Bone sarcomas are extremely rare neoplasms, which precludes determination of their true incidence. In 2009, approximately 2,570 new cases of cancer of the bones and joints will be diagnosed in the United States, and some 1,470 patients will succumb to the disease. Population-based tumor registries seldom separate bone sarcomas into various histologic types.

Osteosarcoma is the most common malignant primary bone tumor (excluding multiple myeloma), comprising 30% of all such malignancies. The annual incidence of osteosarcoma is approximately 800 cases per year in the United States. Chondrosarcoma is the second most common malignant primary tumor of bone; its annual incidence is approximately half that of osteosarcoma. Ewing's sarcoma represents approximately 6% of all primary malignant bone tumors, with an annual incidence of 200 cases. Malignant fibrous histiocytoma (MFH) comprises < 1% of primary bone sarcomas.

Epidemiology

Gender
The incidence of primary bone sarcomas is higher in males than in females, regardless of histologic type. A low-grade variant of osteosarcoma (parosteal osteosarcoma) is observed more frequently in females.

Age
Osteosarcoma and Ewing's sarcoma develop primarily in children and adolescents. A biphasic pattern of incidence of osteosarcoma has been observed; peaks have been noted among adolescents (rapid growth of long bones) and in the elderly (secondary tumors arising in association with Paget's disease or within previously irradiated tissue). Chondrosarcomas are rarely seen in skeletally immature patients. They usually develop in middle-aged and older adults. MFH is observed in adults.

Race
No predilection has been noted in any particular race. However, Ewing's sarcoma is extremely rare in American and African blacks.

Disease site
Any bone and any site within a given bone may be affected. Most osteosarcomas occur in the metaphyseal region of skeletally immature long bones (ie, distal femur, proximal tibia, and proximal humerus), which have the greatest growth potential. Ewing's sarcoma is classically described as a diaphyseal lesion, but it may arise in any region within an involved long bone. It commonly arises in the flat bones of the pelvis and scapula. Primary bone tumors of any histologic type are extremely rare in the spine and sacrum.

Survival
Low-grade sarcomas are associated with the most favorable survival, which approaches 90% in patients with adequately treated tumors. With regard to high-grade sarcomas, survival has improved dramatically in patients with osteosarcoma or Ewing's sarcoma due to the advent of effective multiagent chemotherapy regimens. Survival has improved with multimodality therapy from historic rates of < 20% to current rates of 50% to 75%.

Etiology and risk factors

For the majority of bone sarcomas, no specific etiology has been established. A few predisposing factors have been identified.

Genetic factors
Children with familial retinoblastoma have a 13q chromosome deletion and an increased incidence of osteosarcoma. Li-Fraumeni syndrome is also associated with an increased risk of bone sarcomas, as well as such other cancers such as breast, leukemia, soft-tissue sarcoma, brain, and adrenal cortical tumors. Li-Fraumeni syndrome results from a genetic loss of TP53.

Radiation therapy
Bone sarcomas constitute a rare, but devastating, consequence of therapeutic irradiation. Radiation-associated sarcomas develop within the radiation field, usually after a latent period of at least 3 years. The majority of these tumors are osteosarcomas. MFH and other histologies also can arise within a radiation field.

Chemotherapy
Alkylating agents and anthracyclines administered for unrelated cancers have been implicated as etiologic factors in the development of second malignant neoplasms, particularly osteosarcoma.

Preexisting benign tumors/conditions
Osteosarcomas can arise in association with Paget's disease and rarely in association with benign bone tumors (ie, fibrous dysplasia). Chondrosarcomas can develop in the cartilaginous component of osteochondromas (solitary and multiple hereditary exostosis) and in patients with enchondromatosis (Ollier's disease and Maffucci's syndrome). MFH can arise in association with bone infarcts.

Trauma
A traumatic event often prompts medical intervention, at which time the bone sarcoma is detected. The short temporal relationship between the traumatic event and the diagnosis of the tumor usually rules out a causal relationship.

Orthopedic implants
Case reports of bone sarcomas arising in the region in which a metallic prosthetic device has been implanted have been published. The rarity of these clinical situations relative to the vast number of devices implanted makes a causal relationship unlikely.