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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Objective

To identify which gait deviations are consistently associated with knee osteoarthritis (KOA) and how these are influenced by disease severity, the involved compartment, and sex.

Methods

Five electronic databases and reference lists of publications were searched. Cross-sectional, observational studies comparing temporospatial variables, joint kinematics, and joint moments between individuals with KOA and healthy controls or between KOA subgroups were considered for review. Only publications scoring ≥50% on a modified methodology quality index were included. Because of the number of gait deviations examined, only biomechanical variables reported by ≥4 publications were further analyzed. Where possible, a meta-analysis was performed using effect sizes (ES) calculated from discrete variables.

Results

In total, 41 publications examining 20 variables were included. The majority of consistent gait deviations associated with KOA were exhibited by those with severe disease in the temporospatial domain. Individuals with severe KOA exhibited greater stride duration than controls (ES 1.35 [95% confidence interval (95% CI) 1.03, 1.67]) and a decrease in cadence (ES −0.75 [95% CI −1.12, −0.39]) compared with controls. The evidence for kinematic and joint moment change was primarily limited or conflicting. There was a lack of evidence for alterations in the external knee adduction moment.

Conclusion

Individuals with KOA exhibit a range of gait deviations compared with controls. Despite its common usage in KOA gait studies, we did not find consistent evidence that knee adduction moment differs between those with and without KOA or between disease severity levels. Further research examining the reasons for a lack of difference in many gait variables in those with knee OA is needed.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Knee osteoarthritis (KOA) is a common, chronic joint disease where alterations in gait biomechanics are frequently observed. Disease characteristics such as joint pain and swelling as well as muscle dysfunction are potential factors commonly cited as associated with these gait alterations ([1, 2]). The large number of cross-sectional studies investigating biomechanical changes during gait have demonstrated that individuals with KOA adopt a wide variety of patterns of locomotion depending on their disease severity, sex, or which compartment is primarily affected ([3-5]). This diversity underlines the need for synthesis of evidence to inform clinicians which gait alterations they can primarily expect their KOA patients to exhibit. To examine the type and magnitude of biomechanical gait deviations associated with KOA during level walking, we reviewed cross-sectional observational studies comparing individuals with KOA with matched or similar healthy controls. To examine the influence of disease severity, the involved compartment, and sex on such gait deviations, we reviewed cross-sectional studies comparing differing KOA subgroups. Our aim was to identify which gait deviations are consistently associated with KOA.

Box 1. Significance & Innovations

  • This review presents the first systematic synthesis of available literature for the purpose of identifying consistent temporospatial, kinematic, and joint moment gait alterations exhibited by individuals with knee osteoarthritis.
  • This review indicates that most consistent gait deviations occur in people with more severe disease and that changes in the spatiotemporal characteristics of gait are common.
  • A significant finding of this review is that the external knee adduction moment is not consistently increased in individuals with knee osteoarthritis regardless of their disease severity or lower extremity alignment.
  • This review highlights the need for a standardized knee osteoarthritis classification system that encompasses radiographic, clinical, and mechanical alignment measures in order to facilitate further comparisons between studies.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Literature search strategy

A literature search strategy was devised for electronic databases (Medline, CINAHL, SPORTDiscus, PubMed, and Embase) with no publication, language, or date restrictions, with the last search conducted on June 10, 2012. The search strategy was as follows (identical for all databases): 1) ‘knee osteoarthr*’ or gonarthr*, 2) gait or walking, 3) 1 and 2 and kinematics, 4) 1 and 2 and kinetics, 5) 1 and 2 and load, 6) 1 and 2 and mechanics or biomechanics, 7) 6 and leg or lower limb, and 8) 6 and trunk. Titles and abstracts were screened in the initial search, with the full text of publications meeting the initial inclusion criteria retrieved for further screening. Reference lists of all publications considered for inclusion were hand searched recursively until no additional eligible publications were identified. One reviewer conducted the literature search (KM) and 2 reviewers (KM and MAH) determined the final eligibility of the selected publications.

Selection criteria

Cross-sectional, human-based observational studies comparing level walking biomechanics of individuals with KOA with healthy controls or between differing KOA subgroups (e.g., disease severity, the involved compartment, sex, etc.) were considered for inclusion. No restriction was placed on disease severity, sex, or the involved compartment. Studies permitting participants to walk with walking aids or including participants with confirmed OA in lower extremity joints other than the knee or participants who had undergone total joint arthroplasty were excluded. Similarly, because biomechanical changes in gait can occur as part of the normal aging process ([6]), comparisons between individuals with KOA and healthy controls where the average between-group age discrepancies exceeded 30 years were excluded. Studies were also excluded if biomechanical comparisons were not the main focus orif they utilized mathematical modeling or 2-dimensional motion analysis. The latter criterion was due to movement in the frontal plane being strongly affected by alignment of the foot in the transverse plane ([7]).

To avoid bias that can be introduced through duplicate data, all publications were juxtaposed for author names, affiliations, and participant characteristics. Where identical authors, outcome variables, and exact participant number, age, weight, and sex ratio occurred, the results of publications with the lower methodologic quality score were excluded from further analysis.

Methodology quality

Publications that met the inclusion criteria were assessed for methodologic bias by 2 independent reviewers (KM and MAH), one of whom was blinded to the author, title, affiliation, and journal. Because only observational studies were assessed, a modified version ([8]) of a quality index for nonrandomized trials ([9]) was used. This version contains 16 items (items 1–3, 5–7, 10–12, 15, 16, 18, 20–22, and 25 of the original index) assessing reporting (items 1–3, 5–7, and 10), external validity (items 11 and 12), and internal validity (bias and confounding; items 15, 16, 18, 20–22, and 25). The modified version does not include items related to the validity of the intervention (items 4, 8, 9, 13, 14, 17, 19, 23, 24, 26, and 27), but still includes items detailing the blinding of observers. The quality index awards a point for each item, with the exception of item 5, which awards 2 points for “yes.” For negative items or items unable to be determined, no points are awarded. The maximum score for the modified index is 17 points. The agreement between reviewers was assessed using a kappa statistic, referenced to Hopkins' criteria of very small (0 to 0.1), small (0.11 to 0.3), moderate (0.31 to 0.5), high (0.51 to 0.7), very high (0.71 to 0.9), and almost perfect to perfect (0.91 to 1.0) ([10]). Disagreements were discussed at a consensus meeting. Publications scoring <50% on the quality index were excluded from further analysis ([11]) (Table 1).

Table 1. Quality index*
Author, year (ref.)Reporting itemExternal validity itemInternal validity: bias itemInternal validity: confounding itemTotal (17)
1235a6710111215161820212225
  1. Includes quality scores for publications that were subsequently excluded from further analysis.

  2. a

    This category was interpreted as the knee osteoarthritis diagnosis being clearly described with respect to radiographic severity, clinical severity, and mechanical alignment. If all 3 of the criteria were described, 2 points were awarded for “yes”; if 2 of the criteria were described, 1 point was awarded for “partially.”

Astephen et al, 2008 ([16])11121100001010009
Baliunas et al, 2002 ([41])111111100010100110
Bejek et al, 2005 ([31])11121100001010009
Butler et al, 2011 ([21])111111100011100111
Chen et al, 2003 ([17])11011100001111009
Childs et al, 2004 ([56])111211100011000010
Creaby et al, 2012 ([42])111211100011110113
Deluzio and Astephen, 2007 ([32])11101110001110009
Gök et al, 2002 ([38])111111100010110010
Heiden et al, 2009 ([22])111111100011100111
Huang et al, 2008 ([18])111211100011100112
Hubley-Kozey et al, 2006 ([30])111211100011110012
Hubley-Kozey et al, 2009 ([26])111210000011101010
Hunt et al, 2010 ([19])111211100011100112
Hurwitz et al, 2002 ([40])111210100011100111
Kaufman et al, 2001 ([45])111011100011110111
Kean et al, 2012 ([43])111211100011100112
Ko et al, 2011 ([44])111010100011111111
Krackow et al, 2011 ([59])111111100011100111
Landry et al, 2007 ([34])111210000011100110
Levinger et al, 2012 ([23])111211100011100112
Lewek et al, 2004 ([20])111211100011100112
Lewek et al, 2006 ([29])111211100010100111
Liikavainio et al, 2010 ([60])111211000011010111
Linley et al, 2010 ([35])111211100010110011
Manetta et al, 2002 ([24])111111100011110011
McGibbon and Krebs, 2002 ([61])11101100001110019
McKean et al, 2007 ([36])11110110001110009
Messier et al, 2005 ([47])111111100011100111
Mündermann et al, 2005 ([33])111110100011100110
Rudolph et al, 2007 ([6])111111100011100111
Rutherford et al, 2008 ([25])111210000011111112
Rutherford et al, 2011 ([27])111211100011101113
Sahai et al, 2003 ([46])111101100011110010
Schmitt and Rudolph, 2007 ([39])111211100011110012
Sims et al, 2009 ([4])111211100011111013
Weidow et al, 2006 ([5])11121010001010009
Zeni and Higginson, 2009 ([3])111211100011100112
Zeni and Higginson, 2009 ([37])111211100011110113
Zeni et al, 2010 ([28])110111100011100110
Zeni and Higginson, 2011 ([62])111211100011110113
Frequency of “yes”4647432642383600047384216526 
Frequency of “unable to be determined”0001700047474706321395 
Frequency of “no”1044591100003210316 

Data synthesis

One reviewer (KM) extracted group means, SDs, and sample sizes directly from publications and all reviewers checked the extracted data. These data were used to calculate point estimates of effect size (ES) and 95% confidence intervals (95% CIs; ES = mean difference/pooled SD). ES magnitudes were interpreted based on Hopkins' criteria ([12]) as trivial (0 to 0.2), small (0.21 to 0.6), moderate (0.61 to 1.2), and large (>1.2). Findings from principle component or principal pattern analysis were also extracted. When data were presented as the median and range, the mean and variability were estimated using methods described by Hozo et al ([13]). Authors of publications that did not provide data in an extractable form were contacted.

Based on the search strategy, biomechanical comparisons were categorized as temporospatial variables, joint kinematics, or joint moments. Within these categories, comparisons were divided into those comparing KOA cohorts and healthy controls and those comparing different KOA subgroups. KOA cohorts were further subdivided based on varus malalignment and disease severity. Inclusion in the varus malalignment subgroup was based on the KOA group exhibiting a significantly greater mechanical axis alignment (or other validated alignment measure) than controls. Disease severity was extracted directly from publications based on Kellgren/Lawrence (K/L) grades. The criteria for data pooling were met when publications included a range of severities within a single KOA cohort (i.e., general KOA) or when participants were the same across varus malalignment and disease severity. Comparisons were also made between unilateral and bilateral disease, medial and lateral compartment KOA, symptomatic and asymptomatic individuals, and males and females. Data pooling for these further comparisons was conducted only if the initial criteria of the same alignment and severity were met.

Data pooling was performed in Cochrane Review Manager, version 5.1, using the ES in a fixed-effects model. Evidence of heterogeneity, or consistency, between pooled results was assessed using the I2 index ([14]). Low, moderate, and high heterogeneity were assigned the thresholds of 25%, 50%, and 75%, respectively ([14]). Because this review did not include randomized controlled trials, we adapted the levels of evidence proposed by van Tulder et al ([15]). Evidence of gait deviations associated with KOA was interpreted as strong (large ES and 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), conflicting (high evidence of heterogeneity), and no evidence (95% CI of ES crossed zero).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Search strategy

Forty-seven publications were retrieved for consideration, and following quality assessment, 41 were eligible for review (Figure 1). Because these publications reported on 180 different biomechanical variables, a further analysis only on variables that were reported by ≥4 articles was conducted (Table 2). This reduced the number of biomechanical variables to 20.

image

Figure 1. Flow chart of the study selection process. KOA = knee osteoarthritis.

Download figure to PowerPoint

Table 2. Details of the included studies*
Author, year (ref.)OA cohortClinical measuresRadiographic changesaOA descriptionSeverityComparator cohort
  1. Values are the mean ± SD unless otherwise indicated. OA = osteoarthritis; BMI = body mass index; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index; ACR = American College of Rheumatology; HSS = Hospital for Special Surgery; VAS = visual analog scale; KOS = Knee Outcome Score; KOOS = Knee Osteoarthritis Outcome Score; SF-36 = Short Form 36.

  2. a

    Unless otherwise stated, radiographic changes are based on Kellgren/Lawrence grades: mild = ≤2, moderate = 3, and severe = 4.

Astephen et al, 2008 ([16])
  • Moderate: n = 60, M/F 40/20, age 58.32 ± 9.31 years, BMI 30.91 ± 5.17 kg/m2
  • Severe: n = 61, M/F 28/33, age 64.49 ± 7.75 years, BMI 32.05 ± 5.48 kg/m2
WOMAC
  • Moderate: mild
  • Severe: moderate
Predominantly medial compartment
  • Moderate
  • Severe
N = 60, M/F 23/37, age 50.27 ± 10.09 years, BMI 25.45 ± 4.04 kg/m2
Baliunas et al, 2002 ([41])N = 31, M/F 13/18, age 65 ± 9 years, height 1.68 ± 0.09 m, mass 76 ± 12 kgACR criteria, HSS functional knee evaluationMild to severe
  • Unilateral disease
  • Medial compartment
OA (varus)N = 31, M/F 13/18, age 62 ± 9 years, height 1.68 ± 12 m, mass 74 ± 16 kg
  Varus alignment 7° ± 4°    
Bejek et al, 2005 ([31])N = 20, M/F 8/12, age 68.2 ± 7.1 years, height 1.69 ± 0.11 m, mass 71.1 ± 11.9 kgHSS knee scoring systemSevereBilateral: most symptomatic kneeSevereN = 20, M/F 8/12, age 68.8 ± 9.1 years, height 1.69 ± 0.19 m, mass 73.3 ± 11.4 kg
Butler et al, 2011 ([21])Medial OA: n = 15, age 66.2 ± 7.9 years, BMI 32.2 ± 7.9 kg/m2Pain VASMild to severe
  • Unilateral
  • Medial and lateral compartments
OAN = 15, age 56.3 ± 10.7 years, BMI 27.8 ± 5.7 kg/m2
 Lateral OA: n = 15, age 65.7 ± 6.4 years, BMI 30.4 ± 7.5 kg/m2     
Chen et al, 2003 ([17])N = 20, M/F 0/20, age 65.5 ± 9.3 years, height 1.56 ± 0.7 m, weight 63.2 ± 10.6 kg Ahlback grade: moderate and severe changesBilateral diseaseModerate to severeN = 15, M/F 0/15, age 63.5 ± 11.3 years, height 1.59 ± 0.9 m, mass 62.6 ± 8.2 kg
Childs et al, 2004 ([56])N = 24, M/F 10/14, age 62 ± 10 years, BMI 30 ± 7 kg/m2ACR clinical criteria, WOMAC, KOS≥ Mild
  • Unilateral disease
  • All compartments
ModerateN = 24, M/F 10/14, age 62 ± 10 years, BMI 27 ± 6 kg/m2
Creaby et al, 2012 ([42])
  • Unilateral pain/unilateral radiograph: n = 11, M/F 6/5, age 64.5 ± 7.6 years, BMI 31.1 ± 3.8 kg/m2
  • Unilateral pain/bilateral radiograph: n = 22, M/F 10/12, age 65.1 ± 9.4 years, BMI 26.8 ± 5 kg/m2
  • Bilateral pain/bilateral radiograph: n = 56, M/F 29/24, age 64.5 ± 8 years, BMI 29.9 ± 4.1 kg/m2
  • Pain VAS
  • All groups varus aligned (i.e., <182°)
Mild, moderate, and severeUnilateral/bilateral diseaseOA (varus)N = 31, M/F 11/20, age 63.8 ± 8 years, height 1.67 ± 0.09 m, mass 71.3 ± 12.6 kg, BMI 25.5 ± 3.7 kg/m2
Deluzio and Astephen, 2007 ([32])N = 50, age 70 ± 7.8 years, mean BMI 29.2 kg/m2Scheduled for knee replacement  SevereN = 63, age 65 ± 8.5 years, mean BMI 28.81 kg/m2
Gök et al, 2002 ([38])N = 13, M/F 0/13, age 58 ± 11 years, height 1.57 ± 4.7 m, weight 72 ± 12 kgACR clinical criteriaAhlback grade: joint narrowing (mild changes)Medial compartmentMildN = 13, M/F 0/12, age 57 ± 8 years, height 1.57 ± 7.2 m, weight 77 ± 12 kg
Heiden et al, 2009 ([22])N = 54, M/F 24/30, age 65 ± 8 years, height 1.7 ± 0.09 m, mass 81.4 ± 14.2 kgKOOS and SF-36 BilateralOAN = 30, M/F 11/19, age 64 ± 6 years, height 1.7 ± 0.09 m, mass 81.4 ± 14.2 kg
Huang et al, 2008 ([18])
  • Mild: n = 15, M/F 6/9, age 63.1 ± 11.9 years, height 1.62 ± 0.06 m, mass 68.4 ± 10.3 kg
  • Severe: n = 15, M/F 2/13, age 63.1 ± 8.2 years, height 1.56 ± 0.09 m, mass 64 ± 8.5 kg
VAS and SF-36
  • Mild: mild
  • Severe: moderate and severe
  • Bilateral: most symptomatic knee
  • Medial compartment
Mild SevereN = 15, M/F 6/9, age 63.2 ± 9.9 years, height 1.59 ± 0.08 m, mass 60.5 ± 8.5 kg
Hubley-Kozey et al, 2006 ([30])N = 40, M/F 29/11, age 58.9 ± 8.07 years, BMI 29.94 ± 4.86 kg/m2WOMAC, SF-36, clinical examinationMild to moderateUnilateral diseaseModerateN = 38, M/F 17/21, age 51.08 ± 9.99 years, BMI 24.74 ± 4.25 kg/m2
Hubley-Kozey et al, 2009 ([26])
  • Moderate: n = 56, age 58.0 ± 8.7 years, BMI 30.8 ± 5.5 kg/m2
  • Severe: n = 48, age 63.7 ± 8.2 years, BMI 31.8 ± 5.3 kg/m2
  • Clinical examination
  • Severe group scheduled for total joint arthroplasty
  • Moderate: moderate
  • Severe: severe
Predominantly medial compartment
  • Moderate
  • Severe
N = 63, age 49.2 ± 9.7 years, BMI 25.1 ± 4.2 kg/m2
Hunt et al, 2010 ([19])
  • Mild: n = 25, M/F 10/15, age 61.2 ± 7.7 years, height 1.65 ± 0.08 m, mass 73.7 ± 14 kg
  • Moderate: n = 25, M/F 14/11, age 63.6 ± 8.4 years, height 1.67 ± 0.08 m, mass 78.4 ± 14.8 kg
  • Severe: n = 25, M/F 13/12, age 68 ± 6.6 years, height 1.68 ± 0.09 m, mass 81.7 ± 20.2 kg
  • WOMAC, 11-point knee pain scale
  • All groups varus aligned (i.e., <182°)
  • Mild
  • Moderate
  • Severe
Medial compartment
  • Mild (varus)
  • Moderate (varus)
  • Severe (varus)
N = 20, M/F 5/15, age 63.2 ± 12.4 years, height 1.65 ± 0.06 m, mass 69.3 ± 12.1 kg
Hurwitz et al, 2002 ([40])N = 62, M/F 32/30, age 62 ± 10 years, height 1.71 ± 0.11 m, mass 79 ± 12 kgVarus alignment −9° to 15°Mild to severe
  • Bilateral: most symptomatic knee
  • Primarily medial compartment
OA (varus)N = 49, M/F 24/25, age 59 ± 10 years, height 1.7 ± 0.1 m, mass 76 ± 16 kg
Kaufman et al, 2001 ([45])N = 92, M/F 0/92Clinical examinationDiagnosis confirmed by radiographs; no details provided regarding severity of changesBilateral: most symptomatic kneeOAN = 47, M/F 47/0
Kean et al, 2012 ([43])Mild: n = 87, age 62.3 ± 7.69 years, height 1.65 ± 0.09 m, mass 75.5 ± 15.3 kg
  • WOMAC pain, average walking pain
  • Mild varus: 182° ± 2.4°
  • Severe varus: 179.5° ± 3.0°
  • Mild
  • Severe
Medial compartment
  • Mild
  • Severe
Severe: n = 82, age 65.7 ± 8.0 years, height 1.69 ± 0.09 m, mass 84.6 ± 15.0 kg
Ko et al, 2011 ([44])
  • Symptomatic: n = 17, age 70.24 ± 8.49 years, BMI 28.08 ± 4.33 kg/m2
  • Asymptomatic: n = 24, age 72.33 ± 8.47 years, BMI 27.2 ± 4.31 kg/m2
Clinical examination modeled on ACRDiagnosis confirmed by radiographs; no details provided regarding severity of changes OAN = 112, age 67.69 ± 9.31 years, BMI 26.94 ± 4.34 kg/m2
Krackow et al, 2011 ([59])
  • No torsional deformity: n = 8, M/F 4/4, age 59 ± 11.34 years, height 1.74 ± 0.13 m, mass 101.5 ± 14.75 kg, BMI 33.84 ± 6.9 kg/m2
  • Torsional deformity: n = 6, M/F 5/1, age 61.83 ± 7.96 years, height 1.73 ± 0.1 m, mass 10.2 ± 14.18 kg
 Severe
  • Unilateral/bilateral disease
  • Medial compartment
SevereN = 10, M/F 5/5, age 62.5 ± 4.17 years, BMI 28.44 ± 4.23 kg/m2
Landry et al, 2007 ([34])N = 41, age 58.2 ± 8.3 years, BMI 30.3 ± 4.5 kg/m2On waiting list for arthroscopic surgeryMedian = mild MildN = 43, age 50.7 ± 10.2 years, BMI 24.8 ± 3.9 kg/m2
Levinger et al, 2012 ([23])N = 50, M/F 27/23, age 66.4 ± 7.6 years, BMI 29.6 ± 5.1 kg/m2WOMAC, VAS pain
  • Authors' own criteria
  • Mild to severe
 OAN = 28, M/F 13/15, age 65.1 ± 11.2 years, BMI 25.7 ± 3.9 kg/m2
Lewek et al, 2004 ([20])N = 12, M/F 6/6, age 50.3 ± 7.4 years
  • Scheduled for high tibial osteotomy
  • KOS, weight-bearing line 23.1% ± 10%
Confirmed joint space narrowing in medial compartmentMedial compartmentModerate (varus)N = 12, M/F 6/6, age 49.5 ± 6.1 years, weight-bearing line 46% ± 8.6%
Lewek et al, 2006 ([29])N = 15, M/F 9/6, age 48.7 ± 7.4 years, height 1.75 ± 0.09 m, mass 91.9 ± 17.4 kg
  • KOOS, clinical examination
  • Varus alignment: weight-bearing line 18.9% ± 12.7%
Confirmed joint space narrowing in medial compartment
  • Unilateral disease
  • Medial compartment
Moderate (varus)N = 15, M/F 9/6, age 48.4 ± 6.3 years, height 1.71 ± 0.9 m, mass 83.8 ± 17.3 kg Weight-bearing line 45.1% ± 8.1%
Liikavainio et al, 2010 ([60])N = 54, M/F 54/0, age 59 ± 5.3 years, BMI 29.7 ± 4.7 kg/m2
  • ACR clinical criteria, pain VAS
  • Varus alignment 5.2° ± 3.2°
Mild to severeUnilateral/bilateral: more symptomatic kneeOA (varus)N = 53, M/F 53/0, age 59.2 ± 4.7 years, BMI 27.1 ± 3.1 kg/m2, alignment 2.5° ± 2.0°
Linley et al, 2010 ([35])N = 40, M/F 17/23, age 63 ± 10 years, BMI 27.4 ± 5.5 kg/m2WOMAC scaleMedian = mild
  • Unilateral/bilateral: more symptomatic knee
  • Medial compartment
MildN = 40, M/F 17/23, age 64 ± 9 years, BMI 24.0 ± 3.2 kg/m2
Manetta et al, 2002 ([24])N = 10, M/F 10/0, age 68 ± 11 yearsWOMACNo radiographs taken OAN = 10, age 68 ± 11 years
McGibbon and Krebs, 2002 ([61])N = 13, M/F 2/11, age 72.9 ± 8.9 years Not reportedUnilateral diseaseOAN = 10, M/F 4/6, age 73.3 ± 4.6 years
McKean et al, 2007 ([36])N = 39, M/F 24/15 Women: age 58.32 ± 9.31 years, BMI 31.5 ± 5.2 kg/m2 Men: age 55.1 ± 12.8 years, BMI 29.7 ± 4.6 kg/m2WOMAC, clinical examinationMild to moderate Moderate
  • N = 42, M/F 18/24
  • Women: age 48.7 ± 10.3 years, BMI 24.4 ± 3.6 kg/m2 Men: age 52.2 ± 10.1 years, BMI 24.7 ± 3.2 kg/m2
Messier et al, 2005 ([47])N = 10, M/F 1/9, age 74.1 ± 1.49 years, mass 65.1 ± 2.61 kgACR clinical criteriaMild to severeAll compartmentsOAN = 10, M/F 1/9, age 73 ± 1.61 years, mass 58.3 ± 2.74 kg
Mündermann et al, 2005 ([33])
  • Mild: n = 19, M/F 6/13, age 65.2 ± 12.5 years, BMI 26.9 ± 3.1 kg/m2
  • Severe: n = 23, M/F 13/10, age 65 ± 8 years, BMI 27.8 ± 4.8 kg/m2
  • WOMAC
  • Mild: varus alignment 0.3°
  • Severe: varus alignment 5.7°
  • Mild: mild
  • Severe: moderate to severe
  • Bilateral: more symptomatic knee
  • Medial compartment
  • Mild
  • Severe (varus)
  • Less severe controls: n = 19, M/F 6/13, age 61.7 ± 12.3 years, BMI 26.1 ± 2.6 kg/m2
  • More severe controls: n = 23, M/F 13/10, age 63.7 ± 9.2 years, BMI 27.1 ± 4 kg/m2
Rudolph et al, 2007 ([6])N = 15, M/F 8/7, age 49.2 ± 4.5 years, BMI 30.7 ± 4.8 kg/m2
  • Scheduled for high tibial osteotomy
  • ACR clinical criteria
  • KOS
  • Varus alignment 6.33° ± 2.39°
Radiographs taken but not reported
  • Bilateral: more symptomatic knee
  • Medial compartment
Moderate (varus)N = 15, M/F 8/7, age 49.2 ± 4.25 years, BMI 28.7 ± 5.5 kg/m2
Rutherford et al, 2008 ([25])
  • Mild to moderate: n = 46, M/F 20/26, age 60 ± 9 years, BMI 31 ± 5 kg/m2
  • Severe: n = 44, M/F 20/24, age 67 ± 8 years, BMI 32 ± 5 kg/m2
Functional testing
  • Mild to moderate: mild to moderate
  • Severe: moderate to severe
Predominantly medial compartment
  • Mild to moderate
  • Severe
N = 50, M/F 32/18, age 53 ± 10 years, BMI 26 ± 4 kg/m2
Rutherford et al, 2011 ([27])
  • Moderate: n = 16, M/F 8/8, age 61 ± 6 years, BMI 31.3 ± 3.6 kg/m2
  • Severe: n = 15, M/F 10/5, age 61 ± 9 years, BMI 30.7 ± 5.4 kg/m2
Severe group scheduled for total joint arthroplasty WOMAC
  • Moderate: moderate
  • Severe: severe
Predominantly medial compartment
  • Moderate
  • Severe
N = 16, M/F 8/8, age 56 ± 6 years, BMI 24.6 ± 3.9 kg/m2
Sahai et al, 2003 ([46])N = 15, M/F 15/0, age 68 ± 11 yearsWOMACNo radiographs takenBilateral: average of extremities analyzedOAN = 13, M/F 13/0, age 68 ± 11 years
Schmitt and Rudolph, 2007 ([39])N = 28, M/F 14/14, age 60.4 ± 9.75 years, height 1.7 ± 0.11 m, mass 92.91 ± 16.16 kgKnee laxity assessed Varus alignment 174.82° ± 0.6° (<180° = varus)
  • Mild to severe
  • Mode: mild
  • Unilateral/bilateral disease: more symptomatic knee
  • Medial compartment
Mild (varus)
  • N = 26, M/F 13/13, age 58.5 ± 9.5 years, height 1.68 ± 0.11 m, mass 83.93 ± 1.85 kg
  • Alignment 179.24° ± 0.4°
Sims et al, 2009 ([4])N = 30, M/F 0/30, age 60.4 ± 9.81 years, height 1.63 ± 0.06 m, mass 88.2 ± 16.6 kg/m2ACR clinical criteria
  • Females: moderate
  • Males: severe
Bilateral: most symptomatic knee
  • Moderate
  • Severe
N = 26, M/F 26/0, age 63.69 ± 9.52 years, height 1.75 ± 0.07 m, mass 108.93 ± 18.44 kg
Weidow et al, 2006 ([5])
  • Medial: n = 15, M/F 0/15, age 66.27 ± 8.0 years, BMI 30 ± 5.07 kg/m2
  • Lateral: n = 15, M/F 0/15, age 71.07 ± 5.5 years, BMI 27.35 ± 3.95 kg/m2
On waiting list for total joint arthroplasty
  • Medial Ahlback grade median: severe changes
  • Lateral grade median: moderate changes
  • Bilateral: most symptomatic knee
  • Medial and lateral compartments
SevereN = 15, M/F 0/15, age 71.12 ± 6.5 years, BMI 26 ± 2.27 kg/m2
Zeni and Higginson, 2009 ([3])
  • Moderate: n = 22, age 62.9 ± 7.8 years, BMI 30.2 ± 4.6 kg/m2
  • Severe: n = 12, age 60.5 ± 9.5 years, BMI 30.7 ± 5.0 kg/m2
KOOS
  • Moderate: mild to moderate
  • Severe: severe changes
 
  • Moderate
  • Severe
N = 22, age 58.9 ± 11.4 years, BMI 24.9 ± 3.7 kg/m2
Zeni and Higginson, 2009 ([37])
  • Moderate: n = 21, age 63 ± 9.3 years, height 1.66 ± 0.08 m, mass 81.19 ± 12.5 kg
  • Severe: n = 13, age 59 ± 9.8 years, height 1.7 ± 0.11 m, mass 94.69 ± 15 kg
KOOS
  • Moderate: mild to moderate
  • Severe: severe
 
  • Moderate
  • Severe
N = 22, age 59 ± 11 years, height 1.65 ± 0.05 m, mass 68.81 ± 9.5 kg
Zeni et al, 2010 ([28])
  • Moderate: n = 16, M/F 6/10, age 62.8 ± 10 years
  • Severe: n = 8, M/F 3/5, age 62.2 ± 8 years
 
  • Moderate: mild to moderate
  • Severe: severe
Medial compartment
  • Moderate
  • Severe
N = 18, M/F 8/10, age 61 ± 11 years
Zeni and Higginson, 2011 ([62])N = 30, age 63 ± 7 years, height 1.71 ± 0.1 m, mass 86.83 ± 13.3 kgKOOS≥ Mild
  • Bilateral: most symptomatic knee
  • Compartment not defined
ModerateN = 15, age 58 ± 9 years, height 1.66 ± 0.05 m, mass 70.13 ± 8.5 kg

Methodologic quality

The initial agreement between reviewers in the present study was almost perfect (κ = 0.904) ([10]) and the reliability for individual items ranged from moderate (κ = 0.483 for item 18) to perfect (items 7–11 and 15). Consensus was reached for all items at the initial discussion between the 2 reviewers, and the maximum quality index score was 13 points, indicating publications were generally of low to moderate methodologic quality.

Temporospatial variables

The temporospatial variables examined were walking speed, stride length, stride duration, stance duration, and cadence. Twenty-seven publications examined differences in temporospatial variables between KOA and comparators and 16 publications made comparisons between KOA subgroups (Table 3 and Figure 2).

Table 3. Results of nonpooled data*
AuthorsOutcomeStudy groupComparatorMean difference (95% CI)ES
  1. 95% CI = 95% confidence interval; ES = effect size; OA = osteoarthritis; FW = fast walking; SS = self-selected speed; PCA = principle components analysis.

  2. a

    Authors did not provide estimates of variability.

  3. b

    All kinematic measurements are in degrees. All joint moments are external moments.

  4. c

    Authors did not provide measures of variance.

Temporospatial     
Butler et al, 2011 ([21])Walking speed, m/second
  • Lateral
  • Medial
  • Control
  • Lateral
  • −0.1 (−0.26, 0.06)
  • 0.00 (−0.72, 0.72)
  • 0.44
  • 0.0
Creaby et al, 2012 ([42])Walking speed, m/second
  • Unilateral
  • Bilateral
  • Control
  • Control
  • −0.27 (−0.37, 0.17)
  • −0.22 (−0.30, −0.14)
  • 1.59
  • 1.3
  Unilateral pain, bilateral OAControl−0.14 (−0.25, −0.03)0.7
  UnilateralBilateral−0.05 (−0.13, 0.03)0.32
  Unilateral pain, bilateral OABilateral0.08 (−0.02, 0.18)0.44
  UnilateralUnilateral pain, bilateral OA−0.13 (−0.25, 0.01)0.66
Gök et al, 2002 ([38])Stride duration, secondsMildControl0.1 (−0.2, 0.22)0.61
Huang et al, 2008 ([18])Cadence, steps/minuteMildSevere4.3 (−4.20, 12.80)0.35
 Stride length, % leg lengthMildSevere0.03 (−0.11, 0.17)0.15
 Walking speed, % heightMildSevere0.11 (−0.01, 0.23)0.65
Hunt et al, 2010 ([19])Walking speed, m/second
  • Mild (varus)
  • Mild (varus)
  • Control
  • Severe (varus)
  • −0.1 (−0.2, 0.0)
  • 0.11 (0.02, 0.2)
  • 0.6
  • 0.68
  Moderate (varus)Severe (varus)0.04 (−0.05, 0.13)0.24
Kaufman et al, 2001 ([45])Walking speed, m/secondFemalesMales−0.09 (−0.18, −0.52)0.17
Ko et al, 2011 ([44])Walking speed, m/second
  • Symptomatic OA
  • Asymptomatic
  • Control
  • Control
  • P = 0.153
  • P = 0.076
 
  Symptomatic OAAsymptomaticP = 0.99a 
Krackow et al, 2011 ([59])Walking speed, m/second
  • Severe (tibial torsion)
  • Severe
  • Control
  • Severe (tibial torsion)
  • −0.36 (−0.57, −0.15)
  • 0.1 (−0.11, 0.31)
  • 1.54
  • 0.46
Landry et al, 2007 ([34])Stance duration (FW), secondsMildControl0.02 (−0.01, 0.05)0.3
 Stride duration (FW), seconds  0.01 (−0.03, 0.05)0.1
 Stride length (FW), m  0.0 (−0.06, 0.06)0.0
 Walking speed (FW), m/second  −0.03 (−0.13, 0.07)0.12
Levinger et al, 2012 ([23])Stride lengthOAControl−0.2 (−0.25, −0.15)1.98
Liikavainio et al, 2010 ([60])Stride length (1.2 m/second)OA (varus)Control0.02 (−0.01, 0.05)0.28
 Stride length (1.5 m/second)OA (varus)Control0.0 (−0.03, 0.03)0.0
 Stride length (1.7 m/second)OA (varus)Control0.01 (−0.02, 0.04)0.11
Mündermann et al, 2005 ([33])Walking speed, m/secondMildSevere (varus)0.01 (−0.13, 0.15)0.04
Rutherford et al, 2008 ([25])Walking speed, m/second
  • Mild to moderate
  • Mild to moderate
  • Control
  • Severe
  • −0.07 (−0.15, 0.01)
  • 0.37 (0.27, 0.47)
  • 0.35
  • 1.6
Sahai et al, 2003 ([46])Walking speed, m/secondOAControl−0.34 (−0.53, −0.15)1.29
Sims et al, 2009 ([4])Stride length, % heightFemalesMales0.03 (−0.03, 0.05)0.26
 Walking speed, m/secondFemalesMales0.06 (−0.05, 0.17)0.28
Weidow et al, 2006 ([5])Cadence, strides/ minute
  • Lateral
  • Medial
  • Control
  • Lateral
  • −23.1 (−34.41, −11.79)
  • 6.4 (−6.13, 18.93)
  • 1.42
  • 0.36
 Stride length, mLateralControl−0.18 (−0.30, −0.06)1.02
  MedialLateral0.00 (−0.13, 0.13)0.00
 Walking speed, m/second
  • Lateral
  • Medial
  • Control
  • Lateral
  • −0.43 (−0.60, −0.26)
  • 0.12 (−0.02, 0.26)
  • 1.78
  • 0.6
Zeni and Higginson, 2009 ([3])Cadence (FW), steps/minute
  • Moderate
  • Severe
  • Control
  • Control
  • −9.45 (−17.86, −1.04)
  • −10.09 (−22.92, 2.74)
  • 0.65
  • 0.58
  ModerateSevere0.64 (−11.67, 12.95)0.04
 Cadence (SS), steps/minute
  • Moderate
  • Moderate
  • Control
  • Severe
  • −4.83 (−11.87, 2.21)
  • 3.1 (−9.72, 15.92)
  • 0.4
  • 0.19
 Cadence (1.0 m/second), steps/minute
  • Moderate
  • Severe
  • Control
  • Control
  • −1.28 (−6.36, 3.80)
  • 4.01 (−2.23, 10.25)
  • 0.15
  • 0.41
  ModerateSevere−5.29 (−10.95, 0.37)0.54
 Stride duration (FW), seconds
  • Moderate
  • Severe
  • Control
  • Control
  • 0.04 (−0.01, 0.09)
  • 0.1 (0.05, 0.15)
  • 0.49
  • 1.32
  ModerateSevere−0.06 (−0.11, −0.01)0.79
 Stride duration (1.0 m/second), seconds
  • Moderate
  • Severe
  • Control
  • Control
  • −0.02 (−0.07, 0.03)
  • −0.01 (−0.07, 0.05)
  • 0.23
  • 0.12
  ModerateSevere−0.01 (−0.07, 0.05)0.11
 Stride length (FW), seconds
  • Moderate
  • Severe
  • Control
  • Control
  • −19.57 (−30.38, −8.76)
  • −25.19 (−40.73, −9.65)
  • 1.05
  • 1.19
  ModerateSevere5.62 (−9.6, 20.84)0.28
 Stride length (1.0 m/second), cm
  • Moderate
  • Severe
  • Control
  • Control
  • −6.18 (−12.00, −0.36)
  • 0.51 (−9.51, 10.53)
  • 0.62
  • 0.04
  ModerateSevere−6.69 (−16.12, 2.74)0.58
 Walking speed (FW), m/second
  • Moderate
  • Severe
  • Control
  • Control
  • −0.22 (−0.34, −0.1)
  • −0.32 (−0.47, −0.17)
  • 1.05
  • 1.49
  ModerateSevere0.1 (−0.05, 0.25)0.48
Zeni et al, 2010 ([28])Walking speed (FW), m/second
  • Moderate
  • Severe
  • Control
  • Control
  • −0.22 (−0.36, −0.08)
  • −0.35 (−0.53, −0.17)
  • 1.02
  • 1.56
  ModerateSevere0.13 (−0.05, 0.31)0.62
Zeni and Higginson, 2011 ([62])Walking speed (FW), m/secondModerateControl−0.33 (−0.47, −0.19)1.47
Kinematicsa     
Astephen et al, 2008 ([16])Knee flexion peak during stance
  • Severe
  • Moderate
  • Control
  • Severe
  • −10.68 (−13.09, −8.27)
  • 5.98 (3.6, 8.36)
  • 1.57
  • 0.89
 Knee flexion excursionModerateControl−2.5 (−4.91, −0.09)0.37
  SevereControl−18.6 (−22.92, −14.28)1.52
  ModerateSevere16.1 (11.65, 20.55)1.28
 Knee peak flexionModerateControl−2.7 (−5.2, −0.2)0.38
  SevereControl−18.1 (−22.25, −13.95)1.53
  ModerateSevere15.4 (11.05, 19.75)1.25
Baliunas et al, 2002 ([41])Knee extension Knee range of motionOA (varus)Control
  • −3.0 (−5.25, −0.75)
  • −6.0 (−9.03, −2.97)
  • 0.65
  • 0.97
 Knee peak flexion  −3.0 (−6.25, 0.25)0.45
Bejek et al, 2005 ([31])Knee extension (1.0 m/second)SevereControl−7.4 (−8.35, 6.45)4.74
 Knee extension (2.0 m/second)  −8.5 (−9.38, −7.62)5.89
 Knee extension (3.0 m/second)  −8.7 (−9.38, −7.62)4.87
 Knee peak flexion (1.0 m/second)  −18.0 (−22.70, −13.3)2.33
 Knee peak flexion (2.0 m/second)  −23.1 (−26.42, −19.78)4.22
 Knee peak flexion (3.0 m/second)  −28.0 (−31.57, −24.43)4.77
 Knee range of motion (1.0 m/second)  −25.4 (−30.95, −19.85)2.78
 Knee range of motion (2.0 m/second)  −31.5 (−36.75, −26.25)3.64
 Knee range of motion (3.0 m/second)  −37.0 (−42.35, −31.65)4.87
Butler et al, 2011 ([21])Hip peak adduction
  • Medial
  • Lateral
  • Control
  • Control
  • −1.5 (−3.60, 0.60)
  • 1.4 (−1.0, 3.8)
  • 0.5
  • 0.41
  MedialLateral−2.9 (−5.04, −0.76)0.95
Creaby et al, 2012 ([42])Lateral trunk lean (average)
  • Unilateral
  • Unilateral pain, bilateral OA
  • Control
  • Control
  • 3.0 (2.53, 3.47)
  • 2.20 (1.85, 2.55)
  • 5.29
  • 4.46
  BilateralControl2.14 (1.88, 2.4)5.11
  UnilateralBilateral0.86 (0.41, 1.31)1.99
  Unilateral pain, bilateral OABilateral0.06 (−1.17, 1.29)0.15
  UnilateralUnilateral pain, bilateral OA0.8 (0.31, 1.29)1.31
 Knee peak flexionUnilateralControl−4.61 (−5.91, −3.31)2.94
  Unilateral pain, bilateral OAControl−6.71 (−7.67, −5.75)4.88
  BilateralControl−6.44 (−6.96, −5.92)5.89
  UnilateralBilateral1.83 (0.59, 3.07)1.54
  Unilateral pain, bilateral OABilateral−0.27 (−0.92, 0.38)0.24
  UnilateralUnilateral pain, bilateral OA1.23 (0.44, 2.02)0.21
Gök et al, 2002 ([38])Knee flexion peak during stanceMildControl−4.0 (−7.73, −0.27)0.8
Deluzio and Astephen, 2007 ([32])Knee range of motion Knee peak flexionSevereControlPCA: OA patients had less range of motion PCA: knees of OA patients were less flexed throughout the gait cycle 
Huang et al, 2008 ([18])Hip peak adduction
  • Mild
  • Mild
  • Control
  • Severe
  • −1.55 (−4.96, 1.86)
  • 1.48 (−1.65, 4.61)
  • 0.32
  • 0.33
 Knee flexion during loading (excursion)
  • Mild
  • Severe
  • Control
  • Control
  • −2.21 (−8.18, 3.76)
  • −7.48 (−13.08, −1.88)
  • 0.26
  • 0.93
  MildSevere5.27 (0.22, 10.32)0.73
Hunt et al, 2010 ([19])Lateral trunk lean (peak)
  • Mild (varus)
  • Moderate (varus)
  • Control
  • Control
  • 0.7 (−0.61, 2.01)
  • 1.5 (0.19, 2.81)
  • 0.31
  • 0.67
  Severe (varus)Control3.4 (2.04, 4.76)1.46
  Mild (varus)Moderate (varus)−0.8 (−1.91, 0.31)0.39
  Mild (varus)Severe (varus)−2.7 (−3.87, −1.53)1.26
  Moderate (varus)Severe (varus)−1.9 (−3.07, −0.73)0.89
 Hip peak adductionMild (varus)Control−0.8 (−2.79, 1.19)0.23
  Moderate (varus)Control−3.0 (−5.07, −0.93)0.81
  Severe (varus)Control−4.4 (−6.45, −2.35)1.21
  Mild (varus)Moderate (varus)2.2 (0.06, 4.34)0.56
  Mild (varus)Severe (varus)3.6 (1.49, 5.71)0.93
  Moderate (varus)Severe (varus)1.4 (−0.79, 3.59)0.35
Ko et al, 2011 ([44])Knee range of motionSymptomatic OAControlP = 0.403 
  AsymptomaticControlP = 0.207 
  Symptomatic OAAsymptomaticP = 0.987c 
Landry et al, 2007 ([34])Knee range of motion (FW) Knee range of motion (SS)MildControlPCA: walking faster increased knee range of motion and phase-shifted angles throughout the stride in both groups. No difference between groups 
Linley et al, 2010 ([35])Lateral trunk lean (peak)MildControl0.0 (−0.79, 0.79)0.00
Manetta et al, 2002 ([24])Knee flexion during loading (peak)OAControl−3.1 (−8.8, 2.6)0.46
McGibbon and Krebs, 2002 ([61])Knee range of motionOAControlPCA: OA patients extended knee in mid to late stance and flexed knee less in swing 
McKean et al, 2007 ([36])Knee flexion excursionMild to moderateControlPCA: OA patients exhibited smaller knee flexion angles throughout the entire gait cycle 
 Knee range of motionFemalesControls and malesPCA: females with OA exhibited less range of motion during stance phase than controls and males with OA 
Mündermann et al, 2005 ([33])Knee extension
  • Mild
  • Severe (varus)
  • Control
  • Control
  • −4.09 (−6.48, −1.70)
  • 2.32 (−3.91, 8.55)
  • 1.07
  • 0.21
  MildSevere (varus)−4.66 (−7.72, −1.60)0.87
 Knee flexion at initial contact
  • Mild
  • Severe (varus)
  • Control
  • Control
  • −7.08 (−11.93, −2.23)
  • −3.75 (−9.61, 2.09)
  • 0.91
  • 0.5
  MildSevere (varus)−2.68 (−4.83, −0.53)0.74
Rudolph et al, 2007 ([6])Knee flexion at initial contactModerate (varus)Control1.09 (−2.6, 4.78)0.21
Schmitt and Rudolph, 2007 ([39])Knee flexion excursionMild (varus)Control−2.6 (−4.98, −0.22)0.57
Sims et al, 2009 ([4])Knee range of motionFemalesMales0.94 (−2.37, 4.25)0.15
Weidow et al, 2006 ([5])Hip peak adduction
  • Lateral
  • Medial
  • Control
  • Lateral
  • 3.46 (2.15, 4.77) −9.53
  • (−10.78, −8.28)
  • 1.83
  • 5.29
 Knee peak extensionMedialControl5.67 (−8.3, −3.04)1.5
  LateralControl−5.0 (−7.39, −2.61)1.46
  MedialLateral−0.67 (−3.19, 1.85)0.19
 Knee peak flexionMedialControl−9.4 (−12.79, −6.01)1.93
  LateralControl−10.87 (−14.18, −7.56)2.29
  MedialLateral1.47 (−3.00, 5.94)0.23
Joint momentsb     
Astephen et al, 2008 ([16])Hip peak adduction moment stance, Nm/kg
  • Moderate
  • Moderate
  • Control
  • Severe
  • −0.18 (−0.28, −0.08)
  • 0.03 (−0.08, 0.14)
  • 0.66
  • 0.1
 Hip peak internal rotation moment, Nm/kg
  • Moderate
  • Moderate
  • Control
  • Severe
  • −0.04 (−0.07, 0.00)
  • 0.04 (0.02, 0.07)
  • 0.4
  • 0.62
 Knee peak flexion moment, Nm/kg
  • Moderate
  • Moderate
  • Control
  • Severe
  • −0.12 (−0.21, −0.03)
  • 0.07 (−0.00, 0.14)
  • 0.46
  • 0.33
 Knee peak internal rotation moment, Nm/kg
  • Moderate
  • Moderate
  • Control
  • Severe
  • −0.02 (−0.04, 0.00)
  • 0.07 (0.04, 0.1)
  • 0.32
  • 0.92
Baliunas et al, 2002 ([41])Knee peak adduction moment, Nm/kg and mOA (varus)ControlOA group was significantly higher (P = 0.003) 
Butler et al, 2011 ([21])Hip peak adduction moment, Nm/kg and m
  • Medial
  • Lateral
  • Medial
  • Control
  • Control
  • Lateral
  • 0.00 (−0.72, 0.72)
  • 0.03 (−0.05, 0.11)
  • −0.03 (−0.12, 0.06)
  • 0.00
  • 0.25
  • 0.24
 Knee peak adduction moment, Nm/kg and m
  • Lateral
  • Medial
  • Control
  • Lateral
  • −0.14 (−0.21, −0.07)
  • 0.23 (0.16, 0.3)
  • 1.42
  • 2.33
Creaby et al, 2012 ([42])Knee peak adduction moment, Nm/kg and m
  • Unilateral
  • Unilateral pain, bilateral OA
  • Control
  • Control
  • −0.19 (−0.38, 0.0)
  • −0.1 (−0.21, 0.0)
  • 0.84
  • 0.5
  BilateralControl−0.26 (−0.34, −0.18)1.67
  UnilateralBilateral0.07 (−0.11, 0.25)0.41
  Unilateral pain, bilateral OABilateral0.16 (−0.07, 0.25)1.01
  UnilateralUnilateral pain, bilateral OA−0.09 (−0.29, 0.11)0.36
 Knee peak flexion moment, Nm/kg and m
  • Unilateral pain, bilateral OA
  • Bilateral
  • Control
  • Control
  • −1.97 (−2.11, −1.83)
  • −2.09 (−2.19, −1.99)
  • 7.51
  • 10.26
  UnilateralBilateral0.51 (−0.28, 0.74)2.33
  Unilateral pain, bilateral OABilateral0.12 (0.0, 0.24)0.59
  UnilateralUnilateral pain, bilateral OA0.39 (0.14, 0.64)1.23
Gök et al, 2002 ([38])Knee peak flexion moment, Nm/kgMildControl−0.21 (−0.38, −0.04)0.9
Deluzio and Astephen, 2007 ([32])Knee peak adduction moment, Nm/kgSevereControlPCA: OA patients exhibited a higher average moment, but a lower moment during early stance 
 Knee peak flexion moment, Nm/kg  PCA: OA patients exhibited an overall lower magnitude of flexion moment during stance, lower positive flexion moment during the first half of stance, and lower absolute magnitude of negative flexion moment 
Hunt et al, 2010 ([19])Hip peak adduction moment, Nm/kg and m
  • Mild (varus)
  • Moderate (varus)
  • Mild (varus)
  • Control
  • Control
  • Moderate (varus)
  • −0.43 (−0.94, 0.08)
  • −0.71 (−1.26, −0.16)
  • 0.28 (−0.3, 0.86)
  • 0.46
  • 0.70
  • 0.26
  Mild (varus)Severe (varus)0.69 (0.16, 1.22)0.71
  Moderate (varus)Severe (varus)0.41 (−0.16, 0.98)0.39
 Hip peak abduction moment, Nm/kg and m
  • Mild (varus)
  • Moderate (varus)
  • Mild (varus)
  • Control
  • Control
  • Moderate (varus)
  • 0.28 (−0.39, 0.95)
  • 0.37 (−0.34, 1.08)
  • −0.09 (−0.8, 0.62)
  • 0.23
  • 0.28
  • 0.07
  Mild (varus)Severe (varus)−0.62 (−1.48, 0.24)0.39
  Moderate (varus)Severe (varus)−0.53 (−1.42, 0.36)0.32
 Knee peak adduction moment, Nm/kg and m
  • Mild (varus)
  • Moderate (varus)
  • Moderate (varus)
  • Severe (varus)
  • −0.04 (−0.61, 0.53)
  • −0.14 (−0.7, 0.42)
  • 0.04
  • 0.14
Hurwitz et al, 2002 ([40])Knee peak adduction moment, Nm/kg and mOA (varus)ControlOA group was significantly higher (P = 0.027) 
Kaufman et al, 2001 ([45])Knee peak adduction moment, Nm/kg and mFemalesMales−0.08 (−0.2, 0.36)0.1
 Knee peak flexion moment, Nm/kg and m  −0.16 (−0.42, 0.1)0.22
 Knee peak internal rotation moment, Nm/kg and m  0.09 (−0.02, 0.2)0.3
Landry et al, 2007 ([34])Knee peak adduction moment, Nm/kgMildControlPCA: OA patients exhibited larger overall adduction moments during stance in both fast walking and preferred speeds 
 Knee peak flexion moment, Nm/kg  PCA: OA patients exhibited smaller flexion moments at both fast and preferred speeds 
Linley et al, 2010 ([35])Hip peak adduction moment, Nm/kgMildControl0.02 (−0.03, 0.07)0.17
McKean et al, 2007 ([36])Hip peak internal rotation moment, Nm/kgModerateControlPCA: OA patients walked with a smaller internal/external rotation moment and more internally rotated hip 
 Knee peak adduction moment, Nm/kgFemalesControls and malesPCA: OA females exhibited lower magnitude than controls and OA males 
 Knee peak flexion moment, Nm/kgFemalesControls and malesPCA: OA females exhibited lower moment than controls and OA males 
 Knee internal rotation moment, Nm/kgFemalesControls and malesPCA: OA females exhibited lower knee internal rotation moment during stance than controls and OA males 
Messier et al, 2005 ([47])Knee peak internal rotation momentOAControl−0.03 (−0.05, 0.01)1.44
Mündermann et al, 2005 ([33])Hip peak adduction moment, Nm/kg and m
  • Mild
  • Mild
  • Control
  • Severe (varus)
  • −0.13 (−0.66, 0.40)
  • 0.52 (−0.06, 1.10)
  • 0.15
  • 0.54
 Hip peak abduction moment, Nm/kg and m
  • Mild
  • Mild
  • Control
  • Severe (varus)
  • 0.97 (0.14, 1.81)
  • −0.57 (−1.45, 0.31)
  • 0.73
  • 0.41
 Knee peak adduction moment, Nm/kg and mMildSevere (varus)−0.79 (−1.28, −0.40)1.17
Rutherford et al, 2008 ([25])Knee peak adduction moment, Nm/kg
  • Mild to moderate
  • Severe
  • Control
  • Control
PCA: the mild to moderate OA and control groups displayed 2 distinct peaks in the moment. The first peak was delayed by 7% of the gait cycle in the severe group and the second peak was not easily distinguished. There appeared to be no difference in amplitude between the groups 
Schmitt and Rudolph, 2007 ([39])Knee peak flexion moment, Nm/kg and mMild (varus)Control0.00 (−0.53, 0.53)0.00
Sims et al, 2009 ([4])Hip peak abduction moment, Nm/kgFemalesMales0.04 (−0.08, 0.17)0.18
 Knee peak adduction moment, Nm/kg  −0.13 (−0.22, −0.03)0.7
Weidow et al, 2006 ([5])Hip peak adduction moment, Nm/kg
  • Lateral
  • Medial
  • Control
  • Lateral
  • −0.18 (−0.28, −0.08)
  • 0.05 (−0.05, 0.15)
  • 1.29
  • 0.34
 Hip peak abduction moment, Nm/kg
  • Medial
  • Lateral
  • Control
  • Control
  • 0.02 (−0.06, 0.1)
  • 0.13 (0.07, 0.19)
  • 0.17
  • 1.45
  MedialLateral−0.11 (−0.17, −0.05)1.33
 Hip peak internal rotation moment, Nm/kg
  • Lateral
  • Medial
  • Control
  • Lateral
  • 0.03 (−0.02, 0.08)
  • −0.05 (−0.1, 0.00)
  • 0.45
  • 0.65
 Knee peak adduction moment, Nm/kg
  • Medial
  • Lateral
  • Control
  • Control
  • 0.18 (0.06, 0.30)
  • −0.32 (−0.42, −0.21)
  • 1.09
  • 2.32
  MedialLateral0.50 (0.42, 0.58)4.52
 Knee peak flexion moment, Nm/kg
  • Lateral
  • Medial
  • Control
  • Lateral
  • −0.21 (−0.34, −0.08)
  • −0.08 (−0.20, 0.04)
  • 1.14
  • 0.46
 Knee peak internalLateralControl−0.01 (−0.02, 0.00)0.49
 rotation moment, Nm/kgMedialLateral0.0 (−0.02, 0.02)0.0
Zeni and Higginson,Knee peak adduction moment, Nm/kg
  • Moderate
  • Severe
Control
  • No difference reported
  • No difference reported
 
2011 ([62])Knee peak flexion moment, Nm/kgModerate At SS, there was significant reduction 
  Severe At both SS and FW, there were significant reductions 
image

Figure 2. Forest plot of data pooling for temporospatial variables. Open diamonds indicate the effect size and bars indicate the 95% confidence intervals (95% CIs). Solid diamonds represent pooled data. Contributing studies were weighted based on intersubject variability (i.e., width of CIs). OA = osteoarthritis; %BH = percentage of body height.

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KOA versus controls

Data pooling was possible for walking speed, stride length, stance duration, and cadence (Figure 2). The effect of KOA on these variables appeared to be dependent on disease severity. Strong evidence suggested that individuals with severe KOA exhibited greater stride duration than controls (ES 1.35 [95% CI 1.03, 1.67], I2 = 19%) ([3, 16, 17]) and a moderate decrease in cadence (ES −0.75 [95% CI −1.12, −0.39], I2 = 0%) ([3, 5, 17, 18]). There was conflicting evidence for deviations in walking speed and stride length associated with severe KOA. However, this was most likely due to variations in ES magnitude between pooled publications because most publications showed a reduction in walking speed and stride length.

Moderate evidence suggested that individuals with moderate KOA and varus malalignment walked slower than controls (ES −0.87 [95% CI −1.23, −0.44], I2 = 0%) ([6, 19, 20]). For individuals with mild and moderate KOA as well as those with severe KOA and varus malalignment, pooled data revealed conflicting evidence or a small ES. Interestingly, there was no evidence for walking speed alterations in general KOA cohorts compared with healthy controls ([21-24]). Data from publications that did not meet the criteria for pooling also indicated that the magnitude of temporospatial gait deviations associated with KOA was influenced by disease severity ([3, 18, 19, 25]).

Between KOA subgroups

Data pooling between moderate and severe KOA subgroups was possible for walking speed, stride length, and stride duration. The pooled results revealed moderate evidence that those with severe KOA exhibited longer stride duration (ES −0.99 [95% CI −1.32, −0.65], I2 = 0%) ([3, 16]) and conflicting evidence of reduced walking speed (ES −1.14 [95% CI −1.39, −0.89], I2 = 85%) ([3, 16, 26-28]) and stride length (ES −0.99 [95% CI −1.24, −0.74], I2 = 81%) ([3, 16, 26, 27]) (Figure 2).

It was not possible to pool data for comparisons between mild and severe, unilateral and bilateral involvement, and medial and lateral compartment subgroups. No consistent effects were observed between any subgroups for walking speed, cadence, and stride length; however, Zeni and Higginson ([3]) reported a moderate reduction in stride duration in individuals with severe KOA compared with those with moderate KOA during fast walking (Table 3).

Joint kinematics

Twenty-five publications reported kinematic alterations associated with KOA during gait. Lateral trunk lean, hip adduction, knee flexion at initial contact (IC), knee flexion (peak and excursion during loading, stance, and stride), knee range of motion, and knee extension were included in this review. Twenty-eight publications compared KOA kinematics with healthy controls, while 10 compared kinematics between KOA subgroups (Table 3 and Figure 3).

image

Figure 3. Forest plot of data pooling for joint kinematics and moments. Open diamonds indicate the effect size and bars indicate the 95% confidence intervals (95% CIs). Solid diamonds represent pooled data. Contributing studies were weighted based on intersubject variability (i.e., width of CIs). OA = osteoarthritis; Nm/kg*m = Nm/kg and meters; IC = initial contact.

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KOA versus controls

The criteria for data pooling were met for comparisons investigating peak hip adduction, knee flexion at IC, knee flexion excursion during loading, and peak knee flexion. There was moderate evidence indicating that individuals with moderate KOA and varus malalignment exhibited reduced knee flexion excursion during loading (ES −1.12 [95% CI −1.59, −0.66], I2 = 0%) ([6, 20, 29]) and that normally aligned individuals with moderate KOA had reduced peak knee flexion (ES −0.63 [95% CI −0.92, −0.34], I2 = 0%) ([16, 30]). Limited evidence suggested that general KOA cohorts also exhibited reduced knee flexion excursion during loading and increased flexion at IC compared with controls. Large pooled ES and a high evidence of heterogeneity were observed for peak hip adduction comparisons between individuals with severe KOA and controls, indicating conflicting evidence; however, this was most likely due to variations in the magnitude of effect between pooled publications.

The largest ES from nonpooled data indicating the greatest differences from healthy controls involved individuals with severe KOA (Table 3). Specifically, large reductions were reported in peak hip adduction during stance ([19]), knee range of motion ([31, 32]), and knee flexion (peak, excursion, and during loading) ([16, 18, 31]). Contrasting results were reported for knee extension, with Bejek et al ([31]) reporting large reductions at several different walking speeds between individuals with severe KOA and varus malalignment and controls, while Mündermann et al ([33]) reported no differences. A large increase was reported in lateral trunk lean in individuals with severe KOA and varus malalignment ([19]), whereas a moderate increase was observed in those with moderate KOA and varus malalignment. Multiple studies reported no difference in lateral trunk lean angle between individuals with mild KOA and controls ([19, 34, 35]), and there was no difference found in knee motion between those with mild KOA and controls ([34]).

Between KOA subgroups

The criteria for pooling were not met for any kinematic comparisons between KOA subgroups. Nonpooled comparisons, however, were made between mild, moderate, and severe KOA, medial and lateral compartment involvement, males and females with KOA, and symptomatic and nonsymptomatic individuals (Table 3). Significant differences were observed in lateral trunk lean ([19]) and knee extension ([33]) between individuals with mild and severe KOA. Significant and large increases in lateral trunk lean and knee flexion (peak and excursions) were also observed in individuals with severe KOA compared with those with moderate KOA ([16, 19]). Individuals with medial compartment involvement exhibited reduced peak hip adduction compared with individuals with lateral compartment KOA ([5, 21]). A waveform analysis of sagittal plane knee motion revealed that greater changes occurred in females with KOA compared with males ([36]); however, this was not supported by a study examining discrete variables between females and males ([4]).

Joint moments

The most common peak external joint moments reported were hip adduction, abduction, and internal rotation moments, and knee flexion, adduction and internal rotation moments. Twenty publications compared KOA with healthy controls, while 19 compared joint moments between KOA subgroups (Table 3 and Figure 3).

KOA versus controls

Comparisons involving individuals with severe KOA most frequently met the criteria for data pooling (Figure 3). Moderate evidence suggested that individuals with severe KOA with or without varus malalignment exhibited reduced hip adduction moments (ES −0.96 [95% CI −1.4, −0.52], I2 = 7% [[19, 33]] and ES −0.73 [95% CI −1.06, −0.4], I2 = 0% [[5, 16]], respectively). In contrast, pooled data revealed limited evidence of an increase in peak hip abduction moment values ([19, 33]) for those with severe disease and varus malalignment and conflicting evidence regarding hip internal rotation moment in those with severe nonvarus KOA compared with healthy controls ([5, 16]). Regarding knee moments, the evidence of alteration in the knee adduction moment associated with mild KOA was conflicting, although the pooled ES suggested small increases. For more severe and general KOA cohorts, there was no evidence of a change in knee adduction moment compared with healthy controls based on 8 different studies. Similarly, evidence of alterations in knee flexion and internal rotation moments in individuals with severe KOA was conflicting. However, this was most likely due to a difference in magnitude of ES of pooled studies because both Astephen et al ([16]) and Weidow et al ([5]) reported reductions.

Significant results of nonpooled comparisons between KOA and controls indicated that individuals with moderate KOA exhibited a moderate reduction in peak hip adduction moment ([16, 19]) and small reductions in peak hip internal rotation, knee internal rotation, and knee flexion moments ([16, 37]). Those with mild KOA also exhibited a reduction in peak knee flexion moment ([38]), although there was no difference between individuals with mild KOA and varus malalignment and controls ([39]). These findings were confirmed in waveform comparisons ([32, 34, 36]) (Table 3). An analysis of waveforms also revealed a larger knee adduction moment throughout stance for individuals with mild ([34]) and moderate KOA ([36]) compared with healthy controls. This finding was supported by 2 publications comparing general KOA cohorts and healthy controls that did not provide enough data to calculate ES ([40, 41]), but was in contrast to other nonpooled data ([25, 37, 42]). Deluzio and Astephen ([32]) reported that individuals with severe KOA exhibited an increased average knee adduction moment throughout stance, but this was reduced (compared with controls) during early stance. Rutherford et al ([25]) reported a change in shape of the knee adduction moment waveform in individuals with severe KOA compared with controls and those with moderate KOA, but reported no change in amplitude.

Between KOA subgroups

The only data meeting criteria for pooling indicated no difference in knee adduction moment between individuals with mild and severe KOA with varus malalignment ([19, 43]) (Figure 3). Similar findings have been reported when comparing individuals with mild KOA and varus malalignment with those with moderate KOA and varus malalignment as well as those with moderate and severe disease and varus malalignment ([19]). Significant increases in knee adduction moment were reported in individuals with primarily medial compartment involvement compared with those with lateral KOA ([5, 21]) and in males with KOA compared with females ([4, 36]) (Table 3).

Of the remaining comparisons between KOA cohorts, there was a moderately increased hip internal rotation moment and knee internal rotation moment in individuals with moderate KOA when compared with severe KOA ([16]). Hunt et al ([19]) reported that individuals with mild KOA and varus malalignment exhibited a moderate increase in hip adduction moment compared with individuals with severe KOA and varus malalignment. However, this was not supported by the findings of Mündermann et al ([33]), whose mild KOA group exhibited normal alignment. The hip abduction moment in individuals with medial compartment KOA was larger than those with lateral compartment involvement ([5]).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

A comprehensive search of the literature revealed that individuals with KOA exhibited a variety of biomechanical alterations during gait compared with their healthy counterparts. However, the only gait alteration with strong and consistent evidence was increased stride duration for those with severe KOA compared with healthy controls. Moderate evidence indicated that individuals with moderate KOA (varus malalignment only) exhibited reduced knee flexion excursion during loading, peak knee flexion, and walking speed, while individuals with severe KOA (varus malalignment only) reduced their cadence and hip adduction moment. Those with severe KOA also increased their stride duration compared with those with moderate disease. There was limited evidence for general KOA cohorts exhibiting reduced knee flexion excursion during loading and increased knee flexion at IC compared with healthy controls. Similarly, limited evidence indicated that individuals with moderate (nonvarus) KOA exhibited reduced walking speed (although faster than those with severe KOA) and individuals with severe KOA and varus malalignment exhibited increased hip abduction moments. The remaining pooled data resulted in conflicting or no evidence of biomechanical alterations.

A likely cause of conflicting evidence was the high amount of heterogeneity between pooled publications. While K/L grade was primarily used to determine disease severity, the Ahlback scale ([5, 17, 38]) and magnetic resonance imaging ([20, 29]) were also utilized. Furthermore, not all studies described the mechanical axis alignment of their cohorts. When classifying the severity of KOA cohorts, some studies considered radiographic and clinical findings ([3, 26, 30, 32, 37]), while other studies solely referenced radiographic changes ([19, 33]) and others used radiographs to confirm the presence of KOA but only reported clinical findings ([44-47]). The lack of homogeneity in KOA description and classification schemes highlights the need for standard classification systems to be used and reported in future studies.

The key findings from nonpooled data indicated that temporospatial and kinematic gait alterations associated with KOA increased in magnitude with increasing disease severity. Therefore, individuals with severe KOA exhibited the greatest alterations, while there were few differences observed between those with mild KOA and controls. There was insufficient evidence to support or refute the influence of mechanical alignment, the involved compartment, sex, and symptoms on most of the biomechanical variables examined. However, in joint moment comparisons, larger moments were observed in milder KOA severities, except for knee adduction moment, where there were no differences between KOA subgroups. For knee adduction moment, those with medial compartment involvement and males were reported to exhibit larger moments.

It has been suggested that individuals with KOA adopt gait strategies that result in immediate reduction in knee joint load, particularly medial compartment load ([33, 48]). This is particularly pertinent for individuals with primarily medial compartment KOA, who constitute the majority of individuals examined in the studies included in this review. The present data support this hypothesis because there was no evidence of increased knee adduction moment, which is a proxy for medial knee joint load ([49]). Likewise, although pooled evidence was conflicting, knee flexion and internal rotation moments were also reduced (more so in those with severe KOA). These moments have been correlated with the magnitude of adduction moment and compressive knee load in KOA ([50, 51]).

The lack of evidence of alterations in knee adduction moment is surprising (although similar to findings from a previous systematic review examining knee adduction moment [52]), given the importance of this variable in the progression of KOA ([53]) and the large number of studies that have utilized knee adduction moment as a primary outcome. It is likely that alterations in knee adduction moment are driven by alterations of known moment-modifying gait characteristics. A recent systematic review reported that increased lateral trunk lean demonstrated the largest reductions in early stance knee adduction moment ([54]), with other kinematic alterations such as foot progression angle and walking speed also affecting knee adduction moment magnitudes. In the current study, the magnitude of trunk lean and resultant alterations at the hip (reduced hip adduction moment and increased hip abduction moment and peak abduction) was greatest in those with severe KOA. Similarly, changes in temporospatial characteristics (i.e., walking speed, cadence, and stride length) were also greatest in those with severe KOA. Such changes potentially decrease the ground reaction forces, moment arm, and cumulative load acting on the knee joint ([55]) and potentially explain why, unlike Foroughi et al ([52]), we did not find that the knee adduction moment increased with severity of KOA. In contrast, those with mild KOA demonstrated the smallest number and magnitude of kinematic and temporospatial alterations while demonstrating small increases in the knee adduction moment. Therefore, this review demonstrates that differences in knee adduction moment between individuals with KOA and healthy controls are not guaranteed and can potentially be explained by kinematic and temporospatial differences.

While some observed gait alterations might reflect attempts to reduce pain and protect the knee in the short term, they may have long-term adverse effects. Specifically, it has been postulated that gait modification strategies that are successful in reducing joint loading and/or pain are attenuated by increased knee flexion excursion/angles ([51]). Childs et al ([56]) hypothesized that reduced knee motion stiffens the knee, making it less capable of dissipating potentially harmful localized impact loads. A caveat to these long-term effects is that this review was limited to cross-sectional studies, meaning that the above adverse effects are speculated. Longitudinal data are required to make a causative statement regarding gait adaptions and KOA progression, which is beyond the scope of this review.

Along with the lack of homogeneity in disease severity classification and dearth of long-term studies, several other methodologic factors influenced and limited the findings of this review. The external and internal validity of the included publications was limited because the publications did not provide sufficient information regarding participant recruitment and did not blind assessors to group allocation/KOA diagnosis. It must be acknowledged that such limitations affect the validity of the findings of this review; however, this should be counterbalanced by the increased precision gained from data synthesis. Another limitation is that there is currently no consensus regarding an accepted standard reference frame for calculating joint moments and no consensus on whether walking speed is considered a confounding factor in publications where participants set their own speed. Both of these factors have been shown to influence the magnitude of joint moments ([16, 57]) and make comparisons across publications difficult. Similarly, there is no standard for normalizing external joint moments. Normalizing moments by height and body weight has the smallest residual effect on joint moments, but may also overcorrect data relative to normalizing by body weight only due to the correlation between height and body weight ([58]). However, by choosing to pool data based on point estimates of effect rather than mean differences, such comparisons were possible regardless of joint reference frame, walking speed, and normalization protocol.

In summary, there is a range of evidence indicating that individuals with KOA exhibit altered gait biomechanics during gait compared with those without KOA. The majority of strong and moderate evidence is for adaptations occurring in the temporospatial domain, whereas evidence for kinematic and joint moment change is primarily limited or conflicting. An interesting finding from the present data synthesis is the lack of evidence from pooled and discrete data for alterations in knee external adduction moment. This was likely due to changes in known moment-modifying gait characteristics such as lateral trunk lean and temporospatial characteristics, all of which were more altered in those with more severe KOA. However, some gait adaptations such as decreased knee motion are theorized to have long-term adverse effects on the joint. Therefore, further research into the long-term effects of consistently occurring biomechanical gait adaptations, as identified by this review, is needed. Such research would benefit from a standardized KOA classification system that encompasses radiographic and clinical findings and includes measurement of mechanical axis alignment.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Ferber had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Mills, Hunt, Ferber.

Acquisition of data. Mills, Ferber.

Analysis and interpretation of data. Mills, Hunt.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
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