Metastatic bone lesions (pathological fractures)

Introduction 

More than one million new cases of cancer are diagnosed annually in the United States. The most common primary malignancies that metastasize to the bone are breast, lung, kidney, prostate, and thyroid carcinomas, which account for approximately 700,000 (www.seer.cancer.gov) new cases of cancer annually. Bone pain is often a significant problem in bone metastases, and pathologic fracture can severely restrict the patient's activities and quality of life and lead to complications resulting in death.  

Location 

Skeletal metastases are often multifocal; however, renal and thyroid carcinomas are notorious for producing solitary lesions.  By far the most common location for osseous metastases is the axial skeleton, followed by the proximal femur and proximal humerus. Approximately 10% of all cancer patients develop clinically significant spinal metastases.  In autopsy series, vertebral body metastases were found in over one third of patients dying of cancer (Wong et. al.).

Presentation 

Patients with metastatic bone disease have varied presentations. Lesions may vary from extremely painful / disabling to asymptomatic. Most metastases present with a destructive bone lesion detected on bone imaging. Metastases from lung, renal, and thyroid tumors tend to be entirely lytic.  Breast metastases may be lytic or show a mixed lytic-blastic appearance. The majority of prostatic bone metastases are blastic though lytic lesions do occur. Bone metastases rarely present with an associated soft-tissue mass; the presence of such a mass should increase the suspicion of a primary bone tumor. Fractures after a minor or insignificant injury should always raise the suspicion of an underlying lesion in patients with a previously diagnosed malignancy.  Most symptomatic patients with metastatic bone disease present with mechanical pain, pain at night, and pain that is unresponsive to anti-inflammatory medications and narcotics. Neurological complaints may be the presenting symptoms especially in cases of spinal metastases with associated nerve root or cord compression. It is also common for patients with pelvic metastases to present with leg pain, which mimics sciatica.   

Diagnosis 

Laboratory tests: 

The laboratory workup in a patient with bone metastases can be involved if the primary tumor has not already been diagnosed. A complete blood count (CBC) with a differential is important when working up any suspected malignancy. Elevated erythrocyte sedimentation rates (ESR) and c-reactive protein (CRP) levels signal that an inflammatory process is involved, but cannot consistently differentiate an infectious process from a malignancy. Carcinoembryonic antigen (CEA) is a marker of adenocarcinomas such as colonic, rectal, pancreatic, gastric, and breast. Prostate specific antigen (PSA) levels can help diagnose prostate cancer. A thyroid panel can help eliminate the suspicion of a rare thyroid primary.  Lactate dehydrogenase (LDH) isoenzymes 2 and 3 can suggest a diagnosis of lymphoma. To evaluate for liver cancer, alpha fetal protein (AFP) levels are often obtained in patients with hepatitis C or those that are heavy drinkers. A chemistry panel can be used to assess kidney function and allows calcium and phosphate levels to be followed to detect and avoid the development of malignant hypercalcemia. Urinary N-telopeptices serve as an indicator for bone collagen breakdown, which parallels tumor burden, and can provide a baseline to evaluate treatment progress. 

Imaging: 

High quality, plain radiographs (anteroposterior and lateral views) that show the involved bone including one joint proximal and distal are the standard for initial assessment of metastatic bone disease. Pelvic radiographs should include an anteroposterior view and Judet (obturator and iliac oblique) views of the pelvis.  A significant amount of bone must be destroyed before a lesion will appear lytic on radiographs. Therefore, a patient with a malignancy and bone pain often requires further evaluation despite normal appearing plain radiographs. 

Computed tomography (CT) is the study of choice when looking for bone detail and cortical destruction, but is not adept at assessing marrow replacement.  Magnetic resonance imaging (MRI) on the other hand, is very sensitive to early marrow replacement and can locate metastases prior to their appearance on radiographs and CT, but shows less boney detail.   

Total body radionuclide bone scan is useful in searching for other skeletal sites of tumor involvement.  It is a fairly sensitive technique for the detection of bone metastases and can detect these lesions earlier than plain films; however, one weakness is low specificity. Bone scans demonstrate areas of osteoblastic activity, and the radionuclide accumulates at sites of fracture, infection, degenerative disease, bone metastases, and benign tumors such as hemangioma and fibrous dysplasia.  False negative bone scans are often due to destructive activity that exceeds blastic activity, as in multiple myeloma and in tumors which are confined to the medullary cavity and do not affect the cortex. 

Treatment 

The goals of surgery for impending or pathologic fracture are to provide pain relief and a stable, durable construct that will allow the patient to ambulate shortly after surgery and will last for the life of the patient.  Given the frequent large amount of bone loss, the degree of osteoporosis in the elderly, and the decreased ability of bone to heal at the tumor site, this is often quite a challenge.  Thus the techniques used in these patients differ from those used in young trauma patients in which fixation is placed as a temporary stabilizing measure while fracture healing occurs.  The idea in the fixation of metastatic pathologic fractures is to reinforce or replace the compromised bone with a rigid and durable construct.  This typically requires plates or intramedullary rods with the addition of bone cement to fill the bone defects.  If the fracture is near a joint, and stable and durable fixation cannot be achieved by the described methods, joint arthroplasty may provide a more durable construct and may require less operative time and blood loss. Occasionally, segmental replacement prostheses, which not only replace the joint surface and nearby bone but also replace varying lengths of diaphyseal bone with metal, can be used.  These are typically used in malignant primary tumors of bone where large segments of bone must be resected to achieve cure; however in special cases, they may play a role in metastatic bone disease.  Treatments involving medication, radiation, and are too broad for this article. However, an outline of non-surgical treatments is provided: 

• Chemotherapy
• Radiotherapy
• Prophylaxis against DVT with pharmacologic agents and/or SCD's  
• Bisphosphonates to decrease or delay pathologic fractures due to bone metastases in breast cancer (Hortobagyi et. al.) and multiple myeloma (Berenson et. al.) patients.

Complications 

• Failure of fixation due to insufficient bone quality or fixation construct 
• Nonunion due to local tumor 
• Progression of local osseous metastasis despite radiation therapy 
• Poor wound healing due to poor health, radiation, chemotherapy 
• Complications and early death secondary to poor health status, coagulopathy, and/or inability to mobilize patient due to other impending fractures 

Red Flags and Controversies 

One difficult area of clinical decision making is deciding when to fix impending fractures.  In 1989, Mirels developed a scoring system designed to predict the risk of pathologic fracture due to bone metastases in the extremities.  It is based on the degree of pain, lesion size, lytic vs. blastic nature, and anatomic location as shown in following table.  Mirels recommended prophylactic fixation for a total score ?9.  This is currently the most helpful scoring system, although it has limitations.  The variability in quality of surrounding bone, behavior of metastases from different tumor types, response of these metastases to treatment including radiation, and patient activity level can also have an effect on the probability of fracture.  This system is helpful, but many experts feel that the most reliable predictor of impending fracture is mechanical pain.  Mechanical pain is a physiologic indicator that the involved bone cannot withstand the physical stresses placed upon it, and is therefore at risk of fracture.  As a result, all metastatic lesions in the extremities that exhibit mechanical pain, should be considered for prophylactic fixation.    

Table 1. Mirel's criteria 

Outcomes 

Generally, outcomes are poor in patients with metastatic tumors.  Surgical treatment very rarely can result in cure.  The clinical course varies dramatically depending on the type of primary tumor present.  Patients with more aggressive tumor types (lung) succumb have a much shorter life expectancy than those with less aggressive types (prostate).  However, by achieving the goals of surgery (to provide pain relief and a stable, durable construct that will allow the patient to ambulate shortly after surgery and will last for the life of the patient) can significantly improve the quality of and duration of life in these patients. With advances in diagnosis and treatment of malignancies, patients with metastases will continue to live longer.  Thus we must constantly strive to improve the stability and durability of these constructs.