What Is Osteosarcoma?

Overview

Although many people are unfamiliar with the medical terminology osteosarcoma, they experience fear upon hearing it due to the assumption that it is related to a frightening condition. Unfortunately, the assumption is right, as osteosarcoma is the most common cancer affecting teenagers and young adults.

Osteosarcoma, which is also called osteogenic sarcoma, is a primary bone cancer that begins in the osteoblast (cells that form the bone). It most commonly affects the long bones around the knee. However, it can also happen in other sites like the arm or any bone in the body, including those in the shoulder, skull, and pelvis. In addition, osteosarcoma can affect nearby tissues like muscles and tendons and can spread through the blood to other bones or organs in the body.

The exact cause of osteosarcoma is still unknown, but many studies attributed it to inherited or acquired DNA mutations inside bone cells.

Types of osteosarcoma

Osteosarcoma can be divided into three categories according to histological appearance: high-grade, intermediate-grade, and low-grade, with a number of subtypes under each group.^1,2

High-Grade

It is a fast-growing type of osteosarcoma that spreads quickly to other body parts. Under a microscope, the cells look different from normal bone, in which many of the cancer cells are in the process of dividing into new cells. There are nine types of high-grade osteosarcoma; however, the first three are the most common types:

• Osteoblastic: It commonly happens in the lower long bones and less frequently in the upper bones. It frequently occurs in children and adolescents³
• Chondroblastic: This tumour affects the leg and thigh. It occurs mainly in individuals in their 20s.⁴
• Fibroblastic: It originates in the connective fibrous tissue at the ends of the leg or arm bones and then spreads to the surrounding soft tissues⁵
• Small cell: It is a rare subtype of osteosarcoma that accounts for 1.5% of all osteosarcomas. It affects the metaphysis of long bones and occurs in individuals in their 20s or 30s, with a slight predominance in people assigned female at birth⁶
• Telangiectatic: It is a rare and aggressive form of osteosarcoma, accounting for 2 to 12% of all osteosarcoma cases. It happens in the upper arm bone, the thigh, and the leg and is most commonly seen in children, adolescents, and young adults⁷
• High-grade surface: It develops from the surface of the bone, with  high division activity identical to that of conventional osteosarcoma⁸
• Pagetoid: It is a type of osteosarcoma that happens in the elderly with Paget's disease of the bone. It occurs in the bones of the pelvis, thigh, and upper arm⁹
• Extraskeletal: It is a very rare tumour that develops in a part of the body other than a bone. In contrast to conventional osteosarcoma, the extraskeletal variant affects adults in their 40s. The lower extremity is most commonly affected¹⁰
• Post-radiation: It is a late complication of radiotherapy for diseases including pelvic cancer, breast cancer, and Hodgkin’s disease¹¹

Intermediate-Grade

It is an uncommon type of osteosarcoma that fall between high-grade and low-grade tumours, and it includes only one type:

• Periosteal: It is a distinct type of surface osteosarcoma that develops from the inner layer of the periosteum (a membrane that covers the outer surface of the bone) and therefore elevates the periosteum. It usually arises on the surface of the bones of the leg, thigh, forearm, and upper arm⁸

Low-Grade

It is the slowest-growing form of osteosarcoma, in which the tumour looks like normal bone and has few dividing cells under a microscope. It includes two types: 

• Parosteal: It originates from the outer fibrous layer of the periosteum. Its cells are fibroblasts⁸
• Intramedullary or intraosseous well-differentiated: It is a rare tumour with histological characteristics similar to those seen in parosteal osteosarcoma

The grade and stage of the tumour are important factors in determining the most appropriate treatment to be used. The grade gives an idea of how quickly the cancer may develop. For example, low-grade tumours recur only locally (in the same area), whereas high-grade tumours spread to other parts of the body and can recur anywhere in the body. Children's osteosarcomas are mostly high-grade.¹² On the other hand, the stage of cancer describes its size and whether it has spread beyond its original site.

Causes of osteosarcoma

Although many studies have been conducted to understand the causes of osteosarcoma, the exact cause is not clear. Researchers assume that osteosarcoma occurs due to mutations (changes) in the DNA or the genetic codes.

The tumour starts when a healthy bone cell experiences changes in its DNA. The DNA contains the instructions that tell the cell what to do. Upon changes in the DNA instructions, the cell will start to make new bone at the wrong time resulting in poorly formed bone cells that act as a tumour. The tumour cells can spread throughout the body and destroy healthy cells and tissues.¹³

Signs and symptoms of osteosarcoma

Signs and symptoms of osteosarcoma may vary among individuals. However, the most common signs and symptoms include:¹⁴

• Swelling and redness at the site of the bone tumour
• Pain or tenderness in the affected bone
• Increase pain with lifting or activity
• Limping
• Limited movement of the affected limb
• Increased bone injury or bone fractures  

Management and treatment for osteosarcoma

Choosing a suitable treatment for osteosarcoma depends on several factors, such as the patient's age, overall health, and medical history, as well as the type, stage, size, and location of the tumour. ¹ The treatment may include:

1. Surgery: The surgery aims to remove all the tumours. The type and extent of the surgery will be determined based on the location and size of the tumour¹
   • Limb-sparing surgery: It is surgery to remove a tumour from the affected limb (leg or arm) and some of the surrounding tissues without removing the whole limb. The removed part of the limb can be replaced with a prosthesis or bone graft (replace the affected bone with bone taken from another part of the body).¹⁵
   • Amputation: It is surgery to remove the whole limb because the tumour size is large  and has spread into surrounding nerves or blood vessels. The removed limb will be replaced with an artificial limb¹⁶
   • Rotationplasty: It is a surgery used to treat bone tumours near the knee. The bottom of the thigh, the knee, and the upper leg are surgically removed. Then, the lower leg is rotated 180 degrees and reattached to the thigh bone. With the help of a prosthesis, the ankle works as a new knee joint¹⁷

2. Chemotherapy: It involves the use of anti-cancer drugs to kill cancer cells. It is usually given to the patient before surgery (neoadjuvant chemotherapy) to shrink the tumour and after surgery (adjuvant chemotherapy) to reduce the risk of recurring. The neoadjuvant chemotherapy is started 10 weeks before surgery.^15,16 While adjuvant chemotherapy is continued up to 18 weeks after surgery.^{1, 16} 
3. Radiotherapy: It is used in areas where surgery is not possible or when the tumour is not fully removed. There are two types of radiation, external radiation therapy, and internal radiation therapy. The external type uses a machine to focus a high-energy beam on the tumour part of the body to kill it.¹⁷ In contrast, the internal type involves the insertion of a substance (samarium or radium) through a needle or catheter.¹⁷ The substance will be taken up by the tumour, thus delivering radiation to the cancer site¹

Diagnosis of osteosarcoma

Firstly, the doctor will start with a complete medical history and physical examination. Then, the doctor will check for unusual lumps around the bones and might use certain diagnostic tests, including:

1. Blood tests: These tests can provide information about the size, count, and maturity of blood cells, in addition to the organs' condition (kidney and liver). These tests do not detect the presence of a bone tumour.¹⁸
2. Imaging tests:¹⁸
   • X-ray: To detect abnormal bone growth
   • Bone scans: To detect changes in the joint or bone and determine the cause of bone pain or inflammation by injecting a small amount of radioactive material into the body
   • Magnetic resonance imaging (MRI): It is a procedure that uses a combination of magnets, radio waves, and a computer to produce clear images of body parts and provide clear pictures if the X-ray results were abnormal
   • Computed tomography (CT) scan: It is an imaging test that uses a computer and many X-rays to provide details of the bones, muscles, organs, and fats
   • Positron emission tomography (PET) scan: In this test, radioactive glucose is injected into the bloodstream. Tumour tissues consume glucose more than normal tissues and thus can be detected by a scanning machine. The PET scan is usually used to find small spreading tumours or to check whether the treatment for a known tumour is effective

3. Biopsy: It is a procedure where the doctor takes tissue samples from the affected area to examine it under a microscope and determine if cancer or other abnormal cells are present¹⁸

Risk factors

Some risk factors increase the incidence of developing osteosarcoma, including: 

• Teenage growth spurts
• Treatment like radiation therapy and anticancer drugs called alkylating agents
• Other bone disorders, like fibrous dysplasia and Paget's disease of the bone
• Certain genetic or inherited conditions such as hereditary retinoblastoma (eye tumour), Rothmund-Thomson syndrome, Li-Fraumen syndrome, Diamond-Blackfan anaemia or Werner syndrome

It is important to note that osteosarcoma is not caused by injuries or damage to the bone; however, the injury may draw attention to a bone tumour.

Complications

Osteosarcoma and its treatment can result in complications, including:

• Bone fractures
• Prosthesis breakage
• Slow wound healing
• Prosthetic or wound infection
• Local recurrence
• Joint instability
• Side effects of chemotherapy include: anaemia, gastrointestinal reactions such as nausea and vomiting, hearing loss, kidney damage, and heart failure¹⁹

FAQs

How can I prevent osteosarcoma

Unfortunately, there is no known way to prevent osteosarcoma or protect against it.

How common is osteosarcoma

The incidence of osteosarcoma in people younger than 25 years is 4 per million, ages 25-59 years is 2 per million, and older than 60 years is 3.5 per million.^20,21

When should I see a doctor

Make an appointment with the doctor if you or your child experience the following:

• Bone pain, swelling, or lumps near the bone
• Changes in mobility
• Unexplained bone fractures

These signs may not indicate osteosarcoma, but it's important to undergo a thorough examination to identify the underlying cause and treat it.

Summary

• Osteosarcoma is a type of bone cancer that primarily affects children and young adults
• The cause of osteosarcoma is unknown, but risk factors like radiation therapy, bone disorder, or genetic diseases increase the incidence of cancer
• Signs and symptoms of osteosarcoma may vary among individuals; however, bone swelling and pain, limited movement, and unexplained bone fractures are the most common
• The right diagnosis of osteosarcoma is crucial to determine the stage and grade, thus choosing the appropriate treatment
• Treatment can include a combination of chemotherapy, radiotherapy, or surgery
• Unfortunately, there is no way to prevent osteosarcoma; however, early detection and treatment can significantly improve the outcomes