Although most surgeons and patients choose internal fixation of fractures as the most effective and expedient way to control pain and restore function, external fixation is occasionally successful. It is particularly suitable for (1) patients with extensive localized disease that cannot be immobilized by internal means; (2) preterminal patients in whom analgesic modalities such as narcotics or rhizotomy can control symptoms, or (3) patients in whom infection, nadir sepsis, pneumonia, or other temporary medical problems prevent surgery. These nonoperative measures can be used in the hospital and translate well to outpatient, home, or hospice care sitations. Stabilization of a fracture requires control of the proximal and distal fracture fragments.
TUMOR EXCISION

The secondary metastatic deposit should be excised under most circumstances. Treatment options consists of intralesional excision, wide excision, or other excision method plus a surgical adjuvant.
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Intralesional therapy either occurs at the time of biopsy or as a planned intervention. Once the biopsy confirms metastatic disease, a decision must be made whether to remove all gross disease, in essence debulking the tumor, or to rely on external radiation and systemic therapy to control the lesion. The surgeon must anticipate this eventuality and discuss the treatment options with other members of the oncology team. Only in this way is it possible to prepare the patient and his or her family appropriately before surgery. The variety of treatment options and contingencies make such a discussion and education process difficult. It is the benchmark of clinical skill to guide a patient and family through the decision-making process. Judgment, sensitivity, and skill are needed to integrate the biopsy process with overall tumor management. It is far more than a technical surgical exercise. The combination of tumor removal and bone stabilization best meets the goals of diagnosis, pain relief, and functional restoration. This is particularly so because biopsy further disrupts already weak bone and the structural restoration process is long and undependable.

Intralesional curettage of tumor in and around the fracture site is the principal strategy. It is important in several respects. Tumors have a high degree of vascularity so extensive hemorrhage occurs frequently. When the lesional tissue can be removed back to normal bone, the tumor vessels can contract, seal off, and stop the bleeding. Tumor removal is therefore important in controlling hemorrhage. Eliminating the gross tumor achieves an immediate “partial response” that could take weeks to achieved by other methods. Furthermore, it identifies the remaining structural bone. The resultant defect can be filled much more effectively with methylmethacrylate cement. This gives better tumor control and long-term stability to the fractured bone.

Extralesional excision can be accomplished by either marginal or wide excision. The appeal of complete local excision is obvious. It is the most effective way to achieve local tumor control. It obviates the need for adjuvant radiotherapy and is the fastest, most effective way to eliminate the biologic contribution to pain while correcting the structural deficiency. Isolated solitary metastases should be evaluated for potential resectability. Occasional cures are reported following resection of bone metastases, but they are infrequent. Radical ablative surgery is usually not appropriate. Dispensable bones such as fibula, iliac wing, ribs, clavicle, and scapula are the most appropriate for excision. Occasionally, solitary metastases in the femur, ischium, proximal humerus, and phalanges provide opportunities to cure the patient. Long intervals between primary tumor presentation and the development of a secondary deposit auger well for cancer respectability. Patients with a long projected survival, such as those with renal or thyroid cancers, are the most suitable to undergo radical excision of metastases. Unfortunately, the sacroiliac region and spine are common sites for “solitary” metastases. The tumors are large and bulky, and the surgery is dangerous. Plasmacytomas should be considered for resection. Even if systemic disease later develops, some clinicians contend that survival may be prolonged in surgically resected cases. Isolated thyroid lesions, particularly follicular or papillary carcinomas, are more effectively treated by resection than by radiation, according to Niederle.
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Surgical adjuvants are helpful whether intralesional or excisional procedures are considered. Preoperative angiography and tumor embolization greatly reduce blood flow and intraoperative hemorrhage. This is also helpful in reducing the hypervascularity around the tumor. Marcove pioneered the use of cryosurgery in metastatic disease. Cryosurgery extends the surgical margin without causing an immediate disruption in the surrounding bone structure. Liquid nitrogen freezes and sterilizes the host bed when the temperature is reduced to below -30C°. Typically, three freeze-thaw cycles, achieving approximately 70% to 80% tumor kill from each cycle would be performed. Although long-term cure had been reported for renal and lung cancers by Marcove, the goal is local tumor control for the short and intermediate term. This is particularly suited for cancers that have failed to respond to systemic treatment, local radiation therapy, or both and in which local tumor progression is expected. Tumor control can prevent destabilization of the internal fixation device. Radiation therapy is the principal surgical adjuvant. It should be delivered to the entire surgical field and extend the length of any internal fixation device.

This imaging technique is the best method to evaluate bone marrow, the first site of most metastatic cancers. It is especially sensitive for round cell lesions such as leukemia, lymphoma, and multiple myeloma that replace the marrow space. The high fat content of marrow translates to high signal intensity or brightness. This essentially provides a contrast medium juxtaposed with tumor. Three-dimensional anatomic delineation is also very good throughout the skeleton. MRI is especially suited to the spine because it is sensitive for tumor, and shows sagittal alignment, cross-section, and crisp detail of dural and spinal cord compression. Of particular concern is to distinguish pathologic fracture due to osteoporosis from that due to tumor. This distinction is particularly important for postmenopausal women, who may suffer from both conditions and be subject to hormone manipulation as well. MRI is a helpful but imperfect discriminator.
ANGIOGRAPHY

Angiography is used as a therapeutic adjunct more than for the diagnosis of metastatic disease. Embolization of tumor for pain relief or to reduce vascularity is of great therapeutic value. Diagnostic use is limited to the preoperative identification of the artery of Adamkowitz before treating thoracic spine lesions.
BONE HEALING
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Cancer precludes bone healing in most pathologic fracture situations. The rapid growth of metastatic cancers overwhelms the healing response. Few studies have been done to measure this process. Gainor and Bruchert evaluated 129 long bone fractures. Healing occurred in 45 cases (36%). Among patients who live 6 months or more, 50% of fractures healed. The best healing rates were in multiple myeloma (67%), kidney (44%), and breast cancer (37%). No patients with lung cancer healed their fracture. The length of patient survival correlated best with fracture healing rates, although healing was considered multifactorial. Five factors determined the healing of pathologic fractures.
DIAGNOSIS

Lung, colorectal, and melanoma tumors failed to heal. These lesions tended to occur late in the course of disease and were purely lytic. Multiple myeloma and breast and kidney cancers healed most frequently. These lesion often occurred early in the course of disease when patients had more therapeutic options available. Bone formation and reossification were often seen in these cases.
INTERNAL FIXATION

Rigid internal fixation supplemented with bone cement increases the probability of bone union. Alignment and position of bone fragments are also important as in the case of nonpathologic fractures. Bone cement not only contributes to stability but may present a mechanical obstacle to tumor regrowth in the fracture region.
SURVIVAL

Longer survival occurred in patients with earlier or more slowly progressing disease. This correlated with improved healing rates for patients living longer than 6 months.
POSTOPERATIVE RADIATION

High doses (greater than 3000 cGy) were associated with poor healing.
CHEMOTHERAPY

There were no data regarding the impact of chemotherapy of healing in this series.

Chemotherapy effects in animal models are difficult to extrapolate to the human condition because of the variation in dose intensity and treatment scheduling. Most studies suggest that healing is reduced 50% by common agents such as methotrexate or doxorubicin.

Other systemic factors may make a minor contribution to fracture healing. For example, osteoporosis, hormone manipulation, cachexia, and other factors may be important. Newly released bisphosphonates reportedly benefit bone healing in experimental animal models. These agents have not been shown to augment healing in a clinically significant way, however. The magnitude of osteoblast suppression and the adverse effect of radiation on healing is debated. Doses as low as 2000 cGy begin to interfere with normal fracture healing in animals. In adults, fracture healing is very difficult to achieve when more than 5000 cGy is administered, although healing has been reported in children with fractures through heavily irradiated bone treated for Ewing’s sarcoma.

Diagnosis

Technicium diphosphonate bone scans are extremely valuable in identifying occult lesions and diagnosing metastatic disease. Whereas nearly 30% of bone mineral must be lost for a lesion to appear on plain radiograph, bone scans show disease much earlier. This test (1) is an essential part of cancer staging for skeletal metastases, (2) identifies sites of symptomatic disease, and (3) identifies potential sources of referred pain. Certain cancers such as lung and melanoma grow rapidly and evoke little reactive bone formation, leading to false-negative scans. Multiple myeloma is also notorious for having false-negative bone scans.
Treatment Evaluation

Bone scan can be used to evaluate the response to chemotherapy, hormone therapy, or radiation therapy. Much more sensitive than plain radiographic evaluation, it reflects the biology of the lesion and the extent of the host response. The method has been most useful in evaluating the treatment of breast cancer patients. Up to 15% of patients will have an initial increase in activity, the so-called flare phenomenon. This reflects new bone formation around the quiescent lesion. Over time, the surrounding bone can heal, and osteoblast activity, estimated by the bone activity, will diminish. Development of “new” scintigraphic lesions early in treatment does not necessarily reflect disease progression; sometimes it reflects healing and ossification of areas where the tumor did not evoke a response initially.
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One limitation of this technique is that it merely measures metabolic activity and does not evaluate the structural integrity of the skeleton. Biologic control of the tumor does not translate into mechanical restoration of the skeleton in all cases. Therefore, the bone scan findings must be evaluated in parallel with plain radiographs, CT scan, or both.

Radioimmunoisotope scanning holds promise to improve both the sensitivity and specificity of bone scans in patients with metastatic disease. As better, humanized antibodies become available, both the diagnosis of occult disease and the monitoring of established disease will become more reliable. Preliminary results in imaging breast cancer metastases are encouraging.
COMPUTED TOMOGRAPHY
Computed tomography is very effective in evaluating the three-dimensional integrity of bone and to better visualize abnormal lesions identified on bone scan. This is helpful to confirm the presence of metastatic disease, particularly when evaluating tumors in the pelvic and shoulder girdles. Spine lesions can also be seen by CT, but are probably better evaluated by magnetic resonance imaging (MRI) in most circumstances. In all locations CT demonstrates the bone mineral content and cortical integrity better than MRI, at present. These characteristics thus reflect the structural integrity of the diseased bone. Commonly MRI will show extensive marrow involvement in a bone while the structural strength is preserved. CT helps to discriminate between the presence of cellular and structurally significant disease.

RADIOGRAPHY

Radiographs are the fastest, least expensive, and most readily available technique to diagnose metastases. Even though other techniques may be more sensitive, the radiograph gives the best integration of overall bone structure and alignment. It remains the cornerstone for evaluation of the mechanical properties of bone and correlates best with clinical features. It should therefore be the first test ordered in the evaluation of pain. Radiographs greatly assist surgical planning. The ease of measuring and monitoring lesions makes the plain radiograph indispensable.

Disease spreads diffusely within long bones. A frequent problem occurs in patients with proximal femoral metastases in whom radiographic evaluation is confined to the hip and potential lesions distal in the femur are overlooked. It is very important to image the entire bone before internal fixation so that all lesions can be stabilized during the same operative procedure.

Metastatic disease is characterized by the presence of multiple bone lesions. Single metastases occur rarely and must be differentiated from primary bone tumors. Typically, the so-called “solitary metastasis” is merely the first of many lesions to be identified. Thyroid and renal cancers and myeloma (plasmacytoma) are the most likely to present as isolated metastases. Even these favorable cases typically develop widespread disease, suggesting that there is unrecognized dissemination of cancer at the time the first bone metastasis is identified.

There are three typical radiographic patterns of metastatic disease: osteolytic, osteoblastic, and mixed. Because of variations in the bone microenvironment and clonal differentiation of tumors, different patterns may exist throughout the skeleton or within one bone. This is also seen during the course of therapy, where one lesion may be partially treated. Osteoblastic areas seen radiographically correspond to the reaction of the host bone to the metastases. They are not the cancer itself. Fast-growing tumors tend to have a mixed pattern where bone reaction cannot keep up with the tumor rate of growth. The reactive bone often lacks mechanical strength despite its deceptively strong appearance. It forms in a random pattern lacking Haversian structure. Just as in Paget’s disease, disorganized sclerotic bone can be weak and incur fracture.

Periosteal changes may occur for several reasons. Rapidly growing tumor can elevate the periosteum, causing an irregular periosteal reaction. Lung cancer and prostate cancer with cortical involvement commonly show this pattern. Stress fracture through the underlying bone can also be associated with periosteal elevation. Nevertheless, periosteal elevation is usually a hallmark of primary bone neoplasm. Sarcoma should be excluded when there is periostitis.

TREATMENT GOALS

Pain relief and bone stabilization are the methods by which the medical goals of patient comfort and independence are achieved. Symptomatic relief is usually satisfactory from radiation therapy and chemotherapy. Most patients without a fracture do not require surgery for the bone metastasis. Fractures are best treated by operative internal fixation. Even when fractures can heal by nonoperative therapy, the protracted treatment time is inappropriate. The duration of any treatment must be carefully considered in a patient with a limited life expectancy. For example, in a patient with a 4-month life expectancy, 2 weeks of treatment for bone metastases may be appropriate, whereas 2 months of treatment would be excessive. Finally, the goal of surgical intervention is to allow immediate weight bearing. If this cannot be achieved, then surgery should be avoided. Prosthetic replacement and stabilization with polymethylmethacrylate are frequently selected, whereas such techniques would be avoided in the treatment of nonneoplastic fractures.

Generally, pathologic fractures through weight-bearing bones (e.g., femur) should be treated if the patient has more than 1 month to live, whereas non-weight-bearing bones should be treated if life expectancy is more than 3 months. Indications for treating impending fractures are discussed later. Impending fractures are worth fixing if it will help eliminate the need for narcotic analgesics or will reduce the patient’s overall pain by approximately 50%, and equally effective nonoperative treatments are lacking.

Pain is the principal symptom of bone metastases. It is composed of a biologic and a mechanical aspect. The biologic component reflects the rate of tumor growth and biologic characteristics of the tumor. The increased blood flow and cytokines are important causes of bone pain and contribute to bone lysis. Finally, nerves within bone have recently been described; these transmit many neuropeptides such as substance P and calcitonin gene-related protein, which are involved in both pain modulation and bone metabolism.

Bone loss reduces bone strength and stiffness, increases strain, and leads to activity-related symptoms: so-called “mechanical bone pain.” Pain from mechanical insufficiency often increases after a treatment reduces turgor within the tumor. Bone collapse and even dislocation can then occur. This is seen most often in “successful” treatment of spinal lesions. Late sequelae such as osteonecrosis and fatigue fracture are other manifestations of mechanical insufficiency.

The initial pain pattern of a metastasis mimics that of primary bone tumors and osteonecrosis. The symptoms are intermittent but may be sharp and severe. Pain tends to be worst at night and maybe partially relieved by activity. As the lesions progresses, symptoms become more constant and take on more of a mechanical character.
General systemic issues are of concern in patients with skeletal metastases. Bed rest or reduced activity is frequently recommended for the bone pain of skeletal metastases. This produces general disuse and weakness. Manifestations commonly include atelectasis and thromboembolic disease. Careful screening for these conditions is imperative. Doppler ultrasound tests are convenient and sensitive to identify deep vein thrombosis. Loss of ambulatory ability is a poor prognostic factor in metastatic disease, particularly spine disease. Performance status should be specifically quantified as part of the preoperative evaluation.
DIAGNOSIS

Plain radiography remains the most specific test to diagnose bone diseases. Scintigraphy is extremely sensitive and practical because it can screen the entire body at one time. Certainly, any abnormality found on bone scan should be assessed with plain radiographs. Only when the diagnosis cannot be discerned from clinical information and these baseline tests should magnetic resonance imaging (MRI) be obtained.

Solitary bone lesions warrant a biopsy before treatment. Primary bone sarcomas occur in the population particularly under consideration. Lytic phases of dedifferentiated chondrosarcoma and Paget’s sarcoma can also produce pathologic fractures. These must not be confused with the pathologic fractures of metastatic disease. A firm diagnosis must be obtained before internally fixing such a fracture.

CT-guided needle biopsy is usually satisfactory when the lesion is osteolytic (diagnostic accuracy, 80%). When the lesion is osteoblastic or there is a thick overlying cortical rim, it is extremely difficult to insert a needle and obtain an adequate tissue sample. Such cases necessitate open surgical biopsy. Whether the biopsy is performed by closed or open technique, fracture risk is worsened by the new hole in the bone cortex. Weight bearing must be protected until bone healing occurs. Experimentally, this requires at least 6 weeks. Adequate tissue is necessary to perform special studies if required. For example, recently, the spectrum of Ki-1 lymphomas has been noted and these tumors frequently mimic metastatic carcinomas. Sufficient tissue for immunohistochemical studies should always be obtained.