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Evaluation of pathologic fracture risk due to a tumor

Evaluation of the Risk of Pathologic Fractures Secondary to Metastatic Bone Disease

Pathologic fractures create a serious morbidity in patients with metastatic bone disease. Orthopedic surgeons who treat patients with metastatic skeletal lesions should focus on proactive treatments designed to prevent pathologic fractures before they occur. Prevention of pathologic fractures result in better patient outcome, lower cost, and less difficult operative procedures. For this reason, it is critical to identify both patients and skeletal lesions that are at increased risk of pathologic fracture. The goal of this review is to establish a systematic screening tool and treatment algorithm that orthopedic surgeons can easily apply to their patients in order to optimize the management of metastatic skeletal disease.

Unlike fractures of normal bone, pathologic fractures occur during normal activity or minor trauma due to weakening of the bone by disease. Conditions associated with pathologic fractures include underlying metabolic disorders, primary benign tumors, and primary and metastatic malignant tumors (q) . The most common condition associated with pathologic fractures is osteoporosis(q). This review will focus on the evaluation of fractures that occur secondary to bone destruction by metastatic cancer. Prevention of pathologic fractures is superior to treatment after the fact. Some of the advantages that have been cited include shorter hospital stays(R,A); easier rehabilitation and nursing with more rapid restoration of function (U,V,K,R); easier radiotherapy treatment (R,A.); more immediate pain relief (U,V,K,R,A); and faster and less complicated surgery (R,A).

In order to determine which patients require prophylactic fixation to prevent pathologic fracture, it is necessary to perform an accurate and reliable risk evaluation. Many different characteristics have been proposed as important criteria for determining risk of fracture. These include type of cancer; type of treatment; size of the lesion; location of the lesion; whether the lesion is lytic or blastic; and symptoms due to the lesion. In addition, some have proposed a detailed biomechanical analysis based on finite element modeling. the use of biomechanics to predict fracture. This article will critically review the literature and provide guidelines for estimating fracture risk that are useful for orthopedic surgeons.

PATIENT FACTORS

Cancer Diagnosis The patient's underlying cancer diagnosis is an important component of their pathologic risk profile (Table 1). Breast cancer is the most important source of bone metastasis, and it is responsible for the majority of the skeletal metastases that require orthopedic consultation (M). The risk of pathologic fracture increases with the duration of metastatic disease. Because breast carcinoma has a relatively long survival, these patients are more likely to sustain a pathological fracture. Based on the author's experience, breast cancer metastases that are purely lytic are more likely to fracture than those that are blastic or mixed lytic and blastic. However, blastic lesions in high risk areas such as the proximal femur have a high rate of fracture.

Prostate cancer, combined with breast cancer, contributes to 80% of all skeletal metastasis (O). Prostate cancer normally forms blastic metastases which are less susceptible to fracture, but blastic lesions have been shown to decrease the longitudinal stiffness of bone (?). In addition, some of the treatments that are commonly given for prostate cancer increase the likelihood of pathologic fracture. These include LHRH agonists, orchiectomy, and radiation. In one study, patients receiving LHRH agnosists had a 9% incidence of fracture, a rate significantly higher than similar patients not receiving LHRH agonists (Cancer 1997, February 1st, Volume 79 (3), Pg 545). Patients with prostate cancer who have had radiation to bony areas, or who have low bone density due to hormone modification therapies should be considered at increased risk for fracture.

Lung cancer has a relatively aggressive course and a short survival after bone metastasis. Thus fewer patients survive long enough to develop pathologic fracture. Metastases are typically lytic and have a correspondingly higher risk of fracture. A small proportion of lung cancer metastasis can occur in bones below the elbow and the knee (acrometastasis). These lesions are frequently painful and require radiation or surgical treatment due to the pain rather than for risk of fracture as the risk of functionally disabling fracture through an acrometastasis is low.

Bone metastasis is diagnosed in 4% - 13% of patients with thyroid cancer (Marcocci et al, Surgery 106:960-966, 1989 and McCormack, Cancer 19:181-184 1965.) The lesions are frequently lytic and their fracture risk depends on their location. Because patients with thyroid cancer may have prolonged survival they are also at increased overall risk of pathological fracture. Approximately 25-50% of renal cell carcinomas metastasize to bone (r,s).

Renal cell metastases to bone can be unusually expansile and destructive, which creates an increased risk of pathologic fracture. Orthopedic surgeons treating metastatic cancers should note that certain selected patients with renal cell metastases may be candidates for aggressive surgical resection for cure (?). Table 1: Origin and Rates of Metastasis to Skeleton Irradiation of Lesion

Irradiation of metastatic bone lesions also appears to increase the risk of pathologic fracture (C, N, 1, G, R, K,A,Z). Keene et al found that 18% of patients who underwent irradiation for metastatic breast carcinoma developed fractures. Other authors have reported much higher incidences ranging from 26%-41% (1,N,Z). Harrington (G) theorizes that radiotherapy increases the risk for fracture because it causes temporary softening of the bone at the tumor site. Radiation may lead to increased fracture risk due failure of reossification after treatment. Beals and Snell reported that only 4% of lesions reossified after treatment (A). However, other authors have found a 65%-85% incidence of reossification under similar circumstances, assuming a fracture has not occurred (4, Q).

Pain Pain is an important but controversial criteria for evaluation of pathologic fractures. In metastatic disease, pain may arise from enlargement of the tumor, perilesional edema, increased intraosseous pressure, or weakness from bone loss (1,X). The direct pressure exerted by the tumor on the bone has been shown to stimulate the release of various pain mediators including porstaglandins, bradykinins, and histamine (o). In addition, tumor invasion of bone can lead to activation of mechanoreceptor and nociceptors which leads to the development of pain (o). The controversy lies in whether or not pain can be used as a sign of impending fracture. Fidler (B) stated that pain could not be considered a reliable sign of an impending fracture because only half of the patients in his study complained of pain. Keene et al (C2 Pair; somo determio atatesionsused a a sign of iaure lik In order to determi(Fng porongitne Dencelained of paiostap of In one of gical treatment d( R)is artained of painrather thaap of In one lytic and treatment dupith mhther10isk(se 1nes belowfihethersuggast a sign of in selea is anstated that racture,d . In additild-cr ih, and hiss the bone at the tumor site(1nces, assuLESIONe useful for ortRed riwhoieldand Rates Simatelyontent"> due failure of t o pugic fede lytl,N,Zflurentil workendin1956failu:961es betlywork raalta relimors (q)ned of paincal fracture. ailu relimors ic or mixedologiesio meign of19(q). This review willrstasis184 196"vietne Dencewith n his study58% sign osent of metas a eite elemnstatuspitaologiol ofRSPain:ondasowever, an. Keene et the les2.5 cmasishese ily . Inradykolvpitaologiemors-i/tumex some asowever, andefssurastasis,agitnese e suryf cancer; urgeonaure ln of and requi)ned es below

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