Bone Cancer: Causes and Risk Factors

When cancer affects the bones, this is most commonly due to a non-bone cancer that has started elsewhere in the body and spread, or metastasized, to the bones. In contrast, the focus here is on those cancers that do begin in the bones, also known as primary bone cancers.

Primary bone cancer is actually a broad category, consisting of many different types of malignancies, some of which are very rare; however, of these, osteosarcoma, chondrosarcoma, and Ewing sarcoma are among the most common.

bone cancer risk factors

Known Causes

Although the causes of bone cancer are not precisely known, changes in the DNA of the cancerous cells are known to be important. In most cases, these changes happen by chance and are not passed on from parents to children.

Scientists have studied the patterns of development to try to understand the risk factors involved. Osteosarcoma is the third most common type of malignancy that affects bone in adolescents, preceded only by leukemia and lymphoma. Chondrosarcoma is also a common primary bone cancer, but it is more common in adults than it is in children and adolescents, with an average age at diagnosis of 51 years. Ewing sarcoma is most often diagnosed in teens, and the average age of diagnosis is 15 years.

Osteosarcoma Risk Profile

Osteosarcoma is the most common primary bone cancer overall. There are a few specific conditions known to increase the odds of developing it. Individuals who have a rare tumor of the eye known as hereditary retinoblastoma have an increased risk of developing osteosarcoma. Additionally, those who have previously been treated for cancer using radiotherapy and chemotherapy have an increased risk of developing osteosarcoma later in life.

Incidentally, most doctors agree that broken and injured bones and sports injuries do not cause osteosarcoma. However, such injuries can bring an already-existing osteosarcoma or another bone tumor to medical attention.

So, there is definitely a link between the two—it’s just that the mechanical injury does not seem to cause the osteosarcoma.

Age, Sex, and Ethnicity-Related Risk Factors

Osteosarcoma primarily affects two peak age groups—the first peak is in the teen years and the second one is among older adults.

  • In older patients, osteosarcoma usually arises from abnormal bone, such as those affected by long-standing bone disease (for example, Paget's disease).
  • Among younger individuals, osteosarcoma is extremely rare before the age of five, and the peak incidence actually occurs during the adolescent growth spurt. On average, a representative “standard age” for osteosarcoma in the younger population is 16 years for girls and 18 years of age for boys.

Osteosarcoma is relatively rare compared to other cancers; it is estimated that only about 400 individuals younger than 20 years of age are diagnosed with osteosarcoma each year in the United States. Boys are affected more frequently in most studies, and the incidence in youth of African descent is slightly higher than in whites.

Risk Factors Applicable to Younger Individuals

  • Presence of certain rare genetic cancer syndromes
  • Age between 10 and 30 years
  • Tall height
  • Male sex
  • African-American race
  • Presence of certain bone diseases  

Risk Factors Applicable to Older Individuals

Certain bone diseases such as Paget's disease, especially over time, are associated with increased risk of osteosarcoma. Still, the absolute risk is low, with only about one percent of those with Paget's disease ever developing osteosarcoma.

Radiation exposure is a well-documented risk factor, and because the interval between irradiation for cancer and the appearance of osteosarcoma is typically longer (for instance, 10 years or more), this is often most relevant to older age groups.

Genetic Predispositions

Predisposing genetic syndromes for osteosarcoma include:

  • Bloom syndrome
  • Diamond-Blackfan anemia 
  • Li-Fraumeni syndrome
  • Paget's disease 
  • Retinoblastoma 
  • Rothmund-Thomson syndrome (also called poikiloderma congenitale) 
  • Werner syndrome
  • Loss of function of the p53 and retinoblastoma tumor suppressor genes is believed to have an important role in osteosarcoma development.

Although germline (egg and sperm) mutations of p53 and retinoblastoma genes are rare, these genes are altered in the majority of osteosarcoma tumor samples, so there is a connection to the development of osteosarcoma. Germline mutations in the p53 gene can lead to a high risk of developing malignancies including osteosarcoma which has been described as the Li-Fraumeni syndrome.

Although alterations in tumor suppressor genes and oncogenes are necessary to produce osteosarcomas, it is not clear which of these events occurs first and why or how it occurs.

Osteosarcomas in Those With Paget's Disease

There is a rare subset of osteosarcomas that have a very poor prognosis. The tumors tend to occur in people who are over the age of 60 years. The tumors are large by the time of their appearance and they tend to be very destructive, making it difficult to get a full surgical resection (removal), and lung metastases are often present at the outset.

The risk profile is that of an older age group. They develop in about one percent of people with Paget's disease, usually when many bones are affected. The tumors tend to occur in the hipbone, thighbone near the hips, and in the arm bone near the shoulder joint; they are difficult to treat surgically, mostly because of the patient's age and the size of the tumor.

Amputation is sometimes necessary, especially when the bone breaks due to the cancer, which is a frequent occurrence.

Parosteal and Periosteal Osteosarcomas

These are a subset that are so named because of their location within the bone; they are usually less aggressive osteosarcomas that arise on the surface of bone in association with the layer of tissue that surrounds the bone, or the periosteum. They rarely penetrate to the inner portions of the bone and rarely become highly malignant osteosarcomas.

The risk profile for parosteal osteosarcoma differs from that of classic osteosarcoma: it’s more common in females than males, is most common in the 20 to 40-year-old age group, and typically arises in the back of the thighbone, near the knee joint, although any bone in the skeleton can be affected.

Higher-Risk Prognosis

Risk factors have been linked to better and worse prognoses, but unfortunately, these same factors have not generally been helpful in identifying patients who might benefit from more intense or less intense therapeutic regimens while maintaining excellent outcomes. Factors known to influence outcomes include the following.

Primary Tumor Site

Of tumors that form in the arms and legs, those that are further away from the body core, or torso, have a better prognosis.

Primary tumors that form in the skull and spine are associated with the greatest risk of progression and death, mostly because it is harder to achieve a complete surgical removal of the cancer in these locations.

Head and neck osteosarcomas in the jaw and mouth area have a better prognosis than other primary sites in the head and neck, possibly because they come to attention earlier.

Hipbone osteosarcomas make up seven to nine percent of all osteosarcomas; survival rates for patients are 20 to 47 percent.

Patients with multifocal osteosarcoma (defined as multiple bone lesions without a clear primary tumor) have an extremely poor prognosis.

Localized vs. Metastatic Disease

Patients with localized disease (no spread to distant areas) have a much better prognosis than do patients with metastatic disease. As many as 20 percent of patients will have metastases detectable on scans at diagnosis, with the lung being the most common site. The prognosis for patients with metastatic disease appears to be determined largely by sites of metastases, number of metastases, and surgical resectability of the metastatic disease.

For those with metastatic disease, the prognosis appears to be better with fewer lung metastases and when the disease has spread to one lung only, rather than to both lungs.

Tumor Necrosis After Chemotherapy

Tumor necrosis here refers to cancerous tissue that has "died off" as a result of treatment.

After chemotherapy and surgery, the pathologist assesses tumor necrosis in the removed tumor. Patients with at least 90 percent necrosis in the primary tumor after chemotherapy have a better prognosis than do patients with less necrosis.

However, researchers note that less necrosis should not be interpreted to mean that chemotherapy has been ineffective; cure rates for patients with little or no necrosis after induction chemotherapy are much higher than cure rates for patients who receive no chemotherapy.

Chondrosarcoma Risk Profile

This is a malignant tumor of cartilage-producing cells, and it represents about 40 percent of all primary bone tumors. Chondrosarcoma can arise on its own or secondarily, in what’s known as “malignant degeneration” of benign tumors (such as osteochondroma or benign enchondroma). Risk factors include:

  • Age: Usually occurs in people over 40 years of age; however, it also occurs in the younger age group, and when it does, it tends to be of a higher-grade malignancy capable of metastases.
  • Gender: Occurs with nearly equal frequency in both sexes.
  • Location: Can occur in any bone, but there is a tendency for development in the hipbone and thighbone. Chondrosarcoma may arise in other flat bones, such as the scapula, ribs, and skull.
  • Genetics: Multiple exostoses syndrome (sometimes called multiple osteochondromas syndrome) is an inherited condition that causes many bumps on a person’s bones, made mostly of cartilage. Exostoses can be painful and lead to bone deformities and/or fractures. The disorder is genetic (caused by a mutation in any one of the 3 genes EXT1, EXT2, or EXT3), and patients with this condition have an increased risk of chondrosarcoma.
  • Other Benign Tumors: An enchondroma is a benign cartilage tumor that grows into the bone. People who get many of these tumors have a condition called multiple enchondromatosis. They also have an increased risk of developing chondrosarcoma.

Ewing Sarcoma Risk Profile

This is much more common among whites (either non-Hispanic or Hispanic) and less common among Asian Americans and extremely rare among African Americans. Ewing tumors can occur at any age, but they are most common in teens and are less common among young adults and young children. They are rare in older adults.

Nearly all Ewing tumor cells have changes that involve the EWS gene, which is found on chromosome 22. Activation of the EWS gene leads to overgrowth of the cells and to the development of this cancer, but the exact way in which this happens is not yet clear.

Frequently Asked Questions

  • What is primary bone cancer?

    Primary bone cancer is a category of cancer that starts in the bone. In contrast, some cancers affecting the bones may have originally started elsewhere in the body and spread (metastasized) to the bones.

    The three most common types of primary bone cancer include:

    • Osteosarcoma
    • Chondrosarcoma
    • Ewing sarcoma
  • Is bone cancer hereditary?

    In the majority of cases, no, bone cancer isn't hereditary, in that it is unlikely to be passed down from parent to child. Most cases of bone cancer are the result of DNA mutations that happen by chance. That said, there are a small number of more rare bone cancers that are hereditary.

  • Does radiation put me at risk for bone cancer?

    Yes. Radiation is a significant risk factor for bone cancer, especially if you underwent radiation therapy when you were young or had high doses of radiation. Traditional X-rays are not considered dangerous, however.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Osteosarcoma Risk Factors. American Cancer Society

  2. Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment (PDQ®)–Health Professional Version. National Cancer Institute

  3. Kumar VS, Barwar N, Khan SA. Surface osteosarcomas: Diagnosis, treatment and outcome. Indian J Orthop. 2014;48(3):255-61. doi:10.4103/0019-5413.132503

  4. Chondrosarcoma. American Cancer Society.

  5. How common is Ewing sarcoma? St. Jude Children's Research Hospital

  6. American Cancer Society. Bone cancer risk factors.

Additional Reading

By Tom Iarocci, MD
Tom Iarocci, MD, is a medical writer with clinical and research experience in hematology and oncology.