Bone Metastases
Encyclopedia
Bone metastases, or metastatic bone disease, is a class of cancer
metastases that results from primary tumor
invasion to bone
. Bone-originating cancers like osteosarcoma
, chondrosarcoma
, and Ewing's sarcoma are rare. And, unlike hematological malignancies
that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial
tumors and form a solid mass inside the bone. Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
. While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment
of the marrow tends to favor particular types of cancer, including prostate
, breast
, and lung cancer
s. Particularly in prostate cancer
, bone metastases tend to be the only site of metastasis.
-mediated bone resorption
and osteoblast
-mediated bone deposition. These processes are normally tightly regulated within bone to maintain bone structure and calcium homeostasis
in the body. Disregulation of these processes by tumor cells leads to either osteoblastic or osteolytic phenotypes. Regardless of the phenotype, though, bone metastases show osteoclast proliferation and hypertrophy
.
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, these periods of breakthrough pain can occur rapidly, without warning, several times a day.
Effects of bone metastasis
Acidosis
is the increased acidity in a given location, whether it is blood
, urine
, or tissue
s. Osteoclast
s generate extracellular proton
s, lowering the pH
of the extracellular matrix
(ECM) around the osteoclast to approximately 4.5. Nociceptors in the bone trigger a pain response in the brain in response to this acidosis. It is thought that this is the primary source of the dull, chronic pain experienced by patients with bone metastasis.
Bone Restructuring
The uncoupled regulation of the osteoclast
s and osteoblast
s leads to malformation of the bone. Malformed bones are unable to withstand the normal mechanical stresses placed on them in day-to-day activity, leading to fractures, spinal compression, and spinal instability. Malformed bones may also mechanically trigger pain receptors both within the bone and in the surrounding tissue
.
, usually in combination with one another. Scientists and pharmaceutical companies are researching drugs to target different types of cancer, including metastatic bone diease.
One treatment that has been considered is bisphosphonate
s. Bisphosphonates have shown great promise in reducing bone cancer pain, bone destruction, and tumor growth. However, they have exhibited side effect such as the induction of arthralgias and osteonecrosis of the jaw.
pain ladder
was designed for the management of cancer-associated pain, and mainly involves various strength of opioids.
Other treatments include bisphosphonate
s, corticosteroid
s, radiotherapy, and radionucleotides.
In palliative therapy, the main options are external radiation and radiopharmaceuticals.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
metastases that results from primary tumor
Primary tumor
A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass....
invasion to bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
. Bone-originating cancers like osteosarcoma
Osteosarcoma
Osteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid...
, chondrosarcoma
Chondrosarcoma
Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Chondrosarcoma is a member of a category of "soft tissue" malignancies known as sarcomas. About 30% of skeletal system cancers are chondrosarcomas...
, and Ewing's sarcoma are rare. And, unlike hematological malignancies
Hematological malignancy
Hematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
tumors and form a solid mass inside the bone. Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
Sources of Bone Metastases
Bone is one of the most common locations for metastasisMetastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
. While any type of cancer is capable of forming metastatic tumors within bone, the microenvironment
Microenvironment
Microenvironment carries different meanings depending on the context.* Medical: a small or relatively small usually distinctly specialized and effectively isolated habitat or environment...
of the marrow tends to favor particular types of cancer, including prostate
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, breast
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, and lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
s. Particularly in prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, bone metastases tend to be the only site of metastasis.
- Breast cancerBreast cancerBreast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
- Prostate cancerProstate cancerProstate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
Phenotypes
Under normal conditions, bone undergoes a continuous remodeling through osteoclastOsteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
-mediated bone resorption
Resorption
Resorption is a process by which a structure is remodeled.Types include:* Bone resorption* Root resorption...
and osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
-mediated bone deposition. These processes are normally tightly regulated within bone to maintain bone structure and calcium homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
in the body. Disregulation of these processes by tumor cells leads to either osteoblastic or osteolytic phenotypes. Regardless of the phenotype, though, bone metastases show osteoclast proliferation and hypertrophy
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...
.
Symptoms
Bone metastases are a major clinical concern that can cause severe pain, bone fractures, spinal cordSpinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
compression, hypercalcemia, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, 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, these periods of breakthrough pain can occur rapidly, without warning, several times a day.
Effects of bone metastasis
- severe pain
- bone fractures
- spinal cordSpinal cordThe spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
compression - hypercalcemia
- anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
- spinal instability
- decreased mobility
Causes of Symptoms
AcidosisAcidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
is the increased acidity in a given location, whether it is blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, or tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s. Osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
s generate extracellular proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
s, lowering the pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) around the osteoclast to approximately 4.5. Nociceptors in the bone trigger a pain response in the brain in response to this acidosis. It is thought that this is the primary source of the dull, chronic pain experienced by patients with bone metastasis.
Bone Restructuring
The uncoupled regulation of the osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
s and osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s leads to malformation of the bone. Malformed bones are unable to withstand the normal mechanical stresses placed on them in day-to-day activity, leading to fractures, spinal compression, and spinal instability. Malformed bones may also mechanically trigger pain receptors both within the bone and in the surrounding tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
Treatment
The traditional treatments for cancer are Radiotherapy and chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, usually in combination with one another. Scientists and pharmaceutical companies are researching drugs to target different types of cancer, including metastatic bone diease.
One treatment that has been considered is bisphosphonate
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
s. Bisphosphonates have shown great promise in reducing bone cancer pain, bone destruction, and tumor growth. However, they have exhibited side effect such as the induction of arthralgias and osteonecrosis of the jaw.
Pain Management
The World Health Organization'sWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
pain ladder
Pain ladder
The pain ladder is a term originally coined by the World Health Organization to describe a method of controlling pain. It was originally described for the management of cancer pain, but is now widely used by medical professionals for the management of all types of pain.The general principle in...
was designed for the management of cancer-associated pain, and mainly involves various strength of opioids.
Other treatments include bisphosphonate
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
s, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, radiotherapy, and radionucleotides.
In palliative therapy, the main options are external radiation and radiopharmaceuticals.
Additional Reading
- Castronovo, A. B. a. V. (1997). "Expression of Bone Matrix Proteins in Human Breast Cancer: Potential Roles in Microcalcifacation Formation and in the Genesis of Bone Metastases." Bull. Cancer 84(1): 17-24.
- Chambers, A. (2001). "The functional and clinical roles of osteopontin in cancer and metastasis. Curr Mol Med. 1(5): 621-32.
- Cheifetz, e. a. S. (2000). "Expression of Bone Sialoprotein and Osteopontin in Breast Cancer Bone Metastasis." Clinical Experimental Metastasis 18(3): 253-60.
- Chung, L. (2007). Prostate Cancer: Biology, Genetics and the New Therapeutics, Humana Press.