metastatic disease to bone - turner white

he skeleton, after the lungs and liver, is thethird most common site of metastatic disease,1,2

and metastatic disease is the most commonmalignancy of bone. Half of the nearly 1.4 mil-

lion cases of newly diagnosed cancers each year involvetumors that frequently metastasize to bone (Table 1).3

Prostate, breast, lung, kidney, and thyroid cancersaccount for 80% of skeletal metastases.1 A predilectionfor the axial skeleton is seen, perhaps owing to thevenous blood flow in Batson’s plexus. Overall, the mostcommon sites of bony metastases are the spine, pelvis,ribs, skull, and proximal femur. When rare acral (ie, dis-tal) metastases to the hands and feet occur, they mostcommonly originate from a lung primary.4,5

As postcancer survival has increased with improve-ments in treatment, the numbers of patients developingmetastatic disease during their lifetime has alsoincreased. In careful postmortem studies of patients whosuccumbed to malignancy, rates of skeletal metastasesapproached 70%.2 This number increased to 85% whenonly breast, lung, kidney, thyroid, and prostate primarycancers were considered. This article reviews the presen-tation and evaluation of patients with metastatic bonedisease and discusses the management of these patients.

CLINICAL EVALUATIONPresentation

The presentation of metastatic bone disease is vari-able, but pain is the most common complaint. The painof metastatic disease is usually insidious in onset and ispresent in 75% of patients at presentation.6 Painlesslesions usually are diagnosed during staging or routinefollow-up (eg, technetium bone scan) in patients with aknown history of carcinoma. Night pain and pain in-completely relieved by rest are not specific for metastasisalone, but they are typical symptoms. Weightbearingbones may become symptomatic early in the course ofdisease, whereas bones such as the flat bones of ribs orsternum may remain asymptomatic until late in the dis-ease, often until pathologic fracture occurs.

Figures 1 and 2 show the algorithms used for evalua-tion of the patient with suspected metastatic bone dis-

ease. The use of a schema such as these will diagnose85% of suspected metastatic malignancies and theirprimary malignancies.7

History

The history in a patient with suspected malignancyshould be more thorough than is often required forother orthopaedic conditions. Risk factors for carcino-ma, such as tobacco abuse, alcohol abuse,8 chronic in-fections (especially viral), exposure to ionizing radia-tion, exposure to carcinogens, and family history ofcancer, must be thoroughly explored and specificallyquestioned. Many patients will not know, for example,that chronic hepatitis is a strong risk factor for hepato-cellular carcinoma, or that ulcerative colitis portends amarkedly increased risk for colon cancer. Past medicalhistory should be carefully discussed and reviewed.Patients may not recall the removal of a small mole ontheir back unless specifically asked.

A review of symptoms should go beyond simply aquestion regarding malaise or weight loss. Inquiriesabout cough, dyspnea, hematuria, flank pain, urinaryhesitancy and/or painful urination, endocrine symp-toms, and the noticing of any “lumps or bumps” areonly some of the required queries in this patient popu-lation. If not specifically addressed, the patient withundiagnosed metastatic prostate cancer, for example,may make no connection between his frequent urina-tion and his hip pain.

Physical Examination

The physical examination should be comprehensive.Examination of the musculoskeletal system in isolationis inadequate in this patient population if one wishes todiagnose a yet undetermined primary malignancy or

T

Dr. Jacofsky is an assistant professor, Department of Orthopaedics, MayoClinic, Rochester, MN. Dr. Deborah Frassica is an associate professor ofradiation oncology and Dr. Frank Frassica is chairman, Department ofOrthopaedic Surgery, and Robert A. Robinson Professor of OrthopaedicSurgery, Johns Hopkins University School of Medicine, Baltimore, MD.

www.turner-white.com Hospital Physician November 2004 21

C l i n i c a l R e v i e w A r t i c l e

Metastatic Disease to Bone

David J. Jacofsky, MDDeborah A. Frassica, MD

Frank J. Frassica, MD

locate additional sites of metastatic disease. In additionto a focused examination in the symptomatic area,examination of the breasts, thyroid, prostate, and skinshould be performed when appropriate. Lymph-adenopathy should be sought by palpation of themajor lymph node chains (axillary, supraclavicular,and inguinal). A stool guaiac study may be helpful if agastrointestinal primary malignancy is suspected.Hyperreflexia (eg, Chovstek’s sign) may be a sign ofhypercalcemia, a risk in patients with bone malignancy.Additionally, careful examination for deep vein throm-bosis is prudent in this high-risk group.

LABORATORY STUDIES

A complete blood count, erythrocyte sedimentationrate, C -reactive protein level, blood chemistries, andliver function tests should be ordered as deemed appro-priate to rule out other diagnoses such as infection,hyperparathyroidism, or metabolic bone disease. A uri-nalysis to search for occult blood should be performed,as occult hematuria may be the only early finding inrenal or bladder carcinoma. Additionally, a urine andserum protein electrophoresis to rule out multiplemyeloma, and a prostate-specific antigen test to ruleout prostate carcinoma, may be wise in some patients.

Subtle findings of anemia, thrombocytopenia,leukopenia, or abnormal liver function tests shouldnot be dismissed without further evaluation, as thesemay support systemic findings of metastatic disease. Anionized calcium level is helpful in the identification ofhypercalcemia, as low albumin levels may make totalcalcium values difficult to interpret. One should alsoremember that many carcinomas can cause fever andelevated acute-phase proteins (eg, C-reactive protein)in the absence of infection. Therefore, these findingsin isolation do not rule out metastatic disease, nor dothey empirically confirm the diagnosis of infection.

Although tumor markers such as carcinoembryonicantigen, CA-125, and CA 19-9 are extremely helpful in

monitoring the response of certain cancers to treat-ment, they are of little, if any, value in the initial work-up of metastatic disease with an unknown primary.

IMAGING STUDIESRadiographs

Radiographs of the symptomatic area are the first stepin the imaging evaluation of suspected bone metastases.In addition, radiographs are important for the interpre-tation of abnormal findings on the technetium bonescan. The clinician should correlate the technetiumbone scan with the plain radiographs prior to confirmingthe diagnosis of metastatic bone disease with the patient.Up to 30% of benign enostoses (bone islands) and mostenchondromas exhibit increased uptake on technetiumscans. Technetium scans are very sensitive but nonspecif-ic in distinguishing malignant and nonmalignant abnor-malities. Radiographs are often diagnostic for enchon-dromas, bone islands, bone infarcts, and other incidentalfindings in the cancer patient. Up to 40% of metastaticlesions may be missed on radiographic survey, because30% to 50% of mineral loss or a lesion size of greaterthan 1.5 cm is typically required for consistent detection.9

One’s ability to see less dramatic findings is certainlyenhanced if a positive bone scan localizes an area ofinterest for scrutiny. One must carefully inspect all thecortices to detect subtle bone destruction.

The radiographic appearance of metastatic diseasemay be purely lytic, purely blastic (sclerotic), or mixed.Metastases from prostate, bladder, medulloblastoma, andbronchial carcinoid tumors are most likely to be blastic innature (Figure 3). Purely lytic metastases are usually sec-ondary to renal, pulmonary, thyroid, uterine, adrenal,melanoma, or gastrointestinal cancers (Figure 4). Mixedlesions are typically due to primary cancers of the breast,ovary, testicle, cervix, or lymphatic tissues.10,11 It is impor-tant to remember, however, that any cancer can appearin any pattern. Traditionally, primary sarcomas are asso-ciated with periosteal reactions (eg, Codman’s triangle,sunburst reactions), but one must avoid the temptationto definitively diagnose metastatic disease from a radio-graphic impression alone. Misdiagnosis of a primarymesenchymal sarcoma of bone as metastatic disease,with subsequent internal fixation rather than resection,can compromise limb-salvage options and even the lifeof the patient.

Technetium Bone Scan

Technetium Tc 99m methylene diphosphonatescanning is a very useful adjunct study in the work-upfor metastatic bone disease in a patient with known orsuspected cancer. Tumor osteolysis (directly caused by

22 Hospital Physician November 2004 www.turner-white.com

J a c o f s k y e t a l : M e t a s t a t i c D i s e a s e t o B o n e : p p . 2 1 – 2 8 , 3 9

Table 1. Incidence of Primary Cancers that FrequentlyMetastasize to Bone (United States, 2004)

Primary Site Estimated Cases Diagnosed

Prostate 230,110

Breast 217,440

Lung 173,770

Kidney 35,710

Thyroid 23,600

Data from Cancer facts and figures—2004. Atlanta: American CancerSociety; 2004. Available at www.cancer.org. Accessed 27 Sep 2004.

osteoclastic resorption) causes a compensatory hyper-emic and coupled osteoblastic response of varyingdegrees; this activity is responsible for the deposition ofradioisotope tracer and, therefore, a positive findingon the test (Figure 5).

Tracer uptake on technetium bone scanning is notspecific for metastatic bone disease. Monostotic lesionsidentified by technetium scanning in patients withknown cancer will be proven to be metastases in only50% of cases, underscoring the importance of a biopsyfor confirmation, even in a patient with a known pri-mary malignancy.10 Benign lesions such as enchon-droma, infection, Paget’s disease, stress fracture, andenostoses also may cause increased tracer uptake. Addi-tionally, second primary cancers of mesenchymal ori-gin (eg, chondrosarcoma) are rare but do occur. Multi-

ple positive polyostotic findings in a patient with aknown cancer are most likely to be metastatic disease,but a biopsy of a readily accessible site is still wise in theabsence of visceral metastases.

A false-negative bone scan may occur despite the pres-ence of single or multiple lesions from multiple myeloma(or solitary plasmacytoma), melanoma, Langerhans cellhistiocytosis, lymphoma, leukemia, thyroid carcinoma,neuroblastoma, purely lytic lung carcinoma, or, rarely,breast cancer. Some authors argue against the use of rou-tine bone scanning for staging of squamous cell cancerof the head and neck,12 bladder cancer, and melanomabecause of the very low incidence of bony metastases inthese cancers. The presence of bone pain, however,should prompt such an evaluation.

In the setting of diffuse metastatic disease, the



Suspicious lesion/normal radiograph

Appropriate work-up

Referral to orthopaediconcologist

Fixation, CTX, XRT,as indicated

Restaging evaluation± biopsy, ± fixation

Referral as indicated forCTX/XRT

Figure 1. Evaluation of patient with known primary cancer. CTX = cytotoxic chemotherapy; MRI = magnetic resonance imaging;XRT = radiation therapy. (Adapted from Hage W, Aboulafia A, Aboulafia D. Incidence, location, and diagnostic evaluation of metastat-ic bone disease. Orth Clin North Am 2000;31:523 with permission from Elsevier.)

Bone scan

Single focus

MRI scan locallyRestaging evaluation

Probable metastaticdisease

Biopsy

Nonrenal, nonthyroidprimary cancer

Renal or thyroid primary cancer

Multiple lesions

Nonmalignant diagnosis

Bone pain/history of cancer

Plain films: hip & pelvisChest radiograph Laboratory tests

Possible sarcoma

increased uptake may be so diffuse and marked that nosingle area appears intense; this can result in the bonescan appearing normal. This phenomenon, termed asuperscan, can be diagnosed by looking for “renal steal,”which is the absence of the normal renal uptake patternthat results from the excretion of excess isotopes. Thispattern may also be seen in patients with poor renalclearance, however, and should not alone lead to thediagnosis of diffuse metastatic disease. Bone scanning

for metastatic thyroid carcinoma can be improved withthe use of technetium-99m methoxyisobutyl isonitrile.13

Computed Tomographic Scan

A computed tomographic (CT) scan of the chest,abdomen, and pelvis can be studied to search for primarydisease, as well as to look for lymphadenopathy ormetastatic disease in the lungs or liver. A CT scan of thelocal site of metastasis is occasionally performed and may



Figure 3. Radiographic appearance of blastic metastases. (A) Anterior-posterior view of the pelvis shows diffuse blastic lesions in thesacral ala on both the left and right sides. In addition, a blastic lesion is visible in the right supra acetabula area. (B) Anterior-posteriorview of the proximal humerus shows a dense sclerotic lesion in the metaphysis with no cortical bone destruction.

A B

Bone pain

Skeletal surveyReferral to oncologist

Plain films: hip & pelvisChest radiograph Laboratory tests

Multiple myeloma

BiopsyAssume sarcoma Referral to orthopaedic

oncologist

Figure 2. Evaluation of patient with noprior cancer history. CT = computed to-mography. (Adapted from from Hage W,Aboulafia A, Aboulafia D. Incidence, loca-tion, and diagnostic evaluation of meta-static bone disease. Orth Clin North Am2000;31:524 with permission fromElsevier.)

Go to Figure 1

Unknown primary monostotic disease

Unknown primarypolyostotic disease

Technetium Tc 99m bone scan

CT: chest, abdomen, pelvis

Primary cancerelucidated

Unknown primary cancer

provide excellent osseous detail. This may be useful in theevaluation of subtle cortical irregularities or mineralizedlesions in the medullary cavity or soft tissues.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is often per-formed at the site of metastatic disease. MRI is oftenuseful in cases in which the bone scan is negative butlocalized symptoms are present. In addition, MRI ismore sensitive than technetium bone scanning in thedetection of bone metastases because earlier marrowabnormalities may be identified14 (Figure 6). MRI isthe gold standard for evaluation of soft tissue masses.In the spine, MRI is valuable in assessing the extentof involvement as well as evaluating for spinal cordor nerve root compression. Additionally, MRI can oc-casionally be helpful in determining the extent of dis-ease and marrow involvement in patients requiringradiotherapy postoperatively or for palliation.

Positron Emission Tomography

Positron emission tomography (PET) utilizing flu-

orodeoxyglucose is becoming more widely available.PET scans have the potential of both high sensitivityand high specificity. In some malignancies, such as thy-roid cancer, the results of the PET scan may be positivewhile results of all other diagnostic modalities (ie,radiograph, bone scan, MRI, CT) are negative. As clini-cal trials of PET scanning in the orthopaedic settingcontinue, the use and understanding of this diagnosticmodality is certain to increase.



Figure 4. Anterior-posterior radiograph of the proximalhumerus showing a lytic destructive lesion in the proximal dia-physis. The lesion is poorly marginated. There is no reactivebone. This is a very common appearance of metastatic renalcell carcinoma.

Figure 5. Technetium bonescan of a patient with metastat-ic prostate carcinoma. Noticethe intense uptake in the sacralala on both sides. There is in-tense uptake in the right su-pra acetabula area and the leftlesser trochanteric area.Notice the marked increaseactivity in the left proximalhumerus and the right sixthrib. There is also metastasis inthe upper lumbar spine.

R Anterior

BIOPSY

It is generally prudent to confirm the diagnosis ofbone metastases with biopsy. A solitary bone lesion in apatient with cancer should not be assumed to be fromthe patient’s cancer. In addition, in cancer patients whodevelop bone lesions without the presence of visceralmetastases, biopsy should be considered to confirm thediagnosis. A biopsy should be viewed as a confirmatorystudy of metastatic disease—in only a minority of pa-tients can the primary site of the malignancy be diag-nosed by biopsy alone.15 In polyostotic lesions, the

most easily accessible lesion should be chosen for biop-sy. If, however, there exists an area of impending frac-ture, this site may be biopsied at the time of surgicalstabilization if frozen section confirmation of metastat-ic disease is available at the institution.

Biopsy may be performed via fine needle aspiration,CT-guided needle or core sampling, or via open tech-niques. Open techniques typically require operative timeand often the risk of anesthesia. The choice of biopsytechnique must be based on the lesion size and loca-tion, the surgeon’s experience, the experience of the



Figure 6. (A) Anterior-posterior radiograph of the hip of apatient with metastatic breast carcinoma. A poorly marginatedlesion in the greater trochanter is visible, with thinning of the cor-tex. (B) Coronal T1-weighted magnetic resonance imaging scan ofthe pelvis. A low-signal lesion can be seen occupying the entiregreater trochanter and extending down to the subtrochantericlevel. On the opposite (left) hip, multiple round, low-density,low-signal lesions are visible in both the proximal femur and theacetabulum, consistent with metastatic bone disease. (C) A coro-nal inversion recovery sequence shows high-signal activity in thegreater trochanter extending to the subtrochanteric level, mask-ing the area of involvement seen on the T1-weighted image.

A

C

B

radiologist, and the preferences of the musculoskeletalpathologist who will be making the histologic diagnosis.

If a primary sarcoma is a possibility, the biopsy mustbe performed in a manner that will not complicate orcompromise future oncologic resection or possiblelimb-salvage procedures. In most cases, if a primarysarcoma is suspected (eg, no primary cancer is foundafter work-up, or a patient with a distant history of can-cer has a solitary lesion and no other evidence of activedisease), the patient should be referred for biopsy toan orthopaedic oncologist who can perform the defini-tive procedure.

In cases of an isolated renal or thyroid metastasis,oncologic resection with wide margins may be indicat-ed because of the possibility of cure in isolated meta-static lesions with these diagnoses. These patientsshould be considered for referral to an orthopaediconcologist as well.

Histologic examination of bone biopsy specimenscan differentiate metastatic disease from multiplemyeloma, lymphoma, or primary sarcoma. Metastaticbone lesions show a consistent pattern of clusters ofepithelial cells grouped in a glandular pattern in afibrous stroma (Figure 7).

TREATMENT

There are 4 basic tenets in the orthopaedic treat-ment of metastatic disease to bone: pain control, pre-vention and treatment of fractures, maintenance ofpatient independence, and prevention of tumor pro-gression.

Pain Control

Pain from bony metastases can be caused by tumorbiology and the local effects of bone destruction or bythe resultant structural insufficiency. Bone pain with-out structural insufficiency is often effectively treatedwith narcotic analgesics and radiation therapy, usuallyexternal-beam irradiation. Patients often benefit fromhormonal therapy (eg, in metastatic prostate carcino-ma), cytotoxic therapy, and/or bisphosphonate thera-py. Bisphosphonates have been shown to improve painand reconstitute bone stock. Some bisphosphonatesmay decrease tumor cell burden through induction oftumor apoptosis.16

Prevention and Treatment of Fractures

Prediction of fracture risk. Surgical stabilization toprevent pathologic fracture can immediately improvepain, mobility, and independence. Clinicians are oftenrequired to determine the appropriateness of surgicalintervention in patients referred for “impending frac-

ture.” The criteria for impending fracture are in noway absolute, and the clinician must consider the pa-tient’s surgical risk stratification, estimated life ex-pectancy, and previous level of function when makingdecisions regarding the appropriateness of surgery aswell as the implant type to be recommended. Many cri-teria exist in the literature for prediction of fracturerisk,17–21 but none have been decisively supported inclinical trials. Important factors include the amountand pattern of bone destruction, the location of thelesion (or lesions), and the quality of associated pain.

The amount of bone destruction is the most impor-tant variable to be considered. The amount of involve-ment requires assessment of 2 orthogonal radiographs,through which 4 cortices are assessed and their involve-ment summed. Fidler20 has shown that fractures arehighly unlikely (2.3% risk) when less than 50% of thecortical bone is involved, but very likely to occur (80%risk) if 75% of the cortical bone is involved. Eccentriclesions are more worrisome than similarly sized lesionsthat are located centrally. The pattern of bone destruc-tion is also significant. Purely blastic lesions are leastlikely to fracture. Purely lytic lesions are the most likelyto cause bone failure and the least likely to heal. Mixedlesions are of intermediate risk.22,23 Location of thelesion is also of paramount importance. Areas of highstress, such as the femoral neck and subtrochantericregions, or the humeri in patients using walkers, aremost likely to be exposed to forces in excess of thebone’s ultimate strength.

Weightbearing pain is another important predictorof fracture. When patients experience pain with everystep that decreases with rest, structural insufficiency islikely present during normal physiologic loading. If,however, pain is present at night and at rest, then thispain may be due to tumor biology rather than struc-tural osseous insufficiency.

Serial radiographs are often helpful in monitoringdisease progression. Certainly, all patients treated con-servatively for metastatic disease should have follow-upradiographs to evaluate progression of disease.

Surgical options. A complete discussion of surgicaloptions for metastatic disease is beyond the scope ofthis review. Plates, intramedullary devices, and prosthet-ics all have their specific places in the orthopaedist’sarmamentarium. Plates with methylmethacrylate aug-mentation are quite useful for metaphyseal and epiphy-seal fixation but require an intact articular surface andsufficient nearby bone stock for fixation. At least 1 in-tact cortex is typically required to achieve rigid fixationand allow full weightbearing postoperatively if plate fix-ation is utilized. Reamed intramedullary nails have a



neutral axis almost identical to that of the bone inwhich they are placed. This load-sharing device, with asmall-moment arm and low transmission of torque,confers excellent implant survival despite immediatefull weightbearing. Large destructive lesions, intra- orperi-articular lesions, and lesions not permitting rigidfixation may require prosthetic replacement. Modularand custom complex prostheses are available.

One useful adjunctive procedure to be considered inthe treatment of metastatic disease is preoperativetumor embolization. Most, if not all, metastatic lesionsare hypervascular. Some lesions, especially renal metas-tases and myeloma, are notorious for the rich vascularnetwork associated with them. This hypervascularity canbe a source of markedly increased perioperative risk, asmassive intraoperative blood loss can cause death, espe-cially in patients with chronic illness and minimal physi-ologic reserve. Significant decreases in blood loss areseen with preoperative embolization.24 Embolizationcan be expected to be successful in up to 90% ofcases.25,26 Metallic coils, polyvinyl alcohol beads, or gela-tinous sponges may be used. With coils or polyvinylalcohol, a 24- to 36-hour delay before surgery will nothave a detrimental effect.24 Surgery should take placewithin 24 hours if gelatin is used to minimize loss ofeffectiveness via resorption of gelatin and recanalizationof vessels. Embolization is especially helpful if reamingthrough a tumor is to be performed. Embolization mayalso be used as a method of pain control in patientswho are not candidates for surgery.27–29

Prevention of Tumor Progression

In virtually all patients undergoing prophylactic fixa-tion for metastatic disease, postoperative external-beam

irradiation is warranted. Townsend et al30 found that15% of patients treated with surgery alone required asecond surgical procedure because of increasing painor subsequent loss of fixation. In comparison, only 3%of patients who received postoperative radiation thera-py needed additional surgical procedures.

Radiation therapy should be initiated after fixationand usually is begun 2 to 4 weeks postoperatively. Thedose administered is 20 to 30 Gy divided into 5 to 10 fractions. The radiation field should include theoriginal site of disease and the entire implant or fixa-tion device, along with an adequate margin.31 In pa-tients with life expectancies greater than 12 months(eg, those with solitary breast or renal metastases withno active primary disease) larger doses (eg, 45 Gydivided into 1.8-Gy fractions) may be warranted.

PROGNOSIS

Unfortunately, virtually all patients with bony metastat-ic disease eventually succumb to cancer. Median survivalranges from 6 to 48 months, but it is difficult to predictan individual patient’s prognosis. The median survivalafter the development of bony metastases is 48 monthsfor thyroid carcinoma, 40 months for prostate cancer, 24 months for breast cancer, and 6 months for melano-ma, kidney, and lung cancers.32 However, these are aver-ages. For example, a patient with renal cell carcinoma, a2-year disease-free interval, no visceral disease, and anonaxial metastasis may live for many years. Discussion ofthe variety of positive and negative prognostic factors foreach disease is beyond the scope of this review.

CONCLUSION

The management of metastatic bone disease is



(continued on page 39)

Figure 7. (A) Photomicrograph of bone tissue in a patient with metastatic breast carcinoma. Clusters of round epithelial cells arrangedin an organoid fashion are visible in a background of fibrous tissue. This histologic appearance is consistent with metastatic carcinoma(hematoxylin and eosin stain). (B) Photomicrograph of bone tissue of a different patient with metastatic renal cell carcinoma. Clear cellsgrouped in clusters are visible. This histologic appearance is consistent with clear cell carcinoma of the kidney (metastatic hypernephro-ma) (hematoxylin and eosin stain).

BA

complex and requires a multidisciplinary approach.The evaluation must be thorough regardless ofwhether the patient has a previously diagnosed cancer.The treatment is geared toward controlling pain, pre-venting and treating fracture, maintaining the patient’sindependence, and preventing progression of thetumor. Surgeons, radiation and medical oncologists,radiologists, physiatrists, therapists, nutritionists, andpain clinicians must collaborate to maximize the pa-tient’s longevity and quality of life and to coordinatecare in an expeditious and logical manner. HP

REFERENCES1. Buckwalter JA, Brandser EA. Metastatic disease of the

skeleton. Am Fam Physician 1997;55:1761–8.2. Jaffe HL. Tumors metastatic to the skeleton. In: Jaffe

HL, editor. Tumors and tumorous conditions of thebones and joints. Philadelphia: Lea & Febiger; 1958.

3. Cancer facts and figures—2004. Atlanta: AmericanCancer Society; 2004. Available at www.cancer.org.Accessed 27 Sep 2004.

4. Healey JH, Turnbull AD, Miedema B, Lane JM. Acro-metastases. A study of twenty-nine patients with osseousinvolvement of the hands and feet. J Bone Joint SurgAm 1986;68:743–6.

5. Libson E, Bloom RA, Husband JE, Stoker DJ. Metastatictumours of bones of the hand and foot. A comparativereview and report of 43 additional cases. Skeletal Radiol1987;16:387–92.

6. Wagner G. Frequency of pain in patients with cancer.Recent Results Cancer Res 1984;89:64–71.

7. Simon MA, Finn HA. Diagnostic strategy for bone andsoft-tissue tumors. J Bone Joint Surg Am 1993;75:622–31.

8. Seitz HK, Stickel F, Homann N. Pathogenetic mecha-nisms of upper aerodigestive tract cancer in alcoholics.Int J Cancer 2004;108:483–7.

9. Bunker SR, Kleiner BC. Bone imaging. In: HarringtonKD, editor. Orthopaedic management of metastaticbone disease. St. Louis: Mosby; 1988:35–52.

10. Rosenthal DI. Radiologic diagnosis of bone metastases.Cancer 1997;80(8 Suppl):1595–607.

11. Rouleau P, Wenger D. Radiologic evaluation of meta-static bone disease. J Am Acad Orthop Surg 2002;10:313–22.

12. Brown DH, Leakos M. The value of a routine bone scanin a metastatic survey. J Otolaryngol 1998;27:187–9.

13. Alam MS, Kasagi K, Misaki T, et al. Diagnostic value oftechnetium-99m methoxyisobutyl isonitrile (99m Tc-MIBI) scintigraphy in detecting thyroid cancer metas-tases: a critical evaluation. Thyroid 1998;8:1091–100.

14. Traill ZC, Talbot D, Golding S, Gleeson FV. Magneticresonance imaging versus radionuclide scintigraphy inscreening for bone metastases. Clin Radiol 1999;54:448–51.

15. Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of

unknown origin. A prospective study of a diagnosticstrategy. J Bone Joint Surg Am 1993;75:1276–81.

16. Shipman CM, Rogers MJ, Apperley JF, et al. Bisphos-phonates induce apoptosis in human myeloma celllines: a novel anti-tumor activity. Br J Haematol 1997;98:665–72.

17. Hipp JA, Springfield DS, Hayes WC. Predicting patho-logic fracture risk in the management of metastaticbone defects. Clin Orthop 1995;(312):120–35.

18. Landis SH, Murray T, Bolden S, Wingo PA. Cancerstatistics, 1998 [published errata appear in CA Cancer JClin 1998;48:192 and 1998;48:329]. CA Cancer J Clin1998;48:6–29.

19. Mirels H. Metastatic disease in long bones. A proposedscoring system for diagnosing impending pathologicfractures. Clin Orthop 1989;(249):256–64.

20. Fidler M. Incidence of fracture of metastases in longbones. Acta Orthop Scand 1981;52:623–7.

21. Fidler M. Prophylactic internal fixation of secondaryneoplastic deposits in long bones. Br Med J 1973;10:341–3.

22. Harrington KD. Orthopaedic management of extremityand pelvic lesions. Clin Orthop 1995;(312):136–47.

23. Harrington KD. Impending pathologic fractures frommetastatic malignancy: evaluation and management.Instr Course Lect 1986;35:351–81.

24. Varma J, Huben RP, Wajsman Z, Pontes JE. Therapeuticembolization of pelvic metastases of renal cell carcino-ma. J Urol 1984;131:647–9.

25. Sun S, Lang EV. Bone metastases from renal cell carci-noma: preoperative embolization. J Vasc Interv Radiol1998;9:263–9.

26. Layalle I, Flandroy P, Trotteur G, Dondelinger RF.Arterial embolization of bone metastases: is it worth-while? J Belge Radiol 1998;81:223–5.

27. Bowers TA, Murray JA, Charnsangavej C, et al. Bonemetastases from renal carcinoma. The preoperative useof transcatheter arterial occlusion. J Bone Joint Surg Am1982;64:749–54.

28. Breslau J, Eskridge JM. Preoperative embolization ofspinal tumors. J Vasc Interv Radiol 1995;6:871–5.

29. Chuang VP, Wallace S, Swanson D, et al. Arterial occlu-sion in the management of pain from metastatic renalcarcinoma. Radiology 1979;133(3 Pt 1):611–4.

30. Townsend PW, Rosenthal HG, Smalley SR, et al. Impactof postoperative radiation therapy and other periopera-tive factors on outcome after orthopedic stabilization ofimpending or pathologic fractures due to metastatic dis-ease. J Clin Oncol 1994;12:2345–50.

31. British Association of Surgical Oncology guidelines. Themanagement of metastatic bone disease in the UnitedKingdom. The Breast Specialty Group of the BritishAssociation of Surgical Oncology. Eur J Surg Oncol1999;25:3–23.

32. Coleman RE. Skeletal complications of malignancy.Cancer 1997;80(8 Suppl):1588–94.


(from page 28)

www.turner-white.com Hospital Physician November 2004 39Copyright 2004 by Turner White Communications Inc., Wayne, PA. All rights reserved.

metastatic disease to bone - turner white

Documents