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ETIOLOGY

RAPID

BONEGROWTH

ENVIRON-

MENTAL

FACTORS

GENETICPREDIS-

POSITION

ABBERATION OFNORMAL BONE

GROWTH

AF

FECT

S

OTHERS:HUMERUS

10%TIBIA

14%

FEMUR

42%

PROXIMALHUMERUS

90%

PROXIMALTIBIA

80%

DISTAL

FEMUR75%

SKULL &

JAW

8%

PELVIS8%

OSTEOSARCOMA

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PATHOPHYSIOLOGY

Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones nearmetaphyseal growth plates. The most common sites are the femur (42%, 75% of which are in the distal

femur), tibia (19%, 80% of which are in the proximal tibia), and humerus (10%, 90% of which are inthe proximal humerus). Other significant locations are the skull and jaw (8%) and pelvis (8%).

A relationship between rapid bone growth and osteosarcoma has been suggested by the fact that its

peak incidence coincides with the adolescent growth spurt, although this is not well defined. The peakincidence of osteosarcoma in girls parallels their earlier growth spurt when compared with boys.

Furthermore, the incidence of the bones in which osteosarcoma occurs is exactly parallel to the rates of

skeletal growth in growth plates, namely distal femur, proximal tibia and proximal humerus. Theseobservations have led several authors to suggest that osteosarcoma is the result of an aberration of the

normal bone growth and remodeling process. However, studies targeting this particular subject have

yielded inconclusive results.

ETIOLOGY

The exact cause of osteosarcoma is unknown. However, a number of risk factors are apparent, asfollows,

Rapid bone growth: Rapid bone growth appears to predispose persons to osteosarcoma, assuggested by the increased incidence during the adolescent growth spurt, the high incidence

among large-breed dogs (eg, Great Dane, St. Bernard, German shepherd), and osteosarcoma's

typical location in the metaphyseal area adjacent to the growth plate (physis) of long bones.

Environmental factors: The only known environmental risk factor is exposure to radiation.Radiation-induced osteosarcoma is a form of secondary osteosarcoma and is not discussed

further in this article.

Genetic predisposition: Bone dysplasias, including Paget disease, fibrous dysplasia,enchondromatosis, and hereditary multiple exostoses and retinoblastoma (germ-line form) are

risk factors. The combination of constitutional mutation of the RB gene (germline

retinoblastoma) and radiation therapy is associated with a particularly high risk of developingosteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson

syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias,

hypogonadism, and cataracts).

SIGNS AND SMPTOMS:

Symptoms may be present for weeks or months (occasionally longer) before patients are diagnosed.The most common presenting symptom of osteosarcoma is pain, particularly pain with activity. Patients

may be concerned that their child has a sprain, arthritis, or growing pains. Often, there is a history of

trauma, but the precise role of trauma in the development of osteosarcoma is unclear.