Osteosarcoma is a type of bone cancer that most often affects teenagers and young adults, typically developing in the long bones near the knee, hip, or shoulder where bones grow most rapidly during adolescence.

Epidemiology

Osteosarcoma stands as the most common primary malignant bone tumor, accounting for approximately twenty percent of all such cases. Despite being relatively uncommon overall, it represents a significant health challenge for young people, particularly during their growing years.^[1][5]

The disease shows a distinctive pattern in who it affects. Around seventy-five percent of cases occur in people younger than twenty-five years old, with the average age at diagnosis being fifteen years. This concentration in adolescence reflects the disease’s connection to periods of rapid bone growth. In the United States, approximately 440 new cases are diagnosed each year in people nineteen years old and younger, while experts estimate that fewer than 1,000 people total develop osteosarcoma annually across all age groups in the country.^[2][6]

The disease also appears in a second, smaller peak among older adults. This later occurrence often happens in people sixty-five years and older, and these cases frequently develop as a consequence of previous radiation exposure or in connection with Paget’s disease of bone, a condition that affects how bones break down and rebuild.^[5]

Causes

The exact cause of osteosarcoma remains uncertain, though researchers have identified several potential contributing factors. The disease originates from primitive bone-forming cells called osteoblasts, which normally help create new bone tissue. In osteosarcoma, these cells transform and begin producing abnormal, cancerous bone called osteoid.^[6][9]

Rapid bone growth appears to play a significant role in the development of osteosarcoma. The risk increases dramatically during growth spurts, which explains why the disease is most common in teenagers whose bodies are developing quickly. The bones that grow fastest and longest – particularly those in the legs and arms – are precisely where osteosarcoma most often appears.^[2]

Exposure to radiation represents another potential cause. People who have received radiation therapy to treat other types of cancer may later develop osteosarcoma in the area that was treated. Similarly, exposure to radiation in the workplace or environment has been associated with an increased risk of this bone cancer.^[2][3]

Genetic factors contribute to some cases of osteosarcoma. Changes in certain genes that normally help prevent tumors from forming can increase the risk of developing this cancer. The p53 gene, sometimes called a tumor suppressor gene because it helps the body stop tumors from forming, may undergo mutations that lead to osteosarcoma. Similarly, changes in the retinoblastoma gene, which is associated with eye cancers in young children, have been linked to osteosarcoma development.^[2]

A condition called bone infarction may also contribute to osteosarcoma formation. This happens when blood supply to bone tissue is cut off, destroying healthy bone cells and potentially allowing cancerous cells to develop in their place.^[2]

Risk Factors

Teenagers represent the group most likely to develop osteosarcoma. More than three out of every four people diagnosed with this cancer are younger than twenty-five, with the average age of diagnosis falling at fifteen years old. This heightened risk during adolescence directly relates to the rapid bone growth that occurs during puberty and the teenage years.^[2]

Previous medical treatments can increase the risk of developing osteosarcoma. People who have undergone chemotherapy or radiation therapy for other conditions, particularly childhood cancers, face an elevated risk. The strong treatments used to cure one cancer can unfortunately increase the likelihood of developing a different cancer later in life.^[6]

Certain bone conditions also raise the risk of osteosarcoma. Paget’s disease of bone, which affects how bones break down and rebuild, increases susceptibility to this cancer, particularly in older adults. Other conditions that elevate risk include fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses – all conditions that affect normal bone structure and development.^[3]

People with specific genetic mutations face heightened risk. A change in the RB1 gene, particularly the deletion of chromosome 13q14 that inactivates the retinoblastoma gene, is associated with a high risk of osteosarcoma development. These genetic factors often run in families, making family history an important consideration in assessing risk.^[3][6]

Symptoms

The symptoms of osteosarcoma can be deceptive because they often develop gradually and may be mistaken for common problems like sports injuries or growing pains. This similarity to more ordinary conditions sometimes leads to delays in diagnosis, as both patients and healthcare providers may initially attribute the symptoms to less serious causes.^[1]

Pain represents the most common symptom of osteosarcoma. Many people first notice bone or joint pain that may come and go at first, often feeling worse at night. Teenagers who are active in sports frequently complain of pain in the lower thigh bone or immediately below the knee. Because this pain can be intermittent and of varying intensity, it may have been occurring for weeks or even months before a person seeks medical attention.^[2][3]

The intensity of pain varies considerably between individuals. Some osteosarcomas cause intense, debilitating pain, while others may be relatively painless. The level of pain depends largely on where the tumor develops and how quickly it grows. For example, a tumor in the arm bones might make lifting objects painful, while one in the leg bones could cause limping or difficulty walking.^[2][6]

Swelling near a bone is another telltale sign of osteosarcoma. If the tumor is large or located close to the skin surface, it may present as noticeable localized swelling. The area around the tumor may feel warm to the touch. However, when tumors develop in deeper locations, such as the pelvis or other bones that are not close to the skin, this swelling may not be apparent from the outside.^[1][3]

Sometimes a person may feel a mass or lump that can be detected by touch. The affected bone may also show discoloration on the skin above it. Limited movement in a joint near the tumor is common, as the cancerous growth interferes with normal joint function and causes stiffness.^[2][6]

In some cases, an unexpected broken bone serves as the first symptom of osteosarcoma. Because the affected bone is weakened by the cancer and not as strong as normal bone, it may fracture abnormally with minor trauma that would not typically cause a break in healthy bone. These are called pathologic fractures. An unexplained fever can also accompany osteosarcoma, though this is less common than the other symptoms.^[2][3]

Prevention

Unlike some other cancers, there are no established lifestyle changes, vaccinations, or supplements that have been proven to prevent osteosarcoma. The disease does not have clear environmental or behavioral risk factors that people can modify to reduce their chances of developing it. Most cases occur during adolescence when bones are growing rapidly, a natural process that cannot be altered or stopped.^[3]

For people with known genetic conditions that increase the risk of osteosarcoma, genetic counseling and testing may help identify those at highest risk. While this does not prevent the disease, it allows for closer monitoring and potentially earlier detection if cancer does develop. Families with a history of hereditary conditions associated with osteosarcoma should discuss testing options with their healthcare providers.^[6]

Regular medical follow-up is particularly important for individuals who have received radiation therapy for other cancers. While the radiation cannot be undone, awareness of the increased risk allows healthcare providers to monitor these patients more closely for any signs of bone changes or tumor development. Similarly, people with Paget’s disease of bone or other bone conditions that elevate risk should maintain regular contact with their doctors.^[3]

One common concern about fluoride in drinking water has been thoroughly investigated. Extensive research has concluded that there is no clear association between water fluoridation and cancer, including bone cancer and osteosarcoma specifically. The concentration of fluoride in water does not associate with osteosarcoma development, and fears about this connection have been scientifically disproven.^[3]

Pathophysiology

Osteosarcoma develops when primitive bone-forming cells undergo transformation and begin behaving abnormally. Normal bone formation involves mesenchymal stem cells differentiating into osteoblasts, which are responsible for creating new bone tissue. In osteosarcoma, something goes wrong in this process, and these cells instead form malignant tumors.^[5][9]

The hallmark of osteosarcoma is the production of osteoid, which is abnormal, immature bone tissue. At first, the cancer cells appear similar to regular bone cells, but they soon create irregular, diseased bone rather than healthy bone structure. This malignant osteoid is what distinguishes osteosarcoma from other types of bone tumors.^[2][6]

The disease most commonly affects long bones, particularly near the ends of bones around joints. This pattern reflects where bone growth is most active during adolescence. The metaphyseal region of long bones – the area between the shaft and the end of the bone – is the typical site where osteosarcoma develops. The bones most frequently involved are the shin bone (tibia), thigh bone (femur), and upper arm bone (humerus).^[2][13]

Osteosarcomas are classified by grades that indicate how quickly they are likely to grow and spread. Low-grade tumors grow slowly and usually remain where they form. High-grade tumors, which are more common, grow quickly and are more likely to spread to other parts of the body through a process called metastasis. The lungs are the most common site for metastatic spread, occurring in approximately ten to twenty percent of patients at the time of diagnosis.^[2][5]

The tumor arises from connective tissue, making it a type of cancer called a sarcoma. The name osteosarcoma or osteogenic sarcoma reflects this origin – “osteo” refers to bone, “genic” means producing or making, and “sarcoma” indicates a cancer of connective tissues like bone, cartilage, or muscle. The cancer cells maintain the ability to produce bone tissue, but the bone they create is malignant and structurally abnormal.^[2]

Research has identified several molecular and genetic changes that contribute to osteosarcoma development. Alterations in genes responsible for controlling cell growth and division, particularly mutations affecting tumor suppressor genes, play a crucial role. Chromosomal abnormalities, including the presence of small extra chromosomes or large abnormal chromosomes in tumor cells, have been observed and are thought to contribute to cancer development.^[3][9]

The relationship between normal bone biology and osteosarcoma development continues to be an active area of research. Scientists are investigating how the factors that drive normal bone growth during adolescence might also contribute to tumor formation. The same rapid cell division and bone production that characterizes healthy growth spurts may, under certain circumstances or with specific genetic changes, lead to the uncontrolled growth that defines cancer.^[9]