients with advanced prostate cancer, including patients with bone metastasis compared to those with low-grade prostate cancer. […] These findings suggest that cancer-associated nerves stimulate bone metastatic progression. […] In this study, we found that (i) sensory nerves expressing CGRP are enriched in the periosteum of mice with bone metastasis; (ii) cancer patients with bone metastatic disease have elevated CGRP serum levels; (iii) tumor samples from patients with bone metastases express higher levels of a CGRP receptor, calcitonin receptor-like receptor (CRLR); (iv) CGRP induces proliferation of cancer cells through the CRLR/p38/HSP27 pathway; and (v) blocking CGRP, derived from sensory nerves, by monoclonal antibody against CGRP can reduce bone metastatic progression in vivo.

• #98 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  Cancer in the bone can increase the levels of calcium in the blood. This can sometimes cause symptoms such as thirst, passing urine more often, vomiting, constipation or confusion. […] Although current treatments for bone metastases are unable to completely remove all cancer cells, many women with bone metastases can live for many years with extremely good quality of life. […] The effect of bone metastasis on your prognosis is individual and depends on what type of cancer you have, where it has spread to and how you respond to various treatments. The main aim of any treatment is to control pain and other symptoms so you can enjoy your day-to-day activities as much as possible.

• #99 Metastatic Bone Disease Fact Sheet | Westmead BCI

  http://www.bci.org.au/breast-cancer-information/fact-sheets/bone-metastases/

  Cancer in the bone can increase the levels of calcium in the blood. This can sometimes cause symptoms such as thirst, passing urine more often, vomiting, constipation or confusion. […] Although current treatments for bone metastases are unable to completely remove all cancer cells, many women with bone metastases can live for many years with extremely good quality of life. […] The effect of bone metastasis on your prognosis is individual and depends on what type of cancer you have, where it has spread to and how you respond to various treatments. The main aim of any treatment is to control pain and other symptoms so you can enjoy your day-to-day activities as much as possible.

• #100 Bone metastasis – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bone-metastasis/diagnosis-treatment/drc-20370196

  Imaging tests are used to investigate signs and symptoms that may indicate bone metastasis. […] Common treatments for bone metastasis include medications, radiation therapy and surgery. […] Medications commonly used to treat people with thinning bones (osteoporosis) may also help people with bone metastasis. These medications can strengthen bones and reduce the pain caused by bone metastasis, reducing the need for strong pain medications. […] Radiopharmaceuticals can help control pain caused by bone metastasis. […] Pain medications may control the pain caused by bone metastasis. […] Steroids can often help to relieve pain associated with bone metastases by decreasing swelling and inflammation around the sites of cancer. […] Radiation therapy may be an option if your bone metastasis is causing pain that isn’t controlled with pain medications or if the pain is confined to a small number of areas. […] Coping with bone metastasis requires more than enduring bone pain. It also involves coming to terms with the news that your cancer has spread beyond its original site. […] Your doctor will work to minimize your pain and to maintain your function so that you can continue your daily activities.

• #101 Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST

  https://www.jcancer.org/v01p0080.htm

  Response criteria represent the standard by which the efficacy of therapeutic agents is determined in cancer trials. […] Because bone metastases are typically located in irregularly shaped bones and are difficult to measure with rulers, they have been previously considered unmeasurable disease. New developments in cancer response criteria have increased awareness of the importance of the response of bone metastases to therapy. […] Bone metastases are a common manifestation of advanced disease with autopsy studies showing an incidence of 33-36% in patients with lung cancer, 68% in prostate cancer, and 73% in breast cancer. […] The absence of measurable tumors can significantly affect patient disease management. […] RECIST 1.1 specifies that up to 5 target lesions, representing all affected organ systems but with no more than 2 target lesions per organ, be selected for measurement throughout the course of a therapeutic trial.

• #102 Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST

  https://www.jcancer.org/v01p0080.htm

  Metabolic imaging criteria can allow bone metastases to be measured in the absence of anatomic change by assessing tumor metabolism. […] Response criteria are of crucial importance to the care of many cancer patients, and the tumor response assessment of bone metastases is assuming a greater role in therapeutic management.

• #103 Bone metastases | Living Beyond Breast Cancer

  https://www.lbbc.org/about-breast-cancer/types-breast-cancer/metastatic-breast-cancer/bone-metastases

  If you have a history of breast cancer, even if it was years ago, report any bone pain that lasts two weeks or more to your healthcare team. […] Anyone diagnosed with breast cancer can develop bone metastases. For many people with metastatic breast cancer, the bones are the first location of cancer spread. In fact, almost 70% of people with metastatic breast cancer develop bone metastases at some point. […] Bone metastases and their symptoms are typically treated with systemic treatments that treat cancer cells no matter where they are in the body. […] In addition to these standard treatments, doctors may recommend these systemic bone-modifying medicines: Bisphosphonates can make bones stronger and reduce bone pain, and in some cases, stop new bone metastases from forming. […] Once there is a clear diagnosis of bone metastases, you and your doctors will decide on a treatment plan. Part of that plan will involve tests that show how well treatment is working and how strong your bones are. […] Your care team will monitor the bone metastases regularly to control the cancer and to help you figure out what your body can handle as you have treatment.

• #104 Bone metastases | Living Beyond Breast Cancer

  https://www.lbbc.org/about-breast-cancer/types-breast-cancer/metastatic-breast-cancer/bone-metastases

  If you have a history of breast cancer, even if it was years ago, report any bone pain that lasts two weeks or more to your healthcare team. […] Anyone diagnosed with breast cancer can develop bone metastases. For many people with metastatic breast cancer, the bones are the first location of cancer spread. In fact, almost 70% of people with metastatic breast cancer develop bone metastases at some point. […] Bone metastases and their symptoms are typically treated with systemic treatments that treat cancer cells no matter where they are in the body. […] In addition to these standard treatments, doctors may recommend these systemic bone-modifying medicines: Bisphosphonates can make bones stronger and reduce bone pain, and in some cases, stop new bone metastases from forming. […] Once there is a clear diagnosis of bone metastases, you and your doctors will decide on a treatment plan. Part of that plan will involve tests that show how well treatment is working and how strong your bones are. […] Your care team will monitor the bone metastases regularly to control the cancer and to help you figure out what your body can handle as you have treatment.

• #105 Metastatic bone disease: Early referral for multidisciplinary care | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/89/7/393

  Patients with known cancer involving the skeleton or those who have had previous radiotherapy to skeletal metastatic deposits are at particular risk of pathologic fracture. […] A sudden change to more intense or severe pain usually indicates a pathologic fracture, particularly in the context of minimal trauma. […] Patients who receive radiotherapy for bony metastasis should be assessed by an appropriate specialist to determine the need for further stabilization or surgical treatment. […] Pathologic fractures caused by metastatic bone disease will not heal, even with radiotherapy. […] Current research favors early diagnosis and a prophylactic surgical approach in managing bony metastases in patients with impending pathologic fractures.

• #106 Symptoms of Bone Metastasis | University of Michigan Rogel Cancer Center

  https://www.rogelcancercenter.org/bone-metastasis/symptoms

  It is important for you to know that not all pain means metastasis. Your doctor may be able to help you to tell the difference between bone metastasis pain and normal aches and pains or pains from other sources. It is important to talk with your doctor about any pain or discomfort that you may be having. […] Bone metastases can weaken your bones and put you at risk for fractures. Not all patients will fracture bones, but it is important to be aware of that possibility. Impending fractures describe those bones that are about to break. If found early, your doctor may be able to treat the bone to keep it from breaking. […] If the secondary tumor is located in the spinal area, it can result in spinal cord compression. Spinal cord compression occurs when the tumor squeezes the spinal cord. This can lead to back pain or make walking painful and difficult. Other symptoms might include numbness and weakness in the legs, problems with the bowels or bladder, or numbness in the abdominal area.

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