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2007;89:2327-2333.  doi:10.2106/JBJS.F.01144 J Bone Joint Surg Am.S.C. Petterson, L. Raisis, A. Bodenstab and L. Snyder-Mackler    

CandidatesDisease-Specific Gender Differences Among Total Knee Arthroplasty

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2327

Disease-Specific Gender Differences Among Total Knee Arthroplasty Candidates

By S.C. Petterson, MPT, PhD, L. Raisis, MD, A. Bodenstab, MD, and L. Snyder-Mackler, PT, ScD, ATC, FAPTA

Investigation performed at the University of Delaware, Newark, Delaware

Background: Women with knee osteoarthritis are less likely to undergo joint replacement despite greater self-reported disability. The primary aim of the present study was to assess gender differences in the type and magnitudeof osteoarthritis-related impairment prior to knee arthroplasty.

Methods: Two hundred and twenty-one knee arthroplasty candidates (ninety-five men and 126 women) and forty-fourhealthy gender, age, and body mass index-matched individuals were tested. Individuals with contralateral limb injuryor abnormality, cardiovascular disease, neurological impairment, and medical conditions limiting activity were ex-cluded. Collected data included Medical Outcomes Study Short Form-36 mental and physical component scores, theKnee Outcome Survey Activities of Daily Living Scale score, knee range of motion, timed up-and-go test time, stair-climb test time, six-minute walk distance, normalized quadriceps strength, and volitional muscle activation.

Results: Women in the arthroplasty group had lower Short Form-36 and Knee Outcome Survey scores, longer timedup-and-go test and stair-climb test times, shorter six-minute walk distances, and lower normalized quadricepsstrength compared with men. Healthy women had longer stair-climb test times and shorter six-minute walk distancesin comparison with healthy men. Between-group comparisons revealed that women in both the control group and thearthroplasty group had reduced normalized quadriceps strength in comparison with men, that healthy women hadhigher voluntary muscle activation in comparison with healthy men, and that female arthroplasty candidates hadlower activation levels in comparison with male candidates.

Conclusions: Observed gender differences in strength and function appear to be inherent but are magnified in ar-throplasty candidates. Strength and functional decline should be closely monitored in women with knee osteoarthritisto serve as an indicator of worsening condition, and preoperative interventions should reflect these gender-specificimpairments.

he multidimensionality of osteoarthritis-related im-pairments provides a good model to study gender dif-ferences in musculoskeletal disease. Women have a

higher risk for the development of osteoarthritis and havehigher rates of disability attributable to osteoarthritis1-5. Fur-thermore, the need for arthroplasty is three times higher inwomen even when the willingness to undergo the procedure istaken into account6-9. Collectively, studies have suggested thatwomen may wait to seek medical attention until pain and se-

vere functional decline can no longer be tolerated10,11.To our knowledge, only one other study has assessed

gender differences in arthroplasty candidates with use of phys-ical performance measures7. In that study, female arthroplastycandidates on waiting lists in Canada reported greater disabil-ity and also had worse walking and stair-climbing perfor-mance as compared with male arthroplasty candidates7. Thelack of a comparison group and the failure to adjust for salientvariables of age, height, and weight made it difficult to discern

T

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside fundingor grants in excess of $10,000 from the National Institutes of Health (R01 HD041055 and T32 HD7490). Neither they nor a member of theirimmediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. Nocommercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice,or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

J Bone Joint Surg Am. 2007;89:2327-33 • doi:10.2106/JBJS.F.01144

A commentary is available with the electronic versions of this article, on our web site (www.jbjs.org) and on our quarterly CD-ROM (call oursubscription department, at 781-449-9780, to order the CD-ROM).

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if differences were truly related to a gender difference in dis-ease impact. In addition, lower extremity muscle strength wasnot measured. Practice patterns in Canada result in long wait-ing times for surgery, and therefore the findings of Kennedy etal. might not reflect disease severity and disability among ar-throplasty candidates in the United States7,12.

Understanding gender differences in disease impact andosteoarthritis-related impairment in arthroplasty candidatesis necessary in order to develop effective preoperative practicepatterns and to help to guide patient counseling and surgicaldecision-making. The primary aim of the present investiga-tion was to quantify differences in the magnitude of impair-ment between men and women with knee osteoarthritis. Wehypothesized that gender differences would be evident inquadriceps strength, activation, and physical performance butnot in self-reported function and that these differences wouldalso be present in an age, gender, and body mass index-matched healthy cohort.

Materials and MethodsEntire Arthroplasty Group

ll individuals with knee osteoarthritis who were scheduledfor total knee arthroplasty from April 2001 to April 2006

by three orthopaedic surgeons (including two of the authors[L.R. and A.B.]) were contacted by mail and telephone. Classifi-cation of end-stage, unilateral knee osteoarthritis by the treatingsurgeon was based on the decision to perform total knee arthro-plasty imminently. The exclusion criteria were lower extremityorthopaedic abnormalities other than unilateral knee osteoar-thritis, contralateral knee pain with a score of >4 of 10 on a ver-bal rating scale, a planned total knee arthroplasty on thecontralateral knee, cardiovascular disease, neurologic impair-ment, and any physical condition limiting daily activity. Twohundred and twenty-one individuals (ninety-five men and 126women) were eligible and were tested at a mean of eleven daysbefore total knee arthroplasty. The entire sample of arthroplastycandidates had a mean age (and standard deviation) of 65.7 ± 8.8

A

TABLE I Clinical Characteristics of the Arthroplasty Cohort Stratified by Gender

VariableMen*

(N = 95)Women*

(N = 126)

Pre-Total Knee Arthroplasty Group (N = 221)

Main Effect of Gender

Main Effect of Leg

Gender-by-Limb Interaction

Medical Outcomes Study Short Form-36 score

Physical component summary score

34.20 ± 9.53 31.04 ± 7.84 F = 7.29, p = 0.007 — —

Mental component summary score

57.44 ± 7.59 53.66 ± 10.12 F = 9.26, p = 0.003 — —

Knee Outcome Survey Activities of Daily Living Scale score

0.56 ± 0.31 0.49 ± 0.18 F = 4.36, p = 0.04 — —

Flexion F = 0.20, p = 0.652 F = 7.77, p = 0.006 F = 0.69, p = 0.408

Uninvolved (deg) 127 ± 11 127 ± 10

Involved (deg) 122 ± 34 119 ± 12

Extension F = 0.54, p = 0.464 F = 65.97, p < 0.001 F = 0.22, p = 0.642

Uninvolved (deg) 0 ± 4 0 ± 4

Involved (deg) 4 ± 5 4 ± 5

Timed up-and-go test (s) 9.16 ± 2.44 11.18 ± 3.29 F = 27.71, p < 0.001 — —

Stair-climb test (s) 16.83 ± 8.10 24.05 ± 10.45 F = 39.58, p < 0.001 — —

Six-minute walk (m) 491 ± 135 421 ± 93 F = 24.46, p < 0.001 — —

Normalized maximal voli-tional isometric contraction

F = 141.36, p < 0.001 F = 36.76, p < 0.001 F = 0.09, p = 0.768

Uninvolved (N/body mass index)

25.88 ± 8.67 17.10 ± 6.26

Involved (N/body mass index)

21.56 ± 7.27 13.09 ± 5.20

Central activation ratio F = 1.00, p = 0.326 F = 11.26, p < 0.001 F = 0.02, p = 0.895

Uninvolved 0.90 ± 0.09 0.89 ± 0.11

Involved 0.86 ± 0.14 0.85 ± 0.14

*The values are given as the mean and the standard deviation.

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years, a mean height of 1.69 ± 0.11 m, a mean weight of 88.4 ±16.2 kg, and a mean body mass index of 30.7 ± 4.6.

Control GroupForty-four (20%) of the 221 patients in the arthroplasty cohortwere matched, according to age, gender, and body mass index,to forty-four healthy individuals (nineteen men and twenty-five women) who were recruited through community adver-tisements. The exclusion criteria for healthy individuals weresimilar to those for patients with end-stage knee osteoarthritis,with the additional exclusion criterion of a history of diag-nosed knee abnormality. The control group had a mean age of61.3 ± 7.7 years, a mean height of 1.72 ± 0.11 m, a mean weightof 79.4 ± 16.2 kg, and a mean body mass index of 26.8 ± 4.4.The individuals in the matched arthroplasty group had a meanage of 62.3 ± 6.8 years, a mean height of 1.71 ± 0.11 m, a meanweight of 82.3 ± 14.8 kg, and a mean body mass index of 27.9 ±3.9. The patients in the matched total knee arthroplasty sub-set, therefore, were an average of 3.4 years younger (p = 0.012)and had an average body mass index that was 2.3 points lower(p < 0.001) than those in the entire arthroplasty group.

All subjects provided written informed consent for par-ticipation in the study, which was approved by the Universityof Delaware Human Subjects Review Committee.

Self-Assessment QuestionnairesPerceived functional ability was measured with use of theMedical Outcomes Study Short Form-36 (SF-36) mental andphysical component scores13 and the Knee Outcome SurveyActivities of Daily Living Scale score14.

The Knee Outcome Survey question “How does pain af-fect the function of your knee during daily activities?” was usedto quantify the influence of pain on the patient’s function.Scores ranged from 0 (pain that prevented the patient from allactivities) to 5 (pain that had no effect on daily activities).

Knee Range of MotionKnee range of motion in flexion and extension was measuredactively in the supine position with a long-axis goniometer15.A positive value indicated a position of knee flexion.

Functional AssessmentFunctional performance was assessed with the six-minute walk(the distance walked in six minutes)16,17 and the average of twotrials of the timed up-and-go test (the time required to risefrom a seated position in an armed chair [seat height, 46 cm],to walk a distance of 3 m, and to return to a seated position inthe chair)18 and the average of two trials of the stair-climb test(the time required to ascend and descend twelve 17.9-cmsteps)19. The instructions were to move as quickly and as safelyas possible with or without the use of an assistive device.

Quadriceps Strength and Activation AssessmentA burst superimposition test was used to quantify quadricepsstrength (maximal volitional isometric contraction) and voli-tional muscle activation20. In brief, participants were seated in

an electromechanical dynamometer (Kin-Com 500 H; Chat-tex, Chattanooga, Tennessee) with the knee flexed and stabi-lized at 75°. Self-adhesive electrodes were placed over therectus femoris muscle belly proximally and the vastus medialismuscle belly distally to deliver a supramaximal burst of anelectrical stimulus (ten-pulse, 1000-µs pulse width, 100 pulsesper second train at 135 V intensity) during a maximal voli-tional isometric contraction attempt.

Volitional muscle activation was quantified as a centralactivation ratio, calculated by dividing the maximal volitionalisometric contraction by the electrically elicited force21. A cen-tral activation ratio of 1.0 signifies complete activation. Test-ing was repeated a maximum of three times if completeactivation was not achieved, with the highest maximal voli-tional isometric contraction test being used for analysis. Afive-minute rest period was given between trials.

Statistical MethodsQuadriceps strength was normalized to the individual’s bodymass index (normalized maximal volitional isometric con-traction, expressed in N/body mass index). For standardiza-tion purposes, the limbs of the subjects in the control groupwere designated as involved or uninvolved to correspond withtheir matched counterparts in the arthroplasty group.

Gender differences in the entire arthroplasty cohortwere analyzed with use of independent samples t tests forquestionnaire scores and knee pain and with use of analysis ofcovariance (with age and body mass index as covariates) forthe timed up-and-go test, stair-climb test, and six-minutewalk. A 2 × 2 (gender × limb) analysis of variance was used toanalyze gender differences in normalized maximal volitionalisometric contraction, central activation ratio, and knee rangeof motion.

Differences between the control group and matched ar-throplasty group were analyzed with use of a 2 × 2 (group ×gender) analysis of variance for questionnaire scores and kneepain; a 2 × 2 (group × gender) analysis of covariance (with ageand body mass index as covariates) for the timed up-and-gotest, stair-climb test, and six-minute walk; and a 2 × 2 × 2(group × gender × limb) analysis of variance for normalizedmaximal volitional isometric contraction, central activationratio, and knee range of motion.

An alpha level of <0.05 was considered to be significant.Independent samples t tests and analysis of covariance wereperformed for post hoc analysis with use of the Bonferronimethod to adjust for multiple comparisons (p < 0.0125).

ResultsEntire Arthroplasty Group

omen in the arthroplasty group had lower SF-36 physi-cal component scores, SF-36 mental component scores,

and Knee Outcome Survey scores in comparison with men(p < 0.05), indicating greater reported disability. With thenumbers available, Knee Outcome Survey scores for pain werenot different between men and women (p = 0.784). Female ar-throplasty candidates had longer timed up-and-go test and

W

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TABLE II Clinical Characteristics of the Matched Arthroplasty Subgroup and the Control Group Stratified According to Gender ➤

Variable

Matched Total Knee Arthroplasty Group (N = 44) Control Group (N = 44)

Men (N = 19)* Women (N = 25)* Men (N = 19)* Women (N = 25)*

Timed up-and-go test (s) 8.16 ± 2.34 10.62 ± 2.68 6.30 ± 1.27 6.90 ± 1.16

Stair-climb test (s) 13.40 ± 6.74 21.35 ± 6.83 8.16 ± 1.73 9.95 ± 2.10

Six-minute walk (m) 589 ± 131 417 ± 90 748 ± 141 627 ± 79

Normalized maximal volitional isometric contraction

Uninvolved (N/body mass index) 34.43 ± 9.79 22.20 ± 5.39 37.48 ± 9.30 26.82 ± 7.09

Involved (N/body mass index) 27.45 ± 6.66 17.49 ± 5.14 35.80 ± 7.86 27.80 ± 6.70

Central activation ratio

Uninvolved 0.93 ± 0.06 0.89 ± 0.10 0.89 ± 0.09 0.94 ± 0.06

Involved 0.93 ± 0.07 0.85 ± 0.12 0.88 ± 0.08 0.94 ± 0.05

*The values are given as the mean and the standard deviation.

Fig. 1

Gender differences between the matched arthroplasty subgroup and the control group. The bars represent the mean group values and the standard

deviation. The black bars represent the male control group, the black hashed bars represent the male arthroplasty group, the gray bars represent

the female control group, and the gray hashed bars represent the female arthroplasty group. A, SF-36 (Medical Outcomes Study Short Form-36)

scores. B, Timed up-and-go and stair-climbing tests. C, Six-minute walk. D, Knee in range of motion flexion and extension. E, Quadriceps strength. F,

Central activation ratio. * = significant difference between the control group and the matched arthroplasty subgroup. † = significantly different from

males within the same group.

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stair-climb test times and shorter six-minute walk distances(p < 0.001). Differences between male and female arthroplastycandidates in knee flexion (p = 0.652) and knee extension (p =0.464) and the gender-by-limb interaction term (differencesbetween genders according to limb) (p > 0.100) for range of

motion were not significant, with the numbers available. Thegender-by-limb interaction term for normalized maximal vo-litional isometric contraction was not significant (p = 0.768);women had lower quadriceps normalized maximal volitionalisometric contraction in comparison with men (p < 0.001),and the involved leg had lower normalized maximal volitionalisometric contraction in comparison with the uninvolved leg(p < 0.001). With the numbers available, differences in thecentral activation ratio between men and women were not sig-nificant (p = 0.326), nor was the gender-by-limb interactionterm (p = 0.895); the central activation ratio was lower in theinvolved limb in both men and women (p < 0.001) (Table I).

Matched Arthroplasty Group Compared with Control GroupLower SF-36 physical component scores and Knee OutcomeSurvey scores were reported in the matched arthroplastygroup as compared with the control group. The matched ar-throplasty group had longer timed up-and-go test and stair-climb test times, shorter six-minute walk distances, lowerquadriceps normalized maximal volitional isometric contrac-tion values, and less range of motion of the knee in flexion andextension (p < 0.001). The SF-36 mental component score(p = 0.118) and the central activation ratio (p = 0.365) werenot different between the control and matched arthroplastygroups, with the numbers available (Fig. 1). Women in boththe control group and the arthroplasty group had significantlylower quadriceps normalized maximal volitional isometriccontraction values and shorter six-minute walk distances incomparison with men (p < 0.001), even when accounting forage and body size.

The group-by-gender interaction terms were significant(that is, differences between groups differed according to gen-der) for the timed up-and-go test (p = 0.012), the stair-climbtest (p = 0.002), and the involved central activation ratio (p <0.001). Post hoc analysis of covariance with use of age and body

TABLE II (Continued)

Main Effect of Group Main Effect of GenderGroup-by-Gender

InteractionGroup-by-Gender-by-Limb

Interaction

F = 41.63, p < 0.001 F = 35.01, p = 0.001 F = 6.65, p = 0.012 —

F = 56.05, p < 0.001 F = 18.42, p < 0.001 F = 10.03, p = 0.002 —

F = 58.05, p < 0.001 F = 39.10, p < 0.001 F = 1.84, p = 0.179 —

F = 35.27, p < 0.001 F = 84.95, p < 0.001 F = 0.632, p = 0.428 F = 0.01, p = 0.927

F = 0.83, p = 0.365 F = 0.08, p = 0.772 F = 17.39, p < 0.001 F = 0.652, p = 0.421

Fig. 1 (continued)

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mass index as covariates revealed no difference in the timed up-and-go test time between male and female controls (F = 1.61,p = 0.212); however, women in the arthroplasty group hadlonger timed up-and-go test times in comparison with men(F = 8.59, p = 0.006). The mean stair-climb test time for femalecontrols was 1.79 seconds (22%) longer than that for male con-trols (F = 8.02, p = 0.007). The gender difference in the stair-climb test time was magnified in the arthroplasty group; themean stair-climb test time for women in the arthroplasty groupwas 7.95 seconds (59%) longer than that for men (F = 11.22,p = 0.002). Central activation ratio values for the matched limbwere significantly higher for female as compared with male con-trols (t = 2.65, p = 0.011). The central activation ratios in the in-volved limb were significantly lower in female as compared withmale arthroplasty candidates (t = 2.06, p = 0.045); however, thecentral activation ratios in the uninvolved limb were not signifi-cantly different between men and women in the arthroplastygroup (t = 1.57, p = 0.124) (Table II).

Discussionifferences in normalized strength, stair-climb test times,and six-minute walk performance were noted between

healthy men and women; however, these gender differenceswere magnified in arthroplasty candidates and gender differ-ences also emerged in timed up-and-go performance and vol-untary muscle activation. These data support the concept thatgender differences in strength and function are inherent. Onthe other hand, the greater degree of difference among arthro-plasty candidates suggests that women are more adverselyaffected by osteoarthritis than men are and that women un-dergo arthroplasty at a more advanced disease state than mendo. The mechanisms underlying these gender differences re-main unclear but could be related to the activity level of thepatient, the duration of symptoms and disability, and the tim-ing of surgery.

Our data support the concept that women report greaterdisability at the time of arthroplasty and provide insight intothe degree of functional impact attributable to osteoarthritis.Similar to the findings of Katz et al.11, female arthroplasty can-didates in the present study had worse self-reported function.Women with osteoarthritis in our study cohort also exhibitedworse functional performance on walking tests, supportingthe findings of Kennedy et al.7. The larger differences infunctional performance between genders in the arthroplastygroup as compared with the control group substantiated thedisproportionate impact of osteoarthritis-related impair-ments on women.

Results from the immobilization model used by Yasudaet al.22 support our findings of the gender-specific impact onquadriceps strength and activation. Those authors reportedthat women have greater weakness following an immobiliza-tion paradigm and suggested that changes in neural activa-tion play a greater role than muscle atrophy does in explainingthe differences between genders. Our novel finding of re-duced muscle activation among female arthroplasty candi-dates supports their hypothesis. Similar findings were not

evident in the control group. Healthy women had greater acti-vation levels than healthy men did. We further hypothesizethat larger activation impairments compounded by osteoar-thritis in women may magnify preexisting strength differ-ences between genders.

Reduced muscle activation levels were related to func-tional performance. Post hoc analyses revealed significant cor-relations between the central activation ratio of the involvedquadriceps and function as measured with the timed up-and-go test (r = 0.33, p < 0.001), the stair-climb test (r = 0.22, p =0.001), and the six-minute walk (r = 0.21, p = 0.006). Thesedata support the argument that physical activity influencesvoluntary muscle activation23,24. The relationship between acti-vation and function provides a strong explanation for thelower activation levels measured in the female candidates andholds important implications when counseling female kneearthroplasty candidates.

The timing of total knee arthroplasty may be crucial foroptimizing postoperative outcomes. Preoperative function andquadriceps strength are the best predictors of postoperativeoutcomes19,25,26. The presence of comorbidities, poor mentalstatus, severe pain, and disability adversely affect outcomes26.Common advice is to delay knee replacement until pain anddisability are no longer tolerable. Delaying surgery may de-crease the need for future revision arthroplasty; however,substantial evidence favors earlier surgical intervention to op-timize postoperative outcomes26-28.

In light of the recent reports regarding gender issues re-lated to knee replacement, it may be prudent to target poten-tial female arthroplasty candidates to inform them of the risksassociated with delaying surgical intervention. In addition,impairment-based rehabilitation should target women earlierin the disease process to try to mitigate declines in function,strength, and activation, with the overall aim of improvingpreoperative function and postoperative quality of life.

The present study had some limitations. First, contralat-eral knee osteoarthritis was not measured radiographically;however, none of the patients were candidates for bilateral orstaged total knee arthroplasty, and all patients reported the“worst pain” as being <3 of 10 on a verbal rating scale. There-fore, we hypothesize that the weakness of the uninvolved limbis likely the consequence of reduced activity levels due to se-vere osteoarthritis in the involved knee. Second, the onset andduration of symptoms in the involved knee were not recorded.All arthroplasty candidates sought medical attention and werescheduled for total knee arthroplasty by experienced surgeons.Evidence in the literature suggests that women wait longer toundergo total knee arthroplasty than men do10,11, giving us rea-son to believe that the studied female arthroplasty cohort hada more advanced disease state despite the absence of genderdifferences in terms of age, radiographic severity, or kneerange of motion. Future research should longitudinally assessgender differences from the onset of symptoms to the time oftotal knee arthroplasty.

Diminished muscle activation is a hallmark of osteoar-thritis and is by far the largest impairment after total knee

D

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arthroplasty29. These data suggest that osteoarthritis has a differ-ential impact on muscle activation in women. Targeting activa-tion failure with use of electrical stimulation, biofeedback, andvolitional exercise to improve strength is an important preo-perative strategy in both genders but may be more critical inwomen. Many strength and functional differences between menand women worsen with knee osteoarthritis, and even moreemerge (for example, quadriceps voluntary muscle activation).Quadriceps activation is related to functional status and helpsto explain the gender differences in rising from a chair, stair-climbing, and walking ability in the arthroplasty cohort.

In conclusion, while some impairments are simply in-herent differences between men and women, others reflectgender differences in disease impact, indicating that osteoar-thritis has a larger impact on function in women, especially atthe time of surgery. Preoperative interventions in patientswith osteoarthritis should be impairment-based, regardlessof gender; however, close monitoring of women with osteoar-

thritis is warranted on the basis of these data. Knowing thesubstantial impact of preoperative strength and function andthat declines in strength and function provide a good indica-tion of disease impact, earlier surgical consideration may en-hance outcomes in women.

NOTE: The authors acknowledge the expertise of the physical therapists at the University of Del-aware Physical Therapy Clinic and the assistance of William Newcomb, MD.

S.C. Petterson, MPT, PhDL. Snyder-Mackler, PT, ScD, ATC, FAPTA301 McKinly Lab, Newark, DE 19701. E-mail address for L. Snyder-Mackler: smack@udel.edu

L. Raisis, MDA. Bodenstab, MDFirst State Orthopaedics, 4745 Ogletown Stanton Road, Newark, DE 19713

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