Although primary bone cancer does not have a clearly defined cause, researchers have identified several factors that increase the likelihood of developing these tumors.
Previous cancer treatment with radiation, chemotherapy, or stem cell transplantation. Osteosarcoma occurs more frequently in people who have had high-dose external radiation therapy (particularly at the location in the body where the radiation was given) or treatment with certain anticancer drugs, particularly alkylating agents; those treated during childhood are at particular risk. In addition, osteosarcoma develops in a small percentage (approximately 5%) of children undergoing myeloablative hematopoietic stem cell transplantation.
Certain inherited conditions. A small number of bone cancers are due to hereditary conditions (3). For example, children who have had hereditary retinoblastoma (an uncommon cancer of the eye) are at a higher risk of developing osteosarcoma, particularly if they are treated with radiation. Members of families with Li-Fraumeni syndrome are at increased risk of osteosarcoma and chondrosarcoma as well as other types of cancer. Additionally, people who have hereditary defects of bones have an increased lifetime risk of developing chondrosarcoma. Childhood chordoma is linked to tuberous sclerosis complex, a genetic disorder in which benign tumors form in the kidneys, brain, eyes, heart, lungs, and skin. Although Ewing sarcoma is not strongly associated with any heredity cancer syndromes or congenital childhood diseases (7, 8), accumulating evidence suggests a strong inherited genetic component to Ewing sarcoma risk (9).
Certain benign bone conditions. People over age 40 who have Paget disease of bone (a benign condition characterized by abnormal development of new bone cells) are at increased risk of developing osteosarcoma.