Causes, Risk Factors, and Prevention of Osteosarcoma

Osteosarcoma is a cancer that most commonly occurs in adolescents, teenagers, and young adults. While there are a few known genetic factors that increase the risk of osteosarcoma, the exact cause of most cases is not known.

What causes osteosarcoma?

Scientists have found some risk factors, but most children with osteosarcoma do not have any known risk factors. A risk factor is anything that affects a person’s chance of getting a disease, such as cancer.

How normal cells become osteosarcoma cells

DNA is the chemical in our cells that makes up our genes, which control how our cells function. Changes (mutations) in the DNA inside our cells can sometimes alter the way some genes work, which can cause cells to grow out of control and become cancer.

Some genes control when our cells grow, divide into new cells, and die:

• Genes that help cells grow, divide, or stay alive can sometimes lose the ability to turn off and become oncogenes.
• Genes that tell cells to stop dividing or cause cells to die at the right time are called tumor suppressor genes.
• DNA repair genes find and fix damage to the DNA that might happen during cell growth or from the environment.

Acquired versus inherited gene changes in osteosarcoma

Cancers can be caused by DNA changes that create oncogenes, turn off tumor suppressor genes, or damage DNA repair genes. These gene changes can happen before birth randomly or be inherited from a parent (most germline events in osteosarcoma occur randomly and are not present in the parents). However, most gene changes that cause osteosarcoma happen by chance during a person’s lifetime. These acquired or de novo gene changes result from environmental exposures, like radiation, but most occur by chance.

Known risk factors for osteosarcoma typically fall into two categories: genetic or environmental. Researchers continue to search for answers about why bone cancers occur.

Genetic risk factors

Some children have gene changes in cells throughout the body. These can be inherited from a parent or randomly occur early in development (always before the child is born), increasing their risk of cancer. Some osteosarcomas are caused by these gene changes.

Genetic syndromes

Some genetic disorders increase a person’s risk of developing osteosarcoma:

Research into other gene changes that may put some children or families at higher risk of having cancers like osteosarcoma is ongoing.

While specific inherited gene changes can cause some osteosarcomas, scientists have also found that conditions where the bones grow or remodel often can also increase the risk of osteosarcoma. These conditions include:

• Paget disease of the bone: Causes quick turnover of the bones, leading to weak and enlarged bones.
• McCune-Albright syndrome: Characterized by a triad of fibrous dysplasia of the bone, early puberty, and skin changes called café-au-lait spots.

Studies have even found that people of above-average height have a higher risk of developing osteosarcoma. This suggests that factors affecting growth and bone turnover may play a role in bone cancer risk.

If you are concerned that you or your child might possibly have an inherited gene change, talk with your doctor about whether genetic testing might be helpful. You can also read more in Genetics and Cancer.

Environmental risk factors

Most osteosarcomas are not caused by inherited gene mutations but instead result from gene changes acquired during a person’s lifetime.

Radiation exposure

People who were treated with radiation therapy for another cancer appear to have a higher risk of developing osteosarcoma in the treated area later. Being treated at a younger age and with higher doses of radiation both increase this risk.

It is not clear if imaging tests that use radiation, such as x-rays, CT scans, and nuclear medicine scans (e.g., PET scans or bone scans), raise the risk of developing osteosarcoma. The amount of radiation used for these tests is much lower than that used for radiation treatments. If there is any increased risk, it is likely very small. Still, doctors try to limit the use of these types of tests whenever possible, especially in children, just in case.

Can osteosarcoma be prevented?

Most known risk factors for osteosarcoma cannot be changed. While the risk for many adult cancers can be reduced with lifestyle changes, these factors do not play a major role in childhood cancers.

Other than exposure to radiation (usually during radiation therapy), there are no known lifestyle-related or environmental causes of osteosarcoma. There is no known way to protect against or prevent most of these cancers.