Introduction

Bone metastases occur as a result of cancer cells from a primary site or tumour spreading to bone. Cancer cells can spread throughout the body by travelling via the blood or lymphatic system. The most common cancers that metastasise to bone include breast, bronchus, thyroid, prostate and kidney. Up to 50% of patients who die from cancer have bone metastases.

Bone metastases can be classified as osteoblastic, osteolytic or mixed. Osteoblastic metastases are due to the deposition of new bone. This type of metastases are found as a consequence of prostate cancer, Hodgkin's lymphoma and small cell lung cancer. Osteolytic metastases are due to the destruction of healthy bone and are found in renal cell cancer, thyroid cancer, melanoma, non-small cell lung cancer and non-Hodgkin's lymphoma. Mixed metastases occur when both osteoblastic and osteolytic lesions are presents and tend to be due to gastrointestinal and breast cancers.

Epidemiology

  • Incidence: 100.00 cases per 100,000 person-years
  • Peak incidence: 70+ years
  • Sex ratio: 1:1
Condition Relative
incidence
Lower back pain: prolapsed disc5.00
Bone metastases1
Osteoporotic vertebral fracture0.50
Osteomyelitis0.20
Lumbar spinal stenosis0.10
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Bone metastases arise from a primary cancerous tumour. Therefore, the risk factors for bone metastases are similar to those that cause the primary tumour. The most common primary cancers that lead to bone metastases are:
  • Breast
  • Bronchus
  • Thyroid
  • Prostate
  • Kidney

Clinical features

Bone metastases can be asymptomatic if small. However, bone metastases can present in a variety of ways:
  • Pain.
    • Characteristically, bone metastases cause severe pain that often wakes a patient from sleep.
    • Classically, the pain caused by metastases is described as a gnawing pain, similar to toothache.
    • In one study, 91.6% of patients with metastatic bone disease experienced pain
  • Weight loss.
  • Symptoms of hypercalcaemia
    • Bone pain, muscle weakness, thirst, excessive urination, confusion, malaise.
    • When hypercalcaemia is found, 80% of patients are found to have metastases.
  • Reduced mobility.
  • Pathological fracture.
  • Rarely, paralysis and weakness if in the spine and compressing a spinal nerve root.
  • Rarely, presents as an acute-onset spinal cord compression

If bone metastases are suspected from a clinical history, it is important to examine the patient to find the primary site or tumour.

Investigations

If a clinical history and examination lead you to suspect the patient may have bone metastases, it is an important differential to confirm or rule out. If there is only one small area that causes pain, a plain x-ray may be best as the pathology may or may not be linked to the original cancer. However, if there is widespread pain or the patient is newly diagnosed with cancer, a whole-body bone scintigraphy scan may be more appropriate.

Bone scintigraphy uses nuclear medicine to visualise areas of increased bone turnover. Technetium-99m is injected intravenously and a gamma camera is used to visualise areas of increased osteoblastic activity. It is normal for there to be symmetrical areas of osteoblastic activity in a healthy adult, but if there is increased uptake of the Technetium-99 or it is asymmetrical, it can indicate pathological processes such as fractures, malignancy and Paget's disease, amongst others. On the scan, there should also be darker areas at the kidneys and bladder as the Technetium-99 is excreted via the kidneys. If the kidneys and bladder are not seen on the scan, this is a worrying sign and may be due to a severe bone disease or bone metastases which are taking up all of the Technetium-99 so none is needed to be excreted.

If the patient presents with pain and features of nerve involvement such as weakness or paralysis, it would be more appropriate to consider a CT or MRI scan as it is easier to visualise soft tissues and if there is any nerve compression.

If bone metastases are found in one area, the whole body should be scanned using bone scintigraphy to find any other areas affected.

Other investigations to consider include blood tests, particularly if the primary site is unknown. Depending on the patient's symptoms, you may wish to consider:
  • FBC (may show anaemia)
  • U&Es
  • LFTs
    • ALP is present in bone and released during the breakdown of bone. It is very likely that a patient with bone metastases will have an increased level of ALP on their blood test, but an isolated rise in ALP does not necessary mean that they have bone metastases.
    • Other causes of an ALP rise include: recent fracture, vitamin D deficiency or a primary bone tumour.
  • CRP
  • Serum calcium
    • Hypercalcaemia can be caused by the primary malignancy or be due to bone metastases, caused by increased osteoclastic activity.
+It is necessary to treat the patient urgently with IV bisphosphonates.
  • Multiple myeloma screen
  • Tumour markers: depending on the demographic of the patient, these may include Ca125, PSA, alpha-fetoprotein and lactate dehydrogenase.

If the primary site is unknown, consider a CT chest/abdomen/pelvis.

Differential diagnosis

As bone metastases most commonly affect the spine, there are a range of differential diagnoses that may present similarly. As a patient gets older, bone metastases become a more likely diagnosis but it is also important to consider other pathology:
  • Spinal stenosis
    • Similarities: both can cause weakness and numbness in the lower limbs
    • Differences: with bone metastases, the pain will be present at rest and may wake a patient from sleep. With spinal stenosis, the pain is present on walking and will be relieved after sitting down.
  • Osteoporotic vertebral fracture
    • Similarities: in both conditions, the pain may be constant and limit movement. Both osteoporosis and bone metastases may cause fragility fractures.
    • Differences: osteoporosis is more common in the general population and is much more common in women than men. Bone metastases are slightly more common in men than women.
  • Lumbar disc prolapse
    • Similarities: both cause back pain, both may limit mobility.
    • Differences: in lumbar disc prolapse, often there is a sudden onset of pain e.g. after lifting something heavy, whereas the onset of pain from bone metastases may be more insidious. Pain from a disc prolapse should resolve within 2-6 weeks, whereas the pain from bone metastases may become progressively worse.
  • Multiple myeloma
    • Similarities: both may cause hypercalcaemia and pathological fractures. Both may look similar on x-ray with 'punched out lesions' common with multiple myeloma. However, bone metastases can also look denser on x-ray.
    • Differences: multiple myeloma is a primary malignancy and can cause bone metastases. Multiple myeloma may also cause anaemia and renal failure.
  • Bone infection
    • Similarities: both cause pain
    • Differences: with a bone infection such as osteomyelitis, the patient may feel systemically unwell and have an acute onset of symptoms, whereas with bone metastases, the patient may be systemically well and have a more insidious onset of symptoms.
  • Lymphoma
    • Similarities: patients with bone metastases and patients with lymphoma may both suffer with B symptoms such as night sweats, fevers and weight loss.
    • Differences: patients with lymphoma may notice non-bony swellings of lymph nodes.

Management

Once the diagnosis of bone metastases has been confirmed, it is important to establish where the primary tumour is. Once this has found, referral to the appropriate specialist teams and oncology is necessary.

Oncology management will depend on the stage of the primary tumour and extent of metastases. Treatment may include surgery to stabilise affected bones, radiotherapy, chemotherapy, or hormone therapy, but this will depend on the primary tumour and be decided by the specialists involved.

Radiotherapy can be used palliatively on bone metastases to reduce pain and improve quality of life. Denosumab is a monoclonal antibody that helps to slow the progression of bone metastases. It works by inhibiting osteoclasts and therefore slowing the rate of bone turnover and bone loss.

Other management will include:
  • Adequate analgesia to relieve pain and increase mobility
    • Start with simple analgesia like NSAIDs and paracetamol, before moving onto weak and strong opioids.
    • Pain relief can be given orally, subcutaneously via a syringe driver or some patients may prefer transdermal patches.
  • Bisphosphonates
    • Reduce risk of fracture and bone destruction
    • Can improve bone pain
  • Physiotherapists and Occupational Therapists may be involved to improve mobility and help with adaptations needed.

Complications

Complications of bone metastases include:
  • Pain
    • The pain caused by bone metastases can be severe and needs to be addressed.
    • As above, management of pain caused by metastases can be lessened by a combination of analgesia, bisphosphonates, radiotherapy or denosumab.
  • Pathological fractures
    • Particularly in the spine, bone metastases can cause fractures which may require surgery to treat.
    • There may be an increase in intensity of pain shortly before the bone fractures. There may also be no-to-little trauma preceding the fracture.
  • Hypercalcaemia
    • Hypercalcaemia is a poor prognostic factor and requires immediate treatment, even if not symptomatic.
    • Symptoms generally do not correlate to severity of hypercalcaemia, with some patients remaining asymptomatic with high serum concentrations of calcium and others becoming very symptomatic with only a small rise in serum calcium.
  • Spinal cord compression
    • Can be caused by direct extension of the metastases into the spinal cord or by collapse of a vertebra.
    • Symptoms of spinal cord compression include: weakness or numbness of limbs, bladder and bowel dysfunction, sensory loss and nocturnal spinal pain.
    • Patients with signs of spinal cord compression should be treated as a medical emergency and require an urgent MRI.