Applied Evidence

Your role in early diagnosis & Tx of metastatic bone disease

Author and Disclosure Information



Pathologic fractures occur frequently in cancer patients. Bone destruction leads to a loss of mechanical support which, in turn, causes microfractures and pain. These microfractures can proliferate and coalesce, causing a pathologic fracture, often in weight-bearing bones.6 Breast cancer with lytic lesions is the single leading cause of all pathologic fractures.22 Lung cancer with its short survival time and prostate cancer with blastic lesions are less common causes.23 In the appendicular skeleton, the vast majority of these fractures occur in the femur and humerus.11

Symptomatic metabolic derangements. The most common metabolic disorder is hypercalcemia, found predominantly in patients with hematologic malignancies, squamous cell lung cancer, renal cell cancer, and breast cancer.6,7,12,24 The clinical presentation is nonspecific and can include polyuria, polydipsia, fatigue, constipation, and confusion. The prevalence is estimated to be 13% in breast cancer, 4% in lung cancers, and 1% in prostate cancer, although results in individual studies vary.12 The pathophysiology is multifactorial and often includes osteolytic lesions and an increased circulating level of parathyroid hormone–related peptide, although other mechanisms contribute.25,26 Ultimately, severe hypercalcemia may be fatal secondary to renal failure and cardiac arrhythmias.6,7,12 Paraneoplastic hypercalcemia independently decreases survival; 1 study found the median survival to be 10 to 12 weeks.11

Primary care work-up and diagnosis

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 is important—­particularly so if the patient received chemotherapy or radiation, which can lead to secondary cancers such as leukemia or sarcoma.20 If a primary site of malignancy is unknown, pursue a general review of systems. Clues to the primary site of disease could be a history of chest pain, shortness of breath, hemoptysis, heat/cold intolerance, or changes in bowel/bladder habits. Also ask about risk factors such as smoking, chemical exposure, and sun exposure.

Pointers on radiographic imaging. If you suspect a destructive bone lesion, order appropriate radiographic imaging. Arrange for plain radiographs with at least 2 views of the specific area of interest that include the entire bone along with the joints above and below. Importantly, the entire bone must be imaged before any surgical procedure to avoid periprosthetic fractures from undetected bone metastases around hardware.20 Keep in mind that plain films can miss early lesions, and computed tomography (CT) or magnetic resonance imaging (MRI) may be needed if suspicion of a pathologic process is still strong and especially if a primary malignancy is known.27

Working back to a primary diagnosis

If imaging confirms a suspicious lesion and the patient has no known primary tumor, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan, and refer the patient to an oncologist. If the bone lesion is painful, initiate protected weight-bearing and additionally refer the patient to an orthopedic surgeon.

Continue to: Appropriate laboratory evaluation


Next Article: