Osteosarcoma should be considered in the differential diagnosis of bone pain, as early recognition may increase the likelihood that radiographically visible metastatic disease, which adversely impacts patient prognosis, will not develop between the time of symptom onset and diagnosis. In addition to its importance as a clinical entity, its rigorous study, beginning with an osteosarcoma registry created under the auspices of the American College of Surgeons in 1921, highlights important oncologic principles, including the concept of microscopic metastatic disease and the role of adjuvant therapy.
PATHOGENESIS AND EPIDEMIOLOGY
Osteosarcoma is the most common primary bone tumor in children. The average annual incidence in children younger than 20 years of age in the United States is 4.8 per million. Approximately 450 children are diagnosed with osteosarcoma each year, with an additional 100 to 200 young adults between the ages of 20 and 29 years receiving this diagnosis. Several epidemiological features suggest a correlation between rapid bone growth and the evolution of osteosarcoma. The peak incidence occurs in the second decade of life when the most longitudinal growth occurs. The adolescent peak occurs at age 13 years in girls and between ages 15 and 17 years in boys, corresponding with the age of greatest growth velocity in each gender. Osteosarcoma is slightly more common in males. Other evidence supporting the relationship with growth includes its skeletal distribution with the majority occurring in regions that undergo the most extensive longitudinal growth (Fig. 449-1). In addition, osteosarcoma typically occurs in the metaphyses of bones, which is the site where new bone arises from the growth plates. Osteosarcoma is rare in children under age 5 years.
Pie chart providing the skeletal distribution of the primary tumor in patients with newly diagnosed osteosarcoma.
Other Etiological Factors
Numerous other well-defined etiological factors for the development of osteosarcoma exist; these include environmental and genetic risk factors. One well-known etiologic factor is ionizing radiation, although there is typically a long interval between irradiation and the development of osteosarcoma, making it less relevant to most pediatric patients. However, it should be noted that the incidence of osteosarcoma is markedly increased among survivors of hereditary retinoblastoma, who harbor germline mutations of the retinoblastoma gene. This risk is further increased in those who received radiotherapy as a component of their treatment. Similarly, germline mutations in the p53 gene (the basis of Li-Fraumeni syndrome) can lead to a high risk of developing multiple malignancies including osteosarcoma; as can Rothmund-Thomson, Werner, and Bloom syndromes. In older patients, disorders that result in increased bone turnover, such as Paget’s disease of the bone and fibrous dysplasia, lead to an increased incidence of osteosarcoma. Despite these associations, no clear etiologic factor can be identified in the vast majority ...