An osteosarcoma (OS) or osteogenic sarcoma (OGS) 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 rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

. Specifically, it is an aggressive

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

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 ever ...

origin (and thus a

sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...

) and that exhibits

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

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. The os ...

. Osteosarcoma is the most common

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

form of primary

bone sarcoma A bone sarcoma is a primary malignant bone tumour, a type of sarcoma that starts in the bones. This is in contrast to most bone cancers that are secondary having developed as a metastasis from another cancer. Bone sarcomas are rare, and mostly ...

. 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 Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...

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 Bone remodeling, cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone ...

fibrous dysplasia Fibrous dysplasia is a very rare nonhereditary genetic 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 fract ...

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 disease, rare disorder in wh ...

, 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 (exostosis, exostoses) in relation to the ends of long bones of t ...

, increase the risk of osteosarcoma. *

Li–Fraumeni syndrome Li–Fraumeni syndrome (LFS) 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 ...

(germline

TP53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

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 initia ...

(i.e. autosomal recessive association of congenital bone defects, hair and skin dysplasias,

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

, 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 28.79 years. It undergoes β− decay into yttrium-90, with a decay energy of 0.546 MeV. Strontium-90 has applications in medicine and ...

, 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 introduced into the body. For example, strontium and radium are chemically similar to calcium and can replace the calcium i ...

, increases the risk of bone cancer and

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce 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 addition of fluoride to Public water supply, public water supplies to reduce tooth decay. Fluoridated water maintains fluoride levels effective for cavity prevention, achieved naturally or through supplem ...

and cancer or deaths due to cancer, both for cancer in general and also specifically for

bone cancer A bone tumor is an neoplastic, abnormal growth of tissue in bone, traditionally classified as benign, noncancerous (benign) or malignant, cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body su ...

and osteosarcoma. Series of research concluded that concentration of fluoride in water does not associate with osteosarcoma. The beliefs regarding association of fluoride exposure and osteosarcoma stem from a study of US National Toxicology program 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 agency of the United States government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it began operation on De ...

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

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 transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

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 describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

end of

tibia The tibia (; : tibiae or tibias), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two Leg bones, bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outsi ...

humerus The humerus (; : humeri) 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 (bone), radius and ulna, and consists of three sections. The humeral upper extrem ...

, or

distal Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...

end of

femur The femur (; : femurs or femora ), or thigh bone is the only long bone, bone in the thigh — the region of the lower limb between the hip and the knee. In many quadrupeds, four-legged animals the femur is the upper bone of the hindleg. The Femo ...

. Osteosarcoma tends to affect regions around the knee in 60% of cases, 15% around the

hip In vertebrate anatomy, the hip, or coxaLatin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) (: ''coxae'') in medical terminology, refers to either an anatomical region or a joint on t ...

, 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 m ...

, and 8% in the

jaw The jaws are a pair of opposable articulated structures 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 ...

. 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, which is characteristic but not diagnostic of osteosarcoma. Surrounding tissues are infiltrated. Osteosarcoma - very high mag

Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumor. Tumor cells are very pleomorphic (

anaplastic Anaplasia () is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells. The term also refers to a group of mor ...

), some are giant, numerous atypical

mitoses Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the ...

. These cells produce osteoid describing irregular

trabeculae A trabecula (: 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 a ...

(amorphous,

eosinophilic Eosinophilic (Greek suffix '' -phil'', meaning ''eosin-loving'') describes the staining of tissues, cells, or organelles after they have been washed with eosin, a dye commonly used in histological staining. Eosin is an acidic dye for stainin ...

/pink) with or without central calcification (

hematoxylin Haematoxylin American and British English spelling differences#ae and oe, or hematoxylin (), also called natural black 1 or Colour Index International, C.I. 75290, is a chemical compound, compound extracted from wood#Heartwood and sapwood, heart ...

ophilic/blue, granular)—tumor bone. Tumor cells are included in the

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

X-rays is the initial imaging of choice to diagnose osteosarcoma. Some characteristics of osteosarcoma on X-rays are sunburst appearance and Codman triangle (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. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

. 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 ma ...

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 non-profit organization dedicated to eliminating cancer. The ACS publishes the journals ''Cancer'', '' CA: A Cancer Journal for Clinicians'' and '' Cancer Cytopathology''. History The society w ...

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 most 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 Pharmaceutical Company, 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 E ...

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 ...

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 (''� ...

and an orthopedic oncologist experienced in managing sarcomas. Current standard treatment is to use

neoadjuvant Neoadjuvant therapy is the administration of 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 size o ...

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

(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. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

(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, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

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 t ...

rescue, intra-arterial

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

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, 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, c ...

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 hemorrhagic cystitis, bleeding from the bladder. It is used either Oral administration, by mouth or ...

, 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 , C=55 , H=84 , N=17 , O=21 , S=3 , SMI ...

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 o ...

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 ...

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 ...

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 (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

counts and

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

counts. Blood transfusions and

epoetin alfa Epoetin alfa, sold under the brand name Epogen among others, is a human erythropoietin produced in cell culture using recombinant DNA technology. Epoetin alfa is an erythropoiesis-stimulating agent. It stimulates erythropoiesis (increasing red ...

help with

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

. 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 tumor, mass in the lung smaller than three centimeters in diameter. A pulmonary micronodule has a diameter of ...

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 (American English) also spelled paediatrics (British English), is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, pediatrics covers many of their youth ...

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 (: metaphyses) 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 epip ...

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

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 Wolfhound The Irish Wolfhound ( Irish: ''Cú Faoil'') is a breed of large sighthound that has, by its presence and substantial size, inspired literature, poetry and mythology. One of the largest of all breeds of dog, the breed is used by coursing hunters ...

Greyhound The English Greyhound, or simply the Greyhound, is a dog breed, breed of dog, a sighthound which has been bred for coursing, greyhound racing and hunting. Some are kept as show dogs or pets. Greyhounds are defined as a tall, muscular, smooth-c ...

German Shepherd The German Shepherd, also known in Britain as an Alsatian, is a German Dog breed, breed of working dog of medium to large size. The breed was developed by Max von Stephanitz using various Old German herding dogs, traditional German herding dog ...

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 is a German breed of medium-large working dog of pinscher type. It was originally bred in Thuringia in about 1890 by Louis Dobermann, a tax collector.

s and

Great Dane The Great Dane is a German list of dog breeds, breed of large mastiff-sighthound, which descends from hunting dogs of the Middle Ages used to hunt bears, wild boar, and deer. They were also used as guardian dogs of German nobility. It is one o ...

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 can cause osteosarcoma of the

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

Clinical presentation

The most commonly affected bones are the proximal

, the distal

radius In classical geometry, a radius (: radii or radiuses) of a circle or sphere is any of the line segments from its Centre (geometry), center to its perimeter, and in more modern usage, it is also their length. The radius of a regular polygon is th ...

, the distal

, and the

, following the basic premise "far from the elbow, close to the knee". Other sites include the ribs, the

mandible In jawed vertebrates, the mandible (from the Latin ''mandibula'', 'for chewing'), lower jaw, or jawbone is a bone that makes up the lowerand typically more mobilecomponent of the mouth (the upper jaw being known as the maxilla). The jawbone i ...

, the spine, and the pelvis. Rarely, osteosarcoma may arise from soft tissues (extraskeletal osteosarcoma).

Metastasis Metastasis is a pathogenic agent's spreading 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, ...

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, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

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 the infectious inflammation of bone marrow. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The feet, spine, and hips are the most commonly involved bones in adults. The cause is ...

. 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 sarco ...

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 tumo ...

Treatment and prognosis

Amputation is the initial treatment, although this alone will not prevent metastasis.

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

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 bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

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 ...

Molecular alterations

Canine osteosarcoma shows similar patterns of molecular somatic alterations to the human disease. Both are characterized by genetic instability and karyotypic complexity and genes that are recurrently altered include ''TP53, RB1, PTEN, MYC, PIK3CA'.'' In contrast, mutations in the histone methyltransferase gene ''SETD2'' are rare in human osteosarcoma, but have been identified in 21% of canine tumors.

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: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

Dinosaurs

An 2020 study, published in ''The Lancet Oncology'', reports the first confirmed case of osteosarcoma in a dinosaur, a ''Centrosaurus apertus'' from the Late

Cretaceous The Cretaceous ( ) is a geological period that lasted from about 143.1 to 66 mya (unit), million years ago (Mya). It is the third and final period of the Mesozoic Era (geology), Era, as well as the longest. At around 77.1 million years, it is the ...

, about 77 to 75.5 million years ago.Seper Ekhtiari et al. "First Case of Osteosarcoma in a Dinosaur: A Multimodal Diagnosis" ''The Lancet Oncology, 21''. The bone showed typical characteristics of cancer, including areas of cortical destruction, neoplastic bone formations, and disordered organization inconsistent with a simple fracture or infection. The structural and histological similarities with a high-grade human osteosarcoma case strengthened the diagnosis. This study establishes that bone cancers, such as osteosarcoma, have deep roots in the evolutionary history of vertebrates.

References

External links

National Cancer Institute—patient information on osteosarcoma

Osteosarcoma – An Introduction

{{Authority control Cancer in cats Cancer in dogs Causes of amputation Osseous and chondromatous neoplasia Pediatric cancers Sarcoma