BONE METASTASES

The clinical consequences of bone metastases are:

•  Pain

•  Fractures

•  Cord compression

•  Hypercalcemia (in around 10% of patients)

Bone is the third most common site for metastases. 80% of bone metastases are from breast, bronchus and prostate, and 20% from other cancers (including kidney, thyroid, pancreas, stomach, colon and ovary). Kidney and thyroid are less common cancers but commonly metastasize to bone. 75% of myeloma patients have bone metastases at diagnosis.

In a series of 1,000 autopsies bone metastases were found from the following primary cancers:

Metastases occur most commonly in the axial skeleton (spine, pelvis, skull). Spread occurs through the blood stream. Typically the spine, pelvis and ribs are the earliest sites of metastases. Skull, femur, humerus, scapula and sternum are later sites. In the spine, the vertebral bodies are involved more often than the pedicles. Lumbar and thoracic involvement is more common than cervical. Metastases to the bones of the hands are rare. Renal tumors tend to involve the humerus.

The mechanism of bone destruction by tumor cells involves a disturbance of the normal remodeling process in bone, rather than direct destruction of bone cells. The tumor cells release chemicals, including prostaglandins and parathyroid hormone-like factors, which stimulate bone resorption by osteoclasts (probably by means of carbonic anhydrase). It may become possible to use drugs which inhibit osteoclasts (biphosphonates), to decrease bone resorption or to protect bone from further metastases, since bone resorption may release chemotactic factors that attract tumor cells (the “metastatic cascade”). Most metastases also cause increased osteoblastic (bone forming) activity as well, which shows as “hot spots” on a bone scan.

Diagnosis of bone metastases relies on imaging techniques:

•  X-rays

•  Bone scans

•  Computerized tomography (CT)

•  Magnetic resonance imaging (MRI)

X-rays can detect defects if at least 50% of cancellous bone is replaced by a soft tissue mass (contrast difference). Most metastases are multiple. Metastases not visible to x-ray may show up on a radionuclide bone scan.

Radionuclide bone scans can detect 2mm lesions. Hot spots indicate increased osteoblastic activity from any cause, including degenerative disease. Ideally, both x-ray and scan need to be positive to confirm bone metastases. A bone scan can be negative in purely lytic lesions, sometimes found in myeloma and renal carcinoma.

CT scan is useful to detect early bone destruction, and can visualize lesions undetectable by other means.

MRI scan is particularly useful to detect lytic metastases or involvement of the bone marrow. It can accurately visualize the entire skeleton.

Bone biopsy (needle, trephine or open) may be necessary if a patient presents with bone pain and bone lesions and the diagnosis is in doubt. Biopsy may indicate the primary site (kidney, thyroid).

Bone marrow involvement can occur without cortical bone involvement, but is rare in solid tumors. In one study, 2 out of 213 breast cancer patients had bone marrow involvement with no other evidence of metastases in cortical bone or elsewhere. The bone marrow is an organ site susceptible to metastatic involvement. The patient may require transfusions and may be more susceptible to infections.

The mean survival after diagnosis of bone metastases is around one year, but longer with bone metastases from breast or prostate cancer. Occasionally patients with renal or thyroid carcinoma, who undergo excision of a bone metastasis together with the primary tumor, can survive for years.

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