Metastatic Bone Disease

Aetiology

  • Spread occurs via Batson’s venous plexus anterior to the vertebral bodies.
  • Haematological seeding occurs more peripherally.
  • Most common tumours metastasizing:
    • Lung
    • Breast
    • Prostate
    • Kidney
    • Thyroid
  • Most common sites of spread:
    • Spine (Thoracic spine most common)
    • Pelvis
    • Proximal ends of long bones
    • Below the elbow and knee (usually lung)

Mechanism of Bone Destruction

  • Tumours secrete factors that influence bone metabolism:
    • PTHrP
    • Vitamin D
    • Tumour necrosis factor
    • Transforming growth factors
    • Upregulate the RANKL pathway

Imaging Characteristics

  • Typically lytic: Lung, thyroid, kidney, GI
  • Typically sclerotic: Prostate (20% lytic), bladder
  • Mixed: Breast
  • Intervertebral discs spared

Pathologic Fracture

  • Lesser trochanter avulsion is pathognomonic

Differential Diagnosis

  • Myeloma
  • Lymphoma of bone
  • Osteomyelitis
  • Primary bone tumours (e.g., low-grade chondrosarcoma)

Diagnostic Work-Up

History

  • Prior malignancy
  • Systemic problems
  • Bone pain and its character
  • Neurologic, bladder, or bowel symptoms

Laboratory Tests

  • Bloods: FBC, CRP, U&E, LFT, TFT, Ca, Clotting, LDH, Alk Phos, Tumour markers
  • Serum & urinary Bence Jones proteins
  • Bone marrow biopsy for myeloma

Imaging

  • Full views of the affected bone
  • Bone scan (may be negative for renal and myeloma)
  • Skeletal survey (if myeloma suspected): skull, spine, pelvis, femora, humeri
  • MRI for spinal lesions (if neurological involvement suspected)
  • CXR
  • CT chest, abdomen, pelvis (finds the primary tumour in 85% of unknown cases)

Common Clinical Scenarios

  1. Multifocal metastasis with a documented history of cancer
    • Treat as metastasis and manage surgically if necessary.
  2. Solitary lesion with a documented history of cancer
    • Careful evaluation before surgery.
  3. Solitary lesion with no history of cancer
    • Assume it is a primary lesion until proven otherwise. Biopsy mandatory.
  4. Cancer patient with bone pain but no lesion on XR
    • Bone scan and MRI to diagnose metastasis.

Biopsy

  • For any lesion where the diagnosis of metastasis is uncertain.
  • True-cut percutaneous or incisional biopsies are effective.

Pathology

  • Metastases show epithelial cell islands with glandular or squamous differentiation.
  • Epithelial cells are keratin positive.
  • Cells have tight junctions and lie in a fibrous stroma.

Pathophysiology of Metastatic Bone Disease

Metastatic Cascade

  1. Primary tumour cells cross the basement membrane into capillaries.
  2. Disseminate through the vascular system.
  3. End up in distant capillary beds and interact with local growth factors.
  4. Tumour cells proliferate with the aid of host growth factors to form metastases.

RANKL/Osteoprotegerin

  • Tumour cytokines stimulate the RANKL pathway.
  • Osteoblasts produce RANKL.
  • Osteoclast precursors have RANK receptors.
  • OPG (a decoy receptor) binds to RANKL, rendering it inactive.
  • OPG is less effective in metastatic disease.

Breast Cancer and TGF-β Vicious Cycle

  • TGF-β, present in bones, is released during turnover.
  • Stimulates breast cancer cells to release PTHrP.
  • PTHrP acts on osteoblasts to produce RANKL.
  • Osteoclast activation causes bone lysis, releasing more TGF-β.

Prostate Cancer

  • Tumour cells secrete Endothelin 1, stimulating osteoblasts to produce more bone.
  • Results in sclerotic metastases.

Biomechanics of Metastatic Bone

Strength Reduction

  • Lesion length > 75% bone diameter = 90% reduced torsional strength.
  • Central 50% cortical lesion = 60% reduced bending strength.
  • Eccentric 50% cortical defect = 90% reduced bending strength.

Fracture Healing in Metastatic Bone

  • Order of likelihood:
    1. Myeloma
    2. Renal
    3. Breast
    4. Lung

Other Complications

Hypercalcaemia

  • Common in breast and lung cancer (due to ectopic PTH secretion).
  • Calcium level does not correlate with the number of metastases.

Thromboembolic Disease

  • Higher risk in malignancy.

Predicting Pathologic Fracture

Non-Spinal Lesions: Mirel’s System

Factor 1 Point 2 Points 3 Points
Size <1/3 diameter 1/3–2/3 >2/3
XR Appearance Blastic Mixed Lytic
Pain Mild Moderate Unable to WB
Location UL LL Per-trochanteric
  • Score >8: 33% fracture risk.

Spinal Lesions – Risk of Fracture

  • Thoracic: >50% body involved, or >25% body + costovertebral joint involved.
  • Lumbar: >40% body involved, or >25% body + pedicle involved.

Management

Non-Operative

  • Indications:

    • Unfit patients.
    • Non-WB bones.
    • Minimal pain.

  • Bisphosphonates: Reduce pain and fracture risk (proven for breast, lung, and prostate cancer).

  • Radiation:

    • Good for pain relief.
    • Good for spinal lesions with neurologic deficit.
    • Do after surgical wounds have healed.

Operative

  • Principles:
    • Span bone with nails.
    • Protect the femoral neck.
    • Augment fixation with cement if ORIF and curettage of bone.
    • Use techniques for stronger fixation.
    • Around joints, use endoprostheses.
    • In hip/acetabulum, use cemented THR with long stems to span bone.
    • Embolize renal cell pre-operatively to prevent bleeding.
  • Spine:
    • Kyphoplasty or vertebroplasty.
    • Vertebrectomy/corpectomy.
    • Anterior/posterior instrumented fusion.
    • Decompress neural elements as early as possible.
  • Adjuvant radiotherapy is very useful post-operatively.
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