The exact cause of bone cancer has not been identified. Recently researchers have gained a greater understanding of how specific changes in DNA can cause bone cells to become cancerous.

Some forms of cancer are caused by DNA mutations that activate oncogenes (genes that speed up cell division) or deactivate tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). With bone cancer, these genetic mutations usually develop during a person’s life. They may be due to factors such as exposure to radiation but often occur for no apparent reason.

Few inherited genetic mutations (which are present in the cells at birth) have been linked to bone cancer. However, new research has discovered a gene called MET that may play a role in the development of osteosarcoma. MET is normally found in all cells at birth and is responsible for producing a substance that helps cells grow. When MET becomes overactive, it causes too much cell growth and can lead to bone cancer, as well as other cancers. Scientists found that more than 80 percent of cases of osteosarcoma have an overactivity of the MET gene.

Researchers have identified a number of factors that may make a person more likely to develop bone cancer. These risk factors include:

• Inherited genes. Certain types of bone cancers appear to be hereditary, particularly osteosarcoma. Children with a few rare inherited cancer syndromes have an increased risk of developing bone cancer. These syndromes include:
  
  
• • Li-Fraumeni syndrome. This inherited disorder runs in families and is characterized by children developing several types of cancer, including osteosarcoma and soft-tissue sarcoma. Most cases are triggered by a mutation of a specific type of tumor suppressor gene.
    
    
  • Rothmund-Thompson syndrome. Patients with this disorder are short and have skeletal problems and skin rashes. They are also at an increased risk of developing osteosarcoma.
    
    
  A rare eye cancer of children, retinoblastoma, has been linked to bone cancer. The disease is caused by inherited genes in 6 to 10 percent of cases. This genetic predisposition also increases the patient’s risk of developing osteosarcoma. In addition, children who have received radiation therapy for their retinoblastoma have an increased risk of developing osteosarcoma in the bones of the skull.
  
  

  

  There are also families where several members have developed osteosarcoma without the presence of any identifiable gene defects. The inherited gene mutation that may be causing the cancers in these families has not yet been uncovered.
  
  
• Paget’s disease. This bone disease involves excessive breakdown of bone tissue, followed by abnormal bone formation. It is a precancerous condition that involves one or more bones. Bone cancer, usually osteosarcoma, develops in 5 to 10 percent of people with severe cases of Paget’s disease. This typically occurs when many bones are affected. 
  
  
• Multiple exostoses. Exostoses are local overgrowths of bone tissue. A person with multiple exostoses has an increased risk of developing osteosarcoma.
  
  
• Multiple osteochondromas. An osteochondroma is a benign tumor containing bone and cartilage. Every osteochondroma has a minor risk of developing into osteosarcoma. However, most osteochondromas are cured by surgery. People with multiple osteochondromas have an increased risk of developing osteosarcoma because it may not be possible to surgically remove all of their osteochondromas.
  
  
• Multiple enchondromas. Enchondromas are tumors consisting of cartilaginous tissue. Although the likelihood is quite low, people with multiple enchondromas are at an increased risk for developing chondrosarcoma.
  
  
• Exposure to radiation. Bone exposure to large doses of radiation may increase a person’s risk of developing bone cancer. Receiving radiation therapy to treat another form of cancer increases a person’s risk, as does being treated at a young age. Being treated with higher doses of radiation can also increase the risk. Exposure to radium, radioactive strontium and other radioactive materials may also cause bone cancer because these minerals build up in bones.
  
  
• Bone marrow transplant. Osteosarcoma has been reported in a small number of patients who received bone marrow transplantation.

Although bone cancer is associated with these risk factors, most patients with the disease have no known risk factors.