Clinical Topics & News

Bone Metastasis: Concise Overview

A review of diagnostic tools for bone metastasis and therapeutic options for pain and symptom relief.

Fed Pract. 2015 February;32(2):24-30

Author(s):

Hong Chin, MD, PhD

Jyung Kim

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References

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Bone metastasis is a relatively common complication of cancer, often developing as they advance, especially in prostate cancer and breast cancer. Bone metastasis can profoundly affect patients’ daily activities and quality of life (QOL) due to severe pain and associated major complications. Prompt palliative therapy is required for symptomatic pain relief and prevention of the devastating complications of bone metastasis.

Epidemiology

Bone is the most common and preferred site for metastatic involvement of cancer. Advanced cancers frequently develop metastases to the bone during the later phases of cancer progression. At least 100,000 patients develop bone metastases every year, although the exact number of bone metastases is not known.¹ Multiple myeloma (MM), breast cancer, and prostate cancer are responsible for up to 70% of bone metastases cases.² Gastrointestinal cancers contribute least to bone metastases: < 15% of all cases.²

The prognosis of bone metastases is generally poor, although it partly depends on the primary site of the original cancer and on the presence of any additional metastases to visceral organs. For example, it is known that survival times are longer for patients with primary prostate or breast cancer than for patients with lung cancer primary tumors.^3,4

Prostate and breast cancers are the most common primary cancers of bone metastases. At postmortem studies, patients who died of prostate cancer or breast cancer revealed evidence of bone metastases in up to 75% of cases (Figure 1). Regardless of their survival expectancy, however, most patients with bone metastasis need immediate medical attention and active palliative therapy to prevent devastating complications related to bone metastasis, such as pathologic bone fractures and severe bone pain.

Clinical Features

The most common clinical symptom of bone metastasis is bone pain, which is usually localized and progresses slowly. Patients may experience worsening of pain at night or while ambulating, depending on the site of bone metastasis. Pain may radiate to the lower extremities; however, radiating pain may not always correlate with nerve impingement. Other symptoms related to bone metastases include hypercalcemia, spinal cord compression, immobility, vertebral fractures, and fractures of the long bones (Table 1). The most common site of bone metastases is the axial skeleton, with the lumbar spine being the most frequent site of bone metastasis as a single site (Figure 2).^5,6

Multiple Myeloma

Multiple myeloma is the second most common hematologic malignancy and is caused by an abnormal accumulation of clonal plasma cells in the bone marrow. Characteristic clinical manifestations include bony destruction and related features of bone pain, anemia (80% of cases), hypocalcemia, and renal dysfunction. Pathologic fractures, renal failure, or hyperviscosity syndrome often develops. More than 20,000 new patients are diagnosed with MM and about 11,000 patients in the U.S. die of MM every year. Multiple myeloma and is twice as likely to develop in men as it is in women. A large number of MM cases are under the care of VAMCs (about 10%-12% of all MM cases).^7,8

Abnormal laboratory tests show an elevated total protein level in the blood and/or urine (Bence Jones proteinuria). Serum electrophoresis detects M-protein in about 80% to 90% of patients. Patients may also present with renal failure. The differential diagnosis includes other malignancies, such as metastatic carcinoma, lymphoma, leukemia, and monoclonal gammopathy.

Pathophysiology

Normal bone tissue is made up of 2 different types of cells: osteoblasts and osteoclasts. New bone is constantly being produced while old bone is broken down. When tumor cells invade bone, the cancer cells produce 1 of 2 distinct substances; as a result, either osteoclasts or osteoblasts are stimulated, depending on tumor type metastasized to the bone. The activated osteoclasts then dissolve the bone, weakening the bone (osteolytic phenomenon), and the osteoblasts stimulate bone formation, hardening the bone (osteoblastic or sclerotic process).

Diagnosis and Evaluation

The most important first step in evaluating bone metastasis in a patient is to take a thorough, careful medical history and perform a physical examination. The examination not only helps locate suspected sites of bone metastases, but also helps determine necessary diagnostic studies.

The radiographic appearance of bone metastasis can be classified into 4 groups: osteolytic, osteoblastic, osteoporotic, and mixed. Imaging characteristics of osteolytic lesions include the destruction/thinning of bone, whereas osteoblastic (osteosclerotic) lesions appear with excess deposition of new bones. In contrast to malignant osteolytic lesions, osteoporotic lesions look like faded bone without cortical destruction or increased density.

Although 1 type of lesion generally predominates, osteolytic lesions are most common in renal cell cancers and MM. Bone metastases in prostate cancers are typically characterized by an osteoblastic picture due to excess bone deposition.