Osteosarcoma: Causes

Pathogenesis (disease development)

Osteosarcoma is one of the osseous tumors of bone. It arises from mesenchymal stem cells (mesenchyme = part of embryonic connective tissue) and can differentiate into various forms: bone-forming tumors (osteoblastic), cartilage-forming tumors (chondroblastic), connective tissue tumors (fibroblastic), and others. A characteristic feature of osteosarcoma is that its cells form osteoid (soft, not yet mineralized ground substance (matrix) of bone tissue/”immature bone”).

Etiology (causes)

The exact causes of primary osteosarcoma are still unclear. Children and adolescents with genetic diseases such as Paget’s disease (a disease of the skeletal system involving bone remodeling) are more likely to develop osteosarcoma.

Biographic causes

  • Genetic burden
    • Genetic diseases (secondary osteosarcoma).
      • Bilateral retinoblastoma – malignant neoplasm of the eye.
      • Bloom syndrome (BLM) – rare disorder; symptoms: increased tumor risk esp. for leukemias (blood cancers) and solid tumors, photosensitivity, pigmentary abnormalities, fertility disorders, growth disturbances.
      • Li-Fraumeni syndrome – autosomal dominant hereditary disease leading to multiple tumors (including astrocytomas).

Disease-related causes (secondary osteosarcoma).

  • Fibrous dysplasia (synonym: Jaffe-Lichtenstein) – Systemic disease of the skeleton that begins in childhood and may affect only one bone (monostotic) or multiple bones (polyostotic). Due to marrow fibrosis (pathological proliferation of connective tissue) and spongiosis (porous-spongy, pathological remodeling of bone tissue) of the compacta (outer marginal layer of the bone), the affected bones lose load-bearing capacity; sporadic occurrence.
  • Multiple osteochondromas (MO) – multiple bony outgrowths (osteochondomas) of the individual long bones covered with cartilage.
  • Paget’s disease (synonyms: Paget’s disease of bone) – disease of the skeletal system with bone remodeling.
  • Osteonecrosis (ON; bone necrosis; colloquially bone infarction) – due to various causes without the presence of infection (aseptic).
  • Osteomyelitis – acute or chronic inflammation of bone and bone marrow, usually due to bacterial infection; combination of osteitis and myelitis (bone marrow/spinal cord).

Radioactive exposure

X-rays

Tumor therapies

Osteosarcoma is more common in people who have undergone chemotherapy and/or radiatio (radiation therapy) in childhood due to another tumor disease. The aggressive tumor therapies alter the genome (genetic material) of osteoblasts.