Applied Evidence

Your role in early diagnosis & Tx of metastatic bone disease

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This approach to the work-up and diagnosis will help you to ensure prompt treatment while maximizing your patient’s quality of life.


› Initiate appropriate lab and imaging work-ups for any patient without known malignancy who has a suspicious bone lesion. C

› Prescribe protected weight-bearing for the patient who has a painful bone lesion, and refer promptly to an orthopedic surgeon to prevent pathologic fracture. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Since the early 1990s, modern treatments have steadily reduced overall cancer mortality from primary tumors.1 Consequently, more people are at risk of metastatic bone disease, with subsequent pain and pathologic fractures1,2 and death from metastasis.3 Patients who have bone metastases present with a variety of signs and symptoms including pain, fractures, and metabolic derangements. The primary care approach to work-up and diagnosis described in this article enables prompt treatment, either surgical or nonsurgical, to maintain a high quality of life for patients.

Primary tumors determine types of metastases and prognosis

Metastasis, a complex pathologic process in which cancerous cells migrate to distant organs, implant, and grow,3 is a poor prognostic indicator in cancer patients. Bone is the third most common site of metastasis, behind the liver and lungs.4 While the true prevalence of metastatic bone cancer is unknown, studies have estimated it to be > 280,000 cases in the United States.5

Bone metastases interfere with normal bone metabolism and turnover in several different characteristic patterns. These changes—radiographically defined as osteoblastic, osteolytic, or mixed lesions—are determined by the primary tumor type.

  • Osteoblastic lesions, comprised of new, disorganized bone formation, often occur secondary to prostate cancer, small cell lung cancer, and carcinoid malignancies, among others.
  • Osteolytic lesions, in which bone is destroyed, are more common with breast cancer, renal cell carcinoma, melanoma, and multiple myeloma.
  • Mixed lesions, in which areas of bone destruction and growth are simultaneously found, occur with some GI cancers and a few breast cancers.6,7

Most bone metastases result from carcinomas, of which up to 50% eventually spread to bone, although this process can take 10 to 15 years.8,9 The likelihood of bone metastasis depends on the primary tumor and its stage. Breast and prostate cancer account for most skeletal metastases, although these lesions are often asymptomatic.6,9 Other malignancies, such as ovarian and gastrointestinal, metastasize to bone much less frequently.7,10 Virtually any cancer at an advanced stage can spread to bone. These metastases are usually multifocal and incurable, with the patient’s prognosis varying from a few months to years.6,11,12

Factors that influence prognosis. Metastatic bone disease arising from melanoma and lung cancers has the shortest life expectancy of roughly 6 months from initial diagnosis; metastasis following prostate, breast, and thyroid cancers has the longest, usually 2 to 4 years.11TABLE 113 shows survival estimates from a large Danish population at various time points following bone metastasis diagnosis for several primary cancer types.

One-year, 3-year, and 5-year survival estimates after bone metastasis diagnosis (all) by primary cancer type

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer—even if such a history is remote. It’s important.

When surgical intervention for bony metastasis is required, prognosis is generally poorer, likely due to more advanced disease. The overall 1-year survival following surgery varies, but several large studies have found a rate of around 40% when considering all primary tumors.14,15 The most common metastases, from breast and prostate cancers, have 1-year survivals of around 50% and 30%, respectively, following surgical intervention.16-18

What you’re likely to see on presentation

Bone metastases are one of the leading causes of morbidity in cancer patients from resultant pain, pathologic fractures, metabolic derangements, and reduced activities of daily living.8,19 The most common cause of cancer pain is bone involvement.6 Patients report pain that is usually worse at night, poorly localized, and not alleviated with rest. They often mistakenly relate the pain to an injury.20 The pathophysiology of bone pain is not completely understood but is likely multifactorial and includes inflammatory and mechanical processes.7,21 Spine involvement can lead to stenosis or nerve root compression, with symptoms dependent on level and severity of nerve or cord compromise.20 Overall, the most common site of bone metastasis is the thoracic spine, followed by the ribs, pelvis, and proximal long bones.20

Continue to: Pathologic fractures


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