A Systematic Review and Meta-Analysis of Lower Limb Neuromuscular Alteration Associates With Knee Osteoarthritis During Level Walking

8/10/2019 A Systematic Review and Meta-Analysis of Lower Limb Neuromuscular Alteration Associates With Knee Osteoarthri

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Review

A systematic review and meta-analysis of lower limb neuromuscularalterations associated with knee osteoarthritis during level walking

Kathryn Mills a, Michael A. Hunt b, Ryan Leigh a, Reed Ferber a,a Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canadab Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada

a b s t r a c ta r t i c l e i n f o

Article history:

Received 21 February 2013Accepted 16 July 2013

Keywords:

Knee osteoarthritis

Neuromuscular alterations

Level walking

Systematic review

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 individualsand 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

wereincluded. 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 in-

creased 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 dataindicated prolonged activity of these muscles.Increased medial kneeneuromuscular

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 andmedial joint laxitydemonstrate up-regulationof medialknee muscles. Future research inves-

tigating the ef

cacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation 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 indi-

viduals with KOA during walking. The results of these studies provide

compelling evidence that neuromotor control of the lower limb is al-

tered 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 me-

dial activity or decrease in lateral activity, at the knee may increase the

demand on lateral soft tissue to resist the external knee adduction mo-

ment (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 be-

lieved to substantially increase in compressive forces and accelerate de-

generation of the medial compartment.

As the medial compartment degenerates, the distance between the

medialligamentinsertions is reduced andthe medialsoft tissuecontrib-

uting to joint stability can become lax (Lewek et al., 2004; Sharma et al.,

1999). Impairment in this passive stabilization system increases the de-

mand for coordinated neuromuscular activity to compensate. An inabil-

ity 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 neuro-

muscular activity of the medialknee muscles hasrecentlybeen correlat-

ed with rate of knee cartilage volume loss in individuals with medial

Clinical Biomechanics 28 (2013) 713724

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

2500 University Drive NW, Calgary, Alberta, T2N 1N4 Canada.

E-mail address:[email protected](R. Ferber).

0268-0033/$ see front matter 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.clinbiomech.2013.07.008

Contents lists available atScienceDirect

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

2012).

A growing number of studies are reporting neuromuscular out-

comes 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 re-

view of cross-sectional observational studies comparing neuromuscular

activity in individuals with KOA with either similar healthy controls oracross KOAsubgroups. Our aim was to determinewhichneuromuscular

alterations are consistently observed in individuals with KOA and how

these alterations may be different in the presence of knee varus align-

ment 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 forall databases: (1) Knee osteoarthr*

OR gonarth*, (2) Walking OR gait, (3) Combined 1 AND 2, (4)

Neuromotor OR neuromuscular OR electromyography OR EMG OR mus-

cle 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 in-

clusion in the review. Reference lists of included papers and published

knee osteoarthritis reviews were hand-searched (KM) to ensure alleligible data were included.

2.2. Selection criteria

Publications were required to be human-based, cross-sectional ob-

servational studies examining neuromuscular activity in a KOA cohort

and a comparator group during level walking. Diagnosis of KOA was re-

quired 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 imposeddue 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 num-

bers, 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 quanti-ed usingHopkins (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, shapeand placement,sampling fre-

quency and amplitude normalization) and point estimates of effect di-

rectly 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 differ-

ences and 95% condence intervals (CI) between groups. An effect size

(ES = mean difference/pooled standard deviation) was used to quanti-

fy the magnitude of the differences and permit a common metric be-

tween 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 descriptionsof differences be-

tween 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 theI2 index to measureinconsistency (the percentage of total variation due to heterogeneity)

across included papers and referenced to thresholds of low (N25%),

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 thesame time periods of thegaitcycle, (c) thesame 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 byvan Tulder et al. (2003). Evi-

dence 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 evidenceof 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 se-

lection criteria and underwent quality assessment. No studies met the

criteria for duplicate data, although several studies were published

from thesame laboratory. Onepaper wasexcluded based on poor meth-

odological 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

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


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radiographiccriteria. KOAseverity 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 ofseverities 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 stud-

ies also exhibited increased medial knee joint laxity, quantied by stress

radiographs, compared with controls (Table 1).

Samplesizes ranged from 8 to 60 individuals in KOA groupsand 12 to

63 individuals in healthycontrol groups. Neuromuscular variables exam-

inedwere: (a) indicesof 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 withmuscle 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

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: 20Search results combined: 489

Excluded n = 450

Non-human

Not knee OA

Duplicates

Post surgical

Experimental design

Review paper

Abstracts screened on the basis of title

n = 39

Full text paper retrieved on basis of

abstract n = 19

Excluded n = 20

No neuromotor variables

Modeling study

Not level walking

Papers considered for inclusion

n = 15

Excluded n = 4

Within group design (no

comparison group)

Papers included in review

n = 14

Excluded n = 1

Quality index score


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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)

Moderate Radiographic Medial compartment and PFJ OA excluded

Clinical Scheduled for high tibial osteotomy

Control n = 15 (6/9) Age: 48.4 (6.3), height 1.71 m (0.09),

mass 83.8 kg (17.3)

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)

Liikavainio et al.

(2010)

OA n = 54 (men only) Age: 59 (5.3), BMI 29.7 kg/m2 (4.7) General OA Radiographic Most symptomatic limb used in analysis

Control n = 53 (men only) KL grade 1 to 4

Varus ranged from 3.2 (2.5) for

KL = 1 to 9.5 (2.5) for KL = 4

Rudolph et al.

(2007)

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

varus

Age: 49.2 (4.5), BMI 30.7 kg/m2 (4.8) Moderate Radiographic Scheduled for high tibial osteotomy

Control n = 15 (8/7) Age: 49.2 (4.25), BMI 28.7 kg/m2 (5.5) Clinical 6.33 (2.39) varus

Rutherford et al.

(2010)

OA n = 17 (10/7) Age: 56 (8.8), BMI 29.8 kg/m2 (6.5) Moderate Radiographic Unil ateral knee OA

Control n = 20 (7/13) Age: 46.5 (7), BMI 25.9 kg/m2 (4.8) Clinical Able to walk a city block, reciprocally

negotiate

10 stairs and jog 5 m

Rutherford et al.

(2011)

Moderate n = 16 (8/8) Age: 61 (6), BMI 31.3 kg/m2 (3.6) Moderate Radiographic Predominantly medial compartment

Severe n = 15 (10/5) Age: 61 (9), BMI 30.7 kg/m2 (5.4) Severe Clinical Severe group scheduled for TKA

Control n = 16 (8/8) Age: 56 (96), BMI 24.6 kg/m2 (3.9) All OA groups able to walk N1.0 m/s

Schmitt and

Rudolph

(2007)

OA n = 28 (14/14) Age: 60.4 (9.75), Height 1.7 m (0.11),

mass 92.91 kg (16.16)

Median =

mild

Radiographic Unilateral and bilateral knee OA

(most symptomatic knee analyzed)

Control n = 26 (13/13) Age: 58.5 (9.5), height 1.68 m (0.07),

mass 83.93 kg (1.85)

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)

Zeni et al. (2010) Moderate n = 16 (6/10) Age: 62.8 (10) Moderate Radiographic KL grades 2 to 3 for moderate and 4 for

severe.

Severe n = 8 (3/5) Age: 62.2 (8) Severe Medial compartment

Control n = 18 (8/10) Age 61 (11)


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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 (KOAor control) duringanalysis of primary outcomemeasures, and few stud-

ies 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, compari-

sons were partitioned into those examining general, mild, moderatedand 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 systemat-

ically 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 indi-

viduals with KOA walk with increased lateral muscle co-contraction re-

gardless 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 co-

contraction between knee extensors and knee exors. However, lateral

thigh muscle co-contraction was only signicantly increased duringmidstance (Lewek et al., 2006; Schmitt and Rudolph, 2007). This sug-

gests that while lateral shank muscle co-contraction is increased in

KOA during all phases of the stance phase, increased thigh muscle co-

contraction only occurs when the osteoarthritic limb is fully loaded.

Non-pooled data of medial co-contraction indices suggests that me-

dial knee joint laxity may inuence the magnitude of medial co-

contraction 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 forcesacross the knee.

Non-pooled data of medial and lateral thigh muscle co-contraction

suggested disease severity might inuence the magnitude of co-

contraction (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 healthycontrols, in general and severe KOAco-

hortswhentheywalked 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

Table 2

Modied quality index.

Reporting External validity Internal validity - bias Internal validity - confounding

Publication

1.Hypothesis

clearlydescribed?

2.Mainoutco

mesclearly

described?

3.C

haracteristicsofthepatients

includedclearlydescribed?

5.D

istributionofprinciple

confoundero

feachgroupclearly

described?a

6.Mainfindingsclearly

described?

7.Estimateso

frandom

variabilityprovidedforthemain

outcomes?

10.Actualprobabilityvalues

reportedformainoutcomes?

11.Werethe

subjectsaskedto

participatere

presentativeofthe

entirepopula

tion?

12.Werethe

subjectswhowere

preparedtop

articipate

representativ

eoftheentire

15.Wasthereanattempttoblind

thosemeasur

ingthemain

outcomes?

16.Wasitcle

ariftheresults

werebasedondatadredging

18.Werethe

statisticaltests

appropriate?

20.Werethe

mainoutcome

measuresvalidandreliable?

21.Wereallp

atientsandcontrols

recruitedfrom

thesame

population?

22.Wereallp

atientsand

controlsrecruitedoverthesame

timeperiod?

25.Wastheir

adequate

adjustmentforconfounding?

b

Total(17)

Astephen et al. (2008) 1 1 0 2 0 1 1 0 0 0 1 1 1 0 0 0 9

Childs et al. (2004) 1 1 1 2 1 1 1 0 0 0 1 1 0 0 0 0 10

Heiden et al. (2009) 1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 1 11

Hortobgyi et al. (2005) 1 1 1 1 1 1 0 0 0 0 1 1 1 0 0 0 9

Hubley-Kozey et al. (2006) 1 1 1 2 1 1 1 0 0 0 1 1 1 1 0 0 12

Hubley-Kozey et al. (2009) 1 1 1 2 1 0 0 0 0 0 1 1 1 0 1 0 10

Lewek et al. (2004) 1 1 1 2 1 1 1 0 0 0 1 1 1 0 0 1 12

Lewek et al. (2006) 1 1 1 2 1 1 1 0 0 0 1 0 1 0 0 1 11

Liikavanio et al. (2010) 1 1 1 2 1 1 0 0 0 0 1 1 0 1 0 1 11

Rudolph et al. (2007) 1 1 1 2 1 1 1 0 0 0 1 1 1 0 0 1 11

Rutherford et al. (2010) 1 1 1 1 1 1 1 0 0 0 1 1 1 0 0 0 10

Rutherford et al. (2011) 1 1 1 2 1 1 1 0 0 0 1 1 1 0 1 1 13

Schmitt and Rudolph (2007) 1 1 1 2 1 1 1 0 0 0 1 1 1 1 0 0 12

Zeni et al. (2010) 1 1 0 1 1 1 1 0 0 0 1 1 1 0 0 1 10

Kappa levels of agreement 0.98 1.0 0.63 1.0 0.98 1.0 1.0 0.98 0.97 0.97 1.0 0.44 1.0 1.0 1.0 0.56 0.877

Allitems,except item5, were scored1 forfullling thecriterionor 0 ifthe criterion were notlled. Publications that didnot providesufcient detailsto fulll thecriterionwere alsogivena

0 for unable to be determined as perinstructions of theoriginal index. Kappa scores indicate level of initialagreementbetween reviewers prior to theconsensus meeting. Thetotal kappa

score indicates overall level of agreement.a Thiscategorywas interpretedas theKOA diagnosis being clearlydescribedwithrespect to radiographic severity, clinicalseverityand mechanicalalignment.If allthreeof thecriteria were

described, 2 points were awarded for yes. If two of the criteria were described, 1 point was awarded forpartially.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.



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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 resultmay be dueto thestudies using differ-

ent muscles in their calculations of co-contraction or due to calculating

co-contraction using different equations.

3.4. Muscle amplitude

Ten studiesexamined 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 investi-

gated. The potential inuence of disease severity was the focus of sever-

al publications and walking data from those with general, mild,

moderate and severe KOA were examined. ES, calculated from differ-

ences 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 ampli-

tude alteration associated with moderate KOA(Fig. 2B). While this nd-

ings 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 andHeiden et al. (2009)reported a

net increase in muscle amplitude (Table 3). This suggests that if individ-

uals 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 pooleddata 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 am-

plitude in individuals with KOA regardless of disease severity or joint

laxity. This suggests that increases in VL and RF amplitude are consis-

tently associated with KOA regardless of disease severity or joint laxity.

VM mean and net amplitude was only reported to be increased in stud-

ies examining general and predominantly mild KOA cohorts (Heiden

et al., 2009; Liikavainio et al., 2010; Schmitt and Rudolph, 2007).

There was no increasein VM mean amplitude in moderate or severe co-

horts compared with controls (Hubley-Kozeyet al.,2006; Rudolphet 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 (ES1.18 (0.67 to 1.7) I2 = 0%)(Fig. 2B). This nding was supported by a

Schmitt and Rudolph (2007),investigating differences in mean ampli-

tude between a predominantly mild KOA cohort and controls. For gen-

eral andsevere KOAcohorts, 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 ampli-

tude 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;

Rutherford et al., 2011; Zeni et al., 2010). As with KOA-control compar-

isons, 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 wasno differ-

ence 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 mod-

erately 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 be-

tween individuals withKOA and controls. Comparisons of gastrocnemi-

us, 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 du-

rations 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; Ruth-

erford 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 gas-

trocnemius duration between individuals with severe KOA and controls

reported those with severe KOA exhibited longer duration with MG acti-

vating 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 onestudy (Rutherford et al., 2011), hamstringactivity 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 moder-

ate 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. Specical-

ly, pooled resultsdemonstrated that individuals withmoderate KOA con-

sistently 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

719K. Mills et al. / Clinical Biomechanics 28 (2013) 713724


8/12

non-pooled data cannot provide the precision of meta-analysis, the num-

ber of studies reporting elevated lateral muscle co-contraction and

prolonged VL,RF and hamstring duration suggests thatthese arealso con-

sistently 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 muscleco-contractionas it wasonlyconsistent-

ly observed in individuals with laxity, regardless of disease severity. Dis-

ease severity does appear to inuence the presence of increased medial:

lateral muscleco-contraction, as it was only signi

cantlyincreased, acrossa range of walking speeds,in those with moderate KOA (Zeni et al., 2010).

Concurrent increases in medial and lateral muscle amplitudes, as ob-

served inthe general KOA group(Liikavainio et al.,2010), could potential-

ly 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 wasa concurrent increase in medialandlateralmuscleampli-

tudes (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 co-

contraction indices were signicantly greater than controls for individ-

uals with medial knee joint laxity (Hubley-Kozey et al., 2009; Lewek

et al., 2004, 2006; Schmitt and Rudolph, 2007). This suggests that onlythose individuals who have a lack of medial passive knee support, poten-

tially 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 se-

verity. This could also be an attempt to protect and stabilize the knee.

However, current evidence questions the efcacy of increased neuro-

muscular 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 hasrecently been correlated with increasedloss of medi-

al knee cartilage volume (Hodges et al., 2012). Interestingly, it is possi-

ble for increased neuromuscular activity of medial and lateral knee

muscles as well as RF to co-exist as demonstrated in a severeKOA 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 systematiceffect. The con-

sistencyof neuromuscularalterations wasdeterminedbasedon thepresence of a systematiceffectanda low I2 index. (A)PooledES forco-contraction indices.(B) PooledES foramplitude.

Amplitude ES was calculated from mean (SD) factor scores of principal components so mean differences were not calculated.



9/12

Table 3

Results of included papers.

Authors Variable Knee OA Comparator Result/mean difference (95% CI) and effect size (ES)

Co-contraction index

Childs et al. (2004) VL:BF (% MVIC) General OA Control 13.0 (2.37 to 23.63) ES 0.68

TA:MG (% MVIC) 9.0 (4.17 to 13.83) ES1.04

Heiden et al. (2009) Muscles: lateral muscles

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

General OA Control 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

SM:BF (% MVIC) OA group exhibited greater co-contraction during loading, early and midstance.BF activation was the major contributor to the co-contraction index.

Knee exors: knee extensors

(SM, BF, MG, LG:VL, VM, RF %

MVIC)

OA group exhibited greater co-contraction during midstance. There was no

difference between groups during loading and early stance.

Hortobgyi et al. (2005) 200 ms prior to IC to toe-off General OA Control

BF:VL (% MVIC) 41.0 (23.85 to 58.15) ES 1.26

LG:TA (% MVIC) 40 (15.95 to 64.05) ES 0.9

Hubley-Kozey et al.

(2009)

100 ms prior to IC to peak KAM

VL:BF (% MVIC) Moderate Control 10.17 (4.39 to 15.94) ES 0.66

Sever e Control 23 .49 (17 .07 to 2 9.9) ES 1.52

Moderate Severe 13.32 (21.52 to 5.12) ES 0.62

VL:LG (% MVIC) Moderate Control 2.16 (0.69 to 5.02) ES 0.28

Severe Con trol 9. 57 (5.72 to 13.42) ES 1.01


VM:SM (% MVIC) Moderate Control 4.46 (0.73 to 9.65) ES 0.32

Severe Con trol 7. 6 (3.26 to 11.94) ES 0.32

Moderate Severe

3.14 (

9.05 to 2.77) ES

0.2VM:MG (% MVIC) Moderate Control 1.22 (1.27 to 3.71) ES 0.18

Severe Control 6.88 (10.21 to 3.64) ES 0.85


Lewek et al. (2004) 100 ms prior to IC to peak KAM

VL:BF (% MVIC) Moderate

(varus and lax)

Con tro l 5.7 (2.55 to 13.95) ES0.53

VL:LG (% MVIC) 2.8 (3.21 to 8.81) ES 0.36

VM:SM (% MVIC) 0.4 (7.13 to 6.33) ES 0.05

VM:MG (% MVIC) 6.3 (0.5 to 12.1) ES 0.84

Lewek et al. (2006) Preparation Moderate

(varus and lax)

Control

VL:BF (% MVIC) 4.6 (2.63 to 11.83) ES 0.44

VL:LG (% MVIC) 2.9 (2.9 to 8.7) ES 0.35

VM:SM (% MVIC) 0.7 (6.24 to 4.84) ES 0.09

VM:MG (% MVIC) 6.2 (1.01 to 11.39) ES 0.83

Liikavainio et al. (2010) VM: BF (% Max) G eneralOA (var us) C ontrol No d ifferenc e between groups

Rudolph et al. (2007) 100 ms prior to IC to peak KAM Moderate (varus) Control No difference between groups

VL:BF (% MVIC)VL:LG (% MVIC)

VM:SM (% MVIC)

VM:MG (% MVIC)

Schmitt and Rudolph

(2007)

Preparation and weight

acceptance

Mild

(varus and lax)

Control

VL:BF (% Max) No difference between groups

VL:LG (% Max) OA group exhibited a trend towards greater co-contraction during preparation

and signicantly higher co-contraction during weight acceptance.

VM:SM (% Max) OA group exhibited a trend towards greater co-contraction during preparation

and signicantly higher co-contraction during weight acceptance.

VM:MG (% Max) No difference between groups

Midstance OA group exhibited higher co-contraction for all muscles

Zeni et al. (2010) VL:SM (% MVIC) (1.0 m/s) Moderate Control 12.4 (5.81 to 18.99) ES 1.29

Severe Control 11.5 (2.21 to 20.79) E S 1.33


VL:SM (% MVIC) (PW) Moderate Control 11.7 (4.81 to 18.59) E S 1.16

Severe Control 6.8 (2.51 to 16.11) ES 0.75Moderate Severe 4.9 (5.85 to 15.65) ES 0.37

VL:SM (% MVIC) (FW) Moderate Control 14.4 (5. 27 to 23.53) ES 1.08

Severe Control 6.2 (2.24 to 14.64) ES0.72


Muscle amplitude

Astephen et al. (2008) Gastrocnemius (LG, MG % MVIC) Moderate Control No difference between groups

Severe C ontrol No d if ferenc e between groups

Moderate Severe Severe OA group exhibited higher mean MG amplitude in early stance and in

swing phase and lower mean amplitude in late stance.

Quadriceps (VL, VM, RF % MVIC) Moderate Control Mean RF amplitude was higher in moderate OA group throughout the majority

of stance and late swing.

Severe Control Mean RF amplitude was lower in severe OA group during early stance and early

swing but higher mean amplitude in mid to late stance.

Moder ate Sever e No d if ferenc e between groups

(continued on next page)



10/12

Table 3(continued)


Hamstrings (BF, SM % MVIC) Moderate Control No difference between groups

Severe Control Mean SM and BF amplitude was higher in severe OA group during stance.

Moderate Severe No difference between groups

Heiden et al. (2009) Net muscle activity of

BF, SM, VL, RF, VL, MG, LG (%

MVIC)

General OA Control OA group exhibited signicantly greater net muscle activation during weight

acceptance and early stance compared with controls

Hortobgyi et al.

(2005)

BF (% of MVIC) General OA Control 47 (28.18 to 65.82) ES 1.27

VL (% of MVIC) 47 (20.53 to 59.47) ES 1.09

Hubley-Kozey et al.

(2006)

Gastrocnemius (MG, LG % MVIC) Moderate Control 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.

Quadriceps (RF, VL, VM % MVIC) 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.

Hamstrings (BF, SM % MVIC) Mean B F amplitude w as h igher a nd p eak a mplitude o ccurred p rior t o heel s trike i n

OA group compared with controls. Mean BF amplitude was higher than SM for

both groups.

Liikavainio et al.

(2010)

BF (% Max) General OA Control OA group exhibited signicantly higher mean BF amplitude at IC, except when

walking fast.

VM (% Max) Mean VM amplitude in late stance and early swing were signicantly greater in

the OA group for all gait speeds

Rudolph et al. (2007) VL, VM, BF, SM LG, MG (% MVIC) Moderate

(varus)

Control Tendency towards greater mean MG activity in the OA group. No other difference

between groups.

Rutherford et al.

(2010)

Gastrocnemius (MG, LG % MVIC) Moderate Control OA group exhibited moderately less difference between early and late stance

activity than controls for MG activity (ES 0.68) and a moderate tendency ofsmaller difference in LG activity (ES 0.63)

Quadriceps (VL, VM, RF % MVIC) 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.

Ha mstrings ( BF, SM % MVI C) OA group exhib ited which w as m od erately great er overall a mp litu de of B F 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)

Rutherford et al.

(2011)

Gastrocnemius (MG, LG % MVIC) Moderate Control OA group exhibited moderately smaller difference between early and late stance

amplitude (ES 0.83)

Severe Control OA group exhibited large reductions in late stanceearly stance amplitude

differential for MG (ES 1.26) and LG (ES 1.21)

Severe Moderate Moderate OA group exhibited moderately greater mean MG amplitude (ES 0.74)

and moderately larger difference between early and latestance amplitude (ES 0.91).

Quadriceps (RF, VM, VL % MVIC) Severe Control DifferenceinRFamplitudebetweenearlyandmidlatestancewas moderatelylower

in OA group (ES 0.89). Difference between mid

late stance and swing phaseamplitude was moderately higher in OA group for VL (ES 0.82) and RF (ES 0.83).

Moderate Severe 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)

Hamstrings (BF, SM % MVIC) Moderate Control OAgroup exhibited moderate reduction inmean SMamplitude duringmidstance

and late swing burst (P= 0.05, ES 0.69).

Severe Control OAgroup exhibited large reductionsin mean BFamplitude duringmidstance and

late swing burst (P= 0.00, ES 1.46).

Moderate Severe Moderate group exhibited moderately lower BF mean amplitude during

midstance and late swing burst (P= 0.04, ES 0.73)

Schmitt and Rudolph

(2007)

VL (% Max) Mild (varus and

lax)

C ontrol Signicantly greater mean amplitude in OA group during midstance

VM (% Max) Signicantly greater mean amplitude in OA group during weight acceptance and

midstance

BF (% Max) Trend towards greater mean amplitude in OA group during preparation,

signicantly greater mean amplitude during midstance

SM (% Max) Signicantly greater mean amplitude in OA group during weight acceptance

LG (% Max) Trend towards greater mean amplitude in OA group during preparation,

signicantly greater mean amplitude during weight acceptance

MG (% Max) No difference between groups

Sol (% Max) No difference between groups

Zeni et al. (2010) VL (mean % MVIC) (1.0 m/s) Moderate Control 16 (7.06 to 24.94) ES 1.24

Severe Control 10.3 (1.5 to 19.1) E S 1.29


V L (mean % MVI C) ( PW) Mod erate C ontrol 15 .5 ( 6.06 to 24.4 9) ES1 .14



V L (mean % MVI C) ( FW ) Mod erate C ontrol 18.4 ( 5.21 to 31 .5 9) ES 0 .9 7


Mod erate Severe 16.7 ( 2.28 to 31 .1 2) ES0 .73

VL (peak % MVIC) (1.0 m/s) Moderate Control 26.8 (10.99 to 42.61) ES 1.18



Muscle amplitude

Astephen et al. (2008)



11/12

included in this review, no conclusions can be drawn regarding the in-

teraction between the potentially negative effects of increased medial

knee muscle and RF activity and the potential positive effects of in-creased lateral activity. Future research is needed to determine how

this interaction affects KOA progression.

Along with the inability to draw conclusions regarding inuenceson

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 indi-

ces highlighting the numerous methods to achieve a single number.

As such, interpretation of this index is difcult unless there is also an in-

vestigation into how this number is reached. The relative contributions

of muscles involved in any co-contraction formula are of particular in-

terest to clinicians, particularly if the ratio contains both medial and lat-

eral 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 thendings of this

review is that the majority of studies normalized their neuromotor data

to MVIC. Normalizing EMGdata to MVIC provides information regarding

the relative degree of muscle activation and facilitates comparisons be-

tween groups. However, in injured and post-operativepatients, the abil-

ity 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 physi-

cal 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 pro-

duce an accurate MVIC and subsequent signicant differences in neuro-

muscular activity may be erroneous. Conversely, reported increases in

Table 3(continued)


VL ( peak % MVIC) (PW) Moder ate Control 23 .7 (7.31 to 40 .0 2) ES 1 .0 1



VL ( peak % MVIC) (FW) Moder ate C ontrol 40 .20 (14 .31 to 6 6.09 ) ES 1.08


Moder ate Sever e 38 .8 (11.21 to 6 6.39) ES 0.86

SM (mean % MVIC) (1.0 m/s) Moderate Control 8.9 (1.64 to 16.16) ES 0.84



SM (mean % MVI C) ( PW) Moder ate C ontrol 8.0 (2 .18 to 1 3.82 ) ES 0 .92

Severe Control 10.0 (5.02 to 25.02)


SM (mean % MVI C) ( FW) Moder ate Control 8.6 (1.3 9 to 1 5.81 ) ES 0 .81



SM (peak % MVIC) (1.0 m/s) Moderate Control 16.5 (4.7 to 28.3) ES 0.96

S ev ere Control 17.5 (2.78 to 32.22) ES 1.25


SM (peak % MVI C) ( PW) Mod er ate Control 14 .7 (2.53 to 26 .8 7) ES 0.8 1



SM (peak % MVIC) (FW) Moderate Control 12.7 (1.0 to 26.40) ES 0.62



Muscle activity duration

Astephen et al. (2008) Gastrocnemius (MG) Moderate Control MG was active for the majority of the gait cycle in severe OA group whereas

moderate

Sever e OA group and c ontr ols exhibited MG ac tivity during late stance.

Childs et al. (2004) VL (ms) General OA Control 165 (82.98 to 247.02) ES 1.12

SM (ms) 167 (99.89 to 234.11) ES 1.38

TA (ms) 158 (108.92 to 207.08) ES 1.79

MG (ms) 140 (59.27 to 220.73) ES 0.97

Hubley-Kozey et al.

(2006)

Gastrocnemius (MG, LG) Moderate Control There was no difference in temporal characteristics of LG or MG.

Quadriceps (RF, V L, VM) VL and RF a ctivities wer e prolonged during mid- to lat e-sta nce. T here wa s no

change in temporal characteristics for VM.

Hamstrings (BF, S M) BF activity was highe r and prolon ged in OA group compared with con trols. BF

activity was higher than SM for both groups.

Rutherford et al. (2010) Gastrocnemius (MG, LG) Moderate Control No phase differences between groups for MG and LG

Quadriceps (VL, VM, RF) No phase shift between groups for VL, VM and RF

Hamstrings (BF, SM) Duration o f BF and SM activities w as moderately p rolonged in O A group compared

with controls (ES 1.16 and 0.91)

Rutherford et al. (2011) Gastrocnemius (MG, LG % MVIC) Moderate Control MG onset was moderately earlier than LG onset for both groups (OA:ES 1.18.

Control:ES 1.01).

Severe Control OA group exhibited moderately later MG onset compared with controls (ES 1.1)

Moderate Severe Severe group exhibited largely later MG onset than moderate group (ES1.2)

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.

Muscle amplitude

Zeni et al. (2010)



12/12

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 investi-

gation is needed into the association between pain, KOA severity and

neuromuscular control during gait.

5. Conclusion

Pooled and non-pooled data from moderate quality observationalstudies demonstrate individuals with KOA exhibit altered lower limb

neuromuscular activity during gait compared with healthy controls. In-

dividuals 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 activ-

ity of RF was also increased and prolonged for many KOA cohorts and

medial knee muscle activity was also increased. Based on current evi-

dence, this suggests thatindividuals with KOAare 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 degener-

ative neuromuscular pattern occur simultaneously. Therefore, while re-

sults 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 pro-

gression, future research into the efcacy of such a program is needed.

Such research needs to further investigate how simultaneous up-

regulation in medial and lateral knee muscle activities inuences dis-

ease 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 au-

thors declare no conicts of interest.

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