Bone metastases
- Lesion
Most cancers in bone came from somewhere else, usually prostate, breast, lung, kidney or thyroid; they eat or build bone.
What it is
Metastases are by far the commonest malignant tumours in bone. In adults, about four of every five come from the prostate, breast, kidney, lung or thyroid; in children, neuroblastoma, Wilms tumour, osteosarcoma, Ewing sarcoma and rhabdomyosarcoma. They favour the red-marrow axial skeleton: vertebrae, pelvis, ribs, skull and proximal femur, partly through the valveless vertebral venous plexus. Tumour cells alter local remodelling: most metastases are lytic, by recruiting osteoclasts through PTHrP and RANKL, while prostate cancer is typically blastic.
Structure
- Lytic metastasis: tumour nests in the marrow with active osteoclasts and lost trabeculae.
- Blastic metastasis: tumour cells with dense reactive woven bone laid down by osteoblasts.
- Immunohistochemistry identifies the primary: PSA and NKX3.1 for prostate, GATA3 for breast, TTF-1 for lung, PAX8 for kidney and thyroid, thyroglobulin for thyroid.
- Bone scan is often positive in blastic disease and may miss purely lytic myeloma.
Step by step
- Tumour cells enter veins and reach the marrow sinusoids, especially through the vertebral venous plexus.
- They adhere to bone matrix and marrow niche cells.
- Tumour PTHrP, IL-6 and other factors raise RANKL on osteoblasts; osteoclasts resorb bone.
- Resorbed matrix releases TGF-β and IGFs, which stimulate the tumour further: the vicious cycle.
- In blastic metastases, tumour endothelin-1 and Wnt signals drive osteoblasts to build disorganized bone.
Common primaries and their bone lesions
| Primary | Usual pattern | Clue |
|---|---|---|
| Prostate | Blastic | High PSA; lumbar spine and pelvis |
| Breast | Lytic or mixed | GATA3, oestrogen receptor; spine, pelvis, ribs |
| Lung | Lytic | TTF-1; may also go to hands and feet |
| Kidney (renal cell carcinoma) | Lytic, expansile, vascular | PAX8; bleeds at biopsy |
| Thyroid | Lytic, vascular | Thyroglobulin; follicular type |
| Myeloma (not a metastasis) | Punched-out lytic | Monoclonal protein; bone scan may be negative |
Clinical notes
- New back pain in a patient with a history of cancer is metastasis until proven otherwise; weakness or bladder problems point to cord compression and are an emergency.
- Hypercalcaemia of malignancy causes confusion, constipation, polyuria and dehydration.
- Antiresorptive drugs reduce skeletal events in bone metastases.
Test yourself
Think of the answer, then tap the question to see it.
What is the most common malignant tumour in bone?
Metastatic carcinoma.
Which primary typically causes blastic metastases?
Prostate carcinoma.
How do lytic metastases destroy bone?
Tumour PTHrP and cytokines raise osteoblast RANKL, activating osteoclasts; released matrix factors feed the tumour.
Why are spinal metastases common from prostate and breast?
Tumour cells reach the spine through the valveless vertebral venous plexus (Batson plexus).
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Prostate Cancer (StatPearls (NCBI Bookshelf), 2025); Breast Cancer (StatPearls (NCBI Bookshelf), 2025); Bone Cancer | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.