Metastatic Bone Disease

Metastasis, or metastatic disease, is the spread of cancer from an initial or primary site in one organ or part of the body to a secondary non-adjacent organ or part.

Epidemiology

It is estimated that there are over 20,000 new cases of metastatic bone disease (MBD) in the UK each year.

Although any type of cancer can in theory spread to bone, MBD is most commonly seen in Breast, Prostate, Lung, Renal and Thyroid cancers.

In Breast and Prostate cancer in particular, the incidence of MBD is approximately 70% in advanced disease.

Presentation

The most common presenting feature is pain, usually exacerbated by weight-bearing and often worse at night.

Pathologic fracture occurs in about 20% of patients with MBD.

Patients may also present with symptoms of hypercalcaemia in about 20% of cases. Symptoms include generalised bone pain, nausea and vomiting, polyuria, abnormal heart rhythms, depression, cognitive dysfunction, and in extreme cases depressed consciousness.

Acute spinal cord or neural compression manifests in around 10% of patients, and bone marrow failure presenting as a pancytopaenia has been reported in up to 9% of patients with MBD.

Assessment 

Never assume that a solitary lesion is a metastasis!

A full medical history and examination must be performed and the general condition of the patient assessed.

Baseline blood tests, including a bone profile to look for hypercalcaemia, plasma electrophoresis to screen for myeloma, and tumour markers as indicated by the history and physical.

If the primary source of MBD is unknown, further investigations should be directed to finding it (CT chest/abdo/pelvis, mammogram, etc)

As a minimum, a full length radiograph of the affected bone must be obtained to rule out other lesions within the same bone. An isotope bone scan can help elicit other  sites of MBD, although it is often cold in myeloma.

If diagnostic doubt remains,  or the lesion is solitary, a biopsy is indicated. If done early, it can also help guide other investigations. Read more about the principles of how to biopsy a musculoskeletal tumour.

Assessing Fracture Risk

Mechanical or functional pain is a good indicator of imminent fracture risk, as are avulsion of the lesser trochanter, and >50% erosion through the cortex of a long bone on any view.

Mirels developed a scoring system to help rationalise the decision making process regarding the risk of pathological fracture and when to intervene with prophylactic fixation. The system has four categories scored 1-3, giving a maximum total of 12 points. Patients with scores of 8 and above are at high risk of fracture and should be considered for prophylactic fixation. The categories are:

  • Site: upper limb (1pt), lower limb (2pts), intertrochanteric (3pts).
  • Pain: mild (1pt), moderate (2pts), limits function (3pts).
  • Lesion: blastic (1pt), mixed (2pts), lytic (3pts).
  • Size: (maximal cortical destruction in any view) <1/3 (1pt), 1/3-2/3 (2pts), >2/3 (3pts).

Prognosis, pre-morbid functional status, and the likelihood that the lesion may respond to non-surgical treatment should also be taken into consideration.

Non-Surgical Treatment

Radiotherapy is usually palliative and is generally given in a single fraction. It may prevent a fracture from occurring  if the lesion subsequently heals.

Chemotherapy clearly has a role in chemo-sensitive tumours and should be discussed with oncologists in the setting of the MDT.

Bisphosphonates are a class of drug which block the mechanisms of bone resorption by stimulating apoptosis (programmed cell death) in osteoclasts, the cells which normally resorb bone. Their use is essential in cases of hypercalcaemia related to MBD. Critically, The addition of zoledronic acid to adjuvant endocrine therapy has been shown by Gnant et al to improve disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. You can read the paper by Gnant et al in the New England Journal of Medicine.

Prophylactic Fixation

Read more about the principles for surgical treatment of metastatic bone disease.

References

British Orthopaedic Association Guidance on Metastatic Bone Disease.

Mirels H. Metastatic Disease in long bones. A proposed Scoring System for diagnosing impending pathologic fracture. Clin Orthop Rel Res 1989: 249; 256-264

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Osteosarcoma

An osteosarcoma is a malignant tumour containing cells of mesenchymal origin and which is characterised by the formation of malignant osteoid.  Osteosarcomas are the most common primary bone sarcoma, but osteosarcomas also (rarely) occur in bone – in other words the prefix “osteo-” relates to the production of osteoid matrix rather than an origin in bone.

  • Incidence is around 1-2 per million per annum, which is around 131 new cases in England per annum
  • Osteosarcomas have a peak incidence in the second decade of life, and a smaller peak in the elderly
  • They classically occur in the metaphyseal regions of long bones  where most growth occurs (ie distal femur, proximal tibia, proximal humerus)
The WHO histological classification of osteosarcoma recognises the following groups:
1. Central (Medullary) tumours
  • conventional central osteosarcomas (the most common type)
  • telangiectatic osteosarcoma
  • intraosseous well-differentiated (low-grade) osteosarcomas
  • small-cell osteosarcomas
2. Surface (peripheral) tumours
  • parosteal (juxtacortical) well-differentiated (low-grade) osteosarcomas
  • periosteal osteosarcoma: low to intermediate-grade osteosarcoma
  • high-grade surface osteosarcoma

References:

Bone Sarcomas: incidence and survival rates in England – NCIN Data Briefing. National Cancer Intelligence Network 2010.