230 Journal of Pain and Symptom Management Vol. 39 No. 2 February 2010

Original Article

Patterns of Pain and Interference in Patientswith Painful Bone Metastases: A Brief PainInventory Validation StudyJackson S.Y. Wu, MD, MSc, FRCPC, Dorcas Beaton, MSc, PhD, PeterM. Smith, PhD, and Neil A. Hagen, MD, FRCPCDepartments of Oncology (J.S.Y.W., N.A.H.), Clinical Neurosciences (N.A.H.), and Medicine (N.A.H.)

and Cancer Pain Clinic (N.A.H.), Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta;

Institute for Work & Health (D.B., P.M.S.), Toronto; and St. Michael’s Hospital (D.B.) and Dalla Lana

School of Public Health (P.M.S.), University of Toronto, Toronto, Ontario, Canada

Abstract

Bone metastases are prevalent, painful, and carry a poorer prognosis for pain controlcompared with other cancer pain syndromes. Standard tools to measure pain have not beenvalidated in this patient population, and particular subgroups with more challengingsymptoms have yet to be identified and studied. The objectives of this study were 1) to validatethe psychometric properties of the Brief Pain Inventory (BPI) and its Pain and Interferencesubscales in patients with clinically significant metastatic bone pain requiring palliativeradiotherapy and 2) to examine differences in BPI subscales among predefined subgroups ofbone metastases patients. A total of 258 patients evaluated and treated through a rapidaccess radiation therapy clinic between July 2002, and November 2006, were included in theanalysis. High internal consistency of the BPI subscales of Pain, Activity interference, andAffect interference was demonstrated by Cronbach’s alpha between 0.81 and 0.89. Removingsleep interference improved model fit in confirmatory factor analysis. The BPI revealed analarming pattern in patients with lower body metastases, who reported substantialinterference of activity even though pain levels were mild or moderate. Such patients mayrequire prompt clinical attention to better meet their needs. Finally, the allocation ofinterference from sleep within the BPI framework, in our population of pain patients,requires further study. J Pain Symptom Manage 2010;39:230e240. � 2010 U.S.Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Key Words

Bone neoplasms, skeletal metastases, validation study, pain evaluation

This study was supported in part by the CanadianInstitute of Health Research Team grant in DifficultPain Problems (#PET 69772). Dr. Jackson S.Y. Wu’seducational fellowship in clinical epidemiology atthe University of Toronto was funded by the AlbertaCancer Board. Dr. Peter M. Smith is supported bya New Investigator Award from the Canadian Insti-tute of Health Research.

Address correspondence to: Jackson S.Y. Wu, MD, De-partment of Oncology, Tom Baker Cancer Centre,University of Calgary, 1331e29th St NW, Calgary,Alberta T2N 4N2, Canada. E-mail: jackson.wu@cancerboard.ab.ca

Accepted for publication: July 15, 2009.

� 2010 U.S. Cancer Pain Relief CommitteePublished by Elsevier Inc. All rights reserved.

0885-3924/10/$esee front matterdoi:10.1016/j.jpainsymman.2009.07.006

Vol. 39 No. 2 February 2010 231Pain and Interference in Patients with Bone Metastases

IntroductionPain is a highly prevalent symptom and a se-

rious public health issue in patients withadvanced, metastatic, or terminal cancer.1

Despite the prevalence of pain, a recent sys-tematic review concluded that interventionsto improve pain among hospitalized cancerpatients fall far short of fully meeting patients’needs2 and other reports have documenteda similar undertreatment of pain among can-cer outpatients.3,4

Bone is the most frequent site of spread inadvanced malignancies such as cancers of thebreast, prostate, and lung. Although fracture,hypercalcemia, and nerve entrapment are seri-ous complications of bone metastases, pain isthe most common clinical accompanimentand it is often difficult to control. Pain hasbeen correlated with underlying bone destruc-tion, but surprisingly, the various potentialpathophysiological mechanisms of metastaticbone pain and their interconnections haveyet to be fully delineated. The net result ofunrelieved bone pain, however, is grim, fre-quently including diminished quality of lifeand increased reliance on pharmacologic orother therapeutic interventions.5

Accurate pain assessment techniques are animportant tool to guide clinical decision makingand evaluate treatment effectiveness in this het-erogeneous population of patients with variousstages of disease, mechanisms of pain, responsesto analgesics, and comorbidities such as delir-ium, asthenia, and other contributors to highburden of illness. The Brief Pain Inventory(BPI) is a measurement tool that has demon-strated construct validity in two out of the fourcore outcome domains outlined by the Initiativeon Methods, Measurement, and Pain Assess-ment in Clinical Trials (IMMPACT) consensusrecommendations:6 pain intensity and interfer-ence of function by pain.7e13 Although most val-idation studies of the BPI confirm the legitimacyof these two factors, namely, pain intensity andinterference of function, Cleeland et al.14 havesuggested that the interference factor can befurther separated into subscales of Activity andAffect. Two subsequent studies have confirmedthis three-factor structure.11,12

Even though cancer-related bone pain andsometimes its treatment can seriously impair

patients’ functional ability, most studies havefocused only on the construct validity of thepain-interference domains of the BPI, broadlygrouping together cancer patients without in-vestigating its ability to discriminate or charac-terize subgroups of cancer pain with respect toits anatomic origin. There is emerging evi-dence that some cancer pains predictably carrya poorer prognosis, such as breakthrough can-cer pain. Breakthrough cancer pain is preva-lent in patients with bone metastases.15,16

Based on our clinical experience within a rapidaccess radiotherapy clinic for bone pain,17 wehave been suspicious that bone pain arisingfrom the lower part of the body, including pel-vis and lower extremity (lower skeletal pain),results in greater impairment of activity func-tions compared with bone pain arising fromthe upper body (upper skeletal pain), therebyrequiring greater attention and proactive man-agement. As such, an interaction may existbetween the location of skeletal pain and func-tional interference, even when pain severityappears to be tolerable.

Therefore, the present study has two mainobjectives: 1) to validate the psychometricproperties of the BPI and its pain and interfer-ence subscales in patients with clinically signif-icant metastatic bone pain requiring palliativeradiotherapy and 2) to confirm our a priori hy-pothesis that lower skeletal metastases are asso-ciated with greater functional interferencecompared with upper body bone pain.

MethodsPopulation and Setting

The Tom Baker Cancer Centre providesregional radiotherapy services to a catchmentarea of 1.8 million residents within southern Al-berta. Approximately one hundred patients withpainful bone metastases per year are referred toa specialized rapid access radiotherapy clinic formanagement. Most of the patients attendingthis clinic are managed as outpatients. The studypopulation comprised all patients referred tothis clinic treated between July 2002, andNovember 2006. This tool validation study waspart of a quality assurance audit approved bythe Conjoint Health Research Ethics Board,University of Calgary (ID #18955).

232 Vol. 39 No. 2 February 2010Wu et al.

Brief Pain InventoryThe BPI consists of a body diagram, docu-

mentation of analgesia consumption, and 11items on an ordinal scale from 0 to 10 in sin-gle-digit increments.4 Two factors includepain perception and interference by pain.Pain perception is measured by four items:worst pain, average pain, least pain, and painright now, which are anchored between ‘‘nopain’’ and ‘‘pain as bad as you can imagine.’’Interference by pain is assessed by seven itemsanchored between ‘‘does not interfere’’ and‘‘completely interferes’’: general activity,mood, walking ability, normal work includingboth work outside the home and housework,relations with other people, sleeping, and en-joyment of life. In the studies that reporteda three-factor solution, interference was di-vided into Activity interference (general activ-ity, walking ability, and normal work) andAffect interference (mood, relations, andenjoyment). Sleep interference was includedas an Activity item in one study14 but as an Af-fect item in the other.12 An additional item ofpercentage pain relief is in the BPI question-naire, but this item was not incorporated intoanalysis in prior validation studies.

Two minor modifications to the BPI weremade for our patient population: 1) the item‘‘pain at its least’’ was deleted from the ques-tionnaire as this item has been reported tocarry poor discrimination18 and 2) patientswere asked to rate their pain and interferenceitems during ‘‘the past three days’’ rather than‘‘last 24 hours.’’ This latter modification wasmade because an international consensus ofendpoint measures for radiotherapy trials inbone pain recommended patients be askedto recall their pain experience over threedays when scoring bone pain.19 The consensusstatement reasoned that incidental or break-through pain is intermittent in nature anda longer recall period seems appropriate. Weposit that these modifications would have nodeleterious impact on the overall psychometricand clinical performance of the BPI instru-ment in this population of patients.

Inclusion and Data CollectionPatients with radiographically confirmed

bone metastases who completed the Englishversion of the BPI and subsequently

underwent palliative radiotherapy were in-cluded in the study. Occasionally, patients re-quired assistance by a dedicated clinic nurseor a family member to read the questionnaire,but most patients completed the question-naires on their own within 10e15 minutes, be-fore interview by physician. Patients who weretoo frail to fill out a questionnaire, who indi-cated zero pain on all three pain severity items,or those who completed the form partially(i.e., rated pain items but none of the interfer-ence) were excluded. Demographics and ra-diotherapy data, including anatomic site(s) oftreatment and number of prescribed fractions,were collected at the time of treatment. Forpatients who had multiple evaluations andcourses of bone radiotherapy over time, onlythe first available BPI evaluation was includedin this analysis.

For the purpose of examining discrimina-tory properties of the BPI, patient groupswere predefined by location of clinically signif-icant bone pain as treated by a single volumeof radiotherapy. Patients who required radio-therapy to the lumbar spine, sacrum, or anyof pelvic girdle (iliac wing, acetabulum, pubicbone, and ischial tuberosity), femur (head,neck, or shaft), and tibia were categorized ashaving ‘‘lower skeletal’’ pain. Patients whorequired radiotherapy to the cervical or tho-racic spine, shoulder girdle/upper extremity,ribs, and skull were categorized as having‘‘upper skeletal’’ bone pain. Patients whorequired radiotherapy to more than one areaof pain were excluded from the discriminatoryanalysis.

BPI assessments were completed by 312 pa-tients. Fifty patients (16%) had missing valuesin one or more interference items (‘‘normalwork’’ missed most commonly in 23 out of50 patients). Four patients indicated zeropain. Therefore, 258 patients were includedin the analysis. Patient characteristics betweenthose who completed the instrument in itsentirety vs. those with missing item(s) weregenerally comparable, as shown in Table 1,with the exception that older patients weremore likely to have missing responses. Exam-ining the frequency of missing values acrossthe seven interference items showed no dif-ference in the pattern of missing values be-tween patients with lower and upper skeletalpain.

Table 1Characteristics of Patients at Time of BPI Evaluation Before Radiotherapy

Patient/Treatment Characteristics

Study Patients Excluded Patientsa

No Missing BPI Values One or More Missing BPI Values

n¼ 258 n¼ 50

Median age at time of evaluation(IQR)

67 (18) 71 (16)

Cancer type (%)Breast 91 (35) 11 (22)Genitourinary 107 (42) 23 (46)Lung 24 (9) 8 (16)Myeloma 16 (6) 3 (6)Others 20 (8) 5 (10)

History of prior radiotherapy forbone pain (%)

Yes ¼ 53 (21) Yes ¼ 11 (22)No ¼ 205 (79) No ¼ 39 (78)

Median time from initial cancerdiagnosis to evaluation (IQR),months

39 (76) 25 (89)

Median time from bone diagnosisto evaluation (IQR), months

8.1 (22) 6.3 (14)

Radiotherapy fractions (%)Single 162 (64) 28 (57)Multiple 92 (35) 21 (43)

Radiotherapy volume (%)1 anatomic area 196 (76) 35 (70)>1 anatomic area 62 (24) 15 (30)

Radiotherapy area (%) Total¼ 324 areas in 258 patients Total¼ 68 areas in 50 patientsUpper skeleton (%) 123 (38) 24 (35)

Cervical and thoracic spine 63 (19) 15 (22)Shoulder/humerus 30 (9) 4 (6)Ribs/sternum/clavicle/skull 30 (9) 5 (7)

Lower skeleton (%) 201 (65) 44 (65)Lumbar spineþ sacrum 100 (31) 16 (24)Pelvis/hip 80 (24) 23 (34)Femur/tibia/fibula 21 (6) 5 (7)

Median 24-hour oral morphineconsumption (IQR)

30 mg equivalent daily (150 mg) 29 mg equivalent daily (89 mg)

Median Karnofsky PerformanceScore (IQR)b

70 (10) 60 (10)

Mean pain score (SD)Worst pain 6.9 (2.1) 6.9 (2.6)Average pain 5.1 (2.1) 5.1 (2.4)

IQR¼ interquartile range; SD¼ standard deviation.aExcluded patients due to missing values of BPI item(s) were significantly older (71 years vs. 67 years, t-test P¼ 0.0280).bEvaluated for 122 of 258 study patients and 21 of 50 excluded patients. Other patient characteristics were comparable.

Vol. 39 No. 2 February 2010 233Pain and Interference in Patients with Bone Metastases

Statistical AnalysisItem Analysis and Internal Consistency. Mea-sures of central tendency and individual itemresponse frequencies were summarized.Item-item correlations were examined to iden-tify items that were redundant with otheritems. Internal consistency was examinedwith items divided into Pain and Interferencesubscales (two-factor model) and with items di-vided into Pain, Activity, and Affect subscales(three-factor model). We further examinedchanges in Cronbach’s alpha within each sub-scale after the removal of individual items, not-ing situations where Cronbach’s alpha scoresincreased.

Confirmatory Factor Analysis. Scale structure ofthe BPI as a single construct, two-factor andthree-factor models, was examined using con-firmatory factor analysis (CFA), as describedby Hatcher.20 Models were compared usingvarious model fit statistics (e.g., normed Chi-square statistic, goodness of fit index, Bentler’scomparative fit index). Revisions were madebased on both suggested modification indicesand the theoretical or practical interpretationof such changes. Covariance terms were addedto the structural equations between latent fac-tors and between error terms of indicator vari-able without cross-loading of indicator variableon more than one factor. Composite reliability

234 Vol. 39 No. 2 February 2010Wu et al.

and convergent validity were examined for thebest fitting two-factor and three-factor models.Discriminant validity tests (Chi-square differ-ence test, confidence interval test, and vari-ance extracted test) were carried out tofurther evaluate highly correlated factorswithin the three-factor model. The resultantmodel of choice was applied to the predefinedlower and upper skeletal groups to reveal po-tential differences in measured factors. Inter-action was explored between skeletalgrouping and mean pain intensity subgroups,stratified as mild (mean pain intensity # 4),moderate (mean pain intensity > 4 and < 7),and severe (mean pain intensity $ 7).

All statistical analyses were performed usingSAS 9.1.3 (SAS Institute, Inc., Cary, NC). Con-firmatory factor modeling was carried outusing the covariance analysis of linear struc-tural equations (PROC CALIS) procedure.

ResultsPatient Characteristics

Median age of the study group was 67 years,with 35% (91 out of 258) and 42% (107 out of258) having breast and genitourinary cancers,respectively (Table 1). Sixty percent of studypatients expressed severe pain, with the worst

Table 2Summary of BPI Scores by Item and Internal Consistenc

Two Subscales

Pain Subscale(Cronbach’s Alpha¼ 0.

Item StatisticsCorrelationwith Total

Alpha wDeleBPI Items Mean SD

Worst pain 6.9 2.1 0.68 0.8Average pain 5.1 2.1 0.78 0.7Pain now 4.6 2.5 0.71 0.8

Interference Subscale (CronbAlpha¼ 0.87)

Generalactivity

6.6 2.8 0.76 0.8

Walk 6.5 3.0 0.66 0.8Work 7.2 3.0 0.75 0.8Sleep 5.3 3.1 0.38 0.8

Mood 5.0 2.9 0.65 0.8Enjoy 6.5 2.9 0.77 0.8Relations 3.9 2.9 0.60 0.8

High Cronbach’s alpha for Pain, Interference, Activity, and Affect subscales.Sleep interference was least correlated with total. [¼when sleep was deleted

pain score being seven or more out of 10;worst pain scores in this range correspondedwith expression of high interference on allitems, suggesting high levels of symptoms.The median oral morphine equivalent of30 mg/d (interquartile range 150 mg/d) indi-cated that most patients were already receivingstrong opioid analgesics (World Health Orga-nization ladder, step 3), and additional painrelief intervention was warranted.

Item Analysis and Internal Consistency ofSubscales

Pain was moderately severe, with a mean of6.9 (SD 2.1) at its worst and a mean of 5.1(SD 2.1) on average. Interference levels werealso moderate to severe, with the mean rang-ing from 3.9 to 7.2 across the seven items.Left-sided skewness was notable for generalactivity, walking, and enjoyment, with ceilingeffect for normal work interference in particu-lar. Conversely, relations with others hada right-sided skewness, with more responsesin lower levels of the scale. The sleep itemmapped out with a nearly uniform distributionof responses across all values from 0 to 10. Theinternal consistency of the subscales was high,whether items are grouped into two subscales(Pain and Interference) or three subscales

y Among Subscales in Study Population (n¼ 258)

Item Grouping

Three Subscales

85)Pain Subscale

(Cronbach’s Alpha¼ 0.85)

ith Itemted

Correlation withTotal

Alpha with ItemDeleted

4 0.68 0.844 0.78 0.741 0.71 0.81ach’s Activity Subscale (Cronbach’s

Alpha¼ 0.79)4 0.76 0.66

5 0.68 0.704 0.77 0.659[ 0.26 0.89[

Affect Subscale (Cronbach’s Alpha¼ 0.80)5 0.68 0.684 0.62 0.756 0.62 0.74

, alpha increased.

Table 3Comparison of Model Fit of Different Structural Models

Model ModificationsGoodness of Fit

Index (Adjusted) Chi-Square (df) RMSEA (Upper CL)Comparative Fit

IndexNon-normed Fit

Index

1 factor: 10 items None (no structure) 0.56 433.5 (35) 0.23 0.72 0.642 factors: Pain and

InterferenceNone (default

structure)0.76 199.3 (34) 0.16 0.88 0.84

2 factors: Pain andInterference

Covary error termsof avgpain-painnow, mood-relation, mood-enjoy, relation-enjoy

0.86 111.2 (30) 0.12 0.94 0.91

2 factors: Pain andInterference

Drop sleep; covaryerror terms ofavgpain-pain now,mood-relation,mood-enjoy,relation-enjoy

0.93 42.48 (22) 0.09 0.98 0.97

3 factors: Pain,Activity, andAffect

None (load sleep onactivity)

0.83 152.6 (32) 0.14 0.91 0.88

3 factors: Pain,Activity, andAffect

Drop sleep; covaryerror terms ofavgpain-pain now,mood-relation

0.94 37.9 (22) 0.08 0.99 0.98

Avgpain¼ average pain; df¼ degrees of freedom; CL ¼ confidence limit.Modifications included covariance of error terms of paired items. Correlated error terms suggest that the two corresponding indicator variables measure something in common that is not explicitly repre-sented in the model. Fit statistics improved when sleep was dropped from models. Goodness of fit index (adjusted for degrees of freedom) examines the ability of the model to explain the variance in thesample covariance matrix (perfect fit¼ 1), analogous to corrected R-square. Model Chi-square (i.e., likelihood ratio Chi-square) represents the value of the statistical criterion minimized in maximum likeli-hood estimation (smaller value¼ better fit). RMSEA (root mean square error of approximation) measures the lack of fit of the model to the population covariance matrix (RMSEA $ 0.10 suggests poor fit).Comparative fit index (CFI) measures the improvement in the overall fit of the model compared with a model assuming that all observed variables are uncorrelated. Non-normed fit index (NNFI) correct formodel complexity. CFI and NNFI above 0.9 suggest acceptable model fit.

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236 Vol. 39 No. 2 February 2010Wu et al.

(Pain, Activity, and Affect), with Cronbach’s al-pha ranging between 0.81 and 0.89 (Table 2).However, removing sleep interference fromthe subscales resulted in a noticeable increasein internal consistency. In both situations,sleep displayed low correlations with subscaletotals (0.43 and 0.32), whereas other itemsshowed consistently moderate correlationsfrom 0.61 to 0.80.

Confirmatory Factor AnalysisGiven the low correlations between sleep in-

terference with other model subscales withinthis data set, we compared CFA models withand without sleep. Table 3 summarizes the cor-responding model fit statistics. The ‘‘null’’model of 10-item single factor showed verypoor fit, which was expected given the well-established two-factor solution to the BPI.However, a two-factor default model of Painand Interference still performed poorly withlarge normalized residuals (>5.0). Removingsleep from the two-factor and three-factormodels improved fit considerably, with addi-tional improvements in measures of model fitgained by allowing specific error terms tocovary. Factor loadings and associated statisticsfor the best two-factor and three-factor modelsare summarized in Table 4 for comparison.Each factor (Pain, Interference, Activity, andAffect) fulfilled the minimum requirement ofthree indicator variables per factor. All factorloadings were highly significant, with t valuesbetween 8.7 and 17.7 (NB: minimum criticalt value of 3.29 for P¼ 0.001), supporting theconvergent validity of items on their respectivefactor. Indicator reliability of individual items(R-squared) ranged from 0.29 (relation) to0.93 (worst pain). Composite reliability dem-onstrated high internal consistency of the fac-tors in both models, ranging from 0.76 to 1.0(minimum acceptable level ¼ 0.70).

For the three-factor model, moderate butnear-identical correlations of Pain-Activity(correlation ¼ 0.52) and Pain-Affect (correla-tion ¼ 0.55) were observed, with high correla-tion between Activity and Affect (correlation ¼0.83), suggesting that Activity and Affect couldbe representative of the same latent variable.Tests of discriminant validity provided mixedsupport for Activity and Affect: the Chi-squaredifference test (Chi-square difference 28.4,df¼ 1, P< 0.001) and the confidence interval

Vol. 39 No. 2 February 2010 237Pain and Interference in Patients with Bone Metastases

test (correlation 0.83, 95% confidence interval0.76e0.90) were significant, but the varianceextracted test failed to confirm discriminantvalidity because the variance extracted esti-mate for Affect (0.52) was lower than thesquare of correlation between Activity and Af-fect (0.69), even though the variance extractedestimate for Activity was high (0.74).

In summary, both the two-factor (Pain andInterference) and the three-factor models(Pain, Activity, and Affect) demonstrated rea-sonably high levels of internal consistency,composite reliability, and convergent validity.Overall, the three-factor model was preferredbecause fewer covariance terms were neededto fit the model, and those three factors repre-sented three of the four IMMPACT core do-mains, which could be useful indifferentiating patients with different sourcesof pain. The final three-factor model (exclud-ing sleep) with standardized factor loadingsand correlations is illustrated in Fig. 1.

Pattern of Pain, Activity, and AffectInterference in Lower vs. Upper Skeletal Pain

Table 5 presents mean scores of BPI mea-surements according to three factors of Pain,Activity interference, and Affect interferenceof patients treated for either upper skeletalor lower skeletal bone metastases (patients re-quiring radiotherapy to more than one volumewere excluded). Even though the mean Painscores were nearly identical between the lowerand upper skeletal groups (5.7 vs. 5.6, respec-tively), the mean Activity score was significantlyworse in the lower skeletal group (7.4 vs. 5.7,

0.89 0.81

ActivPain

C=0.52

C=0.5

FactorLoading 0.620.95 0.71

Worst Pain

Average Pain

PainNow

E1 E2 E3

C=0.51

E4 E5

General Activity

WalkingAbility

Fig. 1. Final measurement model of BPI evaluations of 258factors: Pain, Activity interference, and Affect interference wispective factor. E ¼ residual for each item; C ¼ correlation

P< 0.0001), thus demonstrating a clinicaland significant detriment in activity functionas a result of skeletal metastases in the lowerskeleton. Further examination of mean Activ-ity score in Pain subgroups, stratified as mild,moderate, and severe categories, demon-strated greater impact of lower skeletal painon Activity among patients expressing mild tomoderate pain (Table 6). Patients already ex-periencing severe pain suffered severe interfer-ence of function, regardless of site of skeletalinvolvement.

DiscussionThe goal of the present study was to first val-

idate the psychometric properties of the BPI inpatients with clinically significant metastaticbone pain requiring palliative radiotherapyand then to evaluate whether BPI subscaleswere able to discriminate clinically importantgroups of bone metastases patients, specificallywith relation to the site of the pain (lower vs.upper skeletal pain). We verified that the psy-chometric properties of the BPI instrumentwere robust in our population of advancedcancer pain patients referred for palliative ra-diotherapy. Either a two-factor (Pain and Inter-ference) or a three-factor (Pain, physicalinterference or Activity, psychosocial interfer-ence or Affect) confirmatory factor modeldemonstrated adequate model fit. We also con-firmed our clinical suspicion that interferencewith activity was significantly worse in patientswith metastatic bone pain to the lower skeletal

0.89 0.65 0.88 0.60

ity Affect

C=0.83

5

E6

NormalWork

C=0.34

E7 E8 E9

Mood RelationEnjoy-ment

bone metastases patients. Model showing 3 distinctth standardized factor loading of each item onto re-estimate. Model’s adjusted goodness of fit ¼ 0.94.

Table 5Summary of Subscale Mean Scores in Patients with Upper vs. Lower Skeletal Paina

Subscales

Upper Skeletal Pain (n¼ 72) Lower Skeletal Pain (n¼ 124)

Mean SD Mean SD

Mean Paina 5.7 2.0 5.6 2.0Mean Activityb 5.7 2.9 7.4 2.3Mean Affect 5.0 2.6 5.1 2.4

aMean score represents average of item scores within each subscale (e.g., mean Pain score¼ average of worst pain, average pain, and pain now).bMean activity of lower skeletal pain group significantly higher than upper skeletal pain group (t¼ 4.2, P< 0.0001). Mean activity difference of 1.7(95% confidence limits 0.9e2.5) and effect size of 0.68 suggest clinically meaningful difference between these two groups.

238 Vol. 39 No. 2 February 2010Wu et al.

areas compared with those with upper skeletalpain alone. This clinically substantial differ-ence in activity interference was most pro-nounced in patients indicating only mild tomoderate pain intensity.

The main limitation of this validation studyis the absence of data from other validatedtools, which would have allowed multitrait-multimethod analysis. Although our study hasprovided initial evidence of differences inpain subscales in relation to site of bonepain, further evaluation and validation withother musculoskeletal function scales, such asthe Western Ontario and McMaster UniversityOsteoarthritis Index (WOMAC) WOMAC21 orthe Toronto Extremity Salvage Score,22 couldhelp confirm our findings. Others have vali-dated BPI results against the Short-Form 36Health Survey (SF36) or the European Organi-zation for Research and Treatment of Cancerquality of life 30-item core questionnaire(EORTC QLQC-30) questionnaires,8,12 butnone attempted to characterize pain by com-paring BPI measurements with instrumentsdeveloped for the musculoskeletal system.Considering the intermittent nature of meta-static bone pain, further studies also may aimat exploring the possible interaction between

Table 6Mean Activity Scores in Upper and Lower Skeletal Pati

Moderate, and Severe M

Pain Subgroupsa

Upper Skeletal Pain (n¼ 7

n Mean Activity

Mild (mean Pain # 4)b 17 3.4Moderate (mean Pain 4e7)b 33 5.6Severe (mean Pain $ 7)b 22 7.5

aTest of heterogeneity of effect on mean Activity scores between pain subgrotistical significance (P¼ 0.026, general linear model), suggesting that effectinvolvement.bSignificantly higher mean Activity interference in lower skeletal group amondence limits 1.1e4.2, t¼ 3.4, P¼ 0.0016), and moderate pain, mean differenot among patients with severe pain, mean difference 0.6 (95% confidence

breakthrough pain and anatomic sites on func-tional interference, which may lead to riskstratification among the heterogeneous popu-lation of bone metastases patients.

Despite its brevity, one in six referredpatients in our study population was unableto complete the BPI in its entirety. The mostcommonly missed item was normal work,which contained the qualifying phrase ‘‘bothwork outside the home and housework.’’ El-derly patients, particularly those requiring pal-liative cancer therapies, might have felt thatthey were not required to perform houseworkor employed work, resulting in an absence ofrating on this item. Further consideration ofitem wording and sensibility might improvethe performance of this item or identify poten-tial substitution. Because we have excludedthis small group of elderly patients from factoranalysis, we caution against generalizing ourfindings to this subpopulation.

Our analysis of pain experience in patientswith lower vs. upper skeletal pain did nottake into account potential confounders,such as age, disease severity, and performancestatus, because some variables were not re-corded consistently. With respect to test-retestreliability and longitudinal construct validity,

ent Groups Stratified by Pain Subgroups (Mild,ean Pain Scores)

2) Lower Skeletal Pain (n¼ 124)

SD n Mean Activity SD

2.1 27 6.0 2.82.8 61 7.5 2.22.4 36 8.1 1.7

ups and upper/lower skeletal groups (interaction term) shows sta-of pain on Activity interference is modified by location of skeletal

g patients expressing mild pain, mean difference 2.6 (95% confi-nce 1.9, (95% confidence limits 0.9e2.9, t¼ 4.1, P¼ 0.0004), butlimits �0.5 to 1.6, t¼ 1.1, P¼ 0.29).

Vol. 39 No. 2 February 2010 239Pain and Interference in Patients with Bone Metastases

our practice was not designed to consistentlyrequire repeated measurementsdwhich lim-ited our ability to examine the BPI as an eval-uative tool to detect changedor to show howrelationships among symptom clusters mightchange over time, as suggested by Hadiet al.23 Recently completed and ongoing clini-cal trials of palliative radiotherapy for bonepain using the BPI as a pain instrument are ex-pected to provide opportunities to exploresuch issues in this setting.24,25

As far as we are aware, our study is the firstvalidation study of the BPI in patients withskeletal metastases. Exploring patterns ofpain and its interference revealed a subpopula-tion of patients whose relatively mild pain in-tensity could conceal clinically significantfunctional impairment. Attention to activityfunction is critical when managing patientswith lower body skeletal metastases. Otherstudies have distinguished subgroups accord-ing to mild, moderate, and severe pain inten-sity26 and observed differences betweencancer and non-cancer patients in scoring in-terference.27 In our practice, patients are typi-cally referred for palliative radiotherapy whenpain is moderately severe or is unresponsiveto opioids. But as lower skeletal metastasesappear to confer greater interference withfunction, such patients may benefit from rou-tine monitoring or early referral for proactivemanagement before pain becomes severe.Apart from pain relief, increased bone mineraldensity in lytic metastatic lesions has beendemonstrated after focal palliative radiother-apy.28 This provides a reasonable conjecturetoward a strategy of fast-tracking patients forradiotherapy or, alternatively, orthopedic eval-uation based on the site of skeletal involve-ment (i.e., lumbosacral spine, pelvis/hip,femur), focusing on its interference with activ-ity more than its pain intensity.

In this highly symptomatic population of pa-tients, we were surprised to find that sleep inter-ference was not contributory to either theActivity or Affect subscale. Possible explana-tions include adaptability of patients to interfer-ence of sleep by pain (e.g., use of physicalmeasures to splint painful body parts, increas-ing time in bed to make up for disrupted sleep),variable interpretation of item wording, and var-iable effects of opioid analgesics on either sedat-ing or disrupting normal sleep patterns. The

lack of internal consistency of sleep interfer-ence in either Activity or Affect can be discernedfrom previous studies where sleep was includedwith Activity in one study,14 with Affect in an-other,12 and excluded in another.11 Sleep disor-ders are prevalent in cancer patients, arecorrelated with pain, and are typically multifac-torial.29 Clearly, further study of the interrelat-edness of pain and sleep disorders is neededto understand this complex area.

In summary, the BPI is a valid and reliable toolfor pain measurement in patients with bone me-tastases. We have demonstrated its discriminantproperties in a cohort of patients referred forpalliative radiotherapy. Sleep interference didnot add to the pain construct, and elderly pa-tients had difficulty responding to interferenceitems, particularly regarding housework orwork outside home. CFA of the BPI items iden-tified comparable two-factor and three-factormodels, but the latter is recommended for itsrelatively simple covariance structure. Patientswith metastatic lesions in the lower body experi-ence significant interference on activity evenwhen pain is mild to moderate and may requireparticular attention because of higher risk offunctional impairment.

AcknowledgmentsThe authors thank Dr. Charles Cleeland for

his permission to use the BPI.

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