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Clinical Biomechanics 28 (2013) 713724

Contents lists available at ScienceDirect

Clinical Biomechanics
journal homepage: www.elsevier.com/locate/clinbiomech

Review

A systematic review and meta-analysis of lower limb neuromuscular


alterations associated with knee osteoarthritis during level walking
Kathryn Mills a, Michael A. Hunt b, Ryan Leigh a, Reed Ferber a,
a
b

Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada


Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada

a r t i c l e

i n f o

Article history:
Received 21 February 2013
Accepted 16 July 2013
Keywords:
Knee osteoarthritis
Neuromuscular alterations
Level walking
Systematic review

a b s t r a c t
Background: Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA)
during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals
and how these may be inuenced by osteoarthritis severity, varus alignment and/or joint laxity.
Methods: Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing
lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts
were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude
of observed differences. Where studies were homogenous, effect sizes were pooled using a xed-effects model.
Findings: Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude
and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris
(ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean
amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular
activity was prevalent for those exhibiting varus alignment and medial knee joint laxity.
Interpretation: Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee
muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease,
varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efcacy of neuromuscular rehabilitation programs should consider the effect of simultaneous upregulation of medial and lateral knee muscles on disease progression.
2013 Elsevier Ltd. All rights reserved.

1. Introduction
Knee osteoarthritis (KOA) is a progressive disease resulting in the
breakdown of joint cartilage and bone that is characterized by joint
pain, stiffness and swelling (Bombardier et al., 2011). Recently, several
studies have examined neuromuscular control of the lower limb in individuals with KOA during walking. The results of these studies provide
compelling evidence that neuromotor control of the lower limb is altered in this population. Altered neuromuscular control in individuals
with KOA is concerning due to the deleterious effects on joint loading
and stability.
Co-ordinated agonistic and antagonistic muscle activities play major
roles in distributing load between the medial and lateral tibiofemoral
joints during walking. Altered muscle activity, either an increase in medial activity or decrease in lateral activity, at the knee may increase the

Corresponding author at: Faculties of Kinesiology and Nursing, University of Calgary,


2500 University Drive NW, Calgary, Alberta, T2N 1N4 Canada.
E-mail address: rferber@ucalgary.ca (R. Ferber).
0268-0033/$ see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.clinbiomech.2013.07.008

demand on lateral soft tissue to resist the external knee adduction moment (the biomechanical proxy for medial knee joint load) (Schipplein
and Andriacchi, 1991). A high external knee adduction moment in an
individual with varus alignment and/or lateral joint laxity could lead
to a condition where the entire external knee adduction moment, and
potentially the dynamic load, occurs through the medial compartment
of the tibiofemoral joint (Schipplein and Andriacchi, 1991). This is believed to substantially increase in compressive forces and accelerate degeneration of the medial compartment.
As the medial compartment degenerates, the distance between the
medial ligament insertions is reduced and the medial soft tissue contributing to joint stability can become lax (Lewek et al., 2004; Sharma et al.,
1999). Impairment in this passive stabilization system increases the demand for coordinated neuromuscular activity to compensate. An inability to adequately perform this task has been theorized to lead to
recurrent episodes of instability and further degenerative changes
(Lewek et al., 2004; Sharma et al., 1999). Thus, knee joint stability and
load distribution is achieved through an interaction between active
and passive strategies. As such, it is not surprising that increased neuromuscular activity of the medial knee muscles has recently been correlated with rate of knee cartilage volume loss in individuals with medial

714

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

compartment KOA and varus lower limb alignment (Hodges et al.,


2012).
A growing number of studies are reporting neuromuscular outcomes during walking in individuals with KOA. As such, a review of
how neuromuscular control of the lower limb is altered, with respect
to amplitude, duration and antagonistic activity, in individuals with
KOA is timely. To accomplish this task we conducted a systematic review of cross-sectional observational studies comparing neuromuscular
activity in individuals with KOA with either similar healthy controls or
across KOA subgroups. Our aim was to determine which neuromuscular
alterations are consistently observed in individuals with KOA and how
these alterations may be different in the presence of knee varus alignment and/or knee joint laxity. As there is evidence to suggest that the
nature and magnitude of neuromuscular alterations may be inuenced
by the severity of KOA (Astephen et al., 2008), we also examined the
effect of disease severity on neuromuscular alterations during level
walking. Our ndings will assist clinicians in designing conservative
rehabilitation programs that incorporate neuromuscular retraining as
well as highlight areas for future research.
2. Methods
2.1. Search strategy
We devised a search strategy for the following electronic databases:
MEDLINE, EMBASE, CINAHL, SportDiscus, PubMed and Web of Science
and included all references listed until the 30th July 2012. The search
terms and strategy were identical for all databases: (1) Knee osteoarthr*
OR gonarth*, (2) Walking OR gait, (3) Combined 1 AND 2, (4)
Neuromotor OR neuromuscular OR electromyography OR EMG OR muscle activity and (5) Combined 3 AND 4. No restrictions were placed on
the year, status or language of publication. All titles returned by the
search strategy were reviewed by a single reviewer (KM), with abstracts
of those papers potentially meeting the selection criteria retrieved for
further consideration. Full text versions of studies meeting the selection
criteria, as determined by two reviewers (KM, RL), were obtained for inclusion in the review. Reference lists of included papers and published
knee osteoarthritis reviews were hand-searched (KM) to ensure all
eligible data were included.
2.2. Selection criteria
Publications were required to be human-based, cross-sectional observational studies examining neuromuscular activity in a KOA cohort
and a comparator group during level walking. Diagnosis of KOA was required to be made using radiographic or clinical criteria. No restriction
was placed on disease severity, involved compartment or lower limb
alignment. Papers were excluded if they contained: (a) participants
with radiographically conrmed OA in other weight-bearing joints,
(b) participants who had undergone a total joint arthroplasty or joint
preservation surgery in the study limb or (c) participants who required
the assistance of walking aids. These exclusion criteria were imposed
due to potential confounding of results (Ouellet and Moffet, 2002;
Rudolph et al., 2007; Simic et al., 2011).
Included publications were juxtaposed for author names, afliation
and participant characteristics to reduce the risk of bias introduced
through duplicate data. Where multiple studies, authored by identical
authors, presented outcome variables from the same participant numbers, age, weight and sex ratio, only results of the publication with
higher methodological quality were included.
2.3. Methodological quality
Methodological quality of included papers was assessed using a
modied version (Munn et al., 2010) of a validated quality index for
non-randomized trials (Downs and Black, 1998). This version included

16 items assessing reporting quality, external validity, and internal


validity (bias and confounding). It does not include items relating to
an intervention but still includes items relating to the blinding of
observers. Two independent reviewers (KM, MAH) assessed all
papers, with the second reviewer blinded to author names, title,
afliation and journal name. Disagreements in initial ratings were
discussed at a consensus meeting. Publications scoring less than 50%
on the quality index were excluded from further review (Coombes
et al., 2010).
2.4. Data synthesis
Inter-rater reliability of the modied quality index was evaluated
with the kappa () statistic. The magnitude of agreement was quantied using Hopkins (2000) system of very small (0 to 0.1), small (0.1
to 0.3), moderate (0.3 to 0.5), high (0.5 to 0.7), very high (0.7 to 0.9),
and almost perfect to perfect (0.9 to 1.0).
Two independent reviewers (KM, RL) extracted publication details
(authors, year, publication source and type), sample characteristics
(sample size, sampling technique, source of participants and selection
criteria), participants' characteristics (age, gender, severity of KOA,
limb alignment, knee joint laxity and method of diagnosis), neuromotor
characteristics (electrode type, size, shape and placement, sampling frequency and amplitude normalization) and point estimates of effect directly from included papers. Differences were settled by consensus.
Authors were contacted to provide any missing data and, if these were
not provided, they were qualitatively extracted from graph or result
sections. Point estimates of effect were used to calculate mean differences and 95% condence intervals (CI) between groups. An effect size
(ES = mean difference/pooled standard deviation) was used to quantify the magnitude of the differences and permit a common metric between studies. The magnitude of ES was interpreted using Hopkins
et al. (2009) criteria: trivial (0.0 to 0.2), small (0.21 to 0.6), moderate
(0.61 to 1.2) and large (N1.2). Qualitative descriptions of differences between groups were also extracted from principle component analysis of
electromyography (EMG) waveforms.
Meta-analysis was performed using the ES in a xed-effects model
within Cochrane Review Manager (V5.1), using the I2 index to measure
inconsistency (the percentage of total variation due to heterogeneity)
across included papers and referenced to thresholds of low (N 25%),
moderate (50%) and high (75%) evidence of heterogeneity (Higgins
et al., 2003). The criteria for pooling were: (a) participants exhibiting
the same KOA severity, (b) neuromuscular activity being examined
over the same time periods of the gait cycle, (c) the same normalization
methods and (d) co-contraction indices formulated using identical
methods. As this review did not include randomized control trials, a
combination of ES and heterogeneity index was used to quantify levels
of evidence based on those proposed by van Tulder et al. (2003). Evidence of neuromotor alterations associated with KOA was interpreted
as strong (large ES with low evidence of heterogeneity), moderate
(moderate ES and low evidence of heterogeneity), limited (small ES
with low heterogeneity or moderate/large ES with moderate evidence
of heterogeneity), conicting (high evidence of heterogeneity) and no
evidence (95% CI of ES crossed zero).
3. Results
3.1. Search strategy and study characteristics
The search strategy retrieved 489 papers. Fifteen papers met the selection criteria and underwent quality assessment. No studies met the
criteria for duplicate data, although several studies were published
from the same laboratory. One paper was excluded based on poor methodological quality, thus 14 papers were included in the review (Fig. 1).
For 11 papers, inclusion in the KOA group was based on radiographic
and clinical criteria while the remaining three papers used only

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

Literature search: knee osteoarthr*, gonarth*, walking, gait,


neuromotor, neuromuscular, electromyography, EMG, muscle activity
Databases:
MEDLINE: 39
EMBASE: 94
CINAHL: 31
Sportdiscus: 63
PubMed: 89
Web of Science: 153
Hand search: 20
Search results combined: 489

Abstracts screened on the basis of title


n = 39

715

Excluded n = 450
Non-human
Not knee OA
Duplicates
Post surgical
Experimental design
Review paper
Excluded n = 20
No neuromotor variables
Modeling study
Not level walking

Full text paper retrieved on basis of


abstract
n = 19
Excluded n = 4
Within group design (no
comparison group)
Papers considered for inclusion
n = 15
Excluded n = 1
Quality index score <50%

Papers included in review


n = 14

Co-contraction index
n = 10

Muscle amplitude
n = 10

Muscle duration
n=5

KOA versus control n=12


KOA versus KOA n=2

KOA versus control n=13


KOA versus KOA n=3

KOA versus control n=7


KOA versus KOA n=2

Fig. 1. Flow diagram of search strategy. Six publications reported co-contraction and muscle amplitude variables, four publications reported muscle amplitude and duration variables and
one paper reported co-contraction and muscle amplitude variables.

radiographic criteria. KOA severity was reported by the authors of seven


papers and interpreted from the radiographic and clinical ndings
(e.g., joint space narrowing, osteophyte formation, or scheduled for
high tibial osteotomy) from a further two. From these studies, there
were nine cohorts of individuals with moderate KOA and four cohorts
with severe disease. Four studies included individuals with a range of
severities within a single KOA group and were subsequently classied
as KOA. Schmitt and Rudolph (2007) also included individuals with a
range of KOA severities, however as over 60% of their cohort exhibited
mild radiographic changes and symptoms we considered them to be a
predominantly mild KOA cohort. Five studies examined individuals
with varus mechanical alignment. Individuals from three of these studies also exhibited increased medial knee joint laxity, quantied by stress
radiographs, compared with controls (Table 1).
Sample sizes ranged from 8 to 60 individuals in KOA groups and 12 to
63 individuals in healthy control groups. Neuromuscular variables examined were: (a) indices of muscle co-contraction, (b) magnitude of muscle
activation and (c) muscle activity duration. The muscles examined were
vastus medialis (VM), vastus lateralis (VL), rectus femoris (RF),
biceps femoris (BF), semimembranosis (SM), tibialis anterior (TA),

soleus (Sol), medial gastrocnemius (MG) and lateral gastrocnemius


(LG). Electromyography data were primarily obtained using surface
bipolar, circular Ag/AgCl electrodes. The inter-electrode distances
ranged from 18 to 30 mm, which coincides with the distance between
peaks of the propagating action potential (Kamen and Caldwell, 1996).
All studies positioned electrodes over the muscle belly parallel with
muscle bers. Sampling rates ranged from 1000 to 2000 Hz and data
were normalized to maximum voluntary isometric contraction (MVIC)
in 12 papers and to maximum amplitude during walking (% Max) in
the remaining two (Liikavainio et al., 2010; Schmitt and Rudolph, 2007).
3.2. Methodological quality
The quality indices of included papers ranged from nine to 13 (of a
possible 17) and were interpreted as being, on average, moderate quality
(Table 2). Initial inter-rater reliability between the two reviewers was
very high ( = 0.877) with items 18 ( = 0.435) and 25 ( = 0.562)
differing most. For the remaining items, there was almost perfect
agreement (Hopkins et al., 2009) (Table 2). Consensus was reached
on all differing items during the rst discussion. Overall, papers did

716

Authors

Astephen et al.
(2008)

Sample size
(males/females)

Group demographics:
mean (SD)

OA patient characteristics
Severity

Diagnostic
methods

OA characteristics

Moderate: n = 60 (40/20)

Age: 58.32 (9.31),


BMI 30.91 kg/m2 (5.17)
Age: 64.49 (7.75),
BMI 32.05 kg/m2 (5.48)
Age: 50.27 (10.09) BMI 25.45 kg/m2 (4.04)
Age: 62 (10), BMI 30 (7) kg/m2
Age: 56.3 (10.7), BMI 27.8 (5.7) kg/m2
Age: 65 (8), height 1.7 m (0.09),
mass 81.4 kg (14.2)

Moderate
Severe

Radiographic
Clinical

Predominantly medial compartment


Severe group scheduled for TKA

Severe n = 61 (28/33)

Childs et al.
(2004)
Heiden et al.
(2009)

Control n = 60 (23/37)
OA n = 24 (10/14)
Control n = 24 (10/14)
OA n = 54 (24/30)

Hortobgyi et al.
(2005)

OA n = 26 (7/19)

Age: 64 (6), height 1.7 m (0.09),


mass 71.2 kg (13.2)
Age: 58.4 (8.8), height 1.67 m (0.08),
mass 87.1 kg (18.3)

No history of knee pain or surgical interventions.


Able to walk a city block, jog 5 m and walk upstairs
with reciprocal gait.

General OA
General OA

Radiographic
Clinical
Radiographic
Clinical

Control n = 30 (11/9)

Comparator group characteristics

General OA

Radiographic

Unilateral knee OA
All compartments KL grade N2
Most painful or functionally limited limb
used in analysis
5 varus/valgus alignment

No history of OA in lower extremity joints


KL grade 1
Asymptomatic

Bilateral knee OA most symptomatic


knee used in analysis.

Healthy and free from known neuromuscular-skeletal


illness or injury

KL grade 2

Study limb was dominant leg

Unilateral knee OA
Scheduled for arthroscopy
KL grades 1 to 3

No history of knee pain or surgical interventions.

Study limb matched to the OA group

Clinical
Control n = 20 (7/13)
Hubley-Kozey
et al. (2006)

OA n = 40 (29/11)
Control n = 38 (17/21)

Hubley-Kozey
et al.
(2009)

Lewek et al.
(2004)

Age: 58.5 (10.1), height 1.7 (0.08),


mass 68.9 kg (12.3)
Age: 58.9 (8.07), BMI 29.94 kg/m2 (4.86)

Moderate

Radiographic
Clinical

Age: 51.09 (9.99), BMI 24.74 kg/m (4.25)


2

Moderate n = 56
Severe n = 48

Age: 58 (8.7), BMI 30.8 kg/m (5.5)


Age: 63.7 (8.2), BMI 31.8 kg/m2 (5.3)

Control n = 63

Age: 49.2 (9.7), BMI 25.1 kg/m2 (4)

OA n = 12 (6/6)

Age: 50.3 (7.4)

Control n = 12 (6/6)

Age: 49.5 (6.1)

Moderate
Severe

Moderate

Radiographic
Clinical

Radiographic

Clinical

Predominantly medial compartment


KL grades 1 to 3 for moderate and grades
3 to 4 for severe.
Severe group scheduled for TKA
Affected leg used for data collection
Medial compartment (lateral compartment
and PFJ OA excluded)
Scheduled for high tibial osteotomy
Radiographic medial joint space
width = 1.99 (0.84) mm
Medial joint laxity = 5.15 mm (1.5)
Lateral joint laxity = 3.6 mm (1.6)
Weight bearing line = 23.1% (10)

Able to walk a city block, jog 5 m and walk


upstairs with reciprocal gait.
No lower extremity injury within past 6 months.
No OA in lower limb joints
Study limb randomly assigned.
No evidence of OA
Radiographic medial joint space width = 4.9 (1.0) mm
Medial joint laxity = 3.2 mm (1.0)
Lateral joint laxity = 4.3 mm (1.3)
Weight bearing line = 41% (8.6)

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

Table 1
Studies included in review.

Lewek et al.
(2006)

OA n = 15 (6/9)

Age: 47.7 (7.4), height 1.75 m (0.09),


mass 91.9 kg (17.4)

Control n = 15 (6/9)

Age: 48.4 (6.3), height 1.71 m (0.09),


mass 83.8 kg (17.3)

Moderate

Radiographic

Medial compartment and PFJ OA excluded

No evidence of OA

Clinical

Scheduled for high tibial osteotomy


Radiographic medial joint space
width = 1.6 (1.1) mm
Medial joint laxity = 4.9 mm (1.8)
Lateral joint laxity = 3.5 mm (1.5)
Weight bearing line = 28.9% (12.7)
Most symptomatic limb used in analysis
KL grade 1 to 4
Varus ranged from 3.2 (2.5) for
KL = 1 to 9.5 (2.5) for KL = 4
Scheduled for high tibial osteotomy

Radiographic medial joint space width = 5.0 (1) mm


Medial joint laxity = 3.2 mm (0.9)

OA n = 54 (men only)
Control n = 53 (men only)

Age: 59 (5.3), BMI 29.7 kg/m2 (4.7)

General OA

Radiographic

Rudolph et al.
(2007)

OA n = 15 (8/7) 0.1 (1.58)


varus
Control n = 15 (8/7)
OA n = 17 (10/7)
Control n = 20 (7/13)

Age: 49.2 (4.5), BMI 30.7 kg/m2 (4.8)

Moderate

Radiographic

Age: 49.2 (4.25), BMI 28.7 kg/m2 (5.5)


Age: 56 (8.8), BMI 29.8 kg/m2 (6.5)
Age: 46.5 (7), BMI 25.9 kg/m2 (4.8)

Moderate

Clinical
Radiographic
Clinical

Moderate n = 16 (8/8)
Severe n = 15 (10/5)
Control n = 16 (8/8)

Age: 61 (6), BMI 31.3 kg/m2 (3.6)


Age: 61 (9), BMI 30.7 kg/m2 (5.4)
Age: 56 (96), BMI 24.6 kg/m2 (3.9)

Moderate
Severe

Radiographic
Clinical

OA n = 28 (14/14)

Age: 60.4 (9.75), Height 1.7 m (0.11),


mass 92.91 kg (16.16)
Age: 58.5 (9.5), height 1.68 m (0.07),
mass 83.93 kg (1.85)

Median =
mild

Rutherford et al.
(2010)

Rutherford et al.
(2011)

Schmitt and
Rudolph
(2007)

Zeni et al. (2010)

Control n = 26 (13/13)

Moderate n = 16 (6/10)

Age: 62.8 (10)

Moderate

Severe n = 8 (3/5)
Control n = 18 (8/10)

Age: 62.2 (8)


Age 61 (11)

Severe

Radiographic

Radiographic

6.33 (2.39) varus


Unilateral knee OA
Able to walk a city block, reciprocally
negotiate
10 stairs and jog 5 m
Predominantly medial compartment
Severe group scheduled for TKA
All OA groups able to walk N1.0 m/s
Unilateral and bilateral knee OA
(most symptomatic knee analyzed)
Medial compartment
(KL grade N2 in lateral and PFJ excluded)
KL grades 2 to 4 (61% exhibited KL grade =
2)
5.15 (3.43) varus
Medial joint laxity = 4.23 mm (1.8)
Lateral joint laxity = 2.77 mm (1.35)
KL grades 2 to 3 for moderate and 4 for
severe.
Medial compartment

Absence of knee OA was conrmed with radiographs


Study limb randomly chosen
No known symptoms of degenerative joint disease.
Study limb randomly assigned.

No lower extremity injury within past 6 months.


No OA in lower limb joints Study limb randomly
assigned.
No history of knee pain or injury
No radiographic evidence of knee OA
0.76 (2.31) varus
Medial joint laxity = 2.76 mm (0.99)
Lateral joint laxity = 3.52 mm (1.25)
No evidence of joint space narrowing or osteophytes.
No complaints of knee pain
Study limb alternated consecutively

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

Liikavainio et al.
(2010)

Lateral joint laxity = 4.0 mm (1.4)


Weight-bearing line = 45.1% (8.1)
Study limb randomly chosen
No OA or previous injury to pelvis, hip or knee

717

718

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

Table 2
Modied quality index.

7. Estimates of random
variability provided for the main
outcomes?

10. Actual probability values


reported for main outcomes?

11. Were the subjects asked to


participate representative of the
entire population?

12. Were the subjects who were


prepared to participate
representative of the entire

15. Was there an attempt to blind


those measuring the main
outcomes?

16. Was it clear if the results


were based on data dredging

18. Were the statistical tests


appropriate?

20. Were the main outcome


measures valid and reliable?

21. Were all patients and controls


recruited from the same
population?

22. Were all patients and


controls recruited over the same
time period?

25. Was their adequate


b
adjustment for confounding?

Total (17)

Internal validity - confounding

6. Main findings clearly


described?

1
1
1
1
1
1
1
1
1
1
1
1
1
1
1.0

Internal validity - bias

5. Distribution of principle
confounder of each group clearly
described?a

1
1
1
1
1
1
1
1
1
1
1
1
1
1
0.98

External validity

3. Characteristics of the patients


included clearly described?

2. Main outcomes clearly

Astephen et al. (2008)


Childs et al. (2004)
Heiden et al. (2009)
Hortobgyi et al. (2005)
Hubley-Kozey et al. (2006)
Hubley-Kozey et al. (2009)
Lewek et al. (2004)
Lewek et al. (2006)
Liikavanio et al. (2010)
Rudolph et al. (2007)
Rutherford et al. (2010)
Rutherford et al. (2011)
Schmitt and Rudolph (2007)
Zeni et al. (2010)
Kappa levels of agreement

described?

Publication

1. Hypothesis clearly described?

Reporting

0
1
1
1
1
1
1
1
1
1
1
1
1
0
0.63

2
2
1
1
2
2
2
2
2
2
1
2
2
1
1.0

0
1
1
1
1
1
1
1
1
1
1
1
1
1
0.98

1
1
1
1
1
0
1
1
1
1
1
1
1
1
1.0

1
1
1
0
1
0
1
1
0
1
1
1
1
1
1.0

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.98

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.97

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.97

1
1
1
1
1
1
1
1
1
1
1
1
1
1
1.0

1
1
1
1
1
1
1
0
1
1
1
1
1
1
0.44

1
0
1
1
1
1
1
1
0
1
1
1
1
1
1.0

0
0
0
0
1
0
0
0
1
0
0
0
1
0
1.0

0
0
0
0
0
1
0
0
0
0
0
1
0
0
1.0

0
0
1
0
0
0
1
1
1
1
0
1
0
1
0.56

9
10
11
9
12
10
12
11
11
11
10
13
12
10
0.877

All items, except item 5, were scored 1 for fullling the criterion or 0 if the criterion were not lled. Publications that did not provide sufcient details to fulll the criterion were also given a
0 for unable to be determined as per instructions of the original index. Kappa scores indicate level of initial agreement between reviewers prior to the consensus meeting. The total kappa
score indicates overall level of agreement.
a
This category was interpreted as the KOA diagnosis being clearly described with respect to radiographic severity, clinical severity and mechanical alignment. If all three of the criteria were
described, 2 points were awarded for yes. If two of the criteria were described, 1 point was awarded for partially.
b
A full mark was awarded in this category if authors demonstrated no statistically signicant difference in walking speed or pain between KOA group(s) and control or if analyses of
covariance were conducted. Publications that did not investigate differences in walking speed or pain or did not adjust for these potential confounders were awarded unable to be
determined.

not adequately report the sampling method used to recruit participants


(item 11) or provide the proportion of participants who were asked to
participate compared with those who agreed to participate (item 12).
No study reported if they blinded assessors to group allocation (KOA
or control) during analysis of primary outcome measures, and few studies provided adequate information regarding the source of participants
included in the study or the time period for recruitment. These issues
are possible sources of confounding and bias.
3.3. Muscle co-contraction
Ten studies examined the magnitude of co-contraction associated
with KOA. Co-contraction indices were grouped into those specically
comparing medial thigh and shank muscles (VM:SM, VM:MG), those
comparing lateral thigh and shank co-activity (VL:BF, VL:LG, TA:LG)
and those comparing medial muscles with lateral muscle (VM:BF and
VL:SM). In order to examine the inuence of disease severity, comparisons were partitioned into those examining general, mild, moderated
and severe KOA cohorts when compared with healthy controls and
when compared with other KOA severities.
3.3.1. KOA cohorts versus controls
Two studies, examining individuals with moderate KOA, met the
criteria for pooling (Hubley-Kozey et al., 2009; Lewek et al., 2004).
Data pooling revealed the only co-contraction index that was systematically increased was VL:BF, where there was moderate evidence of a
greater co-contraction (ES 0.64 [0.3 to 0.97] I2 = 0%) in individuals
with moderate KOA, compared with healthy controls (Fig. 2A).
Non-pooled data of lateral muscle co-contraction also indicate individuals with KOA walk with increased lateral muscle co-contraction regardless of disease severity, varus alignment and knee laxity (Childs
et al., 2004; Hortobgyi et al., 2005; Lewek et al., 2006; Schmitt and

Rudolph, 2007) (Table 3). Further, Heiden et al. (2009) reported that
lateral muscles provided the greatest contribution to an increased cocontraction between knee extensors and knee exors. However, lateral
thigh muscle co-contraction was only signicantly increased during
midstance (Lewek et al., 2006; Schmitt and Rudolph, 2007). This suggests that while lateral shank muscle co-contraction is increased in
KOA during all phases of the stance phase, increased thigh muscle cocontraction only occurs when the osteoarthritic limb is fully loaded.
Non-pooled data of medial co-contraction indices suggests that medial knee joint laxity may inuence the magnitude of medial cocontraction in KOA. Studies examining KOA participants with medial
knee joint laxity report signicantly increased medial shank and thigh
muscle co-contraction regardless of disease severity (Lewek et al.,
2004, 2006; Schmitt and Rudolph, 2007) (Table 3). In studies by
Lewek et al. (2006, 2004) moderate increases (ES 0.84 and 0.83) in
VM:MG were observed during preparation and weight acceptance.
Thus, the presence of greater medial muscle co-contraction may reect
an attempt to increase medial stability by increasing compressive forces
across the knee.
Non-pooled data of medial and lateral thigh muscle co-contraction
suggested disease severity might inuence the magnitude of cocontraction (Table 3). Zeni et al. (2010) reported VL:SM co-contraction
was only consistently increased across a range of walking speed in
those with moderate KOA. In contrast, co-contraction indices were not
increased, compared with healthy controls, in general and severe KOA cohorts when they walked at a self selected, or fast speeds (Liikavainio et al.,
2010; Zeni et al., 2010).
3.3.2. Between KOA cohorts
Two studies compared co-contraction between individuals with
moderate and severe KOA (Hubley-Kozey et al., 2009; Zeni et al.,
2010). No data pooling was possible. Over similar phases of the gait

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

cycle, Hubley-Kozey et al. (2009) reported individuals with severe KOA


exhibited moderately greater co-contraction indices in both medial and
lateral muscle groups (VL:BF: ES 0.62, VL:LG: 0.68 and VM:MG: 0.61)
than those with moderate disease. In contrast, Zeni et al. (2010) found
no difference in VL:SM co-contraction, regardless of whether
participants walked at 1.0 m/s, self-selected or fast walking speeds
(Table 3). This difference in result may be due to the studies using different muscles in their calculations of co-contraction or due to calculating
co-contraction using different equations.
3.4. Muscle amplitude
Ten studies examined alterations in amplitude of the gastrocnemius,
soleus, quadriceps and hamstrings associated with KOA during level
walking. Alterations in mean, peak and net (the sum of all normalized
muscle activity (Heiden et al., 2009)) muscle amplitude were investigated. The potential inuence of disease severity was the focus of several publications and walking data from those with general, mild,
moderate and severe KOA were examined. ES, calculated from differences in principal components between individuals with moderate
KOA and healthy controls (Rutherford et al., 2010, 2011), was pooled
for gastrocnemius, quadriceps and hamstring amplitudes.
3.4.1. Between KOA and controls
Pooled data revealed no evidence of gastrocnemius overall amplitude alteration associated with moderate KOA (Fig. 2B). While this ndings was supported by results of studies investigating individuals with
severe KOA (Astephen et al., 2008; Rutherford et al., 2011), data from
non-pooled studies investigating those with moderate KOA suggest
that results may be inconclusive. Two studies, that were not pooled,
supported the nding from pooled data (Astephen et al., 2008;
Rudolph et al., 2007). In contrast, Hubley-Kozey et al. (2006) reported
a decrease in mean MG amplitude and Heiden et al. (2009) reported a
net increase in muscle amplitude (Table 3). This suggests that if individuals with moderate KOA exhibit altered gastrocnemius amplitude, there
is no consistency in the direction or magnitude of that alteration.
Moderate increases in VL (ES 0.77 (0.27 to 1.27) I2 = 72%) and RF
(ES 0.73 (0.23 to 1.22) I2 = 0%) amplitude were observed from pooled
data of individuals with moderate KOA compared with healthy controls
(Fig. 2B). Of the eight studies, that were not pooled, only one (Rudolph
et al., 2007) did not report an increase in mean or peak quadriceps amplitude in individuals with KOA regardless of disease severity or joint
laxity. This suggests that increases in VL and RF amplitude are consistently associated with KOA regardless of disease severity or joint laxity.
VM mean and net amplitude was only reported to be increased in studies examining general and predominantly mild KOA cohorts (Heiden
et al., 2009; Liikavainio et al., 2010; Schmitt and Rudolph, 2007).
There was no increase in VM mean amplitude in moderate or severe cohorts compared with controls (Hubley-Kozey et al., 2006; Rudolph et al.,
2007; Rutherford et al., 2011).
Pooled data reveal a systematic, moderate increase in amplitude of
BF in those with moderate KOA compared with healthy controls (ES
1.18 (0.67 to 1.7) I2 = 0%) (Fig. 2B). This nding was supported by a
Schmitt and Rudolph (2007), investigating differences in mean amplitude between a predominantly mild KOA cohort and controls. For general and severe KOA cohorts, there were also trends (Zeni et al., 2010) or
signicant increases (Astephen et al., 2008; Heiden et al., 2009;
Liikavainio et al., 2010) in hamstring mean amplitude (Table 3). While
SM mean and peak amplitude moderately increased compared with
controls, at a range of walking speeds (Zeni et al., 2010), its mean amplitude was consistently lower than BF (Hubley-Kozey et al., 2006;
Rutherford et al., 2010, 2011).
3.4.2. Between KOA cohorts
Three studies examined differences in muscle amplitude between
individuals with moderate and severe KOA (Astephen et al., 2008;

719

Rutherford et al., 2011; Zeni et al., 2010). As with KOA-control comparisons, alterations in gastrocnemius mean amplitude were inconsistent
in direction and magnitude between those with moderate and severe
KOA (Astephen et al., 2008; Rutherford et al., 2011). There was no difference in quadriceps mean amplitude between moderate and severe KOA
groups (Astephen et al., 2008; Rutherford et al., 2011; Zeni et al., 2010),
except during fast walking where mean and peak VL activity was moderately increased in individuals with moderate KOA (ES 0.73 and 0.86)
(Zeni et al., 2010). There was a large reduction in BF mean amplitude
(ES 1.46) in those with moderate disease, but only during midstance
(Rutherford et al., 2011) (Table 3).
3.5. Muscle activity duration
Five studies reported on differences in muscle activity duration between individuals with KOA and controls. Comparisons of gastrocnemius, quadriceps and hamstrings muscles were made between individuals
with moderate and severe KOA and controls (Table 3). No data pooling
was performed.
3.5.1. Between KOA and controls
Data extracted from three studies, which analyzed gastrocnemius durations using principal component analysis, revealed the duration of MG
activity did not differ in individuals with moderate KOA compared with
healthy controls (Astephen et al., 2008; Hubley-Kozey et al., 2006; Rutherford et al., 2011). This nding was not supported by a study examining
duration using discrete variables, which reported a moderate increased in
MG duration (ES 0.97) (Childs et al., 2004). Two studies compared gastrocnemius duration between individuals with severe KOA and controls
reported those with severe KOA exhibited longer duration with MG activating later than LG (Astephen et al., 2008; Rutherford et al., 2011). This
was a different activation pattern than controls.
Waveform and discrete analysis indicate that the activity of the VL
and RF was prolonged in both moderate and severe KOA, compared
with controls (Childs et al., 2004; Hubley-Kozey et al., 2006; Rutherford
et al., 2011). There was no change in VM temporal characteristics for
those with moderate KOA (Hubley-Kozey et al., 2006).
With the exception of one study (Rutherford et al., 2011), hamstring
activity was observed to be prolonged in individuals with KOA. While
both BF and SM durations were increased in those with moderate
KOA, compared with controls (Rutherford et al., 2010), BF activity was
prolonged compared with SM in the KOA group. Analysis of discrete
values suggests a large effect (SM: ES 1.38) (Zeni et al., 2010) (Table 3).
3.5.2. Between KOA groups
Two studies examined differences in muscle activity and duration
between individuals with moderate and severe KOA (Astephen et al.,
2008; Rutherford et al., 2011). Compared with individuals with moderate KOA, those with severe disease exhibited delayed onset of MG
(Rutherford et al., 2011) and longer duration (Astephen et al., 2008).
RF activity was observed to be prolonged for both groups but more so
in the severe group and there was no difference in hamstring duration
(Rutherford et al., 2011).
4. Discussion
The primary nding of this review is that many individuals with KOA
exhibit altered neuromuscular activity across co-contraction, amplitude
and temporal domains, when compared with healthy controls. Specically, pooled results demonstrated that individuals with moderate KOA consistently exhibited moderately increased lateral thigh co-contraction
compared with healthy controls over the period of 100 ms prior to heel
contact until the peak external knee adduction moment (approximately
25% of stance). Pooled data also revealed those with moderate KOA
walk with consistent moderate increases in RF and BF amplitude and a
moderate, although heterogeneous, increase in VL amplitude. While

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K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

non-pooled data cannot provide the precision of meta-analysis, the number of studies reporting elevated lateral muscle co-contraction and
prolonged VL, RF and hamstring duration suggests that these are also consistently associated with KOA regardless of disease severity, knee joint
laxity or varus alignment. Medial knee joint laxity may have an important
inuence on medial knee muscle co-contraction as it was only consistently observed in individuals with laxity, regardless of disease severity. Disease severity does appear to inuence the presence of increased medial:
lateral muscle co-contraction, as it was only signicantly increased, across
a range of walking speeds, in those with moderate KOA (Zeni et al., 2010).
Concurrent increases in medial and lateral muscle amplitudes, as observed in the general KOA group (Liikavainio et al., 2010), could potentially explain the lack of increase in the co-contraction index. However, for
the severe KOA group, who only exhibited an increased co-contraction
when there was a concurrent increase in medial and lateral muscle amplitudes (Zeni et al., 2010), it could be due to the observed slower walking
speeds or reect an arthrogenic muscle inhibition component in the
disease process (Hurely, 1999).
Several authors have hypothesized that the primary reason why
individuals with KOA adopt neuromuscular alterations is to unload
the medial knee joint (Heiden et al., 2009; Hortobgyi et al., 2005;
Hubley-Kozey et al., 2009). Further, they suggest that lateral muscle
activity has a protective effect on the knee and preserves knee function.
Findings from this review demonstrate that increased lateral muscle
activity is a prevalent adaptation, particularly when the knee is
fully loaded. Recently, a delay in lateral knee muscle co-contraction
was correlated with increased lateral cartilage loss in KOA patients
with varus malalignment over a 12-month period (Hodges et al.,
2012). However, further research is needed to determine whether
increased lateral muscle activity is a neuromuscular adaptation that
should be encouraged as a protective mechanism in individuals
with KOA.

A second, frequently postulated reason for increased neuromuscular


activity is the need for increased knee joint stability (Heiden et al., 2009;
Hortobgyi et al., 2005; Hubley-Kozey et al., 2009). Specically, increased
coordinated muscle activity is required when the passive stabilization
provided by soft tissue is compromised (Schipplein and Andriacchi,
1991). The ndings of this review support this statement. Medial cocontraction indices were signicantly greater than controls for individuals with medial knee joint laxity (Hubley-Kozey et al., 2009; Lewek
et al., 2004, 2006; Schmitt and Rudolph, 2007). This suggests that only
those individuals who have a lack of medial passive knee support, potentially through an approximation of medial ligament insertions resulting
from the loss of cartilage and bone height (Lewek et al., 2004; Sharma
et al., 1999), exhibit increased medial muscle activation.
Even though individuals without knee joint laxity exhibited similar
medial knee muscle neuromuscular activity as healthy control, they
exhibited elevated and prolonged activity of RF regardless of disease severity. This could also be an attempt to protect and stabilize the knee.
However, current evidence questions the efcacy of increased neuromuscular activity of the RF and medial knee muscles in accomplishing
this task (Hodges et al., 2012; Schipplein and Andriacchi, 1991;
Schmitt and Rudolph, 2008). Increased neuromuscular activation of
muscles that cross the knee increases compressive forces. While this
would increase stability, it would also increase load on the joint and
could accelerate degeneration of the medial compartment (Schipplein
and Andriacchi, 1991). Further, increased duration medial knee muscle
co-contraction has recently been correlated with increased loss of medial knee cartilage volume (Hodges et al., 2012). Interestingly, it is possible for increased neuromuscular activity of medial and lateral knee
muscles as well as RF to co-exist as demonstrated in a severe KOA cohort
(Hubley-Kozey et al., 2009) and in a predominantly mild KOA cohort
with varus alignment and medial knee joint laxity (Schmitt and
Rudolph, 2007). However, due to the cross-sectional nature of studies

Fig. 2. Forest plot of data pooling. Filled diamonds indicate pooled data ES and 95% condence intervals. Condence intervals that do not cross zero indicate a systematic effect. The consistency of neuromuscular alterations was determined based on the presence of a systematic effect and a low I2 index. (A) Pooled ES for co-contraction indices. (B) Pooled ES for amplitude.
Amplitude ES was calculated from mean (SD) factor scores of principal components so mean differences were not calculated.

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

721

Table 3
Results of included papers.
Authors
Co-contraction index
Childs et al. (2004)
Heiden et al. (2009)

Variable

Knee OA

Comparator Result/mean difference (95% CI) and effect size (ES)

VL:BF (% MVIC)
TA:MG (% MVIC)
Muscles: lateral muscles
(SM, VM, MG:BF, VL, LG % MVIC)

General OA

Control

General OA

Control

General OA

Control

SM:BF (% MVIC)

Hortobgyi et al. (2005)

Hubley-Kozey et al.
(2009)

Knee exors: knee extensors


(SM, BF, MG, LG:VL, VM, RF %
MVIC)
200 ms prior to IC to toe-off
BF:VL (% MVIC)
LG:TA (% MVIC)
100 ms prior to IC to peak KAM
VL:BF (% MVIC)

VL:LG (% MVIC)

VM:SM (% MVIC)

VM:MG (% MVIC)

Lewek et al. (2004)

Lewek et al. (2006)

Liikavainio et al. (2010)


Rudolph et al. (2007)

Schmitt and Rudolph


(2007)

100 ms prior to IC to peak KAM


VL:BF (% MVIC)
VL:LG (% MVIC)
VM:SM (% MVIC)
VM:MG (% MVIC)
Preparation
VL:BF (% MVIC)
VL:LG (% MVIC)
VM:SM (% MVIC)
VM:MG (% MVIC)
VM:BF (% Max)
100 ms prior to IC to peak KAM
VL:BF (% MVIC)
VL:LG (% MVIC)
VM:SM (% MVIC)
VM:MG (% MVIC)
Preparation and weight
acceptance
VL:BF (% Max)
VL:LG (% Max)

41.0 (23.85 to 58.15) ES 1.26


40 (15.95 to 64.05) ES 0.9
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate

Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe

10.17 (4.39 to 15.94) ES 0.66


23.49 (17.07 to 29.9) ES 1.52
13.32 (21.52 to 5.12) ES 0.62
2.16 (0.69 to 5.02) ES 0.28
9.57 (5.72 to 13.42) ES 1.01
7.41 (11.68 to 3.14) ES 0.68
4.46 (0.73 to 9.65) ES 0.32
7.6 (3.26 to 11.94) ES 0.32
3.14 (9.05 to 2.77) ES 0.2
1.22 (1.27 to 3.71) ES 0.18
6.88 (10.21 to 3.64) ES 0.85
5.66 (9.26 to 2.06) ES 0.61

Moderate
(varus and lax)

Control

5.7 (2.55 to 13.95) ES0.53


2.8 (3.21 to 8.81) ES 0.36
0.4 (7.13 to 6.33) ES 0.05
6.3 (0.5 to 12.1) ES 0.84

Moderate
(varus and lax)

Control

General OA (varus) Control


Moderate (varus)
Control

Mild
(varus and lax)

Zeni et al. (2010)

Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate

Control
Control
Severe
Control
Control
Severe
Control
Control
Severe

Gastrocnemius (LG, MG % MVIC)

Moderate
Severe
Moderate

Control
Control
Severe

Quadriceps (VL, VM, RF % MVIC)

Moderate

Control

Severe

Control

Moderate

Severe

VL:SM (% MVIC) (PW)

VL:SM (% MVIC) (FW)

Muscle amplitude
Astephen et al. (2008)

4.6 (2.63 to 11.83) ES 0.44


2.9 (2.9 to 8.7) ES 0.35
0.7 (6.24 to 4.84) ES 0.09
6.2 (1.01 to 11.39) ES 0.83
No difference between groups
No difference between groups

Control

VM:SM (% Max)
VM:MG (% Max)
Midstance
VL:SM (% MVIC) (1.0 m/s)

13.0 (2.37 to 23.63) ES 0.68


9.0 (4.17 to 13.83) ES1.04
OA group exhibited signicantly greater co-contraction during loading and early
stance and signicantly less during midstance. Lateral muscle activation was the
greatest contributor to the co-contraction index
OA group exhibited greater co-contraction during loading, early and midstance.
BF activation was the major contributor to the co-contraction index.
OA group exhibited greater co-contraction during midstance. There was no
difference between groups during loading and early stance.

No difference between groups


OA group exhibited a trend towards greater co-contraction during preparation
and signicantly higher co-contraction during weight acceptance.
OA group exhibited a trend towards greater co-contraction during preparation
and signicantly higher co-contraction during weight acceptance.
No difference between groups
OA group exhibited higher co-contraction for all muscles
12.4 (5.81 to 18.99) ES 1.29
11.5 (2.21 to 20.79) ES 1.33
0.9 (9.91 to 11.71) ES 0.07
11.7 (4.81 to 18.59) ES 1.16
6.8 (2.51 to 16.11) ES 0.75
4.9 (5.85 to 15.65) ES 0.37
14.4 (5.27 to 23.53) ES 1.08
6.2 (2.24 to 14.64) ES0.72
8.2 (3.41 to 19.81) ES 0.5

No difference between groups


No difference between groups
Severe OA group exhibited higher mean MG amplitude in early stance and in
swing phase and lower mean amplitude in late stance.
Mean RF amplitude was higher in moderate OA group throughout the majority
of stance and late swing.
Mean RF amplitude was lower in severe OA group during early stance and early
swing but higher mean amplitude in mid to late stance.
No difference between groups
(continued on next page)

722

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

Table 3 (continued)
Authors

Variable

Knee OA

Comparator Result/mean difference (95% CI) and effect size (ES)

Muscle amplitude
Astephen et al. (2008)

Hamstrings (BF, SM % MVIC)

Moderate
Severe
Moderate
General OA

Control
Control
Severe
Control

No difference between groups


Mean SM and BF amplitude was higher in severe OA group during stance.
No difference between groups
OA group exhibited signicantly greater net muscle activation during weight
acceptance and early stance compared with controls

General OA

Control

Moderate

Control

General OA

Control

Moderate
(varus)
Moderate

Control

Moderate

Control

Severe

Control

Heiden et al. (2009)

Hortobgyi et al.
(2005)
Hubley-Kozey et al.
(2006)

Net muscle activity of


BF, SM, VL, RF, VL, MG, LG (%
MVIC)
BF (% of MVIC)
VL (% of MVIC)
Gastrocnemius (MG, LG % MVIC)

Severe

Moderate

Quadriceps (RF, VM, VL % MVIC)

Severe

Control

Moderate

Severe

Moderate

Control

Severe

Control

Moderate

Severe

Mild (varus and


lax)

Control

47 (28.18 to 65.82) ES 1.27


47 (20.53 to 59.47) ES 1.09
Mean MG amplitude was decreased in OA group and peak amplitude occurred
earlier in gait cycle. The control group recruited MG more than LG, whereas OA
group recruited both muscles equally.
Mean VL amplitude was higher in OA group during initial stance and there was a
trend towards higher mean RF amplitude. Mean VM amplitude was similar
between OA and controls.
Mean BF amplitude was higher and peak amplitude occurred prior to heel strike in
OA group compared with controls. Mean BF amplitude was higher than SM for
both groups.
OA group exhibited signicantly higher mean BF amplitude at IC, except when
walking fast.
Mean VM amplitude in late stance and early swing were signicantly greater in
the OA group for all gait speeds
Tendency towards greater mean MG activity in the OA group. No other difference
between groups.
OA group exhibited moderately less difference between early and late stance
activity than controls for MG activity (ES 0.68) and a moderate tendency of
smaller difference in LG activity (ES 0.63)
OA group exhibited large reduction in difference between mid and late stance
amplitude for RF (ES 1.2) and small tendency towards smaller difference
between mid and late stance amplitude for VL and VM (ES 0.59, 0.55). RF
differential was moderately less than VM in OA group (ES 0.64), and large
reduction compared with VL (ES 1.8) and VM (ES 1.71) in control group.
OA group exhibited which was moderately greater overall amplitude of BF than
SM (ES 1.09). OA group SM amplitude differential between early stance and late
swing versus midstance was moderately greater than control group (ES 0.86)
OA group exhibited moderately smaller difference between early and late stance
amplitude (ES 0.83)
OA group exhibited large reductions in late stanceearly stance amplitude
differential for MG (ES 1.26) and LG (ES 1.21)
Moderate OA group exhibited moderately greater mean MG amplitude (ES 0.74)
and moderately larger difference between early and late stance amplitude (ES 0.91).
Difference in RF amplitude between early and midlate stance was moderately lower
in OA group (ES 0.89). Difference between midlate stance and swing phase
amplitude was moderately higher in OA group for VL (ES 0.82) and RF (ES 0.83).
No difference in mean amplitude. Severe group exhibited moderately greater
difference between midlate stance and swing phase VL amplitude compared
with moderate group (ES 0.83)
OA group exhibited moderate reduction in mean SM amplitude during midstance
and late swing burst (P = 0.05, ES 0.69).
OA group exhibited large reductions in mean BF amplitude during midstance and
late swing burst (P = 0.00, ES 1.46).
Moderate group exhibited moderately lower BF mean amplitude during
midstance and late swing burst (P = 0.04, ES 0.73)
Signicantly greater mean amplitude in OA group during midstance

Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe

Signicantly greater mean amplitude in OA group during weight acceptance and


midstance
Trend towards greater mean amplitude in OA group during preparation,
signicantly greater mean amplitude during midstance
Signicantly greater mean amplitude in OA group during weight acceptance
Trend towards greater mean amplitude in OA group during preparation,
signicantly greater mean amplitude during weight acceptance
No difference between groups
No difference between groups
16 (7.06 to 24.94) ES 1.24
10.3 (1.5 to 19.1) ES 1.29
5.7 (6.46 to 17.86) ES 0.34
15.5 (6.06 to 24.49) ES1.14
8.9 (1.02 to 18.82) ES 1.02
6.6 (6.78 to 19.98) ES 0.37
18.4 (5.21 to 31.59) ES 0.97
1.7 (5.7 to 9.1) ES 0.27
16.7 (2.28 to 31.12) ES0.73
26.8 (10.99 to 42.61) ES 1.18
21.2 (6.29 to 36.11) ES 1.55
5.6 (15.45 to 26.65) ES 0.19

Quadriceps (RF, VL, VM % MVIC)

Hamstrings (BF, SM % MVIC)

Liikavainio et al.
(2010)

BF (% Max)
VM (% Max)

Rudolph et al. (2007)

VL, VM, BF, SM LG, MG (% MVIC)

Rutherford et al.
(2010)

Gastrocnemius (MG, LG % MVIC)

Control

Quadriceps (VL, VM, RF % MVIC)

Hamstrings (BF, SM % MVIC)

Rutherford et al.
(2011)

Gastrocnemius (MG, LG % MVIC)

Hamstrings (BF, SM % MVIC)

Schmitt and Rudolph


(2007)

VL (% Max)
VM (% Max)
BF (% Max)
SM (% Max)
LG (% Max)

Zeni et al. (2010)

MG (% Max)
Sol (% Max)
VL (mean % MVIC) (1.0 m/s)

VL (mean % MVIC) (PW)

VL (mean % MVIC) (FW)

VL (peak % MVIC) (1.0 m/s)

Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

723

Table 3 (continued)
Authors

Variable

Knee OA

Comparator Result/mean difference (95% CI) and effect size (ES)

Muscle amplitude
Zeni et al. (2010)

VL (peak % MVIC) (PW)

Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate
Moderate
Severe
Moderate

Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe
Control
Control
Severe

23.7 (7.31 to 40.02) ES 1.01


16.1 (1.69 to 33.89) ES 1.0
7.6 (15.75 to 30.95) ES 0.24
40.20 (14.31 to 66.09) ES 1.08
1.4 (11.54 to 14.34) ES 0.09
38.8 (11.21 to 66.39) ES 0.86
8.9 (1.64 to 16.16) ES 0.84
10.9 (0.09 to 21.89) ES 1.1
2.0 (14.63 to 10.63) ES 0.13
8.0 (2.18 to 13.82) ES 0.92
10.0 (5.02 to 25.02)
2.0 (17.49 to 13.49) ES 0.13
8.6 (1.39 to 15.81) ES 0.81
8.8 (1.96 to 19.56) ES 0.84
0.2 (12.19 to 11.79) ES 0.01
16.5 (4.7 to 28.3) ES 0.96
17.5 (2.78 to 32.22) ES 1.25
1.0 (18.84 to 16.84) ES 0.04
14.7 (2.53 to 26.87) ES 0.81
18.8 (8.19 to 45.79) ES 0.76
4.1 (32.11 to 23.91) ES 0.15
12.7 (1.0 to 26.40) ES 0.62
13.3 (1.66 to 28.26) ES 0.75
0.6 (17.7 to 16.5) ES 0.03

Moderate

Control

Severe
General OA

Control

Moderate

Control

MG was active for the majority of the gait cycle in severe OA group whereas
moderate
OA group and controls exhibited MG activity during late stance.
165 (82.98 to 247.02) ES 1.12
167 (99.89 to 234.11) ES 1.38
158 (108.92 to 207.08) ES 1.79
140 (59.27 to 220.73) ES 0.97
There was no difference in temporal characteristics of LG or MG.
VL and RF activities were prolonged during mid- to late-stance. There was no
change in temporal characteristics for VM.
BF activity was higher and prolonged in OA group compared with controls. BF
activity was higher than SM for both groups.
No phase differences between groups for MG and LG
No phase shift between groups for VL, VM and RF
Duration of BF and SM activities was moderately prolonged in OA group compared
with controls (ES 1.16 and 0.91)
MG onset was moderately earlier than LG onset for both groups (OA:ES 1.18.
Control:ES 1.01).
OA group exhibited moderately later MG onset compared with controls (ES 1.1)
Severe group exhibited largely later MG onset than moderate group (ES 1.2)

VL (peak % MVIC) (FW)

SM (mean % MVIC) (1.0 m/s)

SM (mean % MVIC) (PW)

SM (mean % MVIC) (FW)

SM (peak % MVIC) (1.0 m/s)

SM (peak % MVIC) (PW)

SM (peak % MVIC) (FW)

Muscle activity duration


Astephen et al. (2008)

Childs et al. (2004)

Hubley-Kozey et al.
(2006)

Gastrocnemius (MG)

VL (ms)
SM (ms)
TA (ms)
MG (ms)
Gastrocnemius (MG, LG)
Quadriceps (RF, VL, VM)
Hamstrings (BF, SM)

Rutherford et al. (2010)

Gastrocnemius (MG, LG)


Quadriceps (VL, VM, RF)
Hamstrings (BF, SM)

Moderate

Control

Rutherford et al. (2011)

Gastrocnemius (MG, LG % MVIC)

Moderate

Control

Severe
Moderate

Control
Severe

BF: biceps femoris, LG: lateral gastrocnemius, MG: medial gastrocnemius, RF: rectus femoris, SM: semimembranosis, Sol: soleus, TA: tibialis anterior, VL: vastus medialis, VM: vastus
medialis.
IC: initial contact, ms: milliseconds, MVIC: maximum isometric voluntary contraction, m/s: meters per second, FW: fast walking, PW: preferred walking speed, KAM: peak external knee
adduction moment.
Preparation: 100 ms prior to heel strike until initial contact.
Weight acceptance: initial contact until single leg stance.

included in this review, no conclusions can be drawn regarding the interaction between the potentially negative effects of increased medial
knee muscle and RF activity and the potential positive effects of increased lateral activity. Future research is needed to determine how
this interaction affects KOA progression.
Along with the inability to draw conclusions regarding inuences on
the progression of KOA, there are several additional limitations of this
review. The primary methodological concern of the studies included
in this review was poor external validity specically a lack of
reporting sampling methods and demonstrating that the people who
participated in the study are representative of the population they
were selected from. This makes generalizing results beyond individuals
who meet specic inclusion criteria difcult. Another methodological
issue was the variety of formulas used to calculate co-contraction indices highlighting the numerous methods to achieve a single number.
As such, interpretation of this index is difcult unless there is also an investigation into how this number is reached. The relative contributions

of muscles involved in any co-contraction formula are of particular interest to clinicians, particularly if the ratio contains both medial and lateral muscle contributions. Some studies explore this (Heiden et al.,
2009; Hubley-Kozey et al., 2009; Zeni et al., 2010) and future studies
would benet from similar exploration.
An interesting issue in interpreting the validity of the ndings of this
review is that the majority of studies normalized their neuromotor data
to MVIC. Normalizing EMG data to MVIC provides information regarding
the relative degree of muscle activation and facilitates comparisons between groups. However, in injured and post-operative patients, the ability to perform an MVIC can be affected by pain (Arvidsson et al., 1986;
Benoit et al., 2003). In KOA cohorts, higher pain levels and lower physical function have been associated with increased neuromotor activity
independent of radiographic disease severity (Heiden et al., 2009;
Wilson et al., 2011). Thus, individuals with KOA may not be able to produce an accurate MVIC and subsequent signicant differences in neuromuscular activity may be erroneous. Conversely, reported increases in

724

K. Mills et al. / Clinical Biomechanics 28 (2013) 713724

neuromotor activity may be due to those with more severe KOA


reporting higher pain levels than moderate or healthy counterparts
rather than the radiographic severity of their diagnosis. Further investigation is needed into the association between pain, KOA severity and
neuromuscular control during gait.
5. Conclusion
Pooled and non-pooled data from moderate quality observational
studies demonstrate individuals with KOA exhibit altered lower limb
neuromuscular activity during gait compared with healthy controls. Individuals with KOA exhibited increased co-contraction, amplitude and
duration of lateral knee muscles regardless of their disease severity,
lower limb alignment or medial knee joint laxity. Neuromuscular activity of RF was also increased and prolonged for many KOA cohorts and
medial knee muscle activity was also increased. Based on current evidence, this suggests that individuals with KOA are adopting neuromotor
patterns during gait that have the potential to protect the medial knee
joint. However, those with severe disease or medial knee joint laxity
and/or varus alignment are also exhibiting neuromuscular patterns
that increase the risk of accelerated medial compartment degeneration.
In some instances, both potentially protective and potentially degenerative neuromuscular pattern occur simultaneously. Therefore, while results of this review suggest neuromuscular rehabilitation focusing on
increasing lateral muscle activity and down-regulating medial muscle
and RF activity shows promise as way of potentially slowing this progression, future research into the efcacy of such a program is needed.
Such research needs to further investigate how simultaneous upregulation in medial and lateral knee muscle activities inuences disease progression and should also consider metrics of pain and function
when comparing individuals with KOA.
Acknowledgments
Kathryn Mills is supported by Alberta Innovates Health Solutions
Team in Osteoarthritis #200700596. Ryan Leigh is supported by Alberta
Innovates Health Solutions Clinical Fellowship #201200131. The authors declare no conicts of interest.
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