Osteosarcoma Background, Pathophysiology, Etiology, Symptoms, And Treatment

Osteosarcoma Background, Pathophysiology, Etiology, Symptoms, And Treatment

 osteosarcomaOsteosarcoma is the most common malignant bone tumor.  It is an ancient disease that is still incompletely understood. Osteosarcoma is thought to arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid. Other cell populations may also be present, as these types of cells may also arise from pluripotential mesenchymal cells, but any area of malignant bone in the lesion establishes the diagnosis as osteosarcoma.

Osteosarcoma is a deadly form of musculoskeletal cancer that most commonly causes patients to die of pulmonary metastatic disease. Most osteosarcomas arise as solitary lesions within the fastest growing areas of the long bones of children. The top three affected areas are the distal femur, the proximal tibia, and the proximal humerus, but virtually any bone can be affected.


Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones near metaphyseal growth plates. The most common sites are as follows:
  1. Femur (42%, 75% of which are in the distal femur)
  2. Tibia (19%, 80% of which are in the proximal tibia)
  3. Humerus (10%, 90% of which are in the proximal humerus)
  4. Skull and jaw (8%)
  5. Pelvis (8%)


The exact cause of osteosarcoma is unknown. However, a number of risk factors have been identified. 

Rapid bone growth appears to predispose persons to osteosarcoma, as suggested by the increased incidence during the adolescent growth spurt, the high incidence among large-breed dogs (eg, Great Dane, St Bernard, German shepherd), and osteosarcoma's typical location in the metaphyseal area adjacent to the growth plate (physis) of long bones.

Genetic predisposition plays a role. Bone dysplasias, including Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses and retinoblastoma (germline form) are risk factors. The combination of constitutional mutation of the RB gene (germline retinoblastoma) and radiation therapy is linked with a particularly high risk of developing osteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts).

The only known environmental risk factor is exposure to radiation. Radiation-induced osteosarcoma is a form of secondary osteosarcoma and is not discussed further in this article.


Symptoms of osteosarcoma vary depending on the location of the tumor. Common signs of this type of cancer include:
  1. bone pain (in motion, at rest, or when lifting objects)
  2. bone fractures
  3. swelling
  4. redness
  5. limping
  6. limitation of motion of joints

How bone pain is experienced may vary. Your child may feel a dull ache or have pain that keeps them awake at night. If your child has bone pain — or if you notice any of the above symptoms — examine their muscles. In the case of osteosarcoma, the muscles in the cancerous leg or arm may appear smaller than those in the opposite limb.

Symptoms of osteosarcoma can mimic growing pains — pain in the legs caused by normal bone growth. However, growing pains typically stop during the early teenage years. Contact a doctor if your child has any chronic bone pain or swelling past their initial growth spurts, or if the pain is causing your child serious issues.

Your child’s doctor can use a variety of tools to diagnose osteosarcoma. They will first conduct a physical examination to look for swelling and redness. The doctor will also request information about your child’s medical history. This includes previous illnesses and past medical treatments.

Your child’s doctor may do a simple blood test to check for tumor markers. These are chemical readings in the blood that indicate the presence of cancer. Other tests used to diagnose osteosarcoma include:
  1. CT scan: a 3-D X-ray used to examine bones and soft organs in the body
  2. MRI: uses sound waves and powerful magnets to create images of internal organs
  3. X-ray: produces images of dense tissue inside the body, including bone
  4. PET scan: a full body scan often used to detect cancer
  5. biopsy: removal of a tissue sample from the bone for testing
  6. bone scan: a sensitive imaging test that shows bone abnormalities that may be missed by other imaging tools (bone scans can also tell doctors whether the cancer has spread to other bones).


Osteosarcoma can be classified as either localized (only present in the bone it started in) or metastatic (present in other areas, such as the lung, or other, unconnected bones).

Osteosarcoma tumors are staged in much the same way as other tumors, using either the Musculoskeletal Tumor Society Staging System or the American Joint Commission on Cancer guidelines.


Chemotherapy and surgery are effective at treating osteosarcoma.

1. Chemotherapy

Chemotherapy is often administered before surgery. This treatment method uses drugs that help shrink and kill cancerous cells. The length of chemotherapy treatment varies and may depend on whether the cancer has spread to other parts of the body. For example, if your child’s cancer hasn’t spread, their doctor may recommend six months of chemotherapy before surgery. Once your child finishes the course of chemotherapy, surgery will be used to remove any remaining tumors.

2. Surgery

In most cases, surgeons can save the cancerous limb. They can surgically remove the tumor and surrounding bone, and replace the missing bone with an artificial one. Chemotherapy may resume after surgery to destroy any microscopic cancer cells.

3. Recurrence

Bone cancer can recur, even after chemotherapy and surgery. Your child will need follow-up CT scans, bone scans, and X-rays to check for new tumors.
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