Bone cancer is an uncontrolled growth of abnormal cells within the bone. Bone provides structure to the body, protects internal organs, and produces and stores blood cells. Bone also acts as levers and braces for muscles to produce movement.

Bone tumors can be either benign (noncancerous) or malignant (cancerous). Both types can grow and compress normal bone tissue and absorb or replace it with abnormal tissue. Benign bone tumors, which are more common, do not spread and are rarely life-threatening.

The two main forms of cancer found in bone are primary bone cancer and secondary bone cancer. Primary bone cancer begins in the bone. Secondary bone cancer, or metastatic bone cancer, does not begin in the bone but has spread there from another area of the body. Secondary bone cancer often results from the spread of cancer from the lung, breast or prostate.

Primary cancer is not the same condition as secondary cancer. These forms of cancer can usually be distinguished from one another when their cells are examined under a microscope. For example, if bone cancer develops from metastasized breast cancer, the cells will look like breast cancer cells, not bone cancer cells. Treatment will vary based on where the cancer originated.

Primary bone cancer is rare and accounts for less than 0.2 percent of all cancers. It is much more common for cancer to spread to a bone from another site of origination. Types of primary bone cancers include:

• Osteosarcoma
• Chondrosarcoma
• Chordoma
• Fibrosarcoma and malignant fibrous histiocytoma
• Giant cell tumor of the bone

The exact cause of bone cancer has not been identified. Recently researchers have gained a greater understanding of how specific changes in DNA may cause bone cells to become cancerous. In addition, researchers have identified a number of factors that may make a person more likely to develop bone cancer, including retinoblastoma (a rare eye cancer of children), Paget’s disease and exposure to large doses of radiation.

A biopsy is required to diagnose primary bone cancer but may not be necessary to verify metastatic bone cancer. The procedure involves removing a sample of the tumor and examining it under a microscope. Once a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and is necessary for physicians to plan treatment. The lower the stage, the earlier the disease has been identified and the better the prognosis for recovery.

After bone cancer is diagnosed and staged, a treatment plan will be recommended. Treatment methods are chosen based on the type, size, location, and stage of the cancer, as well as the patient’s age and general health. The main method used to treat bone cancer is often surgery. Other treatment options include radiation therapy and chemotherapy.

The American Cancer Society (ACS) predicts about 2,300 Americans will be diagnosed with primary cancer of the bones and joints in 2007. Primary bone cancers account for less than 0.2 percent of all cancers. Bone cancer can occur at any age, but approximately 30 percent of the cases develop in children and adolescents. The prognosis for patients diagnosed with bone cancer varies significantly based on the type of cancer and the extent metastasis. In 2007, primary bone cancer is expected to cause about 1,300 deaths.

Secondary bone cancer (cancer that has spread to the bone from another site) is more common than primary bone cancer. According to the ACS, almost all people who die of cancer (approximately 560,000 people per year) will have bone metastasis at some point during their illness. 

Bone cancer is an uncontrolled growth of abnormal cells within the bone. Bone provides structure to the body, protects internal organs, and creates and stores blood cells. It also acts as levers and braces for muscles to produce movement.

Mature bones are composed of three types of tissue:

• Compact tissue (hard outer portion of most bones)
• Cancellous tissue (spongy layer inside the bones that contains bone marrow)
• Subchondral tissue (smooth bone inside the joints)

The hard outer component of bone consists of a network of tissue onto which calcium salts are deposited. The bone is also surrounded by a layer of periosteum, a membrane of connective tissue. Located at each end of a bone is an area of softer tissue known as cartilage. The cartilage serves as cushioning between bones, and in combination with ligaments and additional tissues forms the joints.  

Most bones are hollow. Located inside hollow bones is bone marrow, a type of soft tissue that consists of fat cells and blood-forming cells. Blood-forming cells generate red blood cells, white blood cells and platelets. Additional cells found in the bone marrow include plasma cells, fibroblasts and reticuloendothelial cells. 

The bone itself contains two types of cells:

• Osteoblasts, which form new bone.
• Osteoclasts, which dissolve old bone.

People may think of the bones as not growing in adulthood, but in a process called remodeling the osteoblasts keep replacing bone tissue destroyed by the osteoclasts. This process re-creates every bone over a decade.

Bone tumors can be either benign (noncancerous) or malignant (cancerous). Both types can grow and compress normal bone tissue and absorb or replace it with abnormal tissue. Benign bone tumors, which are more common, do not spread and are rarely life-threatening.

The two main forms of cancer found in bone are primary bone cancer and secondary bone cancer. Primary bone cancer is cancer that begins in the bone. Secondary bone cancer, or metastatic bone cancer, is cancer that does not begin in the bone but has spread from cancer in another site. Cancer of the prostate, lung and breast are the most common cancers that metastasize to the bone. 

Cancer that begins in the bone is not the same condition as cancer that spreads to the bone. These forms of cancer can be distinguished from one another when their cells are examined under a microscope. For example, cancer that has spread from the lungs to the bone will have cells that are similar to lung cancer, not bone cancer. Primary bone cancer is rare. It is much more common for cancer to spread to a bone than to originate there.

The American Cancer Society (ACS) predicts about 2,300 new cases of primary cancer of the bones and joints in the United States in 2007. Men will account for approximately 1,300 of the cases, while 1,000 women will develop this type of cancer. Primary bone cancers account for less than 0.2 percent of all cancers and will cause about 1,300 deaths in 2007. Secondary bone cancer (cancer that has spread from another site) is more common. According to the ACS, almost all people who die of cancer (approximately 560,000 people per year) will have bone metastasis at some point during their illness. 

There are numerous types of bone tumors. These tumors are given names based on the area of bone or surrounding tissue affected and the type of cells forming the tumor. 

Benign (noncancerous) bone tumors do not spread to other tissues or organs. They can usually be cured by surgery and are not life-threatening. Examples of benign bone tumors include:

• Chondromyxoid fibroma
• Osteoid osteoma
• Osteoblastoma
• Osteochondroma
• Enchondroma

The majority of bone cancers are called sarcomas. Sarcomas are cancers that mainly develop from bone, cartilage, muscle fibrous tissue, fatty tissue or nerve tissue. Types of primary bone cancers (cancers that begin in the bone) include:

• Osteosarcoma. This type of cancer is a malignant tumor of the bone itself. It develops in new tissue in growing bones, most often in bones of the arms, legs or pelvis. Also known as osteogenic sarcoma, this type of cancer is the most common primary bone cancer, accounting for 35 percent of cases. It occurs most often in young people between the ages of 10 and 30, and is rare in middle-aged people. Approximately 10 percent of cases develop in people in their 60s and 70s. It is more common in men.
  
  
• Chondrosarcoma. The second most common primary bone cancer, chondrosarcoma, is cancer of the cartilage cells. It accounts for 26 percent of cases. The disease usually develops from normal cartilage. However, it may also develop within benign tumors of cartilage and bone (osteochondromas). It occurs most often in bones of the arms, legs or pelvis but can also develop in the ribs and some other bones. Chondrosarcoma is uncommon in people under age 20. Risk of developing the disease continually increases from age 20 to about age 75. It is most common in people between the ages of 50 and 60. Men and women have an equal risk of developing the disease.
  
  
• Ewing’s tumor. Also known as Ewing’s sarcoma, this cancer is the third most common primary bone cancer, accounting for 16 percent of cases. Named after the physician who first described it in 1921, Ewing’s tumors typically develop in bones. Unlike osteosarcoma, these tumors develop in the cavity of the bone. Research suggests that it develops in immature nerve tissue in bone marrow. 
  
  This form of bone cancer usually develops in the long bones of the legs and arms but may also occur in the pelvis and in other bones. Typically appearing in children and teenagers (ages 10 to 20), this cancer is rare in people over age 30. It is more common in white people and uncommon among African Americans and Asian Americans.
  
  
• Chordoma. Accounting for 8 percent of cases, this type of primary bone cancer typically develops in the base of the skull and bones of the spine. Long-term follow-up is important because these tumors can recur, even 10 or more years after treatment. 
  
  
• Fibrosarcoma and malignant fibrous histiocytoma. Accounting for 6 percent of primary bone cancers, these cancers normally develop from soft tissues and rarely occur in bones. Soft tissues are types of connective tissues other than bone, such as ligaments, tendons, fat and muscle. These cancers are most common in elderly and middle-aged adults. Bones most commonly affected include those of the arms, legs and jaw.
  
  
• Giant cell tumor of the bone. This type of primary bone tumor can occur in benign or malignant forms. Benign forms are most common, with only about 10 percent of giant cell tumors being malignant and spreading to other areas of the body. After surgery, however, malignant giant cell bone tumors can recur locally (come back in the same area where the cancer started). These tumors usually occur in young and middle-aged adults. Bones most commonly affected include the arm and leg bones.

Although non-Hodgkin’s lymphoma, multiple myeloma and leukemia can develop in bone or bone marrow, these forms of cancer are not considered primary bone cancer. 

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.

Bone cancer can produce a variety of signs and symptoms. Common indicators of bone cancer include:

• Bone pain. Pain in the affected bone is the most common complaint of people with bone cancer. Initially, the pain is not constant. It may be worse at night or when the bone is used. As the cancer grows, the pain will become constant. The pain intensifies with activity and may result in a limp if a leg is involved.
  
  
• Swelling. Tumors that develop in or around joints may cause swelling or sensitivity in the affected area. Enlargement, however, may not occur for weeks. Depending on the site of the tumor, it may be possible to feel a lump or mass.

In cases in which the cancer has spread, patients may experience a variety of generalized symptoms which are common to many advancing cancers, including:

• Weight loss
• Fatigue
• Fever
• Anemia

In addition, spread of the cancer to the internal organs may cause a range of symptoms, including breathing difficulty, when the cancer spreads to the lungs. Bone cancer can also weaken bones, occasionally resulting in a fracture.

Symptoms of bone cancer may be overlooked because they may resemble symptoms of less serious conditions, such as injury or arthritis. Patients are encouraged to contact their physician when they experience these signs and symptoms for a long time, without explanation. The best strategy for early diagnosis of bone cancer is awareness of its signs and symptoms and awareness of any risk factors that an individual may have. The earlier the disease is diagnosed, the earlier treatment may begin.

To diagnose bone cancer, a physician will take a patient’s medical history and perform a complete physical examination. Blood tests may be ordered to measure the level of alkaline phosphase. This enzyme, alkaline phosphase, is often present in high amounts when the cells that form bone tissue are extremely active. A high level of alkaline phosphase may indicate bone cancer because levels increase when disease or a tumor cause higher production of abnormal bone tissue. However, high levels can also be found when children are growing and in individuals of all ages when broken bones are mending and in certain liver abnormalities. For this reason, the test alone is not enough for diagnosis.

A variety of imaging tests may be ordered to detect bone cancer. These tests include:

• X-rays. An x-ray is a painless test in which an image is created of part of the body by using low doses of electromagnetic radiation that are reflected on film or fluorescent screens. X-rays may be ordered to show the location, size and shape of a bone tumor. The majority of bone cancers can be detected with x-rays of the bone. Often, a radiologist can determine if the tumor is malignant by its x-ray appearance. A chest x-ray can reveal if bone cancer has spread to the lungs.
  
  
• CAT scan or CT scan. Computed axial tomography allows for multiple x-rays to be taken from different angles around the patient. A computer than analyzes the data and produces detailed cross-sectional images of the patient’s body. CAT scans may be used to guide a biopsy needle into a lesion located deep in the body. The procedure, known as a CT-guided needle biopsy, is used to obtain a sample of tissue for analysis.

• MRI. Magnetic resonance imaging uses a powerful magnetic field to create images of structure and organs within the body allowing a computer to produce clear cross-sectional or three-dimensional images. In some cases, a contrast medium (dye) may be used to more clearly define structures. MRI uses no radiation and may give better visualization of bone and nerve tissue than other imaging tests.
  
  
• Bone scan. A tiny amount of radioactive isotope is injected into a vein and allowed to travel to the bones. The body is then scanned with an external scanner. This test may be ordered to show if the cancer has spread to other bones, or to reveal the extent of damage the cancer has caused to a bone. It can also find metastases (the spread of cancer cells to distant areas of the bone) earlier than regular x-rays.
  
  
• PET scan. In positron emission tomography, the patient receives an injection of glucose (sugar) containing a small amount of radioactive material. Once in the body, the radioactive glucose is preferentially absorbed by the cancer cells. A camera then scans the patient and detects where the radioactive glucose was absorbed. Cancerous cells appear as “hot spots” on the image. This test may be used to determine if and where cancer metastasized in the body.

Although patient symptoms, a physical examination, imaging tests and blood tests may suggest that a patient has bone cancer, biopsies are usually required to diagnose bone cancer. A biopsy can determine the type of cancer and classify it as primary or secondary bone cancer. The procedure involves removing a sample of the tumor cells or tissue for examination under a microscope. Needle biopsies and surgical bone biopsies are two procedures used to diagnose bone cancer. This additional testing allows a physician to eliminate bone infections and other diseases as the cause of the problem.

After a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and is necessary for a physician to plan treatment.

Treatment for bone cancer is usually coordinated by a cancer care team headed by a medical oncologist. Specialists may also include an oncologic orthopedic surgeon, surgical oncologist, radiation oncologist and physical therapist.

After bone cancer is diagnosed and staged, a treatment plan will be recommended. Treatment methods are chosen based on the type, size, location, and stage of the cancer, as well as the patient’s age and general health. Common treatment methods for bone cancer include:

• Surgery. Surgery is often the main treatment method, depending on the type and location of the bone cancer. The goal of surgery is to remove the tumor and at least 1 inch of the tissue surrounding the tumor. When the tumor is in the pelvic bone, however, this amount of surgery is difficult because the tumor may be located next to vital organs that cannot be removed.
  
  Less common than they were a decade or two ago, amputations may only be necessary for certain situations. Pre-operative and post-operative chemotherapy have made limb-salvage surgery a possible alternative in many cases.
  
  Limb-salvage surgery involves removing large pieces of bone. When possible, surgeons avoid amputation by only removing the cancerous portion of the bone and replacing it with a bone grafts and/or metal plates to maintain structure and function in the affected area or limb. Patients may receive chemotherapy and/or radiation therapy before surgery to shrink the tumor. Depending on the site of the tumor and how much it shrinks, the physician can than determine whether limb-salvage surgery is possible.
  
  
• Radiation therapy. Radiation therapy uses precise high-energy x-rays to destroy cancer cells and shrink tumors. It may be used alone or in combination with surgery or chemotherapy. External beam radiation is the form of radiation most commonly used to treat bone cancer. For this procedure, radiation delivered from a machine outside of the body to the cancer site. Another form of radiation therapy used to treat bone cancer is brachytherapy (also called internal radiation therapy). In this method, small pellets of radioactive material are inserted directly into the cancer. It may be used alone or in combination with external beam radiation.
  
  Radiation therapy is occasionally used as the primary method of treatment in some patients with bone cancer. It is most commonly used to treat Ewing’s tumors. All other forms of bone cancer are primarily treated with surgery or a combination of surgery and radiation. It may be ordered after surgery as adjuvant (additional) therapy to destroy small groups of cancer cells that may remain after surgery. Radiation therapy is also used in patients whose health is too poor to undergo surgery. In addition, it may be used to ease symptoms of the disease.
  
  
• Chemotherapy. This treatment method uses powerful drugs to destroy cancer cells. Given by injection, intravenously or taken by mouth, the drugs travel through the bloodstream and reach all areas of the body. It may be used alone or in combination with radiation therapy and surgery. Depending on the type and stage of the cancer, chemotherapy may be given as the primary form of treatment or as an adjuvant treatment to surgery. Chemotherapy may involve the use of one type of drug or a combination of drugs. When used to treat bone cancer, a combination of drugs is frequently used. Common drugs used to treat bone cancer include methotrexate (given in high doses in combination with calcium leucovorin), doxorubicin and cisplatin. Other drugs used to treat bone cancer include ifosfamide and etoposide.

After treatment, patients are encouraged to make healthy lifestyle choices. These should include quitting smoking, limiting alcohol use and eating a nutritious and balanced diet. In addition, patients may be required to have physical therapy. Frequent physical examinations and laboratory or radiological studies may be conducted to look for recurrence, or return of the tumor, or to detect side effects of treatment. Patients should report any new symptoms to their physicians immediately. Such symptoms may be a sign of recurrence or side effects of treatment or even a new, unrelated medical problem. When detected early, most local recurrences and many distant metastases can be successfully treated.

There are no known methods of preventing bone cancer.

There is a great deal of research being conducted on bone cancer. Clinical trials and scientific studies are being conducted in cancer centers and laboratories by a number of medical groups. Areas of research for bone cancer include:

• Soft tissue cells. Researchers are discovering how certain changes in the DNA of soft tissue cells can trigger bone cancers to develop. In addition, scientists are working on ways to ‘silence’ certain genes that have been linked to bone cancers. This process can help inhibit the growth of tumors.  Genetic research is being used to develop new methods of diagnosis, new classification systems and advanced treatment methods.
  
  
• Chemotherapy. New chemotherapy drugs and drug combinations to treat bone cancer and other cancers are being studied, as are new ways to give the drugs. One area of focus is delivering chemotherapy directly into the artery that supplies the blood to the involved bone.
  
  
• Radiation therapy. New radiation therapy methods are being studied, such as when it is best to use external versus internal radiation on bone cancer and when to combine or sequence with chemotherapy.
  
  
• Immunotherapy. Experimental treatments aimed at boosting the patient's immune system to fight bone cancer are currently being studied. In one type of treatment, active immunotherapy, patients are given vaccines that might trigger the immune system to destroy the abnormal cells found in sarcomas. In passive immunotherapy, antibodies developed in a laboratory are used to destroy cancer cell proteins. Immunotherapy shows promise for becoming an innovative and effective treatment of bone cancer.
  
  
• Targeted therapy. There are certain proteins in cancers that cause them to grow. Researchers are studying these proteins and trying to determine how to block the action of these proteins to prevent cancer growth. The drug imatinib has shown some success in clinical trials.
  
  
• Related conditions. Researchers continue to study medical conditions that may develop as the result of bone cancer. Recent studies have found that children and young adults with sarcoma have an increased risk of developing blood clots in their veins. These clots can block normal blood flow and also can break loose and travel to areas where they can be life-threatening. Scientists are examining the link between bone cancer and these blood clots in both children and adults.

A patient’s prognosis varies greatly based on the type of cancer and how far it has spread. Staging enables a physician to determine a patient’s prognosis and choose the most appropriate treatment methods. Results from physical examination, biopsies and imaging tests are used to determine the stage.

These stages are created by a process called stage grouping. In this process information about a number of factors are combined to assign a stage.

The TNM system of the American Joint Committee on Cancer (AJCC) is the most common system used to stage cancer. In this system:

• T represents tumor. The location of the tumor can either be inside the bone or extend outside the bone.
  
  
• N represents absence or presence of spread to lymph nodes. Part of the immune system, lymph nodes are small, bean-shaped organs located in groups in various areas of the body, including the neck, armpit, chest and groin. Their functions include fighting infections and other foreign invaders, such as cancer.
  
  
• M represents absence or presence of metastasis, or spread of the cancer to distant organs.
  
  

  

Typically the stages are described by Roman numerals I to IV. However, some types of childhood bone cancers, such as Ewing’s tumor and osteosarcoma, are not staged this way. Instead, these cancers are often grouped into two stages – localized and metastatic.

According to the American Cancer Society (ACS), the five-year survival rate for patients in the different stages of bone cancer includes:

For patients with the most common form of bone cancer (osteosarcoma), survival rates may be based simply on two categories – cancer that is confined to the bone and cancer that has spread. For those patients whose cancer has not spread, there is a 60 to 70 percent 5-year survival rate. If it has spread only to the lungs, it is estimated to be 40 percent and only 10 percent if the cancer has spread elsewhere in the body.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients or parents of children with bone cancer may wish to ask their doctor the following questions about bone cancers:

1. What are the signs of bone cancer?
   
   
2. What tests will be used if bone cancer is suspected?
   
   
3. What type of biopsy will I receive?
   
   
4. When and from whom will I receive the results of the diagnostic tests?
   
   
5. What is the type and stage of my bone cancer?
   
   
6. What is the prognosis?
   
   
7. How will you determine if the cancer started in my bone or spread from somewhere else?
   
   
8. What are the treatment options for my type of cancer?
   
   
9. What are the risks associated with these treatments?
   
   
10. Am I likely to need an amputation?
    
    
11. What are the chances of the cancer spreading outside of my bones?
    
    
12. How will I be monitored following treatment?
    
    
13. What are the chances that my bone cancer will return?
    
    
14. Are my children at higher risk for bone cancer?
    
    
15. Can you recommend a support group?