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Disease-Specific Gender Differences Among Total Knee Arthroplasty

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

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COPYRIGHT 2007

BY

THE JOURNAL

OF

BONE

AND JOINT

SURGERY, INCORPORATED

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 selfreported disability. The primary aim of the present study was to assess gender differences in the type and magnitude
of osteoarthritis-related impairment prior to knee arthroplasty.
Methods: Two hundred and twenty-one knee arthroplasty candidates (ninety-five men and 126 women) and forty-four
healthy gender, age, and body mass index-matched individuals were tested. Individuals with contralateral limb injury
or abnormality, cardiovascular disease, neurological impairment, and medical conditions limiting activity were excluded. Collected data included Medical Outcomes Study Short Form-36 mental and physical component scores, the
Knee Outcome Survey Activities of Daily Living Scale score, knee range of motion, timed up-and-go test time, stairclimb 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 timed
up-and-go test and stair-climb test times, shorter six-minute walk distances, and lower normalized quadriceps
strength compared with men. Healthy women had longer stair-climb test times and shorter six-minute walk distances
in comparison with healthy men. Between-group comparisons revealed that women in both the control group and the
arthroplasty group had reduced normalized quadriceps strength in comparison with men, that healthy women had
higher voluntary muscle activation in comparison with healthy men, and that female arthroplasty candidates had
lower activation levels in comparison with male candidates.
Conclusions: Observed gender differences in strength and function appear to be inherent but are magnified in arthroplasty candidates. Strength and functional decline should be closely monitored in women with knee osteoarthritis
to serve as an indicator of worsening condition, and preoperative interventions should reflect these gender-specific
impairments.

he multidimensionality of osteoarthritis-related impairments provides a good model to study gender differences in musculoskeletal disease. Women have a
higher risk for the development of osteoarthritis and have
higher rates of disability attributable to osteoarthritis1-5. Furthermore, the need for arthroplasty is three times higher in
women even when the willingness to undergo the procedure is
taken into account6-9. Collectively, studies have suggested that
women 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 physical performance measures7. In that study, female arthroplasty
candidates on waiting lists in Canada reported greater disability and also had worse walking and stair-climbing performance as compared with male arthroplasty candidates7. The
lack of a comparison group and the failure to adjust for salient
variables of age, height, and weight made it difficult to discern

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding
or grants in excess of $10,000 from the National Institutes of Health (R01 HD041055 and T32 HD7490). Neither they nor a member of their
immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No
commercial 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.
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 our
subscription department, at 781-449-9780, to order the CD-ROM).

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

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if differences were truly related to a gender difference in disease impact. In addition, lower extremity muscle strength was
not measured. Practice patterns in Canada result in long waiting times for surgery, and therefore the findings of Kennedy et
al. might not reflect disease severity and disability among arthroplasty candidates in the United States7,12.
Understanding gender differences in disease impact and
osteoarthritis-related impairment in arthroplasty candidates
is necessary in order to develop effective preoperative practice
patterns and to help to guide patient counseling and surgical
decision-making. The primary aim of the present investigation was to quantify differences in the magnitude of impairment between men and women with knee osteoarthritis. We
hypothesized that gender differences would be evident in
quadriceps strength, activation, and physical performance but
not in self-reported function and that these differences would
also be present in an age, gender, and body mass indexmatched healthy cohort.

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Materials and Methods

Entire Arthroplasty Group
ll individuals with knee osteoarthritis who were scheduled
for 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. Classification of end-stage, unilateral knee osteoarthritis by the treating
surgeon was based on the decision to perform total knee arthroplasty imminently. The exclusion criteria were lower extremity
orthopaedic abnormalities other than unilateral knee osteoarthritis, contralateral knee pain with a score of >4 of 10 on a verbal rating scale, a planned total knee arthroplasty on the
contralateral knee, cardiovascular disease, neurologic impairment, and any physical condition limiting daily activity. Two
hundred and twenty-one individuals (ninety-five men and 126
women) were eligible and were tested at a mean of eleven days
before total knee arthroplasty. The entire sample of arthroplasty
candidates had a mean age (and standard deviation) of 65.7 8.8

TABLE I Clinical Characteristics of the Arthroplasty Cohort Stratified by Gender

Pre-Total Knee Arthroplasty Group (N = 221)
Variable

Men*
(N = 95)

Women*
(N = 126)

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

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
F = 0.54, p = 0.464

F = 65.97, p < 0.001

F = 0.22, p = 0.642

Flexion

Extension
Uninvolved (deg)

04

04

Involved (deg)

45

45

9.16 2.44

11.18 3.29

F = 27.71, p < 0.001

24.05 10.45

F = 39.58, p < 0.001

Timed up-and-go test (s)

Stair-climb test (s)

16.83 8.10

Six-minute walk (m)

491 135

421 93

Normalized maximal volitional isometric contraction

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

Uninvolved

0.90 0.09

0.89 0.11

Involved

0.86 0.14

0.85 0.14

Central activation ratio

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

F = 24.46, p < 0.001

F = 141.36, p < 0.001

F = 36.76, p < 0.001

F = 0.09, p = 0.768

F = 1.00, p = 0.326

F = 11.26, p < 0.001

F = 0.02, p = 0.895

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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 Group
Forty-four (20%) of the 221 patients in the arthroplasty cohort
were matched, according to age, gender, and body mass index,
to forty-four healthy individuals (nineteen men and twentyfive women) who were recruited through community advertisements. The exclusion criteria for healthy individuals were
similar to those for patients with end-stage knee osteoarthritis,
with the additional exclusion criterion of a history of diagnosed knee abnormality. The control group had a mean age of
61.3 7.7 years, a mean height of 1.72 0.11 m, a mean weight
of 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 mean
age of 62.3 6.8 years, a mean height of 1.71 0.11 m, a mean
weight 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 subset, 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 participation in the study, which was approved by the University
of Delaware Human Subjects Review Committee.
Self-Assessment Questionnaires
Perceived functional ability was measured with use of the
Medical Outcomes Study Short Form-36 (SF-36) mental and
physical component scores13 and the Knee Outcome Survey
Activities of Daily Living Scale score14.
The Knee Outcome Survey question How does pain affect the function of your knee during daily activities? was used
to quantify the influence of pain on the patients function.
Scores ranged from 0 (pain that prevented the patient from all
activities) to 5 (pain that had no effect on daily activities).
Knee Range of Motion
Knee range of motion in flexion and extension was measured
actively in the supine position with a long-axis goniometer15.
A positive value indicated a position of knee flexion.
Functional Assessment
Functional performance was assessed with the six-minute walk
(the distance walked in six minutes)16,17 and the average of two
trials of the timed up-and-go test (the time required to rise
from 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 in
the chair)18 and the average of two trials of the stair-climb test
(the time required to ascend and descend twelve 17.9-cm
steps)19. The instructions were to move as quickly and as safely
as possible with or without the use of an assistive device.
Quadriceps Strength and Activation Assessment
A burst superimposition test was used to quantify quadriceps
strength (maximal volitional isometric contraction) and volitional muscle activation20. In brief, participants were seated in

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an electromechanical dynamometer (Kin-Com 500 H; Chattex, Chattanooga, Tennessee) with the knee flexed and stabilized at 75. Self-adhesive electrodes were placed over the
rectus femoris muscle belly proximally and the vastus medialis
muscle belly distally to deliver a supramaximal burst of an
electrical stimulus (ten-pulse, 1000-s pulse width, 100 pulses
per second train at 135 V intensity) during a maximal volitional isometric contraction attempt.
Volitional muscle activation was quantified as a central
activation ratio, calculated by dividing the maximal volitional
isometric contraction by the electrically elicited force21. A central activation ratio of 1.0 signifies complete activation. Testing was repeated a maximum of three times if complete
activation was not achieved, with the highest maximal volitional isometric contraction test being used for analysis. A
five-minute rest period was given between trials.
Statistical Methods
Quadriceps strength was normalized to the individuals body
mass index (normalized maximal volitional isometric contraction, expressed in N/body mass index). For standardization purposes, the limbs of the subjects in the control group
were designated as involved or uninvolved to correspond with
their matched counterparts in the arthroplasty group.
Gender differences in the entire arthroplasty cohort
were analyzed with use of independent samples t tests for
questionnaire scores and knee pain and with use of analysis of
covariance (with age and body mass index as covariates) for
the timed up-and-go test, stair-climb test, and six-minute
walk. A 2 2 (gender limb) analysis of variance was used to
analyze gender differences in normalized maximal volitional
isometric contraction, central activation ratio, and knee range
of motion.
Differences between the control group and matched arthroplasty group were analyzed with use of a 2 2 (group
gender) analysis of variance for questionnaire scores and knee
pain; a 2 2 (group gender) analysis of covariance (with age
and body mass index as covariates) for the timed up-and-go
test, stair-climb test, and six-minute walk; and a 2 2 2
(group gender limb) analysis of variance for normalized
maximal volitional isometric contraction, central activation
ratio, and knee range of motion.
An alpha level of <0.05 was considered to be significant.
Independent samples t tests and analysis of covariance were
performed for post hoc analysis with use of the Bonferroni
method to adjust for multiple comparisons (p < 0.0125).
Results
Entire Arthroplasty Group
omen in the arthroplasty group had lower SF-36 physical component scores, SF-36 mental component scores,
and Knee Outcome Survey scores in comparison with men
(p < 0.05), indicating greater reported disability. With the
numbers available, Knee Outcome Survey scores for pain were
not different between men and women (p = 0.784). Female arthroplasty candidates had longer timed up-and-go test and

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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.

TABLE II Clinical Characteristics of the Matched Arthroplasty Subgroup and the Control Group Stratified According to Gender
Matched Total Knee
Arthroplasty Group (N = 44)
Variable
Timed up-and-go test (s)
Stair-climb test (s)
Six-minute walk (m)

Men (N = 19)*

Women (N = 25)*

Control Group (N = 44)

Men (N = 19)*

Women (N = 25)*

8.16 2.34

10.62 2.68

6.30 1.27

6.90 1.16

13.40 6.74

21.35 6.83

8.16 1.73

9.95 2.10

417 90

748 141

627 79

589 131

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.

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motion were not significant, with the numbers available. The

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

Fig. 1 (continued)

stair-climb test times and shorter six-minute walk distances

(p < 0.001). Differences between male and female arthroplasty
candidates in knee flexion (p = 0.652) and knee extension (p =
0.464) and the gender-by-limb interaction term (differences
between genders according to limb) (p > 0.100) for range of

Matched Arthroplasty Group

Compared with Control Group
Lower SF-36 physical component scores and Knee Outcome
Survey scores were reported in the matched arthroplasty
group as compared with the control group. The matched arthroplasty group had longer timed up-and-go test and stairclimb test times, shorter six-minute walk distances, lower
quadriceps normalized maximal volitional isometric contraction values, and less range of motion of the knee in flexion and
extension (p < 0.001). The SF-36 mental component score
(p = 0.118) and the central activation ratio (p = 0.365) were
not different between the control and matched arthroplasty
groups, with the numbers available (Fig. 1). Women in both
the control group and the arthroplasty group had significantly
lower quadriceps normalized maximal volitional isometric
contraction values and shorter six-minute walk distances in
comparison with men (p < 0.001), even when accounting for
age and body size.
The group-by-gender interaction terms were significant
(that is, differences between groups differed according to gender) for the timed up-and-go test (p = 0.012), the stair-climb
test (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 Gender

Group-by-Gender
Interaction

Group-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

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mass index as covariates revealed no difference in the timed upand-go test time between male and female controls (F = 1.61,
p = 0.212); however, women in the arthroplasty group had
longer timed up-and-go test times in comparison with men
(F = 8.59, p = 0.006). The mean stair-climb test time for female
controls was 1.79 seconds (22%) longer than that for male controls (F = 8.02, p = 0.007). The gender difference in the stairclimb test time was magnified in the arthroplasty group; the
mean stair-climb test time for women in the arthroplasty group
was 7.95 seconds (59%) longer than that for men (F = 11.22,
p = 0.002). Central activation ratio values for the matched limb
were significantly higher for female as compared with male controls (t = 2.65, p = 0.011). The central activation ratios in the involved limb were significantly lower in female as compared with
male arthroplasty candidates (t = 2.06, p = 0.045); however, the
central activation ratios in the uninvolved limb were not significantly different between men and women in the arthroplasty
group (t = 1.57, p = 0.124) (Table II).
Discussion
ifferences in normalized strength, stair-climb test times,
and six-minute walk performance were noted between
healthy men and women; however, these gender differences
were magnified in arthroplasty candidates and gender differences also emerged in timed up-and-go performance and voluntary muscle activation. These data support the concept that
gender differences in strength and function are inherent. On
the other hand, the greater degree of difference among arthroplasty candidates suggests that women are more adversely
affected by osteoarthritis than men are and that women undergo arthroplasty at a more advanced disease state than men
do. The mechanisms underlying these gender differences remain unclear but could be related to the activity level of the
patient, the duration of symptoms and disability, and the timing of surgery.
Our data support the concept that women report greater
disability at the time of arthroplasty and provide insight into
the degree of functional impact attributable to osteoarthritis.
Similar to the findings of Katz et al.11, female arthroplasty candidates in the present study had worse self-reported function.
Women with osteoarthritis in our study cohort also exhibited
worse functional performance on walking tests, supporting
the findings of Kennedy et al.7. The larger differences in
functional performance between genders in the arthroplasty
group as compared with the control group substantiated the
disproportionate impact of osteoarthritis-related impairments on women.
Results from the immobilization model used by Yasuda
et al.22 support our findings of the gender-specific impact on
quadriceps strength and activation. Those authors reported
that women have greater weakness following an immobilization paradigm and suggested that changes in neural activation play a greater role than muscle atrophy does in explaining
the differences between genders. Our novel finding of reduced muscle activation among female arthroplasty candidates supports their hypothesis. Similar findings were not

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evident in the control group. Healthy women had greater activation levels than healthy men did. We further hypothesize
that larger activation impairments compounded by osteoarthritis in women may magnify preexisting strength differences between genders.
Reduced muscle activation levels were related to functional performance. Post hoc analyses revealed significant correlations between the central activation ratio of the involved
quadriceps and function as measured with the timed up-andgo 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). These
data support the argument that physical activity influences
voluntary muscle activation23,24. The relationship between activation and function provides a strong explanation for the
lower activation levels measured in the female candidates and
holds important implications when counseling female knee
arthroplasty candidates.
The timing of total knee arthroplasty may be crucial for
optimizing postoperative outcomes. Preoperative function and
quadriceps strength are the best predictors of postoperative
outcomes19,25,26. The presence of comorbidities, poor mental
status, severe pain, and disability adversely affect outcomes26.
Common advice is to delay knee replacement until pain and
disability are no longer tolerable. Delaying surgery may decrease the need for future revision arthroplasty; however,
substantial evidence favors earlier surgical intervention to optimize postoperative outcomes26-28.
In light of the recent reports regarding gender issues related to knee replacement, it may be prudent to target potential female arthroplasty candidates to inform them of the risks
associated with delaying surgical intervention. In addition,
impairment-based rehabilitation should target women earlier
in the disease process to try to mitigate declines in function,
strength, and activation, with the overall aim of improving
preoperative function and postoperative quality of life.
The present study had some limitations. First, contralateral knee osteoarthritis was not measured radiographically;
however, none of the patients were candidates for bilateral or
staged total knee arthroplasty, and all patients reported the
worst pain as being <3 of 10 on a verbal rating scale. Therefore, we hypothesize that the weakness of the uninvolved limb
is likely the consequence of reduced activity levels due to severe osteoarthritis in the involved knee. Second, the onset and
duration of symptoms in the involved knee were not recorded.
All arthroplasty candidates sought medical attention and were
scheduled for total knee arthroplasty by experienced surgeons.
Evidence in the literature suggests that women wait longer to
undergo total knee arthroplasty than men do10,11, giving us reason to believe that the studied female arthroplasty cohort had
a more advanced disease state despite the absence of gender
differences in terms of age, radiographic severity, or knee
range of motion. Future research should longitudinally assess
gender differences from the onset of symptoms to the time of
total knee arthroplasty.
Diminished muscle activation is a hallmark of osteoarthritis and is by far the largest impairment after total knee

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arthroplasty29. These data suggest that osteoarthritis has a differential impact on muscle activation in women. Targeting activation failure with use of electrical stimulation, biofeedback, and
volitional exercise to improve strength is an important preoperative strategy in both genders but may be more critical in
women. Many strength and functional differences between men
and women worsen with knee osteoarthritis, and even more
emerge (for example, quadriceps voluntary muscle activation).
Quadriceps activation is related to functional status and helps
to explain the gender differences in rising from a chair, stairclimbing, and walking ability in the arthroplasty cohort.
In conclusion, while some impairments are simply inherent differences between men and women, others reflect
gender differences in disease impact, indicating that osteoarthritis has a larger impact on function in women, especially at
the time of surgery. Preoperative interventions in patients
with osteoarthritis should be impairment-based, regardless
of gender; however, close monitoring of women with osteoar-

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thritis is warranted on the basis of these data. Knowing the

substantial impact of preoperative strength and function and
that declines in strength and function provide a good indication of disease impact, earlier surgical consideration may enhance outcomes in women.
NOTE: The authors acknowledge the expertise of the physical therapists at the University of Delaware Physical Therapy Clinic and the assistance of William Newcomb, MD.

S.C. Petterson, MPT, PhD

L. Snyder-Mackler, PT, ScD, ATC, FAPTA
301 McKinly Lab, Newark, DE 19701. E-mail address for L. SnyderMackler: smack@udel.edu

L. Raisis, MD
A. Bodenstab, MD
First State Orthopaedics, 4745 Ogletown Stanton Road, Newark,
DE 19713

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