Osteosarcoma is a type of cancer that starts in the bone. It most commonly occurs in children, teens, and young adults. Osteosarcoma usually affects the large bones near the knee or shoulder and can cause pain, swelling, or problems with movement. This cancer can be serious, but advances in treatment have improved survival and help avoid limb loss, especially when the cancer has not spread. With proper care and ongoing support, many patients can achieve long-term recovery and maintain a good quality of life.

Osteosarcoma is a cancerous tumor that forms in bone, most often in the long bones of the arms or legs, especially near the knee or shoulder. This cancer develops from cells that normally make new bone tissue, called osteoblasts. It most often occurs during periods of rapid bone growth, such as the teenage years, when cells are multiplying quickly, increasing the likelihood of cell changes (mutations) that can cause uncontrolled growth.

Osteosarcoma is the most common primary bone cancer in children and adolescents, but it can also occur in older adults. When osteosarcoma develops later in life, it is sometimes linked to other genetic conditions, bone disorders, or past radiation treatment. There are several subtypes of osteosarcoma based on how aggressive the cancer is or how the cells look under a microscope. High-grade types are more likely to spread, while low-grade types tend to grow more slowly.

Osteosarcoma can occur in any bone, but it most often affects the thigh bone (femur), shin bone (tibia), or upper arm bone (humerus). It can sometimes spread to other parts of the body, most often the lungs or other bones. Early diagnosis and treatment help ensure the best outcomes.

The exact causes of osteosarcoma are not fully understood. Changes (mutations) in certain genes that control cell growth can play a role. Some people inherit genetic conditions that raise their risk of cancer, called cancer predisposition syndromes. These include Li-Fraumeni syndrome (a gene condition that increases risk of several different types of cancer) and hereditary retinoblastoma (a childhood eye cancer linked to an increased risk of other cancers).

Osteosarcoma can also develop as a secondary cancer after previous radiation therapy or chemotherapy, especially in people who were treated for other cancers during childhood. In older adults, osteosarcoma sometimes arises in bones affected by Paget disease, a condition that causes abnormal bone growth.

Risk factors for osteosarcoma include age, genetic conditions, and medical history. However, most people with osteosarcoma do not have any known risk factors.

The following can increase risk:

• Rapid bone growth during the teenage years, which increases the likelihood of cell changes that can cause cancer
• Significant family history of cancers
• Certain rare, inherited genetic conditions that affect cell growth or repair, including Li-Fraumeni syndrome, hereditary retinoblastoma, Rothmund-Thomson syndrome, Bloom syndrome, Werner syndrome, and Diamond-Blackfan anemia
• Previous radiation treatment, especially at a young age, which can damage bone cells and increase cancer risk
• Past treatment with certain chemotherapy drugs
• Paget disease, a condition in older adults that causes abnormal bone growth and can lead to cancer
• History of other benign (noncancerous) bone conditions, such as fibrous dysplasia or certain bone tumors, which can increase risk in rare cases

Not everyone with these risk factors will develop osteosarcoma, and many people with the condition have no clear risk factors.

The main symptoms of osteosarcoma, such as bone or joint pain and swelling with activity, can be mistaken for other common problems, especially in young people. It is important to see a doctor if these symptoms persist.

The pattern and severity of symptoms can vary from person to person but may include:

• Persistent bone pain, often near a joint, which may start with activity in the early stages and occur while at rest in later stages
• Swelling, tenderness, or redness over a bone or joint, which may appear as a lump or mass
• Joint stiffness or restricted movement that makes it hard to bend or straighten the limb
• Limping or difficulty walking, especially if the tumor is in the leg
• Pain when lifting or using the arm, if the tumor is in the shoulder or upper limb
• Bone fracture after a minor injury or routine movement

Contact a health care provider if persistent bone pain, swelling, or a lump that does not go away occurs, especially if it interferes with daily activities or sleep.

Diagnosis of osteosarcoma involves careful review of symptoms and medical history, a physical exam, and several medical tests to confirm (or rule out) cancer and plan treatment.

The doctor may ask about any risk factors related to osteosarcoma and will ask about symptoms, including pain, swelling, or injury. They will check for any lumps, tenderness, changes in joint movement, or signs of bone weakness.

Tests used to diagnose osteosarcoma include:

• X-ray to show bone changes, such as breakdown of bone tissue, new bone formation, or a mass
• Magnetic resonance imaging (MRI) for detailed images of the bone and nearby tissues to see the tumor, including its size and extent
• Computed tomography (CT) scan to check for cancer spread (such as to the lungs or other areas) and to provide more detail about the tumor
• Bone scan to detect areas of rapid bone growth or cancer spread to other bones
• Positron emission tomography (PET) scan to detect areas of increased cancer cell activity in the body
• Blood tests to measure markers such as alkaline phosphatase and lactate dehydrogenase, which can be higher in bone cancer
• Biopsy to remove a small sample of tissue from the tumor, usually with a needle or small surgery for evaluation by a pathologist (a doctor who examines tissue under a microscope) to diagnose and determine the cancer type and grade

In addition to these diagnostic tests, genetic evaluation and counseling can identify hereditary risk factors and make recommendations that can affect treatment and other next steps.

Treatment for osteosarcoma depends on the tumor’s location, size, grade, patient age, and whether it has spread. It usually involves a combination of chemotherapy (cancer-fighting medicines), surgery, and sometimes radiation therapy. Treatment is usually managed by a team of specialists, including oncologists, surgeons, nurses, and therapists.

Some treatment options include:

• Chemotherapy: Medicines such as methotrexate, doxorubicin, cisplatin, and ifosfamide given before and after surgery can kill cancer cells, shrink the tumor, and reduce the risk of spread.
• Surgery: The main goal of surgery is to remove the entire tumor and enough healthy tissue around the tumor to stop progression of the cancer. When possible, limb-sparing techniques can save the affected arm or leg and maintain function by rebuilding with bone grafts or implants. However, in some cases, amputation (removal of part or all of a limb) may be necessary to remove the tumor. Rotationplasty is a special surgery for tumors near the knee, where part of the leg is rotated and reattached to improve function with a prosthesis.
• Radiation therapy: High-energy rays are used to kill cancer cells when surgery is not possible or to treat areas where cancer remains after surgery.
• Targeted therapy: New treatments, such as tyrosine kinase inhibitors or immune-based therapies, may be available through research studies for certain patients, especially if the cancer returns or does not respond to standard treatment.
• Supportive care: Physical therapy, pain management, counseling, and rehabilitation can help improve quality of life during and after treatment.

Complications of osteosarcoma can result from the cancer itself or from its treatment. These complications may affect the bones, other organs, or overall health.

• Spread of cancer (metastasis), most often to the lungs or other bones, which can cause coughing or breathing problems, and can make treatment more complex
• Pathological fractures, in which the bone breaks easily because the tumor has weakened the limb
• Limb loss or amputation, if limb-sparing surgery is not successful or possible
• Side effects of chemotherapy, such as infection risk, kidney or heart problems, and hearing loss, among others, some of which may show up years after treatment
• Issues with fertility from chemotherapy or radiation (egg freezing or sperm banking prior to treatment may be an option for some people)
• Radiation side effects, including skin changes, fatigue, or, rarely, damage to nearby organs
• Secondary cancers, such as leukemia or other tumors, which can develop long after treatment
• Infection or failure of bone grafts or implants used in reconstruction
• Chronic pain, stiffness, or reduced movement in the affected limb
• Emotional and psychological effects, such as anxiety, depression, or changes in body image from the disease experience

The care team should be contacted promptly if new pain, swelling, fever, signs of infection, or any decline in health occurs during or after treatment.

The outlook for people with osteosarcoma depends on several factors, including the tumor’s size, location, grade, and whether it has spread at the time of diagnosis. When the cancer remains localized (has not spread), about 70% of children and young adults can achieve long-term survival or cure with comprehensive treatment. Low-grade types and tumors that can be completely removed have the best outlook.

When osteosarcoma has spread to the lungs or other bones at the time of diagnosis, the chance for cure is lower, with survival rates around 20% to 40%. Individual response to chemotherapy also affects outcomes. Some people who have had osteosarcoma may experience late effects from treatment or cancer recurrence, so long-term follow-up is important.

“The multidisciplinary team of dedicated musculoskeletal oncologic physicians at Yale Medicine has a wealth of experience in treating patients with osteosarcoma and provides patient-focused care with a team approach and excellent outcomes,” says Dieter Lindskog, MD, a Yale Medicine orthopaedic surgeon who specializes in bone and soft tissue sarcoma, and metastatic bone disease.