Chapter 22: Pathologic Fractures

Rajiv Rajani, Robert T. Quinn

Chapter Outline

Introduction

Pathologic fractures occur in abnormal bone. Weakened bone predisposes the patient for failure during normal activity or after minor trauma. Failure (pathologic fracture) of bone under these circumstances should alert the orthopedic surgeon to the presence of an underlying condition. Successful management of the patient requires recognition, diagnosis, and treatment of the condition affecting the bone. The management of the fracture may be dramatically altered by the associated pathologic condition, and failure to recognize a condition such as osteoporosis or metastatic bone disease may be detrimental to the patient’s life or limb. 
When planning the management of patients with a pathologic fracture and systemic, non-neoplastic skeletal disease, it is best to separate the underlying problem into correctable and uncorrectable conditions. Correctable conditions include renal osteodystrophy, hyperparathyroidism, osteomalacia, and disuse osteoporosis. Uncorrectable conditions include osteogenesis imperfecta, polyostotic fibrous dysplasia, postmenopausal osteoporosis, Paget disease, and osteopetrosis. All of these disorders involve weak bones that are predisposed to fracture or plastic deformation. Fracture callus may not form normally, and healing often occurs slowly. Many of these patients have an increased incidence of additional fractures, delayed union, and nonunion. 
If the underlying process is correctable, appropriate medical treatment should be initiated. If the underlying process cannot be corrected, the condition of the remainder of the skeleton must be considered when planning treatment of the fracture. In the management of patients with systemic skeletal disease, it is important to prevent disuse osteoporosis, which may lead to additional pathologic fractures. 
Osteoporosis is the most common condition associated with pathologic fractures, and the management of patients with this condition may only require minor modifications of typical fracture care. In contrast, the treatment of patients with metastatic bone disease who have actual or impending pathologic fractures necessitates a multidisciplinary approach with different principles applied to fracture fixation. 
This chapter will primarily focus on the evaluation and treatment of patients with metastatic bone disease and actual or impending pathologic fractures. It will briefly cover the management of pathologic fractures in patients with primary benign or malignant bone tumors. Treatment of patients with metabolic abnormalities and decreased bone density unrelated to malignancy will be addressed in a less comprehensive fashion. The majority of patients with pathologic fractures are treated by general orthopedic surgeons. It is important that all orthopedic surgeons have a basic understanding of the principles involved in the care of these patients so that pathologic fractures are recognized and appropriate treatment is initiated. 

Demographics

Currently, an estimated 10 million Americans have osteoporosis, while another 34 million have osteomalacia and are at risk for developing osteoporosis.34 It is a major public health concern for 55% of people who are 50 years or older. Eighty percent of those affected by osteoporosis are women, and approximately 2 million people sustain a pathologic fracture related to osteoporosis each year.34 Of patients older than 50 years of age, 24% who sustain a hip fracture die within 1 year.34 One of every two women will have an osteoporosis-related fracture in her lifetime.17 Spine, proximal femur, distal femur, and distal radius fractures are the most common locations for pathologic fractures in this population. Other skeletal conditions such as Paget disease affect an estimated 1 million people in the United States, while approximately 20,000 to 50,000 Americans have osteogenesis imperfecta while worldwide approximately 300,000 are affected.34 
The American Cancer Society predicts almost 1.6 million new cancer cases will be diagnosed in 2011, and nearly 50% of these tumors can metastasize to the skeleton.50 With improved medical treatment of many cancers, especially those originating in the breast and prostate, patients are living longer. There is an increased prevalence of bone metastasis in this population, which increases the chances that these patients will develop a pathologic fracture. The vast majority of bone metastasis originate from cancers of the breast, lung, prostate, thyroid, and kidney.87 The most common sites of metastasis in the skeleton include the spine, pelvis, ribs, skull, proximal femur, and proximal humerus.99 

Evaluation of the Patient with an Impending or Actual Pathologic Fracture

Clinical

History

A comprehensive evaluation of a patient with a lytic bone lesion or pathologic fracture is essential (Table 22-1).81,99 A thorough history must be obtained to understand the circumstances surrounding the current injury. Certain symptoms should alert the orthopedic surgeon to the possibility of an associated pathologic process (Table 22-2). The degree of trauma required to cause the fracture and presence of prodromal pain before the injury may provide information about the underlying bone strength. Pain is the most common presenting symptom before fracture, ranging from a dull constant ache to an intense pain exacerbated by weight bearing. Patients must be asked specifically about previously diagnosed or treated cancer; otherwise, they may consider themselves cured and not volunteer this information. Specifically, breast cancer can have a long latent period until bony metastases present. A history of radiation is important. Standard review of systems questions about constitutional symptoms such as recent weight loss, fevers, night sweats, and fatigue are important. Questions about relevant risk factors such as smoking, dietary habits, and toxic exposures should be asked. 
Table 22-1
Comprehensive Evaluation of a Patient with a Lytic Bone Lesion
  1.  
    History: Thyroid, breast, or prostate nodule
  2.  
    Review of systems: Gastrointestinal symptoms, weight loss, flank pain, hematuria
  3.  
    Physical examination: Lymph nodes, thyroid, breast, lungs, abdomen, prostate, testicles, rectum
  4.  
    Plain x-rays: Chest, affected bone (additional sites as directed by bone scan findings)
  5.  
    99mTc total body bone scan (FDG-PET scan in selected cases such as lymphoma)
  6.  
    CT scan with contrast: Chest, abdomen, pelvis
  7.  
    Laboratory: Complete blood count, erythrocyte sedimentation rate, calcium, phosphate, urinalysis, prostate specific antigen, immunoelectrophoresis, and alkaline phosphatase
  8.  
    Biopsy: Needle vs. open
 

FDG, fluorine-18-deoxyglucose; PET, positron emission tomography; CT, computed tomography.

X
 
Table 22-2
Factors Suggesting a Pathologic Fracture
View Large
Table 22-2
Factors Suggesting a Pathologic Fracture
  •  
    Spontaneous fracture
  •  
    Fracture after minor trauma
  •  
    Pain at the site before the fracture
  •  
    Multiple recent fractures
  •  
    Unusual fracture pattern (“banana fracture”)a
  •  
    Patient older than 45 years
  •  
    History of primary malignancy
X

Physical Examination

The physical examination should include a thorough evaluation of the affected skeletal region. Palpation of a mass, identification of an obvious deformity, and a detailed neurovascular examination of the extremities are essential. All extremities and the entire spine should be evaluated for additional lesions or lymphadenopathy, as patients can have multiple sites of involvement with bone metastasis, lymphoma, multiple myeloma, or osteoporosis. A physical examination should include careful evaluation of all possible primary sites (breast, prostate, lung, thyroid) and a stool test for occult blood.99 

Laboratory Studies

Laboratory tests will not often make the diagnosis, especially in cases of cancer, but they are supporting data relevant to the overall patient evaluation. A baseline laboratory profile should include a complete blood count with manual differential, erythrocyte sedimentation rate (ESR), serum chemistries, blood urea nitrogen (BUN), serum glucose, liver function tests, protein, albumin, calcium, phosphorus, and alkaline phosphatase. Patients with widespread bone metastasis may exhibit anemia of chronic disease, hypercalcemia, and increased alkaline phosphatase. The hemoglobin is also often low in patients with multiple myeloma. A standard urinalysis is necessary to look for microscopic hematuria, which suggests renal cell carcinoma (RCC), and a 24-hour urine collection is necessary for a complete metabolic evaluation. Serum and urine protein electrophoreses are important to exclude multiple myeloma. Thyroid function tests, carcinoembryonic antigen (CEA), CA125, and prostate specific antigen (PSA) are serum markers for specific tumors that can be useful for particular individuals. N-telopeptide and C-telopeptide are new biomechanical markers of bone collagen breakdown that can be measured in the serum and urine. These markers are used to confirm increased destruction caused by bone metastasis, measure the overall extent of bone involvement, and assess the response of the bone to bisphosphonate treatment.22 
Patients with osteoporosis have normal values for the aforementioned laboratory tests, whereas patients with osteomalacia have low serum calcium and phosphorus, high serum alkaline phosphatase, high urinary phosphorus, and high urinary hydroxyproline values (Table 22-3). Patients with primary hyperparathyroidism have high serum calcium, alkaline phosphatase, and parathyroid hormone levels with low serum phosphorus. They also have high urinary calcium, phosphorus, and hydroxyproline levels. Patients with renal osteodystrophy have low serum calcium with high serum phosphorus, alkaline phosphatase, and BUN levels. When secondary hyperparathyroidism develops in these patients, the serum calcium increases to normal or elevated values with elevated parathyroid hormone levels. Urine values are difficult to assess in patients with secondary hyperparathyroidism caused by abnormal glomerular filtration. Patients with Paget disease have normal values for serum calcium and phosphorus, but markedly elevated levels of alkaline phosphatase and urinary hydroxyproline. PSA is a sensitive measurement of prostate cancer. A value less than 10 ng/mL essentially excludes the presence of bone metastasis. Serum calcium is a measurement of unbound calcium in the serum and, therefore, determination of serum protein is necessary to interpret the calcium level. If the serum protein is lower than normal, the normal range of serum calcium is lowered. 
 
Table 22-3
Disorders Producing Osteopenia
View Large
Table 22-3
Disorders Producing Osteopenia
Disorder Laboratory Value
Serum Calcium Serum Phosphorus Serum Alkaline Phosphatase Urine
Osteoporosis Normal Normal Normal Normal calcium
Osteomalacia Normal Normal Normal Low calcium
Hyperparathyroidism Normal to high Normal to low Normal High calcium
Renal osteodystrophy Low High High
Paget disease Normal Normal Very high Hydroxyproline
Myelomaa Normal Normal Normal Protein
X

Associated Medical Problems

The clinical problems encountered by patients with metastatic bone disease are substantial. Patients often have marked pain or pathologic fractures that leave them unable to ambulate or perform their activities of daily living (ADLs). Patients with spinal fractures may develop neurologic deficits that lead to paralysis. Patients with impending or actual extremity fractures may be forced to remain in bed for prolonged periods of time, predisposing them to hypercalcemia. Anemia is a common hematologic abnormality in these patients. The most encompassing and tragic concern of patients with pathologic fractures from metastatic disease is the general loss in their quality of life. 
Approximately 40% of the 75,000 cases of hypercalcemia diagnosed in the United States each year are related to hypercalcemia of malignancy, most commonly associated with cancers of the lung, breast, kidney, genitourinary tract, and multiple myeloma.78 Much of the remainder is caused by primary hyperparathyroidism. Rarely, the two causes occur simultaneously. The orthopedic surgeon managing a patient with metastatic carcinoma to bone must be aware of the risks, symptoms, and management of hypercalcemia as it can be lethal if untreated (Table 22-4). 
 
Table 22-4
Signs and Symptoms of Hypercalcemia
View Large
Table 22-4
Signs and Symptoms of Hypercalcemia
  •  
    Neurologic: Headache, confusion, irritability, blurred vision
  •  
    Gastrointestinal: Anorexia, nausea, vomiting, abdominal pain, constipation, weight loss
  •  
    Musculoskeletal: Fatigue, weakness, joint and bone pain, unsteady gait
  •  
    Urinary: Nocturia, polydipsia, polyuria, urinary tract infections
X
Hypercalcemia is not usually the presenting sign of malignancy, but it portends a poor prognosis for the patient. As many as 60% of patients with hypercalcemia will survive less than 3 months, and only 20% will be alive at 1 year. Often the symptoms are nonspecific, so it is easiest to diagnose the problem by measuring the serum calcium. There is not a reliable correlation between the severity of the hypercalcemia and the degree of metastatic bone disease. Patients with lung cancer may develop hypercalcemia without obvious bone metastases due to PTH-like proteins made by the tumor, whereas hypercalcemia in multiple myeloma or breast carcinoma correlates with the extent of bone metastases.78 Diffuse osteoclastic activity associated with clinical hypercalcemia can be seen histologically without the presence of metastasis in the bone. 
A treatment plan for the patient with hypercalcemia often requires inpatient care. Vigorous volume repletion is a temporizing measure, so treatment must focus on reducing the degree of bone resorption. This can be accomplished by treating the primary tumor directly or by using bisphosphonates to reduce osteoclastic activity.67 Correction of any electrolyte imbalance or hypercalcemia should be done before surgery. 

Radiographic Investigations

Plain Radiographs

The first and most important imaging study used to evaluate a patient with a destructive bone lesion or pathologic fracture is a plain radiograph in two orthogonal planes.99 The radiographs should be carefully reviewed with attention to specific lesions and overall bone quality. Specifically they should be examined for diagnostic clues such as generalized osteopenia, periosteal reaction, cortical thinning, Looser lines, and abnormal soft tissue shadows. A series of questions to assist in determining the underlying process was popularized by W. Enneking, MD, and can be reviewed in Table 22-5. The entire affected bone should be imaged to identify all possible lesions, and it must be remembered that pain referred to distal sites may be caused by a more proximal lesion. 
 
Table 22-5
Evaluation of Plain Radiographs
View Large
Table 22-5
Evaluation of Plain Radiographs
Question Option Interpretation
1. Where is the lesion? Epiphysis vs. metaphysis vs. diaphysis
Cortex vs. medullary canal
Long bone (femur, humerus) vs. flat bone (pelvis, scapula)
2. What is the lesion doing to the bone? Bone destruction (osteolysis)
3. What is the bone doing to the lesion? Well-defined reactive rim
Intact but abundant periosteal reaction
Periosteal reaction that cannot keep up with tumor (Codman triangle)
Benign or slow growing
Aggressive
Highly malignant
4. What are the clues to the tissue type within the lesion? Calcification
Ossification
Ground-glass appearance
Bone infarct/cartilage tumor
Osteosarcoma/osteoblastoma
Fibrous dysplasia
X
Osteopenia is the radiographic term used to indicate inadequate bone (osteoporosis) or inadequately mineralized bone (osteomalacia). These two disorders cannot be definitively distinguished on plain radiographs, but there are some suggestive differential clues. Looser lines (compression-side radiolucent lines), calcification of small vessels, and phalangeal periosteal reaction are features of osteomalacia or hyperparathyroidism. Thin cortices and loss of the normal trabecular pattern without other abnormalities are more suggestive of osteoporosis. 
When an osteolytic or osteoblastic lesion is noted in otherwise normal bone, the process is most likely neoplastic. It is important to determine whether the lesion is inactive, active, or aggressive. Small osteolytic lesions surrounded by a rim of reactive bone without endosteal or periosteal reaction are usually inactive or minimally active benign bone tumors. Lesions that erode the cortex but are contained by periosteum are usually active benign or low-grade malignant bone tumors. Large lesions that destroy the cortex are usually aggressive, malignant lesions that can be primary or metastatic. A permeative or “moth-eaten” pattern of cortical destruction is highly suggestive of malignancy. Most destructive bone lesions in patients older than 40 years of age are caused by metastatic carcinoma followed in order of incidence by multiple myeloma and lymphoma; however, a solitary bone lesion should be fully evaluated to rule out a primary bone tumor such as a chondrosarcoma, malignant fibrous histiocytoma, or osteosarcoma.99 
The radiographic appearance of bone metastasis can be osteolytic, osteoblastic, or mixed. Osteolytic destruction is most common and occurs in metastases from cancers of the lung, thyroid, kidney, and colon (Fig. 22-1). An osteoblastic appearance with sclerosis of the bone is common in metastatic prostate cancer. Metastatic breast cancer often has a mixed osteolytic and osteoblastic appearance in the bone (Fig. 22-2). The radiographic appearance is determined by the balance of bone destruction by osteoclasts and bone production by osteoblasts. Tumor cells secrete factors that interact with host cells in the bone microenvironment and affect the cycle of normal bone turnover.23,79,95,98 An isolated avulsion of the lesser trochanter is almost always pathologic, and this specific injury should arouse suspicion of occult metastatic disease or lymphoma and an imminent femoral neck fracture (Fig. 22-3).9 A cortical lesion in an adult is usually a metastasis, most commonly from lung cancer.37 
Figure 22-1
Anteroposterior (AP) radiograph of a 55-year-old man with metastatic renal cell carcinoma.
 
He had pain for approximately 3 months prior to presentation. The impending pathologic fracture was treated with plate fixation and cement augmentation after embolization and curettage.
He had pain for approximately 3 months prior to presentation. The impending pathologic fracture was treated with plate fixation and cement augmentation after embolization and curettage.
View Original | Slide (.ppt)
Figure 22-1
Anteroposterior (AP) radiograph of a 55-year-old man with metastatic renal cell carcinoma.
He had pain for approximately 3 months prior to presentation. The impending pathologic fracture was treated with plate fixation and cement augmentation after embolization and curettage.
He had pain for approximately 3 months prior to presentation. The impending pathologic fracture was treated with plate fixation and cement augmentation after embolization and curettage.
View Original | Slide (.ppt)
X
Note the collapse of vertebrae even in blastic metastases.
View Original | Slide (.ppt)
Figure 22-2
Multiple lytic and blastic lesions are noted throughout the thoracolumbar spine, consistent with breast cancer.
Note the collapse of vertebrae even in blastic metastases.
Note the collapse of vertebrae even in blastic metastases.
View Original | Slide (.ppt)
X
Figure 22-3
AP radiograph of an isolated lesser trochanter fracture.
 
This is highly suggestive of an impending fracture of the intertrochanteric region or femoral neck.
This is highly suggestive of an impending fracture of the intertrochanteric region or femoral neck.
View Original | Slide (.ppt)
Figure 22-3
AP radiograph of an isolated lesser trochanter fracture.
This is highly suggestive of an impending fracture of the intertrochanteric region or femoral neck.
This is highly suggestive of an impending fracture of the intertrochanteric region or femoral neck.
View Original | Slide (.ppt)
X

Nuclear Medicine Studies

When a bone metastasis is diagnosed or suspected, the remainder of the skeleton should be evaluated for additional bony sites of disease. Technetium bone scintigraphy is helpful in determining the extent of metastatic disease to the skeleton, as it detects osteoblastic activity and is quite sensitive. Multiple myeloma is falsely negative on a bone scan as are occasional cases of metastatic RCC because of the decreased osteoblastic response to the tumor. More recently, positron emission tomography (PET) scanning has been available but the indications for staging patients with metastatic bone disease are not clear at present.74 For lung cancer, fluorine-18-deoxyglucose (FDG)-PET with correlated CT images is superior to standard CT images for detecting metastatic disease in small lesions.94 It has also been useful in staging patients with lymphoma and monitoring response to lymphoma treatment.56 In a recent study, PET/computed tomography (CT) scanning had higher sensitivity and specificity than PET scanning alone for detection of malignant bone lesions.28 

Additional Staging and Three-Dimensional Studies

Further imaging studies are necessary to search for a primary lesion when metastatic carcinoma to the skeleton is suspected.81 The recommended radiographic staging study is a CT scan of the chest, abdomen, and pelvis with oral and intravenous contrast. A mammogram should also be done if breast cancer is suspected; however, MRI can also be used for early detection. If multiple myeloma is considered, a skeletal survey including skull films is recommended. 
Magnetic resonance imaging (MRI) is not generally used to evaluate metastatic lesions in the extremity, but it is useful in the evaluation of patients with spinal metastasis to define the relationship of tumor to the underlying neurologic structures. A standard angiogram is still useful when embolizing feeding tumor vessels in vascular lesions such as metastatic RCC or multiple myeloma as definitive treatment or before surgery. 

When and How to Perform a Biopsy

A thorough history and physical examination with appropriate imaging studies often leads to the correct diagnosis, particularly in the case of widespread metastatic bone disease. However, a solitary bone lesion in a patient with or without a history of cancer should be biopsied to obtain an accurate diagnosis. Presuming a solitary lesion is a bone metastasis in an older patient may lead to the wrong operation, cause extensive contamination, and potentially compromise the life or limb of the patient if the lesion is actually a primary sarcoma of bone. 
If a tissue diagnosis is necessary, a biopsy must be performed. Either a needle or open incisional biopsy is reasonable depending on the availability of expert musculoskeletal radiologists and pathologists.96 A needle biopsy is usually definitive when differentiating a carcinoma from a sarcoma. Specific immunohistochemical staining may allow determination of the primary site of origin of a carcinoma, most commonly from the lung, breast, thyroid, or prostate. When there is a pathologic fracture through a lytic lesion, the biopsy can be complicated due to bleeding and early fracture callus. The fracture should be stabilized initially with traction or a cast to allow preliminary staging studies to be completed, which may allow the diagnosis to be made on imaging alone, or there may be a different lesion more amenable to biopsy. 
If a needle biopsy is nondiagnostic or unable to be done, a careful incisional biopsy should be performed using oncologic principles so as not to preclude subsequent definitive surgical treatment.68 When possible, the tissue should be obtained from a site near but unaffected by the fracture. The biopsy should be as small as possible, in a longitudinal fashion in line with the extremity, and performed with excellent hemostasis. Tissues contaminated by a postbiopsy hematoma must be considered contaminated by tumor cells. Cultures should always be sent at the time of biopsy to rule out infection, which can be confused radiographically with a tumor. If a definitive diagnosis of metastatic disease can be made on an intraoperative frozen section, surgical treatment of the pathologic fracture can be performed at the same operative setting. If the frozen section is not diagnostic, it is best to wait for the permanent sections before definitively treating the tumor and fracture. 

Impending Pathologic Fractures

Bone metastases are painful even without an associated fracture. Treatment options for known skeletal metastasis include (a) prophylactic surgical stabilization before radiation therapy or (b) radiation and/or chemotherapy without prophylactic fixation.49,99 The term impending fracture is used throughout the literature on metastatic disease, but there are no clear guidelines supported by prospective clinical studies to define this term. Retrospective studies have formed the basis to guide the indications for prophylactic fixation, but they are often limited by the use of plain radiographs, subjective patient information, and an inadequate understanding of the biomechanical factors involved in the bone affected by a neoplastic process.31,72,86 Although experienced orthopedic oncologists may have an intuitive sense for which lesions are at high risk for fracture, there is considerable controversy about what constitutes an impending fracture and little reliable data to guide treatment. 

Classification Systems

Factors necessary for the assessment of fracture risk include the radiographic appearance of the lesion and the patient’s symptoms. Fidler31 assessed preoperative and postoperative pain in patients with impending fractures and found that among patients with 50% to 75% cortical involvement, all had moderate to severe pain preoperatively and none or minimal pain after prophylactic internal fixation. Commonly, a lesion is considered to be at risk for fracture if it is painful, larger than 2.5 cm, and involves over 50% of the cortex.86 In an attempt to quantify this risk, Mirels70 developed a scoring system based on the presence or absence of pain and the size, location, and radiographic appearance of the lesion. Each of the four variables is assigned from 1 to 3 points (Table 22-6). Mirels analyzed 78 lesions previously irradiated without prophylactic surgical fixation. Over a 6-month period, 27 lesions (35%) fractured and 51 remained stable. A mean score of 7 in the nonfracture group and 10 in the fracture group was calculated. The author concluded that lesions scoring 7 or lower can be safely irradiated, while lesions scoring 8 or higher require prophylactic internal fixation before radiation.70 However, this is a general treatment guide and each individual patient’s medical comorbidities should also be considered. 
 
Table 22-6
Mirels Criteria for Risk of Fracture
View Large
Table 22-6
Mirels Criteria for Risk of Fracture
Variable Number Assigned
1 2 3
Site Upper extremity Lower extremity Peritrochanteric
Pain Mild Moderate Severe
Lesiona Blastic Mixed Lytic
Size <⅓ diameter of the bone ⅓–⅔ diameter of the bone >⅔ diameter of the bone
 

Each patient’s situation is assessed by assigning a number (1, 2, or 3) to each aspect of his or her presentation (site, pain, lesion, and size) and then adding the numbers to obtain a total number to indicate the patient’s risk for fracture. Mirels’s data suggest that those patients whose total number is 7 or less can be observed, but those with a number of 8 or more should have prophylactic internal fixation.

X
Subsequently, investigators have attempted to quantify the risk of pathologic fracture in patients with metastatic bone disease. Fracture risk is defined as the load-bearing requirement of the bone divided by its load-bearing capacity. The load-bearing requirement depends on the patient’s age, weight, activity level, and ability to protect the site. The load-bearing capacity depends on the amount of bone loss, modulus of the remaining bone, and location of the defect with respect to the type of load applied.72 A biomechanical study of simulated lytic defects in whale vertebral bodies demonstrated that relative fracture risk in vivo could be predicted by a structural rigidity analysis using cross-sectional imaging data.47 Although this system provides a comprehensive method to determine the risk of pathologic fracture, it is not yet routinely used in the clinical setting. Quantitative CT structural analysis has also been proposed as a method for predicting fracture risk, but it also is not routinely used in the clinical setting.61 
Patients treated by prophylactic stabilization of an impending fracture versus those treated after an actual fracture have the following outcomes: Shorter hospitalization (average 2 days), discharge to home more likely (40%), more immediate pain relief, faster and less complicated surgery, less blood loss, quicker return to premorbid function, improved survival, and fewer hardware complications.13,53 Elective stabilization also allows the medical oncologist and surgeon to coordinate operative treatment and systemic chemotherapy. One critical caveat when treating patients with impending pathologic fractures is that fracture risk is greatest during the surgical positioning, preparation, and draping. When patients are anesthetized, they cannot protect the affected extremity and must rely on the surgical team to proceed carefully. Low-energy fractures will occur after very minor trauma or a twisting movement. If a pathologic fracture occurs, damage to the surrounding soft tissues is minimal compared to traumatic fractures in healthy bone. 
The goals of surgical treatment in a patient with an impending pathologic fracture are to alleviate pain, reduce narcotic utilization, restore skeletal stability, and regain functional independence.49,99 However, the decision to proceed with operative intervention is multifactorial and must be individualized. Factors included in the decision making are (a) life expectancy of the patient, (b) patient comorbidities, (c) extent of the disease, (d) tumor histology, (e) anticipated future oncologic treatments, and (f) degree of pain. Patients with a life expectancy of less than 6 weeks may not gain significant benefit from major reconstructive surgery. However, an accurate prognosis is not always possible, and the decision of whether to proceed with surgery should be discussed with the multidisciplinary team, the patient, and the patient’s family. 

Treatment Options for Patients with Metastatic or Systemic Disease

General Considerations

As stated earlier in this chapter, the most common pathologic fracture is caused by osteoporosis. In most situations, these fractures should be managed in a standard fashion as recommended in the accompanying chapters of this text. Modifications such as the addition of methyl methacrylate or locking plate fixation may be necessary because of the weakened bone.6 Pathologic fractures caused by metastatic bone disease demand special considerations, which will be discussed in further detail. 
Patients with cancer are living longer. More patients are living with bone metastasis. Because of the advances in systemic treatment, pain control, and local modalities including radiation and surgery, the philosophy has changed from one of palliation for immediate demise to aggressive care to improve the quality of remaining life. The local bone lesion can be treated with nonsurgical management (radiation, functional bracing, and bisphosphonates) or surgical stabilization with or without resection. Medical treatment with bisphosphonates has decreased the incidence of pathologic fractures because of inhibition of osteoclast-mediated bone destruction.43,64,65 Patients with small bone lesions, especially in nonweight-bearing bones, are often candidates for radiation therapy rather than surgical stabilization. Surgical intervention is usually employed for large lytic lesions at risk for fracture or for existing pathologic fractures. Postoperatively, external beam radiation is used as an adjuvant local treatment for the entire operative field and implant unless the metastatic lesion is completely resected.92,99 
Patients who present with a pathologic fracture are often medically debilitated and require multidisciplinary care. In addition to an orthopedic surgeon, the comprehensive team includes medical oncologists, radiation oncologists, endocrinologists, radiologists, pathologists, pain specialists, nutritionists, physical therapists, and psychologist/psychiatrists. Nutrition is of particular concern; serum prealbumin should be measured and improved if it is low. This may require the addition of enteral or parenteral hyperalimentation perioperatively. Patients may have relative bone marrow suppression and will require adequate replacement of blood products. Perioperative antibiotic coverage, prophylaxis for embolic events, aggressive postoperative pulmonary toilet, and early mobilization are all instituted as standard treatment. 

Nonoperative Treatment

Bracing an impending or actual pathologic fracture is indicated if the patient is not a surgical candidate. Nonsurgical candidates are those with limited life expectancies, severe comorbidities, small lesions, or radiosensitive tumors.99 The use of a fracture brace works well for lesions in the upper extremity. Patients should limit weight bearing on the affected extremity. A braced lesion may heal with or without radiation therapy. Lesions most amenable to bracing are those in the humeral diaphysis, forearm, and occasionally the tibia. Patients with proximal humeral lesions can be treated with a sling, and those with distal humeral lesions can be immobilized in a posterior elbow splint with or without a hinge. If a patient has multiple lesions requiring the use of all extremities to ambulate, surgical stabilization will provide better support than a brace. 
After treatment for a pathologic fracture, the bone may or may not heal. The factors that influence whether healing will occur include location of the lesion, extent of bony destruction, tumor histology, type of treatment, and length of patient survival. Gainor and Buchert33 determined the most important factor affecting union was length of patient survival. Of 129 pathologic long bone fractures, the overall rate of fracture healing was 34%; however, it was 74% in the group of patients who survived greater than 6 months. Among different tumor histologies, fractures secondary to multiple myeloma were most likely to heal.33 

Operative Treatment

Surgical treatment of metastatic bone disease uses the most current internal fixation devices and prosthetic replacements. The ideal reconstruction allows immediate weight bearing and is durable enough to last for the increased total life span of patients with metastatic bone disease.49,99 It should be assumed that the fixation device used will be load bearing, as only 30% to 40% of pathologic fractures unite even after radiation treatment.12,33 
Depending on the external forces, bone quality, and likelihood of tumor progression, standard internal fixation may be contraindicated. An intramedullary device or modular prosthesis provides more definitive stability. Polymethyl methacrylate (PMMA) is often used to increase the strength of the fixation, but it should not be used alone to replace a segment of bone. PMMA improves the bending strength of a fixation construct and the outcome of fixation in both animal and human studies.42,85 It does not affect the use of therapeutic radiation, nor are the properties of the PMMA affected adversely by the radiation.27 Autogenous bone graft is not generally used in the treatment of extremity fractures from metastatic bone disease. Segmental allografts are also rarely indicated, as they have extremely poor rates of healing after radiation. 
The most expedient reconstruction with the least risk of complication or failure should be used for patients with metastatic bone disease. In the vast majority of cases, this requires metal and PMMA. When a prosthesis is used to replace a joint affected by a metastatic lesion or a pathologic fracture, it should be cemented into the host bone. The goal is to have the patient weight bearing as tolerated after the surgical procedure. Another guideline when treating patients with metastatic disease is to prophylactically stabilize as much of the affected bone as possible. When an intramedullary device is indicated, the entire femur, humerus, or tibia should be treated with a statically locked nail.101,107 For femoral lesions, a reconstruction nail is used to stabilize the femoral neck even if no lesion is present there at the time of surgery. Patients with metastatic disease often develop subsequent lesions and the reconstruction nail is helpful in preventing a future pathologic femoral neck fracture. 
Some carcinomas are relatively resistant to chemotherapy and radiation therapy when they spread to the skeleton. RCC is a notable example. Surgical treatment is often indicated for even small RCC lesions, as they tend to progress despite standard medical treatment and external beam radiation.51,88 Depending on the patient’s expected life span and location of the lesion, open treatment with thorough curettage of metastatic RCC followed by intramedullary fixation and PMMA will decrease the tumor burden.63 Postoperative radiation is often used to prevent growth of the residual microscopic disease.92 When complete resection and joint replacement is performed for metastatic disease, the chances of progressive bone destruction from recurrent tumor are decreased.51,88 
Hypervascular metastases put the patient at risk for life-threatening intraoperative hemorrhage when adequate preoperative precautions are not taken. Metastatic RCC is the most likely lesion to cause excessive blood loss, but metastatic thyroid cancer and multiple myeloma are also hypervascular. When possible, a tourniquet should be used during surgery. However, most metastases occur in the proximal extremities, precluding use of a tourniquet. Excessive blood loss can often be avoided if preoperative embolization is performed by an interventional radiologist within 36 hours of the surgical procedure.15 Patients with metastatic RCC may have only one functioning kidney, so a careful evaluation of their renal status should be performed before injecting nephrotoxic dye for angiography. 

Upper-Extremity Fractures

Twenty percent of osseous metastases occur in the upper extremity with approximately 50% occurring in the humerus. Upper-extremity metastases can result in substantial functional impairment by hindering personal hygiene, independent ambulation, meal management, ability to use external aids, and general ADLs.99 When making decisions about treatment of upper-extremity metastasis, the benefits to quality of life should outweigh the risks of potential surgery. Contractures of the shoulder and elbow are common with or without surgical treatment, and these joints should be kept moving. Gentle pendulum exercises can maintain motion in the shoulder and, with appropriate precautions against using torsion, are safe for most proximal and midhumeral impending fractures. Gravity-assisted elbow flexion and extension exercises can also be performed safely by most patients. 

Scapula/Clavicle

Metastatic lesions to the clavicle and scapula are generally treated nonoperatively with shoulder immobilization, radiation, and/or medical management. Occasionally a large, destructive metastasis will occur in the inferior body or articular portion (glenoid) of the scapula. As pain dictates, these areas of the scapula can be resected. 

Proximal Humerus

Pathologic fractures involving the humeral head or neck are treated with a proximal humeral replacement or intramedullary fixation. If enough bone is available in the proximal humerus, an intramedullary locked device with multiple proximal screws is acceptable and maintains shoulder range of motion.107 PMMA may be required to supplement the fixation. When there is extensive destruction of the proximal humerus or a fracture leaving minimal bone for adequate fixation, resection of the lesion and reconstruction with a cemented proximal humeral endoprosthesis are indicated.54 This modular construct replaces a variable amount of proximal humerus and has a long cemented stem to protect the remainder of the bone (Fig. 22-4). In the face of distal disease progression, it can be modified to a total humeral prosthesis. Involvement of the glenoid is rare, so replacement of this articular surface is generally not necessary. The goal of a proximal humeral replacement is pain relief and local control of the tumor: Shoulder range of motion and stability are often compromised because of poor soft tissue attachments (especially the rotator cuff) to the metal construct. A synthetic vascular graft or mesh sutured to the glenoid labrum and around the prosthetic humeral head can offer some stability. Postoperative radiation therapy is used for patients when intralesional treatment is performed. 
Figure 22-4
 
A: A destructive lesion with pathologic fracture through the proximal humerus due to myeloma. B: After proximal humerus megaprosthetic reconstruction, the patient has reasonable function but limitations in abduction and forward flexion.
A: A destructive lesion with pathologic fracture through the proximal humerus due to myeloma. B: After proximal humerus megaprosthetic reconstruction, the patient has reasonable function but limitations in abduction and forward flexion.
View Original | Slide (.ppt)
Figure 22-4
A: A destructive lesion with pathologic fracture through the proximal humerus due to myeloma. B: After proximal humerus megaprosthetic reconstruction, the patient has reasonable function but limitations in abduction and forward flexion.
A: A destructive lesion with pathologic fracture through the proximal humerus due to myeloma. B: After proximal humerus megaprosthetic reconstruction, the patient has reasonable function but limitations in abduction and forward flexion.
View Original | Slide (.ppt)
X

Humeral Diaphysis

Humeral diaphyseal lesions of fractures can be surgically treated with locked intramedullary fixation or an intercalary metal spacer.19,20,107 Locked intramedullary humeral nails span the entire humerus and provide mechanical and rotational stability (Fig. 22-5). In addition, when inserted in a closed fashion, this type of fixation allows unrestricted radiation to the shaft without fear of incisional breakdown. As previously mentioned, PMMA improves implant stability and supplements poor bone quality when used with surgical stabilization.42 Intercalary spacers offer a modular reconstructive option after resection of large diaphyseal lesions.20 They are used in segmental defects and cases of failed fixation caused by progressive disease. Intercalary spacers can be used for reconstruction after complete resection of a metastatic lesion in the humeral diaphysis, minimizing blood loss in hypervascular lesions and often alleviating the need for postoperative radiation. Damron et al. reported that intercalary spacers provide immediate stable fixation, excellent pain relief, and early return of function.20,45 Plate fixation produces good to excellent functional results in nonpathologic humeral fractures; however, drawbacks for their use in metastatic disease include the need for extensive exposure of the humerus and the inability to protect the entire bone. With disease progression, there is risk of hardware failure when plate fixation is used (Fig. 22-6). 
Figure 22-5
 
A: AP radiograph of a right proximal humerus fracture in a 63-year-old male with metastatic lung cancer. Multiple other metastatic lesions were identified on his surveillance examinations and therefore a decision was made not to proceed with resection. B: A biopsy and curettage was performed with intramedullary nailing of the right humerus. At 1 year, the patient has no pain and full range of motion of the shoulder and elbow.
A: AP radiograph of a right proximal humerus fracture in a 63-year-old male with metastatic lung cancer. Multiple other metastatic lesions were identified on his surveillance examinations and therefore a decision was made not to proceed with resection. B: A biopsy and curettage was performed with intramedullary nailing of the right humerus. At 1 year, the patient has no pain and full range of motion of the shoulder and elbow.
View Original | Slide (.ppt)
Figure 22-5
A: AP radiograph of a right proximal humerus fracture in a 63-year-old male with metastatic lung cancer. Multiple other metastatic lesions were identified on his surveillance examinations and therefore a decision was made not to proceed with resection. B: A biopsy and curettage was performed with intramedullary nailing of the right humerus. At 1 year, the patient has no pain and full range of motion of the shoulder and elbow.
A: AP radiograph of a right proximal humerus fracture in a 63-year-old male with metastatic lung cancer. Multiple other metastatic lesions were identified on his surveillance examinations and therefore a decision was made not to proceed with resection. B: A biopsy and curettage was performed with intramedullary nailing of the right humerus. At 1 year, the patient has no pain and full range of motion of the shoulder and elbow.
View Original | Slide (.ppt)
X
Figure 22-6
AP radiograph of the left humerus in a 57-year-old man with multiple myeloma.
 
Initial radiographs showed a small lesion and minimally displaced fracture. Plate fixation was performed but was inadequate as the tumor progressed, resulting in massive bone loss. Ultimately, the patient was treated with a shoulder disarticulation.
Initial radiographs showed a small lesion and minimally displaced fracture. Plate fixation was performed but was inadequate as the tumor progressed, resulting in massive bone loss. Ultimately, the patient was treated with a shoulder disarticulation.
View Original | Slide (.ppt)
Figure 22-6
AP radiograph of the left humerus in a 57-year-old man with multiple myeloma.
Initial radiographs showed a small lesion and minimally displaced fracture. Plate fixation was performed but was inadequate as the tumor progressed, resulting in massive bone loss. Ultimately, the patient was treated with a shoulder disarticulation.
Initial radiographs showed a small lesion and minimally displaced fracture. Plate fixation was performed but was inadequate as the tumor progressed, resulting in massive bone loss. Ultimately, the patient was treated with a shoulder disarticulation.
View Original | Slide (.ppt)
X

Distal Humerus

Distal humeral lesions or fractures are treated with flexible intramedullary nails, bicondylar plate fixation, or resection with modular distal humeral reconstruction. Flexible nails, inserted in a retrograde manner through small medial and lateral incisions, offer ease of insertion, the ability to span the entire humerus, excellent functional recovery, and preservation of the native elbow joint. Curettage of the distal humeral lesion allows an open reduction in the case of a fracture and the opportunity to use PMMA in the lesion to gain rotational stability (Fig. 22-7). Orthogonal plate fixation is similar to nonpathologic fracture care but, when combined with PMMA, it can provide a stable construct about the elbow. This method of fixation does not protect the proximal humerus against a future metastatic lesion or fracture. A distal humeral resection and modular endoprosthetic reconstruction of the elbow is the best option for massive bone loss involving the condyles.100 
Figure 22-7
 
A: AP radiograph of a right distal humerus in a 74-year-old male with metastatic renal cell carcinoma. B: Due to a relatively poor prognosis, the patient underwent curettage, cementation, and plating of the lesion. Numerous nonstructural metastases remain untreated.
A: AP radiograph of a right distal humerus in a 74-year-old male with metastatic renal cell carcinoma. B: Due to a relatively poor prognosis, the patient underwent curettage, cementation, and plating of the lesion. Numerous nonstructural metastases remain untreated.
View Original | Slide (.ppt)
Figure 22-7
A: AP radiograph of a right distal humerus in a 74-year-old male with metastatic renal cell carcinoma. B: Due to a relatively poor prognosis, the patient underwent curettage, cementation, and plating of the lesion. Numerous nonstructural metastases remain untreated.
A: AP radiograph of a right distal humerus in a 74-year-old male with metastatic renal cell carcinoma. B: Due to a relatively poor prognosis, the patient underwent curettage, cementation, and plating of the lesion. Numerous nonstructural metastases remain untreated.
View Original | Slide (.ppt)
X

Forearm/Hand

Metastases distal to the elbow are unusual, and the most common are from the lung, breast, and kidney.59 Metastatic lesions to the radius and ulna can be treated with flexible rods or rigid plate fixation. Pathologic fractures of the radial head can be treated with resection. Intralesional surgery is preferred for hand metastasis with curettage, internal fixation, and cementation. If the lesion is distal or extensive, amputation may be the best option. 

Pelvic/Acetabular Fractures

Many bone metastasis or pathologic fractures in the bony pelvis do not affect weight-bearing functions; consequently, they do not require surgical intervention. Lesions of the iliac wing, superior/inferior pubic rami, or sacroiliac region fit into this category. Insufficiency fractures caused by osteoporosis frequently occur in these locations and are managed with protected weight bearing until the pain diminishes followed by assessment of bone density and appropriate medical treatment.11,73 
Periacetabular lesions or fractures; however, affect ambulatory status and often present a difficult surgical problem.41,55,69,89 The situation is magnified if there is protrusion of the femoral head through a pathologic acetabular fracture or defect (Fig. 22-8). All pathologic fractures or defects in this location should be assessed with CT scans with three-dimensional reconstruction. There are several classification systems for acetabular defects, but various modifications of the Harrington classification are considered to be most useful for assessing metastatic disease. This system classifies the location and extent of the defect and guides the technical considerations of fixation.41 The modification often used describes Class I lesions as minor acetabular defects with maintenance of the lateral cortices, superior walls, and medial walls. A conventional cemented acetabular component provides sufficient support. Class II lesions are major acetabular defects with a deficient medial wall and superior dome. An antiprotrusion device and/or medial mesh is necessary (Fig. 22-9). Class III lesions are massive defects with deficient lateral cortices and superior dome. There is no substantial peripheral rim for fixation of a metal component; therefore, weight-bearing stresses must be transmitted from the acetabular component into bone unaffected by the tumor, usually near the sacroiliac joint. An acetabular cage should be used with long screw fixation into any remaining pubis, ischium, and ilium. The massive bony defect is filled with PMMA to provide immediate stability after long screws and threaded 5/16-inch Steinmann pins anchor the construct. A polyethylene cup is then cemented into the acetabular cage in the correct orientation Class IV lesions involve pelvic discontinuity and can be treated expediently with resection and reconstruction using a saddle prosthesis or a resection arthroplasty depending on patient factors and expected life span.1 With these techniques, satisfactory pain relief and function can be achieved in 70% to 75% of patients. Complications are common and occur in 20% to 30% of cases.1,2,41,55,69,89 Extensive blood loss can be anticipated with massive lytic defects. This demanding surgery is best done by surgeons with extensive experience treating this type of lesion. The trabecular metal tantalum provides new options for acetabular fixation by allowing early bone ingrowth. It can be used in combination with a cemented acetabular cage.80 
Figure 22-8
 
A: An AP pelvis of a 53-year-old male with multiple myeloma. He sustained a fracture of the pelvis at the time of his diagnosis. Due to the severe lack of bone stock and advanced stage, he was treated with intravenous bisphosphonates, radiation, and limited weight bearing. B: At 1 year postinitiation of treatment, he ambulates with a cane, no pain. Radiographs show that the acetabulum, ischium, and proximal femur have increased bone stock. The patient does not desire any surgery.
A: An AP pelvis of a 53-year-old male with multiple myeloma. He sustained a fracture of the pelvis at the time of his diagnosis. Due to the severe lack of bone stock and advanced stage, he was treated with intravenous bisphosphonates, radiation, and limited weight bearing. B: At 1 year postinitiation of treatment, he ambulates with a cane, no pain. Radiographs show that the acetabulum, ischium, and proximal femur have increased bone stock. The patient does not desire any surgery.
View Original | Slide (.ppt)
Figure 22-8
A: An AP pelvis of a 53-year-old male with multiple myeloma. He sustained a fracture of the pelvis at the time of his diagnosis. Due to the severe lack of bone stock and advanced stage, he was treated with intravenous bisphosphonates, radiation, and limited weight bearing. B: At 1 year postinitiation of treatment, he ambulates with a cane, no pain. Radiographs show that the acetabulum, ischium, and proximal femur have increased bone stock. The patient does not desire any surgery.
A: An AP pelvis of a 53-year-old male with multiple myeloma. He sustained a fracture of the pelvis at the time of his diagnosis. Due to the severe lack of bone stock and advanced stage, he was treated with intravenous bisphosphonates, radiation, and limited weight bearing. B: At 1 year postinitiation of treatment, he ambulates with a cane, no pain. Radiographs show that the acetabulum, ischium, and proximal femur have increased bone stock. The patient does not desire any surgery.
View Original | Slide (.ppt)
X
Figure 22-9
 
A: AP radiograph of the pelvis in a 68-year-old-male with multiple myeloma. There is a fracture through a lytic lesion on the left acetabulum and ilium. B: Cement is placed in the location of the lesion with a pelvic cage and long screws in the ilium for stabilization. A cemented total hip replacement is placed to manage the lesions in the femur.
A: AP radiograph of the pelvis in a 68-year-old-male with multiple myeloma. There is a fracture through a lytic lesion on the left acetabulum and ilium. B: Cement is placed in the location of the lesion with a pelvic cage and long screws in the ilium for stabilization. A cemented total hip replacement is placed to manage the lesions in the femur.
View Original | Slide (.ppt)
Figure 22-9
A: AP radiograph of the pelvis in a 68-year-old-male with multiple myeloma. There is a fracture through a lytic lesion on the left acetabulum and ilium. B: Cement is placed in the location of the lesion with a pelvic cage and long screws in the ilium for stabilization. A cemented total hip replacement is placed to manage the lesions in the femur.
A: AP radiograph of the pelvis in a 68-year-old-male with multiple myeloma. There is a fracture through a lytic lesion on the left acetabulum and ilium. B: Cement is placed in the location of the lesion with a pelvic cage and long screws in the ilium for stabilization. A cemented total hip replacement is placed to manage the lesions in the femur.
View Original | Slide (.ppt)
X

Lower-Extremity Fractures

The femur is the most common long bone to be affected by metastasis.101 The proximal third is involved in 50% of cases, with the intertrochanteric region accounting for 20% of cases. Metastatic disease to the femur is the most painful of the bone metastasis, likely because of the high weight-bearing stresses through the proximal region. Pathologic fractures of the femur severely impact the quality of a patient’s life and threaten an individual’s level of independence. Without proper surgical attention, the patient with a pathologic fracture of the femur will be confined to bed, a situation that is medically and psychologically devastating. 
Painful destructive lesions in the proximal femur should be prophylactically stabilized whenever possible because of the high incidence of subsequent fracture and the comparative ease of the operation. The development of bone metastasis is a continuous process, so it is important to stabilize as much of the femur as possible to avoid future peri-implant failure.101 At a minimum, it is recommended that the tip of the chosen fixation device should bypass a given lesion by at least twice the diameter of the femur. 
Femoral Neck.
Pathologic fractures of the femoral head and neck rarely heal, and the neoplastic process tends to progress.58 Accordingly, there is a high incidence of failure if traditional fracture fixation devices are used. The procedure of choice for patients with metastatic disease to the femoral head or neck is a cemented replacement prosthesis (Fig. 22-10).58,75 The decision to use a hemiarthroplasty versus a total hip replacement depends on the presence of acetabular involvement. This must be carefully scrutinized as acetabular disease may go unrecognized and may be present microscopically in a surprisingly high percentage of cases. All tumor tissue should be curetted from the femoral canal before implanting the prosthesis. When there are adjacent lesions in the subtrochanteric region or proximal diaphysis, a long-stemmed cemented femoral component should be used for prophylactic fixation distally, avoiding a future pathologic fracture through a distal lesion and allowing full weight bearing postoperatively. When there are no additional lesions in the femur, the length of the cemented femoral stem is controversial. The risk of cardiopulmonary complications from cement monomer/marrow content embolization after pressurizing the extra cement and long stem within the canal must be weighed against the potential risk of future metastasis distal to the tip of the prosthesis if a shorter stem is used.99 If long-stemmed femoral components are used, it is important to inject the cement into the canal while still in a fairly liquid state after thorough canal preparation.7,16 
Figure 22-10
 
A: AP radiograph of a right hip in a 49-year-old female with metastatic breast cancer. The femoral neck is displaced and due to the presence of tumor, has little biologic ability to heal. B: AP radiograph of a right hip after a cemented long-stem bipolar arthroplasty. The patient has no limitations in activities, no pain, and performs all activities at 2 years postop.
A: AP radiograph of a right hip in a 49-year-old female with metastatic breast cancer. The femoral neck is displaced and due to the presence of tumor, has little biologic ability to heal. B: AP radiograph of a right hip after a cemented long-stem bipolar arthroplasty. The patient has no limitations in activities, no pain, and performs all activities at 2 years postop.
View Original | Slide (.ppt)
Figure 22-10
A: AP radiograph of a right hip in a 49-year-old female with metastatic breast cancer. The femoral neck is displaced and due to the presence of tumor, has little biologic ability to heal. B: AP radiograph of a right hip after a cemented long-stem bipolar arthroplasty. The patient has no limitations in activities, no pain, and performs all activities at 2 years postop.
A: AP radiograph of a right hip in a 49-year-old female with metastatic breast cancer. The femoral neck is displaced and due to the presence of tumor, has little biologic ability to heal. B: AP radiograph of a right hip after a cemented long-stem bipolar arthroplasty. The patient has no limitations in activities, no pain, and performs all activities at 2 years postop.
View Original | Slide (.ppt)
X
Intertrochanteric Region.
Traditional fixation of an intertrochanteric fracture with screw and side-plate fixation has a high rate of failure when used in the setting of metastatic bone disease, even when supplemented with adjuvant PMMA and postoperative radiation. The standard of care is intramedullary fixation or prosthetic replacement.101 The choice of fixation in this region of the femur depends on the extent of the lesion and whether it is radiosensitive. If bone with sufficient strength remains in the femoral head and neck and local control is likely to be achieved with postoperative external beam radiation, an intramedullary reconstruction device is recommended, which will allow the highest level of function. A cephalomedullary nail protects the femoral neck and is used for all metastatic lesions or pathologic fractures of the femur when an intramedullary device is indicated. If the destruction is more extensive, a cemented calcar-replacing prosthesis is required (Fig. 22-9). The same issues arise related to the length of the femoral stem as discussed in the previous section. 
Subtrochanteric Region.
Using plate and screw internal fixation for subtrochanteric fractures in patients with metastatic bone disease will usually end in failure. This region of the femur is subjected to forces of up to four to six times body weight. Statically locked intramedullary fixation with or without PMMA will stabilize the area and provide weight-bearing support.102 Even impending fractures should be statically locked as the lesion can fracture later causing shortening of the femur. A modular proximal femoral prosthesis is reserved for cases with extensive bone destruction or used as a salvage device for failed internal fixation (Fig. 22-11).75 It can also be used when a wide resection is necessary for a pathologic fracture through a primary bone sarcoma. There is an increased risk of dislocation and abductor mechanism weakness with a megaprosthesis, but this should not prevent its use in patients with radioresistant or locally aggressive tumors. A bipolar head is used to provide more stability if the acetabulum is not involved with metastatic disease. Excellent pain relief and local tumor control can be obtained after tumor resection and prosthetic reconstruction. 
Figure 22-11
 
A: AP radiograph of the left proximal femur in a 37-year-old male with metastatic hepatocellular carcinoma. The patient had received radiation therapy and had a long period of hip pain prior to fracture. B: AP radiograph of the left proximal femur shows a cemented long-stem bipolar arthroplasty performed. The greater trochanter is reattached to the prosthesis while still attached to the vastus lateralis and gluteus medius tendons.
A: AP radiograph of the left proximal femur in a 37-year-old male with metastatic hepatocellular carcinoma. The patient had received radiation therapy and had a long period of hip pain prior to fracture. B: AP radiograph of the left proximal femur shows a cemented long-stem bipolar arthroplasty performed. The greater trochanter is reattached to the prosthesis while still attached to the vastus lateralis and gluteus medius tendons.
View Original | Slide (.ppt)
Figure 22-11
A: AP radiograph of the left proximal femur in a 37-year-old male with metastatic hepatocellular carcinoma. The patient had received radiation therapy and had a long period of hip pain prior to fracture. B: AP radiograph of the left proximal femur shows a cemented long-stem bipolar arthroplasty performed. The greater trochanter is reattached to the prosthesis while still attached to the vastus lateralis and gluteus medius tendons.
A: AP radiograph of the left proximal femur in a 37-year-old male with metastatic hepatocellular carcinoma. The patient had received radiation therapy and had a long period of hip pain prior to fracture. B: AP radiograph of the left proximal femur shows a cemented long-stem bipolar arthroplasty performed. The greater trochanter is reattached to the prosthesis while still attached to the vastus lateralis and gluteus medius tendons.
View Original | Slide (.ppt)
X
Femoral Diaphysis.
Pathologic fractures of the femoral diaphysis are treated most effectively with a statically locked cephalomedullary nail, with or without PMMA (Fig. 22-12).101,107 Plate fixation, although more rigid, will not protect a large enough segment of bone and is prone to failure with disease progression. Cephalomedullary nail fixation protects the entire bone and is technically simple, especially when performed prophylactically. A trochanteric or piriformis entry point can be used, and the canal is slowly overreamed 1 to 1.5 mm to avoid high impaction forces during rod placement.7 Because the device will be load bearing if the fracture does not unite, a nail with the largest possible diameter should be used. The fields for postoperative radiation should encompass the entire implant. 
Figure 22-12
 
A: AP radiograph of the left distal femur in a 61-year-old male with multiple myeloma. The patient has a nondisplaced fracture through the lateral cortex of the femur with pain. B: AP radiograph shows a cephalomedullary intramedullary nail coursing the distal femoral lesion with cement augmentation to assist with early stability. A cephalomedullary device is chosen to prophylactically stabilize the femoral neck.
A: AP radiograph of the left distal femur in a 61-year-old male with multiple myeloma. The patient has a nondisplaced fracture through the lateral cortex of the femur with pain. B: AP radiograph shows a cephalomedullary intramedullary nail coursing the distal femoral lesion with cement augmentation to assist with early stability. A cephalomedullary device is chosen to prophylactically stabilize the femoral neck.
View Original | Slide (.ppt)
Figure 22-12
A: AP radiograph of the left distal femur in a 61-year-old male with multiple myeloma. The patient has a nondisplaced fracture through the lateral cortex of the femur with pain. B: AP radiograph shows a cephalomedullary intramedullary nail coursing the distal femoral lesion with cement augmentation to assist with early stability. A cephalomedullary device is chosen to prophylactically stabilize the femoral neck.
A: AP radiograph of the left distal femur in a 61-year-old male with multiple myeloma. The patient has a nondisplaced fracture through the lateral cortex of the femur with pain. B: AP radiograph shows a cephalomedullary intramedullary nail coursing the distal femoral lesion with cement augmentation to assist with early stability. A cephalomedullary device is chosen to prophylactically stabilize the femoral neck.
View Original | Slide (.ppt)
X
Supracondylar Femur.
The choice of fixation for pathologic supracondylar femur fractures depends on the extent of local bone destruction and the presence of additional lesions in the proximal femur. The distal lesions can be a treatment challenge caused by frequent comminution and poor bone stock, especially in older patients. Options include lateral locking plate fixation supplemented with PMMA or a modular distal femoral prosthesis.98 A retrograde nail has the drawback of potentially seeding the knee joint with tumor while failing to provide fixation to the femoral neck region. The locking plate provides stable fixation after curettage and cementation of the metastatic lesion. The modular endoprosthesis is the optimal choice for local control when there is massive destruction of the femoral condyles, as it allows the lesion to be resected en bloc.26 
Tibia.
Metastases distal to the knee are uncommon but, for proximal tibial lesions, similar principles should be used as for lesions in the supracondylar femoral area. A locking plate with PMMA after thorough curettage of the lesion is generally sufficient. Extensive lesions may require a modular proximal tibial prosthesis. Tibial diaphyseal lesions and fractures should be managed with a locked intramedullary device. Various techniques can be employed for pathologic fractures of the distal tibia, but standard internal fixation methods are generally advised with generous use of PMMA to augment the construct.21,59 The treatment of foot and ankle lesions must be individualized to maintain maximal function.44 

Spinal Fractures

Between 5% and 10% of patients who die of metastatic carcinoma will have microscopic disease in their spine. The metastases most commonly involve the vertebral body rather than the posterior elements. The majority of these patients will not have clinically significant spine disease during their lifetime and will not need treatment specific to this location. The lesions are often discovered incidentally on a bone scan during a routine metastatic workup in a patient with known cancer. However, if the disease progresses, it can cause moderate to severe pain persisting for months before the onset of focal neurologic deficits. Occasionally, the onset of pain is sudden following a pathologic compression fracture. 
When the patient does not have a history of cancer, it must be decided whether a compression fracture is secondary to osteoporosis or a bone metastasis. If the patient has a history of cancer or if the patient’s current symptoms, physical examination, laboratory studies, or imaging suggests a primary carcinoma or myeloma, the patient should be evaluated for a compression fracture caused by metastatic disease. It is imperative to consider spinal metastasis in any cancer patient with back pain. A delay in diagnosis can allow progression and possible neurologic compromise, leading to permanent functional deficits. Patients with a suspected malignancy should have a biopsy, but others should be treated symptomatically. If a patient treated for an osteoporotic compression fracture does not respond to the treatment or if there is progressive destruction of bone, a biopsy should be performed. Percutaneous CT-guided needle biopsy of vertebral lesions can be performed with local anesthesia and intravenous sedation. 
The classic plain radiographic finding in metastatic involvement of the spine is loss of a pedicle on an anteroposterior view. MRI can be used to differentiate an osteoporotic compression fracture from one caused by a malignant lesion.108 When there is complete replacement of the vertebral segment, multiple vertebral body lesions, pedicle involvement, and an intact intervertebral disk, metastatic disease is most likely (Fig. 22-13). Some patients with myeloma, lymphoma, or leukemia may present with osteopenia of the vertebra. To determine if the patient has a hematologic malignancy, a bone marrow aspirate should be considered. Most of these patients will have systemic findings (e.g., weight loss, fatigue, fever). If a metastatic lesion in the spine is identified, the patient is at risk of having additional skeletal lesions. 
Figure 22-13
Multiple lytic lesions in a 55-year-old female including the body of L1 and the right femoral neck suggest a malignant process.
 
A biopsy and treatment of the femoral neck lesion revealed a squamous lesion consistent with lung cancer.
A biopsy and treatment of the femoral neck lesion revealed a squamous lesion consistent with lung cancer.
View Original | Slide (.ppt)
Figure 22-13
Multiple lytic lesions in a 55-year-old female including the body of L1 and the right femoral neck suggest a malignant process.
A biopsy and treatment of the femoral neck lesion revealed a squamous lesion consistent with lung cancer.
A biopsy and treatment of the femoral neck lesion revealed a squamous lesion consistent with lung cancer.
View Original | Slide (.ppt)
X
Treatment options for patients with symptomatic metastatic disease to the spine include nonoperative management with radiation, corticosteroids, and/or bracing; minimally invasive techniques such as kyphoplasty and vertebroplasty; and surgical treatment with adjuvant radiation.29,38,40,66,84 Scoring systems for the evaluation of patients with vertebral metastasis have been reported, but no system has been universally adopted to guide treatment.60,90 Quality of life must be considered as these are painful lesions, but surgical treatment is often a major undertaking that has significant morbidity and may require a prolonged recovery.48 
Generally, symptoms from a vertebral compression fracture caused by osteoporosis are minor and can be successfully controlled with temporarily decreased activity or bracing. If the patient has asymptomatic vertebral metastases that are not at risk for pathologic fracture, systemic treatment can be used to address the primary and metastatic disease. Regular imaging of the spine should be performed to ensure that any disease progression is identified quickly. Often, early recognition of a spinal metastasis allows pain relief with nonoperative management. If the patient has pain but no neurologic compromise or risk of impending fracture, radiation treatment is indicated. Radiation is also used for radiation-sensitive tumors such as lymphoma or myeloma even when they present with neurologic compromise. The tumor response is usually sufficiently rapid such that the risk of permanent neurologic loss is no higher than that seen after surgical decompression. When there is minimal or no bone destruction but cord compression is caused by tumor extension, emergent radiation is recommended.77 The patient should also be treated with a short course of high-dose corticosteroids to reduce edema surrounding the tumor that contributes to compression and neurologic damage. Other indications for radiation of vertebral metastasis include patients with medical comorbidities precluding surgery, patients with 6 weeks or less to live, and those with multilevel disease. Radiation should be added preoperatively or postoperatively to improve local disease control when patients are treated with surgery.92 More recently, cyberknife radiosurgery has provided effective pain relief in patients with spinal metastases. It can be used in patients who have had prior external beam radiation as it focuses small beams of radiation into the tumor from many different directions via a robotic arm. This minimizes radiation exposure to the surrounding tissues. Cyberknife is a computer-assisted, minimally invasive procedure that can be performed as an outpatient in only one to three sessions and serves as another alternative to major surgery.35 
Indications for surgical treatment of vertebral metastasis include progression of disease after radiation, neurologic compromise caused by bony impingement or radioresistant tumor within the spinal canal, an impending fracture, or spinal instability caused by a pathologic fracture or progressive deformity. The goals of surgery are to maintain or restore neurologic function and spinal stability. 
When surgical treatment is necessary to relieve compression of the spinal cord, decompression and stabilization are required. Before surgery, MRI is used to verify the level of the lesion and rule out the possibility of compression at additional levels. A preoperative angiogram with embolization of feeder vessels should be considered in patients with highly vascular metastasis, such as RCC, to reduce intraoperative blood loss.15 Relief of symptoms can often be accomplished via a posterior decompression and fusion using instrumentation.3 When there is anterior collapse of the vertebrae and anterior compression of the spinal cord resulting in kyphosis, the patient is also treated with an anterior decompression and stabilization.29,40,52,66 When the posterior elements are involved with tumor and the cord is compressed anteriorly, the patient should have an anterior decompression with posterior stabilization and fusion (Fig. 22-14).90 Internal fixation is indicated to provide immediate stability for all but the most limited decompressions. In recent years, there has been considerable improvement in the available implants to manage structural deficiency of the spine, including pedicle screws, cages, and more sophisticated plates and rods. Specific techniques for anterior and posterior decompression and stabilization, including the use of modern instrumentation systems, are described in the literature.29,90 Surgical implants made of titanium allow easier assessment of recurrent disease on MRI. As patients live longer with their metastatic disease, aggressive surgical treatment of spinal lesions can enhance quality of life. However, the magnitude of the operative procedure should not exceed the patient’s chance of surviving the surgery or the surgeon’s level of competence. 
Figure 22-14
 
A: Sagittal T1-weighted image of the lumbar spine in a 53-year-old male with lung cancer shows an infiltrative lesion throughout L1 with complete marrow involvement and an extraosseous soft tissue mass abutting the anterior cord. The patient had significant leg weakness and inability to ambulate at presentation. B: A T2-weighted image with infiltration along the left epidural space at L1. C: AP radiograph of the lumbar spine after anterior decompression of the lumbar spine with screw fixation from T12 to L2 and allograft strut. D: Lateral radiograph of the thoracolumbar junction showing appropriate screw and hardware position. The patient had resolution of leg pain and weakness.
A: Sagittal T1-weighted image of the lumbar spine in a 53-year-old male with lung cancer shows an infiltrative lesion throughout L1 with complete marrow involvement and an extraosseous soft tissue mass abutting the anterior cord. The patient had significant leg weakness and inability to ambulate at presentation. B: A T2-weighted image with infiltration along the left epidural space at L1. C: AP radiograph of the lumbar spine after anterior decompression of the lumbar spine with screw fixation from T12 to L2 and allograft strut. D: Lateral radiograph of the thoracolumbar junction showing appropriate screw and hardware position. The patient had resolution of leg pain and weakness.
View Original | Slide (.ppt)
Figure 22-14
A: Sagittal T1-weighted image of the lumbar spine in a 53-year-old male with lung cancer shows an infiltrative lesion throughout L1 with complete marrow involvement and an extraosseous soft tissue mass abutting the anterior cord. The patient had significant leg weakness and inability to ambulate at presentation. B: A T2-weighted image with infiltration along the left epidural space at L1. C: AP radiograph of the lumbar spine after anterior decompression of the lumbar spine with screw fixation from T12 to L2 and allograft strut. D: Lateral radiograph of the thoracolumbar junction showing appropriate screw and hardware position. The patient had resolution of leg pain and weakness.
A: Sagittal T1-weighted image of the lumbar spine in a 53-year-old male with lung cancer shows an infiltrative lesion throughout L1 with complete marrow involvement and an extraosseous soft tissue mass abutting the anterior cord. The patient had significant leg weakness and inability to ambulate at presentation. B: A T2-weighted image with infiltration along the left epidural space at L1. C: AP radiograph of the lumbar spine after anterior decompression of the lumbar spine with screw fixation from T12 to L2 and allograft strut. D: Lateral radiograph of the thoracolumbar junction showing appropriate screw and hardware position. The patient had resolution of leg pain and weakness.
View Original | Slide (.ppt)
X
Kyphoplasty/Vertebroplasty.
Minimally invasive treatments for metastatic disease to the spine have been used to control pain in patients who have developed compression fractures.24,84 Vertebroplasty or kyphoplasty can be used for pathologic vertebral body fractures caused by osteoporosis, metastatic carcinoma, or multiple myeloma. The literature suggests that the results are similar in patients with malignancy versus osteoporosis, although these procedures have not been directly compared. Indications include patients with stable compression fractures who have normal neurologic function but persistent pain. One technique, vertebroplasty, involves percutaneous direct injection of PMMA through the pedicle to maintain vertebral height. Kyphoplasty is a way of regaining vertebral body height by expanding the compression fracture with a balloon before injecting the PMMA (Fig. 22-15). Reported complications include extrusion of cement around the neurologic structures, so this procedure should only be performed after careful consideration of the risks. 
Figure 22-15
 
A: Sagittal T2 fat-suppressed image of the L1 vertebra in a patient with metastatic squamous cell carcinoma of the lungs (* = L1 vertebrae). The patient had significant pain associated with this lesion. B: Postvertebroplasty lateral x-ray of the lumbar spine shows cement filling the tumor void. Although restoration of vertebral height was not obtained, pain control was adequate and the deformity was corrected.
A: Sagittal T2 fat-suppressed image of the L1 vertebra in a patient with metastatic squamous cell carcinoma of the lungs (* = L1 vertebrae). The patient had significant pain associated with this lesion. B: Postvertebroplasty lateral x-ray of the lumbar spine shows cement filling the tumor void. Although restoration of vertebral height was not obtained, pain control was adequate and the deformity was corrected.
View Original | Slide (.ppt)
Figure 22-15
A: Sagittal T2 fat-suppressed image of the L1 vertebra in a patient with metastatic squamous cell carcinoma of the lungs (* = L1 vertebrae). The patient had significant pain associated with this lesion. B: Postvertebroplasty lateral x-ray of the lumbar spine shows cement filling the tumor void. Although restoration of vertebral height was not obtained, pain control was adequate and the deformity was corrected.
A: Sagittal T2 fat-suppressed image of the L1 vertebra in a patient with metastatic squamous cell carcinoma of the lungs (* = L1 vertebrae). The patient had significant pain associated with this lesion. B: Postvertebroplasty lateral x-ray of the lumbar spine shows cement filling the tumor void. Although restoration of vertebral height was not obtained, pain control was adequate and the deformity was corrected.
View Original | Slide (.ppt)
X

Complications

Because patients with pathologic fractures are often older with multiple associated medical problems, the chance of them developing a perioperative complication is increased. These patients have the same risks as those with nonpathologic fractures when they consent to surgical treatment, but some complications are more likely in patients with widespread cancer. Two of the most concerning problems are tumor progression with resultant hardware failure and cardiopulmonary compromise. 
Bone metastases that are unresponsive to chemotherapy and radiation will continue to destroy bone so that the existing hardware or prosthesis is load bearing rather than load sharing. Using the principles of surgical treatment outlined in this chapter will minimize the risk of hardware failure, but inevitably some constructs will fail, especially with increasing patient longevity. The salvage of failed reconstructions must be individualized, but modular endoprostheses can frequently be used to salvage failed intramedullary fixation.49 Again, the patient’s life span and general health must be favorable before they are indicated for a prolonged procedure. 
Cardiopulmonary compromise is a noted risk in patients with bone metastasis. First, many of these patients have pulmonary metastasis or primary lung tumors that compromise lung function. Some patients will have a surgical procedure to stabilize a pathologic fracture and fail postoperative attempts at extubation, remaining in an intensive care setting for a prolonged time. Second, the placement of long-stemmed cemented femoral prostheses or prophylactic femoral or humeral nails must be done carefully to avoid embolic events. The orthopedic literature details how thorough canal preparation (brushing, irrigation, and careful suction of the canal in addition to slow reaming and possibly “venting” distally) are all tips to decrease this complication.7,16 It is unclear from the available literature whether the actual incidence of fat emboli is increased during placement of intramedullary rods or long cemented femoral stems in patients with malignancy compared to those without cancer. However, patients with cancer are hypercoagulable and are less likely to be able to compensate for fat emboli to the lung due to significantly reduced cardiopulmonary reserve, than are patients without cancer, especially if they have primary or metastatic pulmonary disease. 

Role of Adjuvant Radiation and Medical Treatment

External Beam Radiation

External beam radiation is used to treat pain secondary to bone metastases, halt the progression of bony destruction, and allow healing of an impending pathologic fracture. It is a reasonable alternative to surgical treatment for certain lesions. When the endpoint is pain relief, local radiation therapy typically results in partial relief in over 80% of patients with bone metastasis and complete pain relief in 50% to 60% of cases.99 Variability in response rates depends on multiple factors including the histology and location of the lesion.104 The onset of symptomatic relief usually occurs in the first 1 to 2 weeks, but maximal relief may take several months. Radiation is used in the postoperative setting to increase local tumor control after surgical stabilization. Retrospective data have shown that postoperative radiation improves limb function and decreases the rates of second orthopedic procedures.92 The majority of patients in this study had the entire prosthesis or internal fixation device included in the treatment field. Radiation can usually begin 2 weeks after the surgical procedure if there are no wound complications. 

Systemic Radionucleotides

Systemic therapy for bone metastasis using radioactive bone-seeking agents provides palliation of bone pain. It may be appropriate for widespread bone metastases when more traditional forms of radiation have reached their limit or when standard radiation techniques are not feasible because of surrounding normal tissue tolerances. Strontium-89 is used clinically and preferentially taken up at sites of active bone mineral turnover, similar to bisphosphonates. There is a greater uptake of the radionucleotides in metastatic lesions than in normal bone. A systematic review of the published literature on palliation of painful bone metastasis with radiopharmaceuticals revealed better pain relief with fewer sites of disease using strontium-89 compared to placebo or local radiation therapy.8 

Bisphosphonates

Bisphosphonates bind preferentially to the bone matrix and inhibit osteoclastic bone resorption. Receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts acts as an activator of osteoclast function. Bisphosphonates act as a competitive inhibitor of RANKL and thus decrease the depth of resorption cavities at osteoclastic binding sites, inhibit osteoclastic function, alter the morphology of the osteoclast ruffled border, and inhibit maturation and recruitment of osteoclasts from the monocyte/macrophage cell line. They promote osteoclast apoptosis, and there are some data to suggest direct effects on tumor cells. Intravenous bisphosphonates have been used with success to treat bone pain and hypercalcemia in breast cancer, and they are most commonly used as an adjunct to other systemic therapies.65 
There have been multiple, well-organized studies that document a decrease in the time to skeletal-related events as well as a decrease in the rate of these events in patients with bone metastasis treated with various bisphosphonates.43,64,65 Acutely, these medications are not used to prevent large lesions from fracture as their ability to provide structural rigidity requires many months of treatment. 

Controversies and Future Directions

Two of the main controversies in the management of patients with metastatic bone disease are (a) the ideal length of a cemented femoral stem in patients with metastatic disease about the hip and (b) the specific characteristics that define an impending fracture. These topics were discussed previously. 
There is also continued debate as to the surgical treatment of patients with a solitary metastasis. There is literature to suggest that wide resection of a solitary RCC metastasis leads to increased survival.51,88 However, it has not been shown that these data are applicable to metastatic disease from other primary sites. The study recommending resection of solitary RCC metastasis was conducted before widespread use of PET scanning, which allows discovery of smaller foci of active disease. It is likely that many patients presumed to have solitary metastasis would have additional sites of disease if screened with PET imaging. However, a patient with a solitary metastasis from any origin who has been tumor free for several years should be theoretically considered a candidate for a resection. RCC and follicular thyroid carcinoma are the two tumor types most likely to produce isolated bone metastasis years after treatment of the primary tumor. 
Future directions in the surgical treatment of patients with metastatic bone disease of the spine and extremities will likely include continued use and new applications for trabecular metal.62 The tantalum acetabular components allow excellent bone ingrowth and are being used more routinely in revision joint arthroplasty to reconstruct large acetabular defects.49,80 Thus, surgical experience with this material in the field of revision joint arthroplasty is rapidly increasing, expanding its use in other situations. Further advances in this type of metal fixation may allow improvement in the attachment of soft tissues to megaprostheses after tumor resection. Endoprostheses made of porous tantalum have been used in limb-sparing surgery in patients with lower-extremity sarcomas with short-term follow-up.46 
Interventional radiologists are working more closely with orthopedic surgeons to manage patients with bone metastasis. Radiofrequency ablation (RFA) and cryotherapy are now being used routinely for palliative treatment of painful metastatic lesions. These techniques provide an alternative to external beam radiation or surgery.36 A recent study of patients with pelvic and sacral metastasis treated with RFA showed a clinical benefit with significant pain relief in 95% of patients.36 Most of these patients had failed to respond to prior treatment or were considered to be poor candidates for narcotic medication or radiation. Another new procedure termed acetabuloplasty is similar to vertebroplasty in that PMMA is injected percutaneously into an acetabular defect to provide pain relief and possibly avoid a major surgical reconstruction.49,103 

Treatment Options for Patients with Pathologic Fractures Through Primary Bone Tumors

Benign Bone Tumors

Benign bone tumors occur most commonly in children and young adults. Most tumors gradually enlarge until the patient reaches skeletal maturity and then resolve or become inactive. Inactive lesions do not require surgical treatment. Active or aggressive benign lesions often require intralesional curettage with or without bone grafting to remove the tumor and allow healing of the underlying bone. A pathologic fracture through a benign bone tumor may change the course of treatment. Due to the younger age and higher activity level of patients who have benign bone tumors, pathologic fractures are not uncommon. 
In general, the treatment of a pathologic fracture through a benign bone lesion depends on the activity of the underlying lesion. Most can be treated nonoperatively in a cast until the fracture heals. At that time, treatment of the benign tumor can be addressed. Indications for surgical treatment of the fracture include unacceptable deformity in a cast, open fracture, fracture nonunion, or an association with active or aggressive lesions such as giant cell tumor (GCT) or aneurysmal bone cyst (ABC). The treatment of pathologic fractures in the context of specific benign bone tumors is discussed next. The reader is referred to comprehensive musculoskeletal oncology textbooks to learn more about the diagnosis and treatment of individual tumors. 

Unicameral Bone Cyst

A pathologic fracture is the presenting complaint in two-thirds of patients with a unicameral bone cyst (UBC).14 The majority of these lytic lesions are located in the proximal humerus or proximal femur (Fig. 22-16). A humeral fracture should be allowed to heal in a satisfactory position as the fracture occasionally stimulates healing of the cyst. If the cyst does not heal spontaneously after the fracture callus remodels, corticosteroid injection with bone graft or bone marrow aspirate into the cyst is recommended. A displaced fracture through a proximal femoral UBC in a child usually requires open reduction, bone grafting of the cyst, and internal fixation due to weight-bearing requirements. 
Figure 22-16
 
A: AP radiograph of a right proximal femur in an 11-year-old male shows a unicameral bone cyst with a medial nondisplaced fracture. B: Treatment with a biopsy, curettage, bone grafting, and side plate allows for full weight bearing, mobilization, and treatment of the cyst.
A: AP radiograph of a right proximal femur in an 11-year-old male shows a unicameral bone cyst with a medial nondisplaced fracture. B: Treatment with a biopsy, curettage, bone grafting, and side plate allows for full weight bearing, mobilization, and treatment of the cyst.
View Original | Slide (.ppt)
Figure 22-16
A: AP radiograph of a right proximal femur in an 11-year-old male shows a unicameral bone cyst with a medial nondisplaced fracture. B: Treatment with a biopsy, curettage, bone grafting, and side plate allows for full weight bearing, mobilization, and treatment of the cyst.
A: AP radiograph of a right proximal femur in an 11-year-old male shows a unicameral bone cyst with a medial nondisplaced fracture. B: Treatment with a biopsy, curettage, bone grafting, and side plate allows for full weight bearing, mobilization, and treatment of the cyst.
View Original | Slide (.ppt)
X

Aneurysmal Bone Cyst

An ABC is an active benign lesion that can grow rapidly in the metaphysis of a young patient, simulating a malignancy.14 Care should be taken in performing a biopsy for a presumed ABC as telangiectatic osteosarcomas can appear radiographically similar. Despite its occasional aggressive growth pattern, pathologic fractures are uncommon. Approximately 15% to 20% of lesions occur in the posterior elements of the spine and can cause neurologic compromise. The standard treatment of an ABC with or without a fracture is intralesional curettage and bone grafting. Depending on the age of the patient and location of the ABC, a pathologic fracture might require internal fixation at the time of curettage. 

Eosinophilic Granuloma

An eosinophilic granuloma is a solitary lesion in the spectrum of disease known as Langerhans cell histiocytosis. It is a benign bone tumor, and affected patients present with pain. This tumor can cause collapse of a vertebral body (vertebra plana) and neurologic symptoms. Patients with symptomatic vertebra plana are braced, and eventually the vertebral height is restored without surgery (Fig. 22-17).76 For extremity lesions that do not spontaneously resolve, the standard of care is an intralesional corticosteroid injection. Open curettage is reserved for selected lesions that fail to respond or are unsuitable for steroid injection because of the size, location, or aggressiveness of the lesion.106 A pathologic fracture should be allowed to heal before performing a needle biopsy and injection, so the fracture callus does not confuse the histologic picture. 
Figure 22-17
Lateral radiograph of the thoracolumbar spine of an 8-year-old female shows a compression of the vertebral body.
 
This is a classic radiographic appearance of eosinophilic granuloma. Over time, the vertebral body will reconstitute in height.
This is a classic radiographic appearance of eosinophilic granuloma. Over time, the vertebral body will reconstitute in height.
View Original | Slide (.ppt)
Figure 22-17
Lateral radiograph of the thoracolumbar spine of an 8-year-old female shows a compression of the vertebral body.
This is a classic radiographic appearance of eosinophilic granuloma. Over time, the vertebral body will reconstitute in height.
This is a classic radiographic appearance of eosinophilic granuloma. Over time, the vertebral body will reconstitute in height.
View Original | Slide (.ppt)
X

Nonossifying Fibroma

Nonossifying fibromas are extremely common lytic lesions in young patients. They spontaneously resolve after skeletal maturity. They are asymptomatic, but large lesions can fracture. Common pathologic fracture locations include the distal tibia, distal femur, and proximal tibia. Patients with multiple lesions have a higher risk of fracture. Pathologic fractures can be treated successfully in the majority of cases with closed reduction and cast immobilization.25 If the lesion persists after fracture consolidation, curettage and bone grafting can be performed if necessary. If a fracture is unstable and cannot be reduced in a closed fashion, curettage and bone grafting is combined with internal fixation. 

Enchondroma

Enchondromas are benign cartilage tumors that are asymptomatic unless associated with a pathologic fracture.82 These lesions, when they occur in long bones, rarely fracture. Those most prone to pathologic fractures and pain occur in the small bones of the hand and foot (Fig. 22-18). Some advocate nonsurgical treatment of these lesions, as the fracture occasionally stimulates resolution of the enchondroma. Most agree that surgical intervention, if performed, should be delayed until the fracture has healed.91 Occasionally, other factors (such as a tendon avulsion fracture through a phalangeal enchondroma) may prompt urgent surgery. Surgical treatment of the enchondroma eliminates the future risk of pathologic fracture and avoids progressive deformity. Whether to perform a bone graft to the defect after curettage remains controversial. Multiple enchondromas with frequent hand fractures and deformities occur in Ollier disease and Maffucci syndrome. Both of these conditions are associated with malignant transformation of the lesion. Although the actual rate of malignant transformation is unknown, Ollier’s is estimated to be 25% lifetime risk, while Maffucci’s is near 100% lifetime risk. 
Figure 22-18
 
A: AP radiograph of a second toe that shows a nondisplaced fracture through the second toe, midshaft proximal phalanx lesion. B: The fracture was allowed to heal and subsequently, a biopsy, curettage, and bone grafting was performed which revealed a low-grade chondroid lesion consistent with enchondroma.
A: AP radiograph of a second toe that shows a nondisplaced fracture through the second toe, midshaft proximal phalanx lesion. B: The fracture was allowed to heal and subsequently, a biopsy, curettage, and bone grafting was performed which revealed a low-grade chondroid lesion consistent with enchondroma.
View Original | Slide (.ppt)
Figure 22-18
A: AP radiograph of a second toe that shows a nondisplaced fracture through the second toe, midshaft proximal phalanx lesion. B: The fracture was allowed to heal and subsequently, a biopsy, curettage, and bone grafting was performed which revealed a low-grade chondroid lesion consistent with enchondroma.
A: AP radiograph of a second toe that shows a nondisplaced fracture through the second toe, midshaft proximal phalanx lesion. B: The fracture was allowed to heal and subsequently, a biopsy, curettage, and bone grafting was performed which revealed a low-grade chondroid lesion consistent with enchondroma.
View Original | Slide (.ppt)
X

Fibrous Dysplasia

Fibrous dysplasia is defined as a developmental abnormality rather than a true neoplasm and occurs in both monostotic and polyostotic forms.39 Most solitary lesions of fibrous dysplasia are asymptomatic, but patients can present with a painful pathologic fracture or a bowed extremity. In the polyostotic form, lesions involve multiple areas of a single bone or multiple bones in one extremity, and fractures occur in 85% of these patients. The structural bone strength is decreased in fibrous dysplasia, and sequential fractures can result in progressive deformity producing the classic shepherd’s crook varus appearance of the proximal femur. The fractures are rarely displaced and heal well. 
Pathologic fractures or symptomatic lesions in the upper extremity and spine can be treated nonoperatively, whereas lower-extremity fractures usually require internal fixation.39 Extensive areas of fibrous dysplasia in high-stress weight-bearing areas are treated with prophylactic internal fixation. The lesion should be biopsied at the time of surgery to confirm the diagnosis before proceeding with intramedullary fixation to stabilize long bones. The goal is to strengthen and straighten the bone, not to resect the lesion. If bone graft is used, it should be allograft, as autograft has the same genetic abnormality as the dysplastic bone and may not heal properly. Internal fixation does not alter the disease process but provides mechanical support and pain relief. Another option is medical treatment with bisphosphonates alone or in combination with surgery.57 

Giant Cell Tumor

GCT is an aggressive benign bone tumor that occurs in young adults. Ten percent of patients present with a pathologic fracture. In patients whose adjacent joint can be preserved, the GCT should be treated with thorough curettage and bone grafting or cementation.93 Internal fixation is often necessary after a pathologic fracture as there is usually extensive bone loss and deformity. Adjuvant treatment with phenol or cryosurgery should be used with caution in patients when a pathologic fracture exposes adjacent soft tissues. Adjuvant treatments such as high-speed burr, argon beam, phenolization, cryosurgery, and cementation have been shown to lower local recurrence rates. Primary wide resection and reconstruction is only necessary when the associated joint is beyond salvage. 

Malignant Bone Tumors

Primary malignant bone tumors are treated with a combination of surgery, chemotherapy, and/or radiation. Multiple myeloma is a primary malignant bone tumor with a systemic presentation that occurs in older patients. Pathologic fractures in patients with myeloma, lymphoma, and metastatic carcinoma can be treated with fixation through the tumor as they are systemic diseases treated primarily with chemotherapy and radiation. The overall survival of these patients is not compromised by palliative surgical stabilization. 
Primary malignant bone tumors such as osteosarcoma, Ewing sarcoma, and chondrosarcoma are treated much differently than systemic neoplastic disease.97 These tumors grow initially in the bone and can metastasize to the lungs. Local control of the primary lesion is achieved by complete surgical resection. A pathologic fracture through the lesion theoretically decreases the chance of local control, because tumor cells spread throughout the hematoma. Amputation should be discussed as a potential surgical option for patients with a pathologic fracture through a primary malignant bone tumor. The traditional literature has suggested that amputation is the treatment of choice for pathologic fractures through a primary malignant bone tumor, but with improved adjuvant care and surgery, there are recent studies that describe good rates of limb salvage with local disease control.30,83,105 Ferguson in 2010 showed that in 31 patients with pathologic fractures associated with an osteosarcoma, the rate of limb salvage and local control was equal to 201 patients without a pathologic fracture with osteosarcoma. However, the overall survival was also shown to be worse in patients with pathologic fracture. To some degree this depends on the amount of fracture displacement, histology of the tumor, and response to chemotherapy. 
Before initiating treatment for a patient with a pathologic fracture through a presumed primary bone sarcoma, the patient should be staged and a biopsy performed. An appropriate staging workup includes a CT scan of the chest for all patients, and a bone marrow biopsy when Ewing sarcoma is suspected. The biopsy of a presumed bone sarcoma is especially difficult in the setting of an associated pathologic fracture. The fracture hematoma and healing process alters the histology and may make the pathology difficult to properly interpret. Whenever possible, the biopsy should be performed away from the fracture. When there is an extraosseous soft tissue mass associated with the tumor, an image-guided needle biopsy is usually adequate. When the lesion is intraosseous and fracture callus is present, an open biopsy may be necessary. The surgeon who will eventually perform the definitive surgical treatment of the lesion should be the one who orders or performs the diagnostic biopsy. 
Internal fixation of a pathologic fracture through a primary sarcoma may compromise the limb and life of the patient. If the patient will be treated with preoperative chemotherapy, cast immobilization or limited internal fixation of the fracture is preferred. The fracture usually heals during systemic treatment, and a cast avoids potential pin tract infections in neutropenic patients stabilized with an external fixator. 
Patients with a pathologic fracture through a primary malignancy of bone require a coordinated multidisciplinary team that includes a medical oncologist, radiation oncologist, musculoskeletal pathologist, radiologist, physical therapist, and orthopedic oncologist; only with the full complement of care can these patients achieve the best quality of life and maximum overall survival. 

Osteosarcoma/Ewing Sarcoma

These are the two most common primary malignant bone tumors in children. Approximately 10% of patients present with a pathologic fracture. Closed treatment of the fracture in a cast is indicated after a needle or open biopsy is performed. When staging is complete, preoperative chemotherapy is used for patients with osteosarcoma or Ewing sarcoma. After 3 to 4 months of systemic therapy, a decision is made about local control of the primary tumor. For patients with osteosarcoma, surgical resection is indicated. If patients have a clinical and radiographic response to chemotherapy, a limb salvage procedure is generally preferred. Articles have shown no difference in local control for patients with osteosarcoma and a pathologic fracture that are treated with limb salvage compared to amputation.5,83 However, if the sarcoma shows a poor response to chemotherapy or neurovascular invasion has progressed since treatment, limb salvage is potentially contraindicated. Close follow-up is necessary to identify a possible local recurrence or the presence of metastatic disease. 
Local control in Ewing sarcoma can be achieved with surgical resection, radiation, or both. In reconstructable sites, most patients are treated with limb salvage surgery to remove all chemotherapy-resistant clones and avoid the risks of radiation in a growing child. However, in patients with a pathologic fracture treated with surgical resection, consideration should be given to adding radiation as a postoperative adjuvant to improve the chance of local control and avoid amputation.32 

Chondrosarcoma

Chondrosarcoma occurs in middle-aged and older adults.10 The pelvis is a common site, but displaced pathologic fractures are rare in this location. The most common location of a pathologic fracture through a chondrosarcoma is in the proximal femur (Fig. 22-19). A serious mistake is to assume the fracture is secondary to metastatic carcinoma and place an intramedullary rod through the lesion. This act contaminates multiple tissue planes (such as the glutei) with malignant cells and generally precludes any safe limb salvage option for the patient. Although no data has shown that reaming directly results in systemic spread of disease, the implication is that tumor cells may be forced into the blood stream or lymphatics and this could lead to seeding distant sites. An older patient with a solitary lytic lesion should be staged appropriately with a biopsy to confirm the diagnosis before any surgical treatment. 
Figure 22-19
 
A: Coronal CT of the pelvis in a 48-year-old male with right hip pain. Note the pathologic fracture through a lesion that was diagnosed as clear cell chondrosarcoma. Initially, a plate was used to stabilize the bone until his pathology was determined. B: After a final diagnosis, he underwent resection of the right proximal femur followed by megaprosthetic reconstruction and bipolar hemiarthroplasty.
A: Coronal CT of the pelvis in a 48-year-old male with right hip pain. Note the pathologic fracture through a lesion that was diagnosed as clear cell chondrosarcoma. Initially, a plate was used to stabilize the bone until his pathology was determined. B: After a final diagnosis, he underwent resection of the right proximal femur followed by megaprosthetic reconstruction and bipolar hemiarthroplasty.
View Original | Slide (.ppt)
Figure 22-19
A: Coronal CT of the pelvis in a 48-year-old male with right hip pain. Note the pathologic fracture through a lesion that was diagnosed as clear cell chondrosarcoma. Initially, a plate was used to stabilize the bone until his pathology was determined. B: After a final diagnosis, he underwent resection of the right proximal femur followed by megaprosthetic reconstruction and bipolar hemiarthroplasty.
A: Coronal CT of the pelvis in a 48-year-old male with right hip pain. Note the pathologic fracture through a lesion that was diagnosed as clear cell chondrosarcoma. Initially, a plate was used to stabilize the bone until his pathology was determined. B: After a final diagnosis, he underwent resection of the right proximal femur followed by megaprosthetic reconstruction and bipolar hemiarthroplasty.
View Original | Slide (.ppt)
X
The treatment of a patient with a pathologic fracture through a chondrosarcoma is wide resection by an orthopedic oncologist. Chemotherapy and radiation are generally not effective for this tumor. Recent studies have shown that proton beam radiation to be useful in some patients with chondrosarcoma.4,18 This is reserved for specific cases that include skull base tumors or recurrent, unresectable tumors. A pathologic fracture greatly compromises the local area, as any stray tumor cells not resected will likely grow into a locally recurrent lesion. A displaced fracture through a chondrosarcoma is a reason to consider amputation, especially if wide resection cannot be achieved with a limb salvage procedure. 

Summary and Key Points

  •  
    Any process that reduces bone strength predisposes a patient to a pathologic fracture during normal activity or after minimal trauma. It must be recognized as a pathologic fracture if the patient is to be treated properly.
  •  
    The most common cause for a pathologic fracture is osteoporosis or osteomalacia.
  •  
    Patients with osteoporosis or osteomalacia require evaluation and management of the underlying disorder.
  •  
    Patients older than 40 years of age with a pathologic fracture through a discrete bone lesion are much more likely to have metastatic bone disease than a primary bone tumor.
  •  
    The prognosis for patients with metastatic bone disease is improving because of early recognition and better adjuvant treatment; therefore, many patients will live longer than 2 years.
  •  
    Do not immediately assume that a lytic lesion or pathologic fracture is from metastatic disease. A thorough workup and possible biopsy are required.
  •  
    Prophylactic fixation for impending (vs. actual) fractures from metastatic disease is technically easier for the surgeon and allows a quicker patient recovery.
  •  
    The Mirels’s scoring system is available to guide the treatment of an impending fracture from metastatic bone disease.
  •  
    Femoral neck fractures caused by metastatic bone disease require a cemented hip prosthesis, as internal fixation has a high rate of failure with disease progression.
  •  
    An isolated fracture of the lesser trochanter is usually a sign of a metastatic femoral neck lesion with impending fracture.
  •  
    When surgery is required for metastatic disease to the spine, decompression and stabilization with internal fixation are generally necessary.
  •  
    Surgical reconstruction for pathologic fractures should be durable enough to allow immediate weight bearing and last the patient’s expected life span.
  •  
    A pathologic fracture through a primary malignant bone tumor is treated much differently than a fracture through a metastatic lesion. The treating surgeon should keep in mind with proper surgery there is a chance for long-term cure.
  •  
    Treatment of patients with pathologic fractures requires the presence of a multidisciplinary team comprises orthopedic surgeons, medical oncologists, radiation oncologists, endocrinologists, radiologists, pathologists, pain specialists, nutritionists, physical therapists, and psychologists/psychiatrists.

References

1.
Aboulafia AJ, Buch R, Mathews J, et al. Reconstruction using the saddle prosthesis following excision of primary and metastatic periacetabular tumors. Clin Orthop Relat Res. 1995;(314):203–213.
2.
Abudu A, Grimer RJ, Cannon SR, et al. Reconstruction of the hemipelvis after the excision of malignant tumors. Complications and functional outcome of prostheses. J Bone Joint Surg Br. 1997;79:773–779.
3.
Akeyson EW, McCutcheon IE. Single-stage posterior vertebrectomy and replacement combined with posterior instrumentation for spinal metastasis. J Neurosurg. 1996;85:211–220.
4.
Amichetti M, Amelio D, Cianchetti M, et al. A systematic review of proton therapy in the treatment of chondrosarcoma of the skull base. Neurosurg Rev. 2010;33(2):155–165.
5.
Bacci G, Ferrari S, Longhi A, et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: Local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand. 2003;74:449–454.
6.
Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive methylmethacrylate on failures of fixation and function in patients with intertrochanteric fractures and osteoporosis. J Bone Joint Surg Am. 1985;67:1094–1107.
7.
Barwood SA, Wilson JL, Molnar RR, et al. The incidence of acute cardiorespiratory and vascular dysfunction following intramedullary nail fixation of femoral metastasis. Acta Orthop Scand. 2000;71:147–152.
8.
Bauman G, Charette M, Reid R, et al. Radiopharmaceuticals for the palliation of painful bone metastasis: A systemic review. Radiother Oncol. 2005;75:258–270.
9.
Bertin KC, Horstman J, Coleman SS. Isolated fractures of the lesser trochanter in adults: An initial manifestation of metastatic malignant disease. J Bone Joint Surg Am. 1984;66:770–773.
10.
Bjornsson J, McLeod RA, Unni KK, et al. Primary chondrosarcoma of long bones and limb girdles. Cancer. 1998;83:2105–2119.
11.
Brahme SK, Cervilla V, Vinct V, et al. Magnetic resonance appearance of sacral insufficiency fractures. Skeletal Radiol. 1990;19:489–493.
12.
Brown RK, Pelker RR, Friedlaender GE, et al. Postfracture radiation effects on the biomechanical and histologic parameters of fracture healing. J Orthop Res. 1991;9:876–882.
13.
Bunting RW, Boublik M, Blevins FT, et al. Functional outcome of pathologic fracture secondary to malignant diseases in a rehabilitation hospital. Cancer. 1992;69:98–102.
14.
Campanacci M, Capanna R, Picci P. Unicameral and aneurysmal bone cysts. Clin Orthop Relat Res. 1986;(204):25–36.
15.
Chatziioannou AN, Johnson ME, Penumaticos SG, et al. Preoperative embolization of bone metastases from renal cell carcinoma. Eur J Radiol. 2000;10:593–596.
16.
Churchill DL, Incavo SJ, Uroskie JA, et al. Femoral stem insertion generates high bone cement pressurization. Clin Orthop Relat Res. 2001;(393):335–344.
17.
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–1767.
18.
Dallas J, Imanirad I, Rajani R, et al. Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: A case report. J Med Case Rep. 2012;6:41.
19.
Damron TA, Rock MG, Choudhury SN, et al. Biomechanical analysis of prophylactic fixation for middle third humeral impending pathologic fractures. Clin Orthop Relat Res. 1999;363:240–248.
20.
Damron TA, Sim FH, Shives TC, et al. Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. Clin Orthop Relat Res. 1996;(324):233–243.
21.
De Geeter K, Reynders P, Samson I, et al. Metastatic fractures of the tibia. Acta Orthop Belg. 2001;67:54–59.
22.
Demers LM, Costa L, Lipton A. Biochemical markers and skeletal metastases. Clin Orthop Relat Res. 2003;(415):S138–S147.
23.
Dougall WC, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone disease. Cancer Metastasis Rev. 2006;25:541–549.
24.
Dudeney S, Lieberman IH, Reinhardt MK, et al. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol. 2002;20:2382–2387.
25.
Easley ME, Kneisl JS. Pathologic fractures through nonossifying fibromas: Is prophylactic treatment warranted? J Pediatr Orthop. 1997;17:808–813.
26.
Eckardt JJ, Kabo M, Kelly CM, et al. Endoprosthetic reconstructions for bone metastases. Clin Orthop Relat Res. 2003;(415 suppl):S254–S262.
27.
Eftekhar NS, Thurston CW. Effect of radiation on acrylic cement with special reference to fixation of pathological fractures. J Biomech. 1975;8:53–56.
28.
Even-Sapir E, Metser U, Flusser G, et al. Assessment of malignant skeletal disease: Initial experience with 18 F-fluoride PET/CT and comparison between 18 F-Fluoride PET and 18 F-fluoride PET/CT. J Nucl Med. 2004;45:272–278.
29.
Feiz-Erfan I, Rhines LD, Weinberg JS. The role of surgery in the management of metastatic spinal tumors. Semin Oncol. 2008;35:108–117.
30.
Ferguson PC, McLaughlin CE, Griffin AM, et al. Clinical and functional outcomes of patients with a pathologic fracture in high-grade osteosarcoma. J Surg Oncol. 2010;102(2):120–124.
31.
Fidler M. Prophylactic internal fixation of secondary neoplastic deposits in long bones. BMJ. 1973;1:341–343.
32.
Fuchs B, Valenzuela RG, Sim FH. Pathologic fracture as a complication in the treatment of Ewing’s sarcoma. Clin Orthop Relat Res. 2003:25–30.
33.
Gainor BJ, Buchert P. Fracture healing in metastatic bone disease. Clin Orthop Relat Res. 1983;(178):297–302.
34.
Gass M, Dawson-Hughes B. Preventing osteoporosis-related fractures: An overview. Am J Med. 2006;119(4 suppl 1):S3–S11.
35.
Gerszten PC, Welch WC. Cyberknife radiosurgery for metastatic spine tumors. Neurosurg Clin N Am. 2004;15:491–501.
36.
Goetz MP, Callstrom MR, Charboneau JW, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: A multicenter study. J Clin Oncol. 2004;22:300–306.
37.
Greenspan A, Norman A. Osteolytic cortical destruction: An unusual pattern of skeletal metastases. Skeletal Radiol. 1988;17:402–406.
38.
Gronemeyer DH, Schirp S, Gevargez A. Image-guided radiofrequency ablation of spinal tumors: Preliminary experience with an expandable array electrode. Cancer J. 2002;8:33–39.
39.
Guille JT, Jumar SJ, MacEwin GD. Fibrous dysplasia of the proximal part of the femur. Long-term results of curettage and bone-grafting and mechanical realignment. J Bone Joint Surg Am. 1998;80:648–658.
40.
Harrington KD. Anterior decompression and stabilization of the spine as a treatment for vertebral collapse and spinal cord compression from metastatic malignancy. Clin Orthop Relat Res. 1988;233:177–197.
41.
Harrington KD. The management of acetabular insufficiency secondary to metastatic malignant disease. J Bone Joint Surg Am. 1981;63:653–664.
42.
Harrington KD, Sim FH, Enis JE, et al. Methylmethacrylate as an adjunct in internal fixation of pathologic fractures. J Bone Joint Surg Am. 1976;58:1047–1055.
43.
Hatoum HT, Lin SJ, Smith MR, et al. Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases: Analysis of a national medical claims database. Cancer. 2008;113:1438–1445.
44.
Hattrup SJ, Amadio PC, Sim FH, et al. Metastatic tumors of the foot and ankle. Foot Ankle. 1988;8:243–247.
45.
Henry JC, Damron TA, Weiner MM, et al. Biomechanical analysis of humeral diaphyseal segmental defect fixation. Clin Orthop Relat Res. 2002:231–239.
46.
Holt GE, Christie MJ, Schwartz HS. Trabecular metal endoprosthetic limb salvage reconstruction of the lower limb. J Arthroplasty. 2009;24(7):1079–1085.
47.
Hong J, Cabe GD, Tedrow JR, et al. Failure of trabecular bone with simulated lytic defects can be predicted noninvasively by structural analysis. J Orthop Res. 2004;22:479–486.
48.
Ibrahim A, Crockard A, Antonietti P, et al. Does spinal surgery improve the quality of life for those with extradural (spinal) osseous metastases? An international multicenter prospective observational study of 223 patients. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2007. J Neurosurg Spine. 2008;8:271–278.
49.
Jacofsky DJ, Papagelopoulos PJ, Sim FH. Advances and challenges in the surgical treatment of metastatic bone disease. Clin Orthop Relat Res. 2003;(415 suppl):S14–S18.
50.
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.
51.
Jung ST, Ghert MA, Harrelson JM, et al. Treatment of osseous metastases in patients with renal cell carcinoma. Clin Orthop Relat Res. 2003;223–231.
52.
Kanayama M, Ng JT, Cunningham BW, et al. Biomechanical analysis of anterior versus circumferential spinal reconstruction for various anatomic stages of tumor lesions. Spine. 1999;24:445–450.
53.
Katzer A, Meenen NM, Grabbe F, et al. Surgery of skeletal metastases. Arch Orthop Trauma Surg. 2002;122:251–258.
54.
Kumar D, Grimer RJ, Abudu A, et al. Endoprosthetic replacement of the proximal humerus. Long-term results. J Bone Joint Surg Br. 2003;85:717–722.
55.
Kunisada T, Choong PF. Major reconstruction for periacetabular metastasis: Early complications and outcome following surgical treatment in 40 hips. Acta Orthop Scand. 2000;71:585–590.
56.
Kwee TC, Kwee RM, Nievelstein RA: Imaging in staging of malignant lymphoma: A systematic review. Blood. 2008;111:504–516.
57.
Lane JM, Khan SN, O’Connor WJ, et al. Bisphosphonate therapy in fibrous dysplasia. Clin Orthop Relat Res. 2001;382:6–12.
58.
Lane JM, Sculco TP, Zolan S. Treatment of pathological fractures of the hip by endoprosthetic replacement. J Bone Joint Surg Am. 1980;62:954–959.
59.
Leeson MC, Makley JT, Carter JR. Metastatic skeletal disease distal to the elbow and knee. Clin Orthop Relat Res. 1986;(206):94–99.
60.
Leithner A, Radl R, Gruber G, et al. Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur Spine J. 2008;17:1488–1495.
61.
Leong NL, Anderson ME, Gebhardt MC, et al. Computed tomography-based structural analysis for predicting fracture risk in children with benign skeletal neoplasms: Comparison of specificity with that of plain radiographs. J Bone Joint Surg Am. 2010;92(9):1827–1833.
62.
Levine BR, Sporer S, Poggie RA, et al. Experimental and clinical performance of porous tantalum in orthopaedic surgery. Biomaterials. 2006;27:4671–4681.
63.
Lin PP, Mirza AN, Lewis VO, et al. Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am. 2007;89:1794–1801.
64.
Lipton A. Efficacy and safety of intravenous bisphosphonates in patients with bone metastases caused by metastatic breast cancer. Clin Breast Cancer. 2007;7(suppl 1):S14–S20.
65.
Lipton A. Treatment of bone metastasis and bone pain with bisphosphonates. Support Cancer Ther. 2007;4:92–100.
66.
Liu JK, Apfelbau RI, Chiles BW III, et al. Cervical spinal metastasis: Anterior reconstruction and stabilization techniques after tumor resection. Neurosurg Focus. 2003;15:E2.
67.
Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19:558–567.
68.
Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. 1996;78:656–663.
69.
Marco RA, Sheth DS, Boland PJ, et al. Functional and oncological outcome of acetabular reconstruction for the treatment of metastatic disease. J Bone Joint Surg Am. 2000;82:642–651.
70.
Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989;249:256–265.
71.
Morrow M, Waters J, Morris E. MRI for breast cancer screening, diagnosis, and treatment. Lancet. 2011;378(9805):1804–1811.
72.
Nazarian A, von Stechow D, Zurakowski D, et al. Bone volume fraction explains the variation in strength and stiffness of cancellous bone affected by metastatic cancer and osteoporosis. Calcif Tissue Int. 2008;83(6):368–379.
73.
Newhouse KE, El-Khoury GY, Buckwalter JA. Occult sacral fractures in osteopenic patients. J Bone Joint Surg Am. 1992;74:1472–1477.
74.
Ohta M, Tokuda Y, Suzuki Y, et al. Whole body PET for the evaluation for bony metastases in patients with breast cancer: Comparison with 99Tcm-MDP bone scintigraphy. Nucl Med Commun. 2001;22:875–879.
75.
Papagelopoulos PJ, Galanis EC, Greipp PR, et al. Prosthetic hip replacement for pathologic or impending pathologic fractures in myeloma. Clin Orthop Relat Res. 1997:192–205.
76.
Raab P, Hohmann F, Kuhl J, et al. Vertebral remodeling in eosinophilic granuloma of the spine. A long-term follow-up. Spine. 1998;23:1351–1354.
77.
Rades D, Blach M, Nerreter V, et al. Metastatic spinal cord compression. Influence of time between onset of motoric deficits and start of radiation on therapeutic effect. Strahlenther Onkol. 1999;175:378–381.
78.
Ralston S, Fogelman I, Gardner MD, et al. Hypercalcemia and metastatic bone disease: Is there a causal link? Lancet. 1982;2:903–905.
79.
Roodman GD. Biology of osteoclast activation in cancer. J Clin Oncol. 2001;19:3562–3571.
80.
Rose PS, Halasy M, Trousdale RT, et al. Preliminary results of tantalum acetabular components for THA after pelvic radiation. Clin Orthop Relat Res. 2006;453:195–198.
81.
Rougraff BT. Evaluation of the patient with carcinoma of unknown primary origin metastatic to bone. Clin Orthop Relat Res. 2003;415:S105–S109.
82.
Scarborough M, Moreau G. Benign cartilage tumors. Orthop Clin North Am. 1996;27:583–589.
83.
Scully SP, Ghert MA, Zurakowski D, et al. Pathologic fracture in osteosarcoma: Prognostic importance and treatment implications. J Bone Joint Surg Am. 2002;84A:49–57.
84.
Siemionow K, Lieberman IH. Vertebral augmentation in osteoporosis and bone metastasis. Curr Opin Support Palliat Care. 2007;1:323–327.
85.
Sim FH, Daugherty TW, Ivins JC. The adjunctive use of methylmethacrylate in fixation of pathological fractures. J Bone Joint Surg Am. 1974;56:40–48.
86.
Snell W, Beals RL. Femoral metastases and fractures from breast carcinoma. Surg Gynecol Obstet. 1964;119:22–24.
87.
Sugiura H, Yamada K, Sugiura T, et al. Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res. 2008;466:729–736.
88.
Swanson DA. Surgery for metastases of renal cell carcinoma. Scand J Surg. 2004;93:150–155.
89.
Tillman RM, Myers GJ, Abudu AT, et al. The three-pin modified “Harrington” procedure for advanced metastatic destruction of the acetabulum. J Bone Joint Surg Br. 2008;90B:84–87.
90.
Tomita K, Kawahara N, Kobayashi T, et al. Surgical strategy for spinal metastasis. Spine. 2001;26:298.
91.
Tordai P, Lugnegard H. Is the treatment of enchondroma in the hand by simple curettage a rewarding method? J Hand Surg. 1990;15B:331–334.
92.
Townsend P, Smalley S, Cozad S. Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease. Int J Radiat Oncol Biol Phys. 1995;31:43.
93.
Turcotte RE, Wunder JS, Isler MH, et al. Giant cell tumor of long bone: A Canadian Sarcoma Group study. Clin Orthop Relat Res. 2002:248–258.
94.
Vansteenkiste JF, Stroobants SS. PET scan in lung cancer: Current recommendations and innovation. J Thorac Oncol. 2006;1(1):71–73.
95.
Virk MS, Petrigliano FA, Liu NQ, et al. Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK/RANKL axis in osteolytic prostate cancer lesion in bone. Bone. 2009;44(1):160–167.
96.
Weber KL. Specialty update: What’s new in musculoskeletal oncology. J Bone Joint Surg. 2004;86:1104–1109.
97.
Weber K, Damron TA, Frassica FJ, et al. Malignant bone tumors. Instr Course Lect. 2008;57:673–688.
98.
Weber KL, Gebhardt MC. Specialty update: What’s new in musculoskeletal oncology. J Bone Joint Surg. 2003;85:761–767.
99.
Weber KL, Lewis VO, Randall L, et al. An approach to the management of the patient with metastatic bone disease. Instr Course Lect. 2004;53:663–676.
100.
Weber KL, Lin PP, Yasko AW. Complex segmental elbow reconstruction after tumor resection. Clin Orthop. 2003;415:31–44.
101.
Weber KL, O’Connor MI. Operative treatment of long bone metastases: Focus on the femur. Clin Orthop Relat Res. 2003;S276–S278.
102.
Weikert DR, Schwartz HS. Intramedullary nailing for impending pathological subtrochanteric fractures. J Bone Joint Surg Br. 1991;73B:668–670.
103.
Weill A, Kobaiter H, Chiras J. Acetabulum malignancies: Technique and impact on pain of percutaneous injection of acrylic surgical cement. Eur Radiol. 1998;8:123–129.
104.
Wu J, Wong R, Johnston M, et al. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys. 2003;55:594.
105.
Xie L, Guo W, Li Y, et al. Pathologic fracture does not influence local recurrence and survival in high-grade extremity osteosarcoma with adequate surgical margins. J Surg Oncol. 2012;106(7):820–825.
106.
Yasko AW, Fanning CV, Ayala AG, et al. Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). J Bone Joint Surg Am. 1998;80:219–228.
107.
Yazawa Y, Frassica FJ, Chao EY, et al. Metastatic bone disease: A study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin Orthop Relat Res. 1990;(251):213–219.
108.
Yuh WTC, Zacharck CK, Barloon TJ, et al. Vertebral compression fractures: Distinction between benign and malignant causes with MR imaging. Radiology. 1989;172:215–218.