What Causes Osteosarcoma?

In general, cancer begins when a genetic mutation (change in certain genes) turns normal, healthy cells into abnormal cells. Healthy cells grow and multiply at a set rate and eventually die at a set time. Abnormal cells grow and multiply out of control, and they do not die. The abnormal cells clump together to create a mass (tumor). Cancer cells invade nearby tissues and can separate from an initial tumor to spread to other parts of the body (metastasize).

Scientists have identified the genetic mutations that cause some inherited forms of osteosarcoma. Specifically, people with the Li-Fraumeni syndrome have a high risk of developing certain kinds of cancer, including osteosarcoma. This disease is caused by inherited mutations that turn off the p53 tumor suppressor gene that normally controls the growth of cells. People with inherited defects in the retinoblastoma (Rb) tumor suppressor gene also have a higher risk of developing retinoblastoma, an eye cancer, and osteosarcoma. When the Rb gene is mutated, or changed, it can no longer control cell growth and tumors form as a result.

Most osteosarcomas are not caused by inherited genetic mutations. Rather, they are a result of mutations acquired during a person's lifetime. People with these mutations do not pass them on to their children.

Radiation treatment is one of the known causes of genetic mutations that can trigger osteosarcoma. For this reason, bones exposed to radiation to treat another cancer are more likely to develop osteosarcoma in the bone that was treated.

Risk Factors for Osteosarcoma

Doctors and researchers believe that certain factors, known as risk factors, increase a person’s chances of getting osteosarcoma. However, not everyone with a risk factor will develop osteosarcoma and people without any risk factors can develop the disease.

Risk factors for osteosarcoma include:

• Age - The risk of osteosarcoma is highest during the teenage “growth spurt.”
• Benign tumors and other bone conditions - Children and teens who have certain noncancerous bone diseases have a higher chance of developing osteosarcoma, usually when they become adults. These diseases include:
  
  • Paget’s disease - A condition that causes heavy and thick bones that are very weak and tend to break. This condition is more common in people over age 50. About 5 percent to 10 percent of people with Paget’s disease develop osteosarcoma.
  • Osteochondroma - A benign bone tumor formed by bone and cartilage that can develop into osteosarcoma, although this is rare.
  • Rothmund-Thomson syndrome - People with this rare disease are usually short, lose their hair, have rashes, and have noncancerous abnormalities in their bones. They also have an increased risk of osteosarcoma.
• Inherited diseases - Children who have certain rare inherited diseases are more likely to develop osteosarcoma:
  
  • Li-Fraumeni syndrome - A condition in which people have an increased chance of several types of cancer, including osteosarcoma.
  • Retinoblastoma - Children with the inherited form of this rare eye cancer are more likely to develop osteosarcoma. If these children are treated with radiation therapy, they have a higher risk of osteosarcoma in the skull bones.
  • Werner’s syndrome - This rare disease causes symptoms of premature aging and is associated with an increased risk of osteosarcoma.
• Lifestyle factors - Some scientists believe that certain lifestyle factors, such as high-fat diets, lack of exercise, smoking, and drinking alcohol, can increase an adult’s risk of osteosarcoma.
• Radiation treatment - People who have been treated with radiation to the bone are at higher risk of osteosarcoma in the same area. Being treated at a younger age or with a higher dose increases the risk of the disease.