Chapter 2 Pathologic Fractures

43R.J. Pignolo et al. (eds.), Fractures in the Elderly, Aging Medicine,DOI 10.1007/978-1-60327-467-8_2, © Springer Science+Business Media, LLC 2011

Abstract Pathologic fractures can be caused by any type of bone tumor, but the overwhelming majority of pathologic fractures in the elderly are secondary to metastatic carcinomas. Multiple myeloma is also common in the elderly and has a high incidence of pathologic fractures. Diagnostic laboratory tests and imaging of multiple myeloma and metastatic tumors allow earlier diagnosis and interven-tion, which lead to decreased morbidity. Chemotherapy and radiation therapy have improved treatment of metastatic disease, but have a variable effect depending on the tumor type. The goals of surgical treatment of impending or pathologic fracture are to provide pain relief and a functionally stable and durable construct that will allow the patient to ambulate shortly after surgery and will persist for the life of the patient. Fixation of metastatic pathologic fractures requires reinforce-ment or replacement of the compromised bone with a rigid and durable construct. Rehabilitation and prevention of postoperative complications are imperative. The overall effectiveness of treatment in pathologic fractures is improved with a multi-disciplinary approach.

Keywords Pathologic fracture • Metastatic • Orthopedic • Tumor • Diagnosis • Treatment

2.1 Introduction

Many pathologic processes, including osteoporosis, weaken bone. Typically, the term pathologic fracture refers to the fracture that occurs in the area of a neoplasm. Pathologic fractures can be caused by any type of bone tumor, but the overwhelming

R.D. Lackman (*) Department of Orthopaedic Surgery, Sarcoma Center of Excellence at the Abramson Cancer Center of the University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA e-mail: [email protected]

Chapter 2Pathologic Fractures

Jesse T. Torbert and Richard D. Lackman

44 J.T. Torbert and R.D. Lackman

majority of pathologic fractures in the elderly are secondary to metastatic carcinomas. Multiple myeloma is also common in the elderly and has a high incidence of patho-logic fractures.

2.2 Metastatic Tumors of Bone

The most common primary malignancies that metastasize to bone are breast, lung, kidney, prostate, and thyroid carcinomas, which account for approximately 700,000 new primary cases in the U.S. annually. Metastatic bone disease can have very detrimental effects on quality of life. The prognosis for patients with metas-tases to bone largely depends on the aggressiveness of the primary tumor, with lung cancer patients having the shortest length of survival. Unlike primary bone tumors, the early diagnosis and treatment of secondary tumors will not result in a cure. However, much of the significant morbidity related to bone metastases and pathologic fracture can be lessened with early intervention. The evaluation and management of patients with metastatic bone disease is best done with a multidis-ciplinary approach including medical oncologist, radiologist, pathologist, orthope-dic surgeon, physical therapist, and social worker.

2.2.1 Location

Skeletal metastases are often multifocal; however, renal and thyroid carcinomas are notorious for producing solitary lesions. By far the most common location for osseous metastases is the axial skeleton, followed by the proximal femur and proximal humerus. Metastatic spine tumors are 40 times more frequent than all primary bone tumors combined [1]. In autopsy series, vertebral body metastases were found in over one-third of patients who died of cancer [2]. The anterior elements of the spine are 20 times more likely to be involved than the posterior elements [3].

2.2.2 Presentation

Patients with metastatic bone disease can have varied presentations. Lesions may vary from extremely painful and disabling to asymptomatic. Most metastases pres-ent with a bone lesion detected on bone imaging after patients complain of local-ized musculoskeletal pain. Bone metastases rarely present with an associated soft-tissue mass, and the presence of such a mass should increase the suspicion of a primary sarcoma. Fractures after a minor or insignificant injury should always raise the suspicion of an underlying lesion, especially in patients with a previously

452 Pathologic Fractures

diagnosed malignancy. Most symptomatic patients with metastatic bone disease present with pain that is mechanical in nature, worse at night, and unresponsive to anti-inflammatory medications and narcotics. Neurological complaints may be the presenting symptoms especially in cases of spinal metastases with associated nerve root or spinal cord compression. It is also common for patients with pelvic metas-tases to present with leg pain, which mimics sciatica. As such, it is important to include imaging of the pelvis in the work-up of patients with metastatic bone dis-ease and leg pain because radiographs and magnetic resonance imaging (MRI) of the lumbar spine may miss these lesions. Thorough clinical examination is manda-tory in all cases to evaluate not only the presenting lesion, but also any other meta-static foci that may be less symptomatic. In patients with previous bony metastasis, regular follow-up evaluation is needed to assess painful sites and screen for impending fractures.

2.2.3 Diagnostic Laboratory Tests

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

2.2.4 Imaging

High quality, plain anteroposterior and lateral radiographs that show the involved bone, including one joint proximally and distally, are the standard for initial assess-ment of metastatic bone disease. One should look for lytic, blastic, or mixed lesions. Metastases from lung, renal, and thyroid tumors tend to be entirely lytic (Fig. 2.1). Breast metastases may be lytic or may show a mixed lytic–blastic


appearance. The majority of prostate bone metastases are blastic (Fig. 2.2) though lytic lesions do occur. Pelvic radiographs should include an anteroposterior view and obturator and iliac oblique Judet views of the pelvis. A significant amount of bone must be destroyed before a lesion will appear lytic on radiographs. Therefore, a patient with a malignancy and bone pain often requires further evaluation despite normal-appearing plain radiographs.

Computed tomography (CT) is the study of choice when looking for bone detail and cortical destruction, but is not as sensitive at assessing marrow replacement. MRI on the other hand is very sensitive to early marrow replacement and can locate metastases prior to their appearance on radiographs and CT, but is not as helpful for bony anatomy.

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

Fig. 2.1 This is an AP radiograph of a right humerus lytic lesion in a patient with metastatic carcinoma. These images are courtesy of UPenn Orthopaedic Trauma Service


2.2.5 Management Options

2.2.5.1 Medical/Radiation Therapy

Patients with cancer are often in a hypercoagulable state. Prophylaxis against deep vein thrombosis (DVT) with pharmacologic agents and/or sequential compression devices (SCD’s) is provided for patients who are non-ambulatory and at risk. Bisphosphonates inhibit osteoclastic activity, suppressing bone resorption, and are commonly used to treat destructive bony lesions from metastatic disease. One com-mon bisphosphonate used in cancer patients is pamidronate, which in conjunction with systemic chemotherapy, has been shown to decrease or delay pathologic frac-tures due to bone metastases in breast cancer [4] and multiple myeloma patients [5]. Zolendronate is also commonly used is many protocols.

Chemotherapy and radiotherapy should be used as indicated to stop or slow the neoplastic progression. Postoperatively, chemotherapy and radiotherapy are often delayed between 7 and 14 days after surgery in order to allow unimpeded would healing.

Prostate, lymphoid, and breast neoplasms are the most sensitive to radiation therapy. Lung and thyroid cancers are intermediately responsive; gastrointestinal, melanoma, and renal tumors are typically radiotherapy-resistant lesions. Treatment for metastatic lesions in the extremities can range from a single 8 Gy dose to a

Fig. 2.2 This is an AP radiograph of the pelvis in a patient with metastatic prostate cancer with multiple blastic lesions in the pelvis and fourth lumbar vertebra


40 Gy dose divided over 15 daily fractions. Large single doses are usually utilized for treating pain related to metastatic lesions, while smaller fractional dosing allows a higher cumulative dose and is often used for definitive treatment or when attempt-ing to decrease the size of metastatic lesions. Metastatic bone lesions with a low risk of fracture may be initially treated with radiation, which may negate the need for subsequent surgical intervention.

2.2.5.2 Surgery

Indications

A pathologic fracture can be devastating in an elderly cancer patient and is a clear indication for surgical intervention, with the patient’s medical condition and expected survival playing a role in the decision to proceed to surgery. The treatment of metastatic bone lesions in the absence of fracture is not so well-defined. Because pathologic fractures are extremely detrimental, prophylactic surgical treatment of impending fractures has been shown to improve outcomes [6]. In 1989, Mirels [7] developed a scoring system designed to predict the risk of pathologic fracture due to bone metastases in the extremities.

The Mirels classification is based on the degree of pain, lesion size, lytic versus blastic nature, and anatomic location as shown in Table 2.1. Mirels recommended prophylactic fixation for a total score ³9. The variability in quality of surrounding bone, behavior of metastases from different tumor types, response of these metas-tases to treatment including radiation, and patient activity level can also have an effect on the probability of fracture. While this scoring system is helpful, we feel that the most reliable predictor of impending fracture is mechanical pain. Mechanical pain is a physiologic indicator that the involved bone cannot withstand the physical stresses placed upon it, and is therefore at risk of fracture. As a result, all metastatic lesions in the extremities that exhibit mechanical pain should be con-sidered for prophylactic fixation.

One important caveat to any surgeon considering operative intervention for a suspected bone metastasis is to recognize the possibility of an unrelated primary bone tumor in a patient with a previously diagnosed malignancy. As a general rule, the first time a tumor presents with metastasis to bone, histological confirmation

Table 2.1 The scoring system proposed by Mirels [7] (reprinted with permission)

Score 1 2 3

Pain Mild Moderate Mechanical painLesional size/diameter

of bone involved<1/3 1/3–2/3 >2/3

Lesion type (blastic versus lytic)

Blastic Mixed Lytic

Anatomic site Upper limb Lower limb Peritrochanteric (proximal femur)


with a biopsy or intra-operative frozen section should precede definitive surgical intervention. When the diagnosis is confirmed, immediate internal fixation is reasonable. If concern for a potential primary bone sarcoma persists, definitive surgery should be postponed. Passing an intramedullary nail through a primary bone sarcoma will result in distal seeding of the medullary canal and will frequently necessitate amputation.

Treatment Options

The goals of surgery for impending or pathologic fracture in the setting of metastatic disease are to provide pain relief and a functionally stable and durable construct that will allow the patient to ambulate shortly after surgery and will persist for the life of the patient. This is quite a challenge in some cases given the large amount of bone loss, the degree of osteoporosis in the elderly, and the decreased ability of bone to heal in the local setting of tumor. Therefore, techniques used in patients with patho-logical fractures differ from those used in young patients with traumatic fractures in which fixation is placed as a temporary stabilizing measure while fracture healing occurs. The idea in the fixation of metastatic pathologic fractures is to reinforce or replace the compromised bone with a rigid and durable construct. This typically requires plates or intramedullary rods with the addition of methylmethacrylate, or bone cement, to fill the bone defects. If the fracture is near a joint, and stable and durable fixation cannot be achieved by the described methods, joint arthroplasty may provide a more durable construct and may require less operative time and blood loss. Occasionally, segmental replacement prostheses may be used (Fig. 2.3), which not only replace the joint surface and nearby bone but also replace varying lengths of diaphyseal bone with metal. These are typically used in malignant primary tumors of bone where large segments of bone must be resected; although they may also play a role in metastatic bone disease. Surgical alternatives, although not all-inclusive, for fixation or reconstruction of impending or pathologic fractures in the extremities were proposed by Lackman et al. [8] and are presented in Table 2.2.

Postoperative Care

The postoperative physical therapy largely depends on the type of construct used and the intra-operative observations made by the surgeon regarding the quality of bone, screw purchase, and overall stability of the construct. The goal is to achieve mobility and independence in order to improve the quality of life and to decrease cardiopul-monary complications that are associated with immobility in the elderly patient.

Adequate pain control is necessary for participation in physical therapy. DVT prophylaxis is very important in cancer patients that are immobilized. Bisphosphonates, radiation therapy, and chemotherapy should be used as indicated, keeping in mind that radiation and chemotherapy decrease wound healing and may be delayed.


Fig. 2.3 These are images of tumor replacement prostheses. The left image is a proximal femur replacement prosthesis. The middle image shows a distal femoral replacement prosthesis which includes the knee replacement. The image on the right is a proximal tibial replacement prosthesis and includes the knee replacement. These images are courtesy of UPenn Orthopaedic Trauma Service

Table 2.2 Surgical alternatives for fixation or reconstruction of impending or pathologic fractures in bones of the extremities [8] (reprinted with permission)

Region Surgical approach

Clavicle and scapula No surgical intervention needed (radiotherapy sufficient)Proximal humerus Plate and cement or intramedullary rod ± cement or

segmental replacement endoprosthesisHumeral shaft Intramedullary rod ± cementDistal humerus Plate and cement or segmental replacement endoprosthesisProximal radius No surgical intervention needed (radiotherapy sufficient)Radial and ulnar shaft Plate/rod ± cement if radiotherapy failsDistal radius Plate and cementFemoral head and neck Endoprosthesis (total or hemiarthroplasty)Intertrochanteric Compression hip screw ± cement or intramedullary rod ±

cement or segmental replacement endoprosthesisSubtrochanteric Intramedullary rod ± cementFemoral shaft Intramedullary rod ± cementDistal femoral metaphysis Plate and cement or retrograde intramedullary rod ± cement

or segmental replacement prosthesisProximal tibial metaphysis Plate and cement or segmental replacement prosthesisTibial shaft Intramedullary rod ± cementDistal tibia Plate and cement


2.3 Multiple Myeloma

Multiple myeloma is a B-cell lymphoproliferative disease that is characterized by involvement of the skeleton at multiple sites. Multiple myeloma causes 1% of all cancer deaths in the Western countries. It is more common in men and those with African descent. The peak incidence occurs between 50 and 60 years of age. Most myeloma patients will present with multiple lesions; however, a small percentage will present with a solitary lesion and a negative bone marrow aspirate. Those with a solitary myeloma have a much better prognosis.

2.3.1 Presentation

The clinical features of multiple myeloma arise from the effects of organs infiltrated with tumor cells and the production of excessive immunoglobulin (Ig). Hypercalcemia resulting from bone resorption can give rise to confusion, weakness, lethargy, constipation, and polyuria. Decreased production of normal Ig predisposes the patient to recurrent infections. Renal insufficiency occurs in half of multiple myeloma patients, and is often an ominous manifestation. Chronic renal failure may develop insidiously or acute renal failure may present with oliguria. Infiltration of bones causes pain, pathologic fractures, spinal cord compressions, and hypercal-cemia. Patients often present with bone pain and pathologic fracture, which is a major source of morbidity. One study followed 165 multiple myeloma patients for an average of 3.2 years and found approximately two pathologic fractures, mostly vertebral and rib fracture, per patient [9].

2.3.2 Diagnostic Laboratory Tests

The diagnosis of myeloma can be confirmed by the identification of monoclonal pro-teins in the serum or urine via serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP). Monoclonal proteins are more often absent or undetectable in solitary myeloma compared to multiple myeloma. A chemistry panel can be used to assess kidney function and allows calcium and phosphate levels to be followed to detect and avoid the development of malignant hypercalcemia. Formal diagnostic cri-teria have been put forth by the Mayo Clinic and the International Myeloma Working Group for the diagnosis of symptomatic multiple myeloma [10–12].

2.3.3 Imaging

Multiple punched-out lesions on a lateral skull radiograph are a classic finding for multiple myeloma. A skeletal survey often reveals other lytic bone lesions. These often appear as medullary lytic lesions with sharp margins, but little periosteal


reaction (Fig. 2.4). Bone scans are often negative secondary to the lack of bone reaction. MRI scans, especially of the spine, are useful.

2.3.4 Management Options

2.3.4.1 Medical Therapy

Chemotherapy and radiation have been the mainstays of treatment. Radiation will often result in less bone pain and decreased need for surgical treatment. Bisphosphonates have been shown to reduce pain, pathologic fractures, and increase survival [13].

2.3.4.2 Surgery

Surgical Treatment Options

Surgical intervention is typically reserved for decompression of neural structures in the case of spinal involvement and stabilization of lower extremity pathologic

Fig. 2.4 This is an AP radiograph of the right hip in an elderly male with multiple myeloma. Multiple, medullary punched-out, lytic lesions, a classic finding, are present. There is little periosteal reaction. The most inferior lesions have sharp margins, another classic finding. This image is courtesy of UPenn Orthopaedic Oncology Service


fractures. Upper extremity fractures may respond well to radiation therapy. Surgery may be the best treatment for recurrent lesions or those that do not respond to radiotherapy. The goals are the same as those for metastatic carcinoma lesions: to provide a functionally stable and durable construct that will allow the patient to ambulate shortly after surgery and will persist for the life of the patient. Again, this can be accomplished with internal fixation and the addition of bone cement for bone defects or joint/bone replacing prostheses.

Postoperative

The postoperative care of multiple myeloma patients is similar to those with metastatic bone metastases. The goal is to achieve mobility and independence in order to improve the quality of life, while decreasing cardiopulmonary complica-tions that are associated with immobility in the elderly patient. Pain control and DVT prophylaxis are necessary. In addition, bisphosphonates are often continued postoperatively due to their demonstrated effects on pain, fractures, and survival.

References

1. Harrington KD. Metastatic disease of the spine. In: Harrington KD, ed. Orthopaedic manage-ment of metastatic bone disease. St. Louis: Mosby, 1988:309–383.

2. Wong DA, Fornasier VL, MacNab I. Spinal metastases: the obvious, the occult, and the impostors. Spine 1990;15:1–4.

3. Brihaye J, Ectors P, Lemort M. The management of spinal epidural metastases. Adv Tech Stand Neurosurg 1988;16:121–176.

4. Hortobagyi GN, Theriault RL, Lipton A. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 1998;16:2038–2044.

5. Berenson JR, Lichtenstein A, Porter L. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996;334:488–493.

6. Ward WG, Holsenbeck S, Dorey FJ. Metastatic disease of the femur: surgical treatment. Clin Orthop Relat Res 2003;(415 Suppl):S230–S244.

7. Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res 1989;(249):256–264.

8. Lackman RD, Torbert JT, Hosalkar HS. Treatment of metastases to the extremities and pelvis. Oper Tech Orthop 2004;14:288–295.

9. Melton LJ, Kyle RA, Achenbach SJ. Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 2005;20:487–493.

10. Smith A, Wisloff F, Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2006;132:410–451.

11. International Myeloma Working Group. Criteria for the classification of monoclonal gam-mopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749–757.

12. Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal gammopathy of undetermined signifi-cance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc 2006;81:693–703.

13. Berenson JR, Rajdev L, Broder M. Bone complications in multiple myeloma. Cancer Biol Ther 2006;5:1082–1085.

http://www.springer.com/978-1-60327-466-1

Documents

Chapter 2 Pathologic Fractures