An osteosarcoma (OS) or osteogenic sarcoma (OGS) (or simply
bone cancer
A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyro ...
) is a cancerous
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
in a
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
. Specifically, it is an aggressive
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
that arises from primitive transformed cells of
mesenchymal
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...
origin (and thus a
sarcoma
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
) and that exhibits
osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
ic differentiation and produces malignant
osteoid
In histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins. When t ...
.
Osteosarcoma is the most common
histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
form of primary
bone sarcoma
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
.
It is most prevalent in teenagers and young adults.
Signs and symptoms
Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for a long time. Teenagers who are active in sports often complain of pain in the lower femur, or immediately below the knee. If the tumor is large, it can present as overt localised swelling. Sometimes a sudden fracture is the first symptom because the affected bone is not as strong as normal bone and may
fracture abnormally with minor trauma. In cases of more deep-seated tumors that are not as close to the skin, such as those originating in the pelvis, localised swelling may not be apparent.
Causes
Several research groups are investigating cancer stem cells and their potential to cause tumors along with genes and proteins causative in different phenotypes.
Radiotherapy for unrelated conditions may be a rare cause.
* A
small supernumerary marker chromosome
A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each d ...
or a giant rod chromosome is present in the tumor cells of low grade OS including low grade central OS and paraosteal OS (see below Variants section),
carry various potentially pro-cancerous genes, and are thought to contribute to the development of these OS.
(See
Small supernumerary marker chromosomes and giant rod chromosomes in osteosarcomas)
* Familial cases where the deletion of chromosome
13q14 inactivates the
retinoblastoma gene
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...
is associated with a high risk of osteosarcoma development.
* Bone dysplasias, including
Paget's disease of bone
Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the ...
,
fibrous dysplasia
Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairme ...
,
enchondromatosis
Enchondromatosis is a form of osteochondrodysplasia characterized by a proliferation of enchondromas.
Ollier disease can be considered a synonym for enchondromatosis. Maffucci syndrome
Maffucci syndrome is a very rare disorder in which multiple b ...
, and
hereditary multiple exostoses
Hereditary multiple osteochondromas (HMO), also known as hereditary multiple exostoses, is a disorder characterized by the development of multiple benign osteocartilaginous masses ( exostoses) in relation to the ends of long bones of the lower li ...
, increase the risk of osteosarcoma.
*
Li–Fraumeni syndrome
Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni, Jr., who first recognized the syndrom ...
(germline
TP53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
mutation) is a predisposing factor for osteosarcoma development.
*
Rothmund–Thomson syndrome
Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive skin condition.
There have been several reported cases associated with osteosarcoma. A hereditary basis, mutations in the DNA helicase ''RECQL4'' gene, causing problems during initi ...
(i.e. autosomal recessive association of congenital bone defects, hair and skin dysplasias,
hypogonadism
Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...
, and cataracts) is associated with increased risk of this disease.
* Large doses of
Sr-90
Strontium-90 () is a radioactive isotope of strontium produced by nuclear fission, with a half-life of 28.8 years. It undergoes β− decay into yttrium-90, with a decay energy of 0.546 MeV. Strontium-90 has applications in medicine and i ...
, nicknamed
bone seeker A bone seeker is an element, often a radioisotope, that tends to accumulate in the bones of humans and other animals when it is introduced into the body. An example is strontium-90, which behaves chemically like calcium and can replace the calcium ...
, increases the risk of bone cancer and
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
in animals and is presumed to do so in people.
There is no clear association between
water fluoridation
Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding ...
and
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
or deaths due to cancer, both for cancer in general and also specifically for
bone cancer
A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyro ...
and osteosarcoma. Series of research concluded that concentration of fluoride in water doesn't associate with osteosarcoma. The beliefs regarding association of fluoride exposure and osteosarcoma stem from a study of
US National Toxicology program
The National Toxicology Program (NTP) is an inter-agency program run by the United States Department of Health and Human Services to coordinate, evaluate, and report on toxicology within public agencies.
The National Toxicology Program is headqua ...
in 1990, which showed uncertain evidence of association of fluoride and osteosarcoma in male rats. But there is still no solid evidence of cancer-causing tendency of fluoride in mice. Fluoridation of water has been practiced around the world to improve citizens' dental health. It is also deemed as major health success. Fluoride concentration levels in water supplies are regulated, such as
United States Environmental Protection Agency
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...
regulates fluoride levels to not be greater than 4 milligrams per liter. Actually, water supplies already have natural occurring fluoride, but many communities chose to add more fluoride to the point that it can reduce tooth decay. Fluoride is also known for its ability to cause new bone formation. Yet, further research shows no osteosarcoma risks from fluoridated water in humans. Most of the research involved counting number of osteosarcoma patients cases in particular areas which has difference concentrations of fluoride in drinking water. The statistic analysis of the data shows no significant difference in occurrences of osteosarcoma cases in different fluoridated regions. Another important research involved collecting bone samples from osteosarcoma patients to measure fluoride concentration and compare them to bone samples of newly diagnosed malignant bone tumors. The result is that the median fluoride concentrations in bone samples of osteosarcoma patients and tumor controls are not significantly different. Not only fluoride concentration in bones, Fluoride exposures of osteosarcoma patients are also proven to be not significantly different from healthy people.
Mechanism
![Predilection sites of osteosarcoma2](https://upload.wikimedia.org/wikipedia/commons/4/40/Predilection_sites_of_osteosarcoma2.png)
Osteosarcomas tend to occur at the sites of bone growth, presumably because proliferation makes osteoblastic cells in this region prone to acquire mutations that could lead to transformation of cells (the
RB gene and
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
gene are commonly involved). The tumor may be localized at the end of the long bone (commonly in the metaphysis). Most often it affects the
proximal
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
end of
tibia
The tibia (; ), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outside of the tibia); it connects ...
or
humerus
The humerus (; ) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius and ulna, and consists of three sections. The humeral upper extremity consists of a roun ...
, or
distal
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
end of
femur
The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with ...
. Osteosarcoma tends to affect regions around the
knee
In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the hu ...
in 60% of cases, 15% around the
hip
In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint.
The hip region is ...
, 10% at the
shoulder
The human shoulder is made up of three bones: the clavicle (collarbone), the scapula (shoulder blade), and the humerus (upper arm bone) as well as associated muscles, ligaments and tendons. The articulations between the bones of the shoulder mak ...
, and 8% in the
jaw
The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term ''jaws'' is also broadly applied to the whole of the structures constituting the vault of the mouth and serv ...
. The tumor is solid, hard, irregular ("fir-tree," "moth-eaten", or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating at right angles. These right angles form what is known as a
Codman triangle
The Codman triangle (previously referred to as Codman's triangle) is the triangular area of new subperiosteal bone that is created when a lesion, often a tumour, raises the periosteum away from the bone. A Codman triangle is not actually a full t ...
, which is characteristic but not diagnostic of osteosarcoma. Surrounding tissues are infiltrated.
![Osteosarcoma - very high mag](https://upload.wikimedia.org/wikipedia/commons/a/ab/Osteosarcoma_-_very_high_mag.jpg)
Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumor. Tumor cells are very
pleomorphic (
anaplastic
Anaplasia (from grc, ἀνά ''ana'', "backward" + πλάσις ''plasis'', "formation") is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to ...
), some are giant, numerous atypical
mitoses
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
. These cells produce osteoid describing irregular
trabeculae
A trabecula (plural trabeculae, from Latin for "small beam") is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has ...
(amorphous,
eosinophilic
Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye.
Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''Eosi ...
/pink) with or without central calcification (
hematoxylin
Haematoxylin or hematoxylin (), also called natural black 1 or C.I. 75290, is a compound extracted from heartwood of the logwood tree (''Haematoxylum campechianum'') with a chemical formula of . This naturally derived dye has been used as a h ...
ophilic/blue, granular)—tumor bone. Tumor cells are included in the
osteoid
In histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins. When t ...
matrix. Depending on the features of the tumor cells present (whether they resemble bone cells, cartilage cells, or fibroblast cells), the tumor can be subclassified. Osteosarcomas may exhibit multinucleated osteoclast-like giant cells.
Diagnosis
![Histopathology of osteosarcoma, high mag](https://upload.wikimedia.org/wikipedia/commons/b/b8/Histopathology_of_osteosarcoma%2C_high_mag.jpg)
X-rays is the initial imaging of choice to diagnose osteosarcoma. Some characteristics of osteosarcoma on X-rays are sunburst appearance and
Codman triangle
The Codman triangle (previously referred to as Codman's triangle) is the triangular area of new subperiosteal bone that is created when a lesion, often a tumour, raises the periosteum away from the bone. A Codman triangle is not actually a full t ...
(elevation of bony cortex by the tumour that caused new bone formation). CT scan is helpful in defining the bony anatomy, the integrity of the bony cortex, detecting
pathologic fracture
A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologies ...
, and assessing
ossification
Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in t ...
(laying of new bone materials) and calcification of the
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
. On the other hand, soft tissue and
medullary cavity
The medullary cavity (''medulla'', innermost part) is the central cavity of bone shafts where red bone marrow and/or yellow bone marrow (adipose tissue) is stored; hence, the medullary cavity is also known as the marrow cavity.
Located in the m ...
is better imaged by MRI scan.
Most times, the early signs of osteosarcoma are caught on X-rays taken during routine dental check-ups. Osteosarcoma frequently develops in the mandible (lower jaw); accordingly, dentists are trained to look for signs that may suggest osteosarcoma. Even though radiographic findings for this cancer vary greatly, one usually sees a symmetrical widening of the periodontal ligament space. A dentist who has reason to suspect osteosarcoma or another underlying disorder would then refer the patient to an Oral & Maxillofacial surgeon for biopsy. A biopsy of suspected osteosarcoma outside of the facial region should be performed by a qualified
orthopedic oncologist. The
American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
states: "Probably in no other cancer is it as important to perform this procedure properly. An improperly performed biopsy may make it difficult to save the affected limb from amputation." It may also metastasise to the lungs, mainly appearing on the chest X-ray as solitary or multiple round nodules most common at the lower regions.
Variants
* Conventional: osteoblastic, chondroblastic, fibroblastic OS
* Telangiectatic OS
* Small cell OS
* Low-grade central OS
* Periosteal OS
* Paraosteal OS
* Secondary OS
* High-grade surface OS
* Extraskeletal OS
Treatment
A complete radical, surgical, ''en bloc'' resection of the cancer, is the treatment of choice in osteosarcoma.
Although about 90% of patients are able to have
limb-salvage surgery, complications, particularly infection, prosthetic loosening and non-union, or local tumor recurrence may cause the need for further surgery or amputation.
Mifamurtide
Mifamurtide (trade name Mepact, marketed by Takeda) is a drug against osteosarcoma, a kind of bone cancer mainly affecting children and young adults, which is lethal in over half of cases. The drug was approved in Europe in March 2009.
Medical u ...
is used after a patient has had surgery to remove the tumor and together with chemotherapy to kill remaining cancer cells to reduce the risk of cancer recurrence. Also, the option to have
rotationplasty
Rotationplasty, commonly known as a Van Nes rotation or Borggreve rotation, is a type of autograft wherein a portion of a limb is removed, while the remaining limb below the involved portion is rotated and reattached. This procedure is used when a ...
after the tumor is taken out exists.
Patients with osteosarcoma are best managed by a medical
oncologist
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
and an
orthopedic oncologist experienced in managing sarcomas. Current standard treatment is to use
neoadjuvant
Neoadjuvant therapy is the administration of therapy, therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the ...
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
(chemotherapy given before surgery) followed by surgical resection. The percentage of tumor cell
necrosis
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
(cell death) seen in the tumor after surgery gives an idea of the prognosis and also lets the oncologist know if the chemotherapy regimen should be altered after surgery.
Standard therapy is a combination of limb-salvage orthopedic surgery when possible (or amputation in some cases) and a combination of high-dose
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
with
leucovorin
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
rescue, intra-arterial
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
,
adriamycin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toget ...
,
ifosfamide
Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cer ...
with
mesna
Mesna, sold under the brand name Mesnex among others, is a medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder. It is used either by mouth or injection into a vein.
Common side effec ...
, BCD (
bleomycin
-13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium
, chemical_formula =
, C=55 , H=84 , N=1 ...
,
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
,
dactinomycin
Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovari ...
),
etoposide
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
, and muramyl tripeptide.
Rotationplasty
Rotationplasty, commonly known as a Van Nes rotation or Borggreve rotation, is a type of autograft wherein a portion of a limb is removed, while the remaining limb below the involved portion is rotated and reattached. This procedure is used when a ...
may be used. Ifosfamide can be used as an adjuvant treatment if the necrosis rate is low.
Despite the success of chemotherapy for osteosarcoma, it has one of the lowest survival rates for pediatric cancer. The best reported 10-year survival rate is 92%; the protocol used is an aggressive intra-arterial regimen that individualizes therapy based on arteriographic response. Three-year event-free survival ranges from 50% to 75%, and five-year survival ranges from 60% to 85+% in some studies. Overall, 65–70% patients treated five years ago will be alive today.
These survival rates are overall averages and vary greatly depending on the individual necrosis rate.
Filgrastim
Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may ...
or
pegfilgrastim
Pegfilgrastim, sold under the brand name Neulasta among others, is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analog filgrastim. It serves to stimulate the production of white blood cells ( neutrophils ...
help with
white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
counts and
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
counts. Blood transfusions and
epoetin alfa
Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis (increasing red blood cell levels) and is used to treat ...
help with
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
. Computational analysis on a panel of osteosarcoma cell lines identified new shared and specific therapeutic targets (proteomic and genetic) in osteosarcoma, while phenotypes showed an increased role of tumor microenvironments.
Prognosis
Prognosis is separated into three groups.
* Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.
* Stage II prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.), size of the tumor mass, and the degree of necrosis from neoadjuvant chemotherapy. Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive, or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases (more than 12 months to 4 months), a smaller number of metastases, and their resectability. It is better to have fewer metastases than longer time to metastases. Those with a longer length of time (more than 24 months) and few nodules (two or fewer) have the best prognosis, with a two-year survival after the metastases of 50%, five-year of 40%, and 10-year of 20%. If metastases are both local and regional, the prognosis is worse.
* Initial presentation of stage III osteosarcoma with lung metastases depends on the resectability of the primary tumor and
lung nodule
A lung nodule or pulmonary nodule is a relatively small focal density in the lung. A solitary pulmonary nodule (SPN) or coin lesion, is a mass in the lung smaller than three centimeters in diameter. A pulmonary micronodule has a diameter of less th ...
s, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall survival prognosis is about 30%.
Deaths due to malignant neoplasms of the bones and joints account for an unknown number of childhood cancer deaths. Mortality rates due to osteosarcoma have been declining at about 1.3% per year. Long-term survival probabilities for osteosarcoma have improved dramatically during the late 20th century and approximated 68% in 2009.
Epidemiology
Osteosarcoma is the eighth-most common form of childhood cancer, comprising 2.4% of all malignancies in
pediatric
Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until the ...
patients, and about 20% of all primary bone cancers.
Incidence rates for osteosarcoma in U.S. patients under 20 years of age are estimated at 5.0 per million per year in the general population, with a slight variation between individuals of black, Hispanic, and white ethnicities (6.8, 6.5, and 4.6 per million per year, respectively). It is slightly more common in males (5.4 per million per year) than in females (4.0 per million per year).
It originates more frequently in the
metaphyseal
The metaphysis is the neck portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, and as it grows it ossifies near the diaphysis and the epiphyses. The metaph ...
region of tubular long bones, with 42% occurring in the femur, 19% in the tibia, and 10% in the humerus. About 8% of all cases occur in the skull and jaw, and another 8% in the pelvis.
Around 300 of the 900 people diagnosed in the United States will die each year. A second peak in incidence occurs in the elderly, usually associated with an underlying bone pathology such as
Paget's disease of bone
Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the ...
.
Other animals
Risk factors
Osteosarcoma is the most common bone tumor in dogs and typically affects middle-aged large and giant breed dogs such as
Irish Wolfhounds,
Greyhound
The English Greyhound, or simply the Greyhound, is a breed of dog, a sighthound which has been bred for coursing, greyhound racing and hunting. Since the rise in large-scale adoption of retired racing Greyhounds, the breed has seen a resurge ...
s,
German Shepherd
The German Shepherd or Alsatian is a German breed of working dog of medium to large size. The breed was developed by Max von Stephanitz using various traditional German herding dogs from 1899.
It was originally bred as a herding dog, for he ...
s,
Rottweiler
The Rottweiler (, ) is a breed of domestic dog, regarded as medium-to-large or large. The dogs were known in German as , meaning Rottweil butchers' dogs, because their main use was to herd livestock and pull carts laden with butchered mea ...
s, mountain breeds (Great Pyrenees, St. Bernard, Leonberger, Newfoundland),
Doberman Pinscher
The Dobermann (; ), or Doberman Pinscher in the United States and Canada, is a medium-large breed of domestic dog that was originally developed around 1890 by Louis Dobermann, a tax collector from Germany.[Great Dane
The Great Dane is a large sized dog breed originating from Germany. The Great Dane descends from hunting dogs from the Middle Ages used to hunt wild boar and deer, and as guardians of German nobility. It is one of the largest breeds in the world ...]
s. It has a 10-fold greater
incidence in dogs than humans.
A
hereditary
Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic inform ...
base has been shown in St. Bernard dogs.
Spayed/neutered dogs have twice the risk of intact ones to develop osteosarcoma.
Infestation with the parasite
Spirocerca lupi Epidemiology
''S. lupi'' is endemic (occurs naturally) from southern Africa all the way up to Israel, Turkey, Greece and India; faecal evidence also exists for it in the southern USA. Although early reports of the disease were American 1-3, few ...
can cause osteosarcoma of the
esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
.
Clinical presentation
The most commonly affected bones are the proximal
humerus
The humerus (; ) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius and ulna, and consists of three sections. The humeral upper extremity consists of a roun ...
, the distal
radius
In classical geometry, a radius ( : radii) of a circle or sphere is any of the line segments from its center to its perimeter, and in more modern usage, it is also their length. The name comes from the latin ''radius'', meaning ray but also the ...
, the distal
femur
The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with ...
, and the
tibia
The tibia (; ), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outside of the tibia); it connects ...
,
following the basic premise "far from the elbow, close to the knee". Other sites include the ribs, the
mandible
In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower tooth, teeth in place. The mandible sits beneath the maxilla. It is the only movabl ...
, the spine, and the pelvis. Rarely, osteosarcoma may arise from soft tissues (extraskeletal osteosarcoma).
Metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
of tumors involving the limb bones is very common, usually to the lungs. The tumor causes a great deal of pain, and can even lead to fracture of the affected bone. As with human osteosarcoma, bone
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
is the definitive method to reach a final diagnosis. Osteosarcoma should be differentiated from other
bone tumours and a range of other lesions, such as
osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
. Differential diagnosis of the osteosarcoma of the skull in particular includes, among others,
chondrosarcoma
Chondrosarcoma is a bone sarcoma, a primary cancer composed of cells derived from transformed cells that produce cartilage. A chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of bone sarcomas ...
and the
multilobular tumour of bone
The multilobular tumour of bone (MTB), also called an osteochondrosarcoma, is the most common tumour of the canine skull, although it is relatively rare in general.
MTB usually presents as a firm, circumscribed and generally slowgrowing bone tum ...
.
Treatment and prognosis
Amputation is the initial treatment, although this alone will not prevent metastasis.
Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
combined with amputation improves the survival time, but most dogs still die within a year.
[ Surgical techniques designed to save the leg (limb-sparing procedures) do not improve the prognosis.
Some current studies indicate ]osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
inhibitors such as alendronate and pamidronate may have beneficial effects on the quality of life by reducing osteolysis, thus reducing the degree of pain, as well as the risk of pathological fracture
A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologies ...
s.
Cats
Osteosarcoma is also the most common bone tumor in cats, although not as frequently encountered, and most typically affect the rear legs. The cancer is generally less aggressive in cats than in dogs, so amputation alone can lead to a significant survival time in many affected cats, though post-amputation chemotherapy is recommended when a high grade is confirmed on histopathology
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
.[
]
Dinosaurs
A 2020 study was able to demonstrate via radiographic and histological analysis along with comparisons with osteosarcoma in humans that a ''Centrosaurus'' from the Cretaceous
The Cretaceous ( ) is a geological period that lasted from about 145 to 66 million years ago (Mya). It is the third and final period of the Mesozoic Era, as well as the longest. At around 79 million years, it is the longest geological period of th ...
period had developed osteosarcoma in its fibula.[Seper Ekhtiari et al. "First Case of Osteosarcoma in a Dinosaur: A Multimodal Diagnosis" ''The Lancet Oncology, 21''.]
References
Further reading
* Osteosarcoma research: past, present and future.
External links
National Cancer Institute—patient information on osteosarcoma
Osteosarcoma – An Introduction
{{Authority control
Cancer in cats
Cancer in dogs
Osseous and chondromatous neoplasia
Pediatric cancers
Sarcoma