ETIOLOGY

GENETIC
RAPID ENVIRON-
PREDIS-
BONE MENTAL
POSITION
GROWTH FACTORS

ABBERATION OF
NORMAL BONE
GROWTH
A
F
F
E
C
T
S

FEMUR TIBIA HUMERUS

OTHERS:
42% 14% 10%

SKULL &
JAW
DISTAL PROXIMAL PROXIMAL 8%
FEMUR TIBIA HUMERUS
75% 80% 90%

PELVIS
8%

OSTEOSARCOMA
 PATHOPHYSIOLOGY

Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones near
metaphyseal 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 in
the 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 peak
incidence 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. These
observations 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, as
follows,

• Rapid bone growth: Rapid bone growth appears to predispose persons to osteosarcoma, as
suggested 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 developing
osteosarcoma, 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.