Arthritis Care & Research Vol. 65, No. 10, October 2013, pp 1643–1665 DOI 10.1002/acr.22015 © 2013, American College of Rheumatology ORIGINAL ARTICLE

Biomechanical Deviations During Level Associated With Osteoarthritis: A Systematic Review and Meta-Analysis

1 2 1 KATHRYN MILLS, MICHAEL A. HUNT, AND REED FERBER

Objective. To identify which deviations are consistently associated with knee osteoarthritis (KOA) and how these are influenced by 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 variety of patterns of locomotion depending on their dis- ease severity, sex, or which compartment is primarily af- Knee osteoarthritis (KOA) is a common, chronic joint dis- fected (3–5). This diversity underlines the need for syn- ease where alterations in gait biomechanics are frequently thesis of evidence to inform clinicians which gait observed. Disease characteristics such as joint pain and alterations they can primarily expect their KOA patients to swelling as well as muscle dysfunction are potential fac- exhibit. To examine the type and magnitude of biome- tors commonly cited as associated with these gait altera- chanical gait deviations associated with KOA during level tions (1,2). The large number of cross-sectional studies walking, we reviewed cross-sectional observational stud- investigating biomechanical changes during gait have ies comparing individuals with KOA with matched or demonstrated that individuals with KOA adopt a wide similar healthy controls. To examine the influence of dis- ease severity, the involved compartment, and sex on such Dr. Mills’ was supported by the Alberta Innovates gait deviations, we reviewed cross-sectional studies com- Health Solutions Team in Osteoarthritis (award 200700 paring differing KOA subgroups. Our aim was to identify 596). which gait deviations are consistently associated with 1 Kathryn Mills, PhD, Reed Ferber, PhD, CAT(C), ATC: KOA. University of Calgary, Calgary, Alberta, Canada; 2Michael A. Hunt, PhD: University of British Columbia, Vancouver, British Columbia, Canada. Address correspondence to Reed Ferber, PhD, CAT(C), ATC, Faculties of Kinesiology and Nursing, University of MATERIALS AND METHODS Calgary, 2500 University Drive NW, Calgary, Alberta, T2N 1N4 Canada. E-mail: [email protected]. Literature search strategy. A literature search strategy Submitted for publication October 24, 2012; accepted in revised form March 20, 2013. was devised for electronic databases (Medline, CINAHL, SPORTDiscus, PubMed, and Embase) with no publication,

1643 1644 Mills et al

strongly affected by alignment of the in the transverse Significance & Innovations plane (7). ● This review presents the first systematic synthesis To avoid bias that can be introduced through duplicate of available literature for the purpose of identify- data, all publications were juxtaposed for author names, ing consistent temporospatial, kinematic, and joint affiliations, and participant characteristics. Where identi- moment gait alterations exhibited by individuals cal authors, outcome variables, and exact participant num- with knee osteoarthritis. ber, age, weight, and sex ratio occurred, the results of ● This review indicates that most consistent gait de- publications with the lower methodologic quality score viations occur in people with more severe disease were excluded from further analysis. and that changes in the spatiotemporal character- istics of gait are common. Methodology quality. Publications that met the inclu- sion criteria were assessed for methodologic bias by 2 ● A significant finding of this review is that the ex- independent reviewers (KM and MAH), one of whom was ternal knee adduction moment is not consistently blinded to the author, title, affiliation, and journal. Be- increased in individuals with knee osteoarthritis only observational studies were assessed, a modified regardless of their disease severity or lower ex- version (8) of a quality index for nonrandomized trials (9) tremity alignment. was used. This version contains 16 items (items 1–3, 5–7, ● This review highlights the need for a standardized 10–12, 15, 16, 18, 20–22, and 25 of the original index) knee osteoarthritis classification system that en- assessing reporting (items 1–3, 5–7, and 10), external va- compasses radiographic, clinical, and mechanical lidity (items 11 and 12), and internal validity (bias and alignment measures in order to facilitate further confounding; items 15, 16, 18, 20–22, and 25). The mod- comparisons between studies. ified 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 language, or date restrictions, with the last search con- “yes.” For negative items or items unable to be deter- ducted on June 10, 2012. The search strategy was as fol- mined, no points are awarded. The maximum score for the lows (identical for all databases): 1) ‘knee osteoarthr*’ or modified index is 17 points. The agreement between re- gonarthr*, 2) gait or walking, 3) 1 and 2 and kinematics, 4) viewers was assessed using a kappa statistic, referenced to 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 , Hopkins’ criteria of very small (0 to 0.1), small (0.11 to and 8) 6 and trunk. Titles and abstracts were screened in 0.3), moderate (0.31 to 0.5), high (0.51 to 0.7), very high the initial search, with the full text of publications meeting (0.71 to 0.9), and almost perfect to perfect (0.91 to 1.0) (10). the initial inclusion criteria retrieved for further screening. Disagreements were discussed at a consensus meeting. Ͻ Reference lists of all publications considered for inclusion Publications scoring 50% on the quality index were ex- were searched recursively until no additional eligi- cluded from further analysis (11) (Table 1). ble publications were identified. One reviewer conducted the literature search (KM) and 2 reviewers (KM and MAH) Data synthesis. One reviewer (KM) extracted group determined the final eligibility of the selected publica- means, SDs, and sample sizes directly from publications tions. and all reviewers checked the extracted data. These data were used to calculate point estimates of effect size (ES) ϭ Selection criteria. Cross-sectional, human-based obser- and 95% confidence intervals (95% CIs; ES mean dif- vational studies comparing level walking biomechanics of ference/pooled SD). ES magnitudes were interpreted based individuals with KOA with healthy controls or between on Hopkins’ criteria (12) as trivial (0 to 0.2), small (0.21 to Ͼ differing KOA subgroups (e.g., disease severity, the in- 0.6), moderate (0.61 to 1.2), and large ( 1.2). Findings volved compartment, sex, etc.) were considered for inclu- from principle component or principal pattern analysis sion. No restriction was placed on disease severity, sex, or were also extracted. When data were presented as the the involved compartment. Studies permitting partici- median and range, the mean and variability were esti- pants to walk with walking aids or including participants mated using methods described by Hozo et al (13). Authors with confirmed OA in lower extremity joints other than of publications that did not provide data in an extractable the knee or participants who had undergone total joint form were contacted. were excluded. Similarly, because biome- Based on the search strategy, biomechanical compari- chanical changes in gait can occur as part of the normal sons were categorized as temporospatial variables, joint aging process (6), comparisons between individuals with kinematics, or joint moments. Within these categories, KOA and healthy controls where the average between- comparisons were divided into those comparing KOA co- group age discrepancies exceeded 30 years were excluded. horts and healthy controls and those comparing different Studies were also excluded if biomechanical comparisons KOA subgroups. KOA cohorts were further subdivided were not the main focus or if they utilized mathematical based on varus malalignment and disease severity. Inclu- modeling or 2-dimensional motion analysis. The latter sion in the varus malalignment subgroup was based on the criterion was due to movement in the frontal plane being KOA group exhibiting a significantly greater mechanical Biomechanical Changes Associated With Knee OA 1645

Table 1. Quality index*

Internal External validity: validity Internal validity: confounding Reporting item item bias item item Total Author, year (ref.) 1235†6710111215161820212225 (17)

Astephen et al, 2008 (16) 1 1 1 2 1 1 0000101000 9 Baliunas et al, 2002 (41) 1 1 1 1 1 1 100010100110 Bejek et al, 2005 (31) 1 1 1 2 1 1 0000101000 9 Butler et al, 2011 (21) 1 1 1 1 1 1 100011100111 Chen et al, 2003 (17) 1 1 0 1 1 1 0000111100 9 Childs et al, 2004 (56) 1 1 1 2 1 1 100011000010 Creaby et al, 2012 (42) 1 1 1 2 1 1 100011110113 Deluzio and Astephen, 2007 (32) 1 1 1 0 1 1 1000111000 9 Go¨k et al, 2002 (38) 1 1 1 1 1 1 100010110010 Heiden et al, 2009 (22) 1 1 1 1 1 1 100011100111 Huang et al, 2008 (18) 1 1 1 2 1 1 100011100112 Hubley-Kozey et al, 2006 (30) 1 1 1 2 1 1 100011110012 Hubley-Kozey et al, 2009 (26) 1 1 1 2 1 0 000011101010 Hunt et al, 2010 (19) 1 1 1 2 1 1 100011100112 Hurwitz et al, 2002 (40) 1 1 1 2 1 0 100011100111 Kaufman et al, 2001 (45) 1 1 1 0 1 1 100011110111 Kean et al, 2012 (43) 1 1 1 2 1 1 100011100112 Ko et al, 2011 (44) 1 1 1 0 1 0 100011111111 Krackow et al, 2011 (59) 1 1 1 1 1 1 100011100111 Landry et al, 2007 (34) 1 1 1 2 1 0 000011100110 Levinger et al, 2012 (23) 1 1 1 2 1 1 100011100112 Lewek et al, 2004 (20) 1 1 1 2 1 1 100011100112 Lewek et al, 2006 (29) 1 1 1 2 1 1 100010100111 Liikavainio et al, 2010 (60) 1 1 1 2 1 1 000011010111 Linley et al, 2010 (35) 1 1 1 2 1 1 100010110011 Manetta et al, 2002 (24) 1 1 1 1 1 1 100011110011 McGibbon and Krebs, 2002 (61) 1 1 1 0 1 1 0000111001 9 McKean et al, 2007 (36) 1 1 1 1 0 1 1000111000 9 Messier et al, 2005 (47) 1 1 1 1 1 1 100011100111 Mu¨ ndermann et al, 2005 (33) 1 1 1 1 1 0 100011100110 Rudolph et al, 2007 (6) 1 1 1 1 1 1 100011100111 Rutherford et al, 2008 (25) 1 1 1 2 1 0 000011111112 Rutherford et al, 2011 (27) 1 1 1 2 1 1 100011101113 Sahai et al, 2003 (46) 1 1 1 1 0 1 100011110010 Schmitt and Rudolph, 2007 (39) 1 1 1 2 1 1 100011110012 Sims et al, 2009 (4) 1 1 1 2 1 1 100011111013 Weidow et al, 2006 (5) 1 1 1 2 1 0 1000101000 9 Zeni and Higginson, 2009 (3) 1 1 1 2 1 1 100011100112 Zeni and Higginson, 2009 (37) 1 1 1 2 1 1 100011110113 Zeni et al, 2010 (28) 1 1 0 1 1 1 100011100110 Zeni and Higginson, 2011 (62) 1 1 1 2 1 1 100011110113 Frequency of “yes” 46 47 43 26 42 38 36 0 0 0 47 38 42 16 5 26 Frequency of “unable to be 0 0 0 17 0 0 0 47 47 47 0 6 3 21 39 5 determined” Frequency of “no” 1 0 4 4 5 9 11 00003210316

* Includes quality scores for publications that were subsequently excluded from further analysis. † 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.”

axis alignment (or other validated alignment measure) (i.e., general KOA) or when participants were the same than controls. Disease severity was extracted directly from across varus malalignment and disease severity. Compar- publications based on Kellgren/Lawrence (K/L) grades. isons were also made between unilateral and bilateral The criteria for data pooling were met when publications disease, medial and lateral compartment KOA, symptom- included a range of severities within a single KOA cohort atic and asymptomatic individuals, and males and fe- 1646 Mills et al

Figure 1. Flow chart of the study selection process. KOA ϭ knee osteoarthritis. males. Data pooling for these further comparisons was of heterogeneity), limited (small ES with low heterogene- conducted only if the initial criteria of the same alignment ity or moderate/large ES with moderate evidence of heter- and severity were met. ogeneity), conflicting (high evidence of heterogeneity), and Data pooling was performed in Cochrane Review Man- no evidence (95% CI of ES crossed zero). ager, 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, moder- ate, and high heterogeneity were assigned the thresholds RESULTS of 25%, 50%, and 75%, respectively (14). Because this review did not include randomized controlled trials, we Search strategy. Forty-seven publications were re- adapted the levels of evidence proposed by van Tulder et trieved for consideration, and following quality assess- al (15). Evidence of gait deviations associated with KOA ment, 41 were eligible for review (Figure 1). Because these was interpreted as strong (large ES and low evidence of publications reported on 180 different biomechanical vari- heterogeneity), moderate (moderate ES and low evidence ables, a further analysis only on variables that were re- Biomechanical Changes Associated With Knee OA 1647 ported by Ն4 articles was conducted (Table 2). This re- ginson (3) reported a moderate reduction in stride duration duced the number of biomechanical variables to 20. in individuals with severe KOA compared with those with moderate KOA during fast walking (Table 3). Methodologic quality. The initial agreement between reviewers in the present study was almost perfect (␬ ϭ Joint kinematics. Twenty-five publications reported ki- 0.904) (10) and the reliability for individual items ranged nematic alterations associated with KOA during gait. Lat- from moderate (␬ ϭ 0.483 for item 18) to perfect (items eral trunk lean, adduction, knee flexion at initial con- 7–11 and 15). Consensus was reached for all items at the tact (IC), knee flexion (peak and excursion during loading, initial discussion between the 2 reviewers, and the maxi- stance, and stride), knee , and knee exten- mum quality index score was 13 points, indicating publi- sion were included in this review. Twenty-eight publica- cations were generally of low to moderate methodologic tions compared KOA kinematics with healthy controls, quality. while 10 compared kinematics between KOA subgroups (Table 3 and Figure 3). Temporospatial variables. The temporospatial vari- KOA versus controls. The criteria for data pooling were ables examined were walking speed, stride length, stride met for comparisons investigating peak hip adduction, duration, stance duration, and cadence. Twenty-seven knee flexion at IC, knee flexion excursion during loading, publications examined differences in temporospatial vari- and peak knee flexion. There was moderate evidence in- ables between KOA and comparators and 16 publications dicating that individuals with moderate KOA and varus made comparisons between KOA subgroups (Table 3 and malalignment exhibited reduced knee flexion excursion Figure 2). during loading (ES Ϫ1.12 [95% CI Ϫ1.59, Ϫ0.66], I2 ϭ 0%) KOA versus controls. Data pooling was possible for (6,20,29) and that normally aligned individuals with mod- walking speed, stride length, stance duration, and cadence erate KOA had reduced peak knee flexion (ES Ϫ0.63 [95% (Figure 2). The effect of KOA on these variables appeared CI Ϫ0.92, Ϫ0.34], I2 ϭ 0%) (16,30). Limited evidence sug- to be dependent on disease severity. Strong evidence sug- gested that general KOA cohorts also exhibited reduced gested that individuals with severe KOA exhibited greater knee flexion excursion during loading and increased flex- stride duration than controls (ES 1.35 [95% CI 1.03, 1.67], ion at IC compared with controls. Large pooled ES and a I2 ϭ 19%) (3,16,17) and a moderate decrease in cadence high evidence of heterogeneity were observed for peak hip (ES Ϫ0.75 [95% CI Ϫ1.12, Ϫ0.39], I2 ϭ 0%) (3,5,17,18). adduction comparisons between individuals with severe There was conflicting evidence for deviations in walking KOA and controls, indicating conflicting evidence; how- speed and stride length associated with severe KOA. How- ever, this was most likely due to variations in the magni- ever, this was most likely due to variations in ES magni- tude of effect between pooled publications. tude between pooled publications because most publica- The largest ES from nonpooled data indicating the great- tions showed a reduction in walking speed and stride est differences from healthy controls involved individuals length. with severe KOA (Table 3). Specifically, large reductions Moderate evidence suggested that individuals with were reported in peak hip adduction during stance (19), moderate KOA and varus malalignment walked slower knee range of motion (31,32), and knee flexion (peak, ex- than controls (ES Ϫ0.87 [95% CI Ϫ1.23, Ϫ0.44], I2 ϭ 0%) cursion, and during loading) (16,18,31). Contrasting re- (6,19,20). For individuals with mild and moderate KOA as sults were reported for knee extension, with Bejek et al well as those with severe KOA and varus malalignment, (31) reporting large reductions at several different walking pooled data revealed conflicting evidence or a small ES. speeds between individuals with severe KOA and varus Interestingly, there was no evidence for walking speed malalignment and controls, while Mu¨ ndermann et al (33) alterations in general KOA cohorts compared with healthy reported no differences. A large increase was reported in controls (21–24). Data from publications that did not meet lateral trunk lean in individuals with severe KOA and the criteria for pooling also indicated that the magnitude of varus malalignment (19), whereas a moderate increase was temporospatial gait deviations associated with KOA was observed in those with moderate KOA and varus malalign- influenced by disease severity (3,18,19,25). ment. Multiple studies reported no difference in lateral Between KOA subgroups. Data pooling between moder- trunk lean angle between individuals with mild KOA and ate and severe KOA subgroups was possible for walking controls (19,34,35), and there was no difference found in speed, stride length, and stride duration. The pooled re- knee motion between those with mild KOA and controls sults revealed moderate evidence that those with severe (34). KOA exhibited longer stride duration (ES Ϫ0.99 [95% CI Between KOA subgroups. The criteria for pooling were Ϫ1.32, Ϫ0.65], I2 ϭ 0%) (3,16) and conflicting evidence of not met for any kinematic comparisons between KOA sub- reduced walking speed (ES Ϫ1.14 [95% CI Ϫ1.39, Ϫ0.89], groups. Nonpooled comparisons, however, were made be- I2 ϭ 85%) (3,16,26–28) and stride length (ES Ϫ0.99 [95% tween mild, moderate, and severe KOA, medial and lateral CI Ϫ1.24, Ϫ0.74], I2 ϭ 81%) (3,16,26,27) (Figure 2). compartment involvement, males and females with KOA, It was not possible to pool data for comparisons between and symptomatic and nonsymptomatic individuals (Table mild and severe, unilateral and bilateral involvement, and 3). Significant differences were observed in lateral trunk medial and lateral compartment subgroups. No consistent lean (19) and knee extension (33) between individuals effects were observed between any subgroups for walking with mild and severe KOA. Significant and large increases speed, cadence, and stride length; however, Zeni and Hig- in lateral trunk lean and knee flexion (peak and excur- 1648

Table 2. Details of the included studies*

Radiographic Author, year (ref.) OA cohort Clinical measures changes† OA description Severity Comparator cohort

Astephen et al, 2008 Moderate: n ϭ 60, M/F 40/20, WOMAC Moderate: mild Predominantly Moderate N ϭ 60, M/F 23/37, age (16) age 58.32 Ϯ 9.31 years, Severe: moderate medial Severe 50.27 Ϯ 10.09 years, BMI 30.91 Ϯ 5.17 kg/m2 compartment BMI 25.45 Ϯ 4.04 kg/m2 Severe: n ϭ 61, M/F 28/33, age 64.49 Ϯ 7.75 years, BMI 32.05 Ϯ 5.48 kg/m2 Baliunas et al, 2002 N ϭ 31, M/F 13/18, age 65 Ϯ ACR criteria, HSS Mild to severe Unilateral disease OA (varus) N ϭ 31, M/F 13/18, age 62 (41) 9 years, height 1.68 Ϯ 0.09 functional knee Medial compartment Ϯ 9 years, height 1.68 Ϯ m, mass 76 Ϯ 12 kg evaluation 12 m, mass 74 Ϯ 16 kg Varus alignment 7° Ϯ 4° Bejek et al, 2005 (31) N ϭ 20, M/F 8/12, age 68.2 Ϯ HSS knee scoring Severe Bilateral: most Severe N ϭ 20, M/F 8/12, age 7.1 years, height 1.69 Ϯ system symptomatic knee 68.8 Ϯ 9.1 years, height 0.11 m, mass 71.1 Ϯ 11.9 1.69 Ϯ 0.19 m, mass kg 73.3 Ϯ 11.4 kg Butler et al, 2011 (21) Medial OA: n ϭ 15, age 66.2 Pain VAS Mild to severe Unilateral OA N ϭ 15, age 56.3 Ϯ 10.7 Ϯ 7.9 years, BMI 32.2 Ϯ 7.9 Medial and lateral years, BMI 27.8 Ϯ 5.7 kg/m2 compartments kg/m2 Lateral OA: n ϭ 15, age 65.7 Ϯ 6.4 years, BMI 30.4 Ϯ 7.5 kg/m2 Chen et al, 2003 (17) N ϭ 20, M/F 0/20, age 65.5 Ϯ Ahlback grade: Bilateral disease Moderate to severe N ϭ 15, M/F 0/15, age 9.3 years, height 1.56 Ϯ 0.7 moderate and 63.5 Ϯ 11.3 years, m, weight 63.2 Ϯ 10.6 kg severe changes height 1.59 Ϯ 0.9 m, mass 62.6 Ϯ 8.2 kg Childs et al, 2004 (56) N ϭ 24, M/F 10/14, age 62 Ϯ ACR clinical Ն Mild Unilateral disease Moderate N ϭ 24, M/F 10/14, age 62 10 years, BMI 30 Ϯ 7 kg/m2 criteria, All compartments Ϯ 10 years, BMI 27 Ϯ 6 WOMAC, kg/m2 KOS Creaby et al, 2012 (42) Unilateral pain/unilateral Pain VAS Mild, moderate, Unilateral/bilateral OA (varus) N ϭ 31, M/F 11/20, age radiograph: n ϭ 11, M/F All groups varus and severe disease 63.8 Ϯ 8 years, height 6/5, age 64.5 Ϯ 7.6 years, aligned 1.67 Ϯ 0.09 m, mass BMI 31.1 Ϯ 3.8 kg/m2 (i.e., Ͻ182°) 71.3 Ϯ 12.6 kg, BMI Unilateral pain/bilateral 25.5 Ϯ 3.7 kg/m2 radiograph: n ϭ 22, M/F 10/12, age 65.1 Ϯ 9.4 years, BMI 26.8 Ϯ 5 kg/m2 Bilateral pain/bilateral radiograph: n ϭ 56, M/F 29/24, age 64.5 Ϯ 8 years, BMI 29.9 Ϯ 4.1 kg/m2 (continued) il tal et Mills imcaia hne soitdWt neOA Knee With Associated Changes Biomechanical

Table 2. (Cont’d)

Radiographic Author, year (ref.) OA cohort Clinical measures changes† OA description Severity Comparator cohort

Deluzio and Astephen, N ϭ 50, age 70 Ϯ 7.8 years, Scheduled for knee Severe N ϭ 63, age 65 Ϯ 8.5 2007 (32) mean BMI 29.2 kg/m2 replacement years, mean BMI 28.81 kg/m2 Go¨k et al, 2002 (38) N ϭ 13, M/F 0/13, age 58 Ϯ ACR clinical Ahlback grade: Medial compartment Mild N ϭ 13, M/F 0/12, age 11 years, height 1.57 Ϯ criteria joint narrowing 57 Ϯ 8 years, height 4.7 m, weight 72 Ϯ 12 kg (mild changes) 1.57 Ϯ 7.2 m, weight 77 Ϯ 12 kg Heiden et al, 2009 (22) N ϭ 54, M/F 24/30, age 65 Ϯ KOOS and SF-36 Bilateral OA N ϭ 30, M/F 11/19, age 64 8 years, height 1.7 Ϯ 0.09 Ϯ 6 years, height 1.7 Ϯ m, mass 81.4 Ϯ 14.2 kg 0.09 m, mass 81.4 Ϯ 14.2 kg Huang et al, 2008 (18) Mild: n ϭ 15, M/F 6/9, age VAS and SF-36 Mild: mild Bilateral: most Mild N ϭ 15, M/F 6/9, age 63.2 63.1 Ϯ 11.9 years, height Severe: moderate symptomatic knee Severe Ϯ 9.9 years, height 1.59 1.62 Ϯ 0.06 m, mass 68.4 Ϯ and severe Medial compartment Ϯ 0.08 m, mass 60.5 Ϯ 10.3 kg 8.5 kg Severe: n ϭ 15, M/F 2/13, age 63.1 Ϯ 8.2 years, height 1.56 Ϯ 0.09 m, mass 64 Ϯ 8.5 kg Hubley-Kozey et al, N ϭ 40, M/F 29/11, age 58.9 WOMAC, SF-36, Mild to moderate Unilateral disease Moderate N ϭ 38, M/F 17/21, age 2006 (30) Ϯ 8.07 years, BMI 29.94 Ϯ clinical 51.08 Ϯ 9.99 years, BMI 4.86 kg/m2 examination 24.74 Ϯ 4.25 kg/m2 Hubley-Kozey et al, Moderate: n ϭ 56, age 58.0 Ϯ Clinical Moderate: Predominantly Moderate N ϭ 63, age 49.2 Ϯ 9.7 2009 (26) 8.7 years, BMI 30.8 Ϯ 5.5 examination moderate medial Severe years, BMI 25.1 Ϯ 4.2 kg/m2 Severe group Severe: severe compartment kg/m2 Severe: n ϭ 48, age 63.7 Ϯ scheduled for 8.2 years, BMI 31.8 Ϯ 5.3 total joint kg/m2 arthroplasty Hunt et al, 2010 (19) Mild: n ϭ 25, M/F 10/15, age WOMAC, 11-point Mild Medial compartment Mild (varus) N ϭ 20, M/F 5/15, age 61.2 Ϯ 7.7 years, height knee pain scale Moderate Moderate (varus) 63.2 Ϯ 12.4 years, 1.65 Ϯ 0.08 m, mass 73.7 Ϯ All groups varus Severe Severe (varus) height 1.65 Ϯ 0.06 m, 14 kg aligned (i.e., mass 69.3 Ϯ 12.1 kg Moderate: n ϭ 25, M/F 14/11, Ͻ182°) age 63.6 Ϯ 8.4 years, height 1.67 Ϯ 0.08 m, mass 78.4 Ϯ 14.8 kg Severe: n ϭ 25, M/F 13/12, age 68 Ϯ 6.6 years, height 1.68 Ϯ 0.09 m, mass 81.7 Ϯ 20.2 kg (continued) 1649 1650

Table 2. (Cont’d)

Radiographic Author, year (ref.) OA cohort Clinical measures changes† OA description Severity Comparator cohort

Hurwitz et al, 2002 N ϭ 62, M/F 32/30, age 62 Ϯ Varus alignment Mild to severe Bilateral: most OA (varus) N ϭ 49, M/F 24/25, age 59 (40) 10 years, height 1.71 Ϯ 0.11 Ϫ9° to 15° symptomatic knee Ϯ 10 years, height 1.7 Ϯ m, mass 79 Ϯ 12 kg Primarily medial 0.1 m, mass 76 Ϯ 16 kg compartment Kaufman et al, 2001 N ϭ 92, M/F 0/92 Clinical Diagnosis confirmed Bilateral: most OA N ϭ 47, M/F 47/0 (45) examination by radiographs; no symptomatic knee details provided regarding severity of changes Kean et al, 2012 (43) Mild: n ϭ 87, age 62.3 Ϯ 7.69 WOMAC pain, Mild Medial compartment Mild Severe: n ϭ 82, age 65.7 Ϯ years, height 1.65 Ϯ 0.09 average walking Severe Severe 8.0 years, height 1.69 Ϯ m, mass 75.5 Ϯ 15.3 kg pain 0.09 m, mass 84.6 Ϯ Mild varus: 15.0 kg 182° Ϯ 2.4° Severe varus: 179.5° Ϯ 3.0° Ko et al, 2011 (44) Symptomatic: n ϭ 17, age Clinical Diagnosis confirmed OA N ϭ 112, age 67.69 Ϯ 9.31 70.24 Ϯ 8.49 years, BMI examination by radiographs; no years, BMI 26.94 Ϯ 4.34 28.08 Ϯ 4.33 kg/m2 modeled on details provided kg/m2 Asymptomatic: n ϭ 24, age ACR regarding severity 72.33 Ϯ 8.47 years, BMI of changes 27.2 Ϯ 4.31 kg/m2 Krackow et al, 2011 No torsional deformity: n ϭ Severe Unilateral/bilateral Severe N ϭ 10, M/F 5/5, age 62.5 (59) 8, M/F 4/4, age 59 Ϯ 11.34 disease Ϯ 4.17 years, BMI 28.44 years, height 1.74 Ϯ 0.13 Medial compartment Ϯ 4.23 kg/m2 m, mass 101.5 Ϯ 14.75 kg, BMI 33.84 Ϯ 6.9 kg/m2 Torsional deformity: n ϭ 6, M/F 5/1, age 61.83 Ϯ 7.96 years, height 1.73 Ϯ 0.1 m, mass 10.2 Ϯ 14.18 kg Landry et al, 2007 (34) N ϭ 41, age 58.2 Ϯ 8.3 years, On waiting list Median ϭ mild Mild N ϭ 43, age 50.7 Ϯ 10.2 BMI 30.3 Ϯ 4.5 kg/m2 for arthroscopic years, BMI 24.8 Ϯ 3.9 surgery kg/m2 Levinger et al, 2012 N ϭ 50, M/F 27/23, age 66.4 WOMAC, VAS Authors’ own criteria OA N ϭ 28, M/F 13/15, age (23) Ϯ 7.6 years, BMI 29.6 Ϯ pain Mild to severe 65.1 Ϯ 11.2 years, BMI 5.1 kg/m2 25.7 Ϯ 3.9 kg/m2 Lewek et al, 2004 (20) N ϭ 12, M/F 6/6, age 50.3 Ϯ Scheduled for Confirmed joint space Medial compartment Moderate (varus) N ϭ 12, M/F 6/6, age 49.5 7.4 years high tibial narrowing in Ϯ 6.1 years, weight- osteotomy medial bearing line 46% Ϯ KOS, weight- compartment 8.6% bearing line 23.1% Ϯ 10% (continued) il tal et Mills imcaia hne soitdWt neOA Knee With Associated Changes Biomechanical

Table 2. (Cont’d)

Radiographic Author, year (ref.) OA cohort Clinical measures changes† OA description Severity Comparator cohort

Lewek et al, 2006 (29) N ϭ 15, M/F 9/6, age 48.7 Ϯ KOOS, clinical Confirmed joint space Unilateral disease Moderate (varus) N ϭ 15, M/F 9/6, age 48.4 7.4 years, height 1.75 Ϯ examination narrowing in Medial compartment Ϯ 6.3 years, height 1.71 0.09 m, mass 91.9 Ϯ Varus alignment: medial Ϯ 0.9 m, mass 83.8 Ϯ 17.4 kg weight-bearing compartment 17.3 kg line 18.9% Ϯ Weight-bearing line 45.1% 12.7% Ϯ 8.1% Liikavainio et al, 2010 N ϭ 54, M/F 54/0, age 59 Ϯ ACR clinical Mild to severe Unilateral/bilateral: OA (varus) N ϭ 53, M/F 53/0, age (60) 5.3 years, BMI 29.7 Ϯ 4.7 criteria, pain VAS more symptomatic 59.2 Ϯ 4.7 years, BMI kg/m2 Varus alignment knee 27.1 Ϯ 3.1 kg/m2, 5.2° Ϯ 3.2° alignment 2.5° Ϯ 2.0° Linley et al, 2010 (35) N ϭ 40, M/F 17/23, age 63 Ϯ WOMAC scale Median ϭ mild Unilateral/bilateral: Mild N ϭ 40, M/F 17/23, age 64 10 years, BMI 27.4 Ϯ 5.5 more symptomatic Ϯ 9 years, BMI 24.0 Ϯ kg/m2 knee 3.2 kg/m2 Medial compartment Manetta et al, 2002 N ϭ 10, M/F 10/0, age 68 Ϯ WOMAC No radiographs taken OA N ϭ 10, age 68 Ϯ 11 years (24) 11 years McGibbon and Krebs, N ϭ 13, M/F 2/11, age 72.9 Ϯ Not reported Unilateral disease OA N ϭ 10, M/F 4/6, age 73.3 2002 (61) 8.9 years Ϯ 4.6 years McKean et al, 2007 N ϭ 39, M/F 24/15 WOMAC, clinical Mild to moderate Moderate N ϭ 42, M/F 18/24 (36) Women: age 58.32 Ϯ 9.31 examination Women: age 48.7 Ϯ 10.3 years, BMI 31.5 Ϯ 5.2 years, BMI 24.4 Ϯ 3.6 kg/m2 kg/m2 Men: age 55.1 Ϯ 12.8 years, Men: age 52.2 Ϯ 10.1 BMI 29.7 Ϯ 4.6 kg/m2 years, BMI 24.7 Ϯ 3.2 kg/m2 Messier et al, 2005 N ϭ 10, M/F 1/9, age 74.1 Ϯ ACR clinical criteria Mild to severe All compartments OA N ϭ 10, M/F 1/9, age 73 (47) 1.49 years, mass 65.1 Ϯ Ϯ 1.61 years, mass 58.3 2.61 kg Ϯ 2.74 kg Mu¨ ndermann et al, Mild: n ϭ 19, M/F 6/13, age WOMAC Mild: mild Bilateral: more Mild Less severe controls: n ϭ 2005 (33) 65.2 Ϯ 12.5 years, BMI 26.9 Mild: varus Severe: moderate to symptomatic knee Severe (varus) 19, M/F 6/13, age 61.7 Ϯ 3.1 kg/m2 alignment 0.3° severe Medial compartment Ϯ 12.3 years, BMI 26.1 Severe: n ϭ 23, M/F 13/10, Severe: varus Ϯ 2.6 kg/m2 age 65 Ϯ 8 years, BMI 27.8 alignment 5.7° More severe controls: n ϭ Ϯ 4.8 kg/m2 23, M/F 13/10, age 63.7 Ϯ 9.2 years, BMI 27.1 Ϯ 4 kg/m2 Rudolph et al, N ϭ 15, M/F 8/7, age 49.2 Ϯ Scheduled for high Radiographs taken Bilateral: more Moderate (varus) N ϭ 15, M/F 8/7, age 49.2 2007 (6) 4.5 years, BMI 30.7 Ϯ 4.8 tibial osteotomy but not reported symptomatic knee Ϯ 4.25 years, BMI 28.7 kg/m2 ACR clinical criteria Medial compartment Ϯ 5.5 kg/m2 KOS Varus alignment 6.33° Ϯ 2.39° (continued) 1651 1652 Table 2. (Cont’d)

Radiographic Author, year (ref.) OA cohort Clinical measures changes† OA description Severity Comparator cohort

Rutherford et al, 2008 Mild to moderate: n ϭ 46, Functional testing Mild to moderate: Predominantly Mild to moderate N ϭ 50, M/F 32/18, age 53 (25) M/F 20/26, age 60 Ϯ 9 mild to moderate medial Severe Ϯ 10 years, BMI 26 Ϯ years, BMI 31 Ϯ 5 kg/m2 Severe: moderate to compartment 4 kg/m2 Severe: n ϭ 44, M/F 20/24, severe age 67 Ϯ 8 years, BMI 32 Ϯ 5 kg/m2 Rutherford et al, 2011 Moderate: n ϭ 16, M/F 8/8, Severe group Moderate: moderate Predominantly Moderate N ϭ 16, M/F 8/8, age 56 (27) age 61 Ϯ 6 years, BMI 31.3 scheduled for Severe: severe medial Severe Ϯ 6 years, BMI 24.6 Ϯ Ϯ 3.6 kg/m2 total joint compartment 3.9 kg/m2 Severe: n ϭ 15, M/F 10/5, age arthroplasty 61 Ϯ 9 years, BMI 30.7 Ϯ WOMAC 5.4 kg/m2 Sahai et al, 2003 (46) N ϭ 15, M/F 15/0, age 68 Ϯ WOMAC No radiographs taken Bilateral: average of OA N ϭ 13, M/F 13/0, age 11 years extremities 68 Ϯ 11 years analyzed Schmitt and Rudolph, N ϭ 28, M/F 14/14, age 60.4 Knee laxity Mild to severe Unilateral/bilateral Mild (varus) N ϭ 26, M/F 13/13, age 2007 (39) Ϯ 9.75 years, height 1.7 Ϯ assessed Mode: mild disease: more 58.5 Ϯ 9.5 years, height 0.11 m, mass 92.91 Ϯ Varus alignment symptomatic knee 1.68 Ϯ 0.11 m, mass 16.16 kg 174.82° Ϯ 0.6° Medial compartment 83.93 Ϯ 1.85 kg (Ͻ180° ϭ Alignment 179.24° Ϯ 0.4° varus) Sims et al, 2009 (4) N ϭ 30, M/F 0/30, age 60.4 Ϯ ACR clinical Females: moderate Bilateral: most Moderate N ϭ 26, M/F 26/0, age 9.81 years, height 1.63 Ϯ criteria Males: severe symptomatic knee Severe 63.69 Ϯ 9.52 years, 0.06 m, mass 88.2 Ϯ 16.6 height 1.75 Ϯ 0.07 m, kg/m2 mass 108.93 Ϯ 18.44 kg Weidow et al, 2006 (5) Medial: n ϭ 15, M/F 0/15, On waiting list Medial Ahlback Bilateral: most Severe N ϭ 15, M/F 0/15, age age 66.27 Ϯ 8.0 years, BMI for total joint grade median: symptomatic knee 71.12 Ϯ 6.5 years, BMI 30 Ϯ 5.07 kg/m2 arthroplasty severe changes Medial and lateral 26 Ϯ 2.27 kg/m2 Lateral: n ϭ 15, M/F 0/15, age Lateral grade median: compartments 71.07 Ϯ 5.5 years, BMI moderate changes 27.35 Ϯ 3.95 kg/m2 Zeni and Higginson, Moderate: n ϭ 22, age 62.9 Ϯ KOOS Moderate: mild to Moderate N ϭ 22, age 58.9 Ϯ 11.4 2009 (3) 7.8 years, BMI 30.2 Ϯ moderate Severe years, BMI 24.9 Ϯ 4.6 kg/m2 Severe: severe 3.7 kg/m2 Severe: n ϭ 12, age 60.5 Ϯ changes 9.5 years, BMI 30.7 Ϯ 5.0 kg/m2 Zeni and Higginson, Moderate: n ϭ 21, age 63 Ϯ KOOS Moderate: mild to Moderate N ϭ 22, age 59 Ϯ 11 2009 (37) 9.3 years, height 1.66 Ϯ moderate Severe years, height 1.65 Ϯ 0.08 m, mass 81.19 Ϯ Severe: severe 0.05 m, mass 68.81 Ϯ 12.5 kg 9.5 kg Severe: n ϭ 13, age 59 Ϯ 9.8 years, height 1.7 Ϯ 0.11 m, mass 94.69 Ϯ 15 kg (continued) il tal et Mills Biomechanical Changes Associated With Knee OA 1653

sions) were also observed in individuals with severe KOA compared with those with moderate KOA (16,19). Individ- uals with medial compartment involvement exhibited re- duced peak hip adduction compared with individuals American 9 years, 0.05 m, 8.5 kg ϭ with lateral compartment KOA (5,21). A waveform analy- Ϯ Ϯ Ϯ sis of sagittal plane knee motion revealed that greater changes occurred in females with KOA compared with males (36); Short Form 36. 11 years however, this was not supported by a study examining dis- ϭ Ϯ 18, M/F 8/10, age 15, age 58 crete variables between females and males (4). ϭ ϭ 61 height 1.66 mass 70.13 N 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 com- pared KOA with healthy controls, while 19 compared joint moments between KOA subgroups (Table 3 and Figure 3). KOA versus controls. Comparisons involving individu- Severe Moderate N als 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 mal- Knee Osteoarthritis Outcome Score; SF-36 4. alignment exhibited reduced hip adduction moments (ES ϭ ϭ Ϫ0.96 [95% CI Ϫ1.4, Ϫ0.52], I2 ϭ 7% [19,33] and ES Ϫ0.73 [95% CI Ϫ1.06, Ϫ0.4], I2 ϭ 0% [5,16], respectively). In contrast, pooled data revealed limited evidence of an in-

symptomatic knee defined crease in peak hip abduction moment values (19,33) for Western Ontario and McMaster Universities Osteoarthritis Index; ACR Medial compartment Moderate Compartment not 3, and severe those with severe disease and varus malalignment and ϭ ϭ conflicting evidence regarding hip internal rotation mo- ment in those with severe nonvarus KOA compared with healthy controls (5,16). Regarding knee moments, the evi- (Cont’d) Knee Outcome Score; KOOS

2, moderate dence of alteration in the knee adduction moment associ- Յ ϭ ated with mild KOA was conflicting, although the pooled changes† OA description Severity Comparator cohort ϭ

Radiographic ES suggested small increases. For more severe and general Mild Bilateral: most moderate

Table 2. KOA cohorts, there was no evidence of a change in knee Moderate: mild to Severe: severe Ն adduction moment compared with healthy controls based body mass index; WOMAC

ϭ 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 visual analog scale; KOS

ϭ studies because both Astephen et al (16) and Weidow et al

KOOS (5) reported reductions. osteoarthritis; BMI Significant results of nonpooled comparisons between ϭ KOA and controls indicated that individuals with moder- ate KOA exhibited a moderate reduction in peak hip ad- duction moment (16,19) and small reductions in peak hip 7 years,

0.1 m, mass internal rotation, knee internal rotation, and knee flexion Ϯ 16, M/F 6/10, Ϯ

10 years moments (16,37). Those with mild KOA also exhibited a ϭ 8, M/F 3/5, age Ϯ 13.3 kg reduction in peak knee flexion moment (38), although ϭ 8 years

Ϯ there was no difference between individuals with mild Ϯ 30, age 63 Hospital for Special Surgery; VAS KOA and varus malalignment and controls (39). These ϭ ϭ age 62.8 62.2 height 1.71 86.83 findings were confirmed in waveform comparisons Severe: n N (32,34,36) (Table 3). An analysis of waveforms also re- SD unless otherwise indicated. OA vealed a larger knee adduction moment throughout stance Ϯ for individuals with mild (34) and moderate KOA (36) compared with healthy controls. This finding was sup- ported 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 non-

Author, year (ref.) OA cohort Clinical measures pooled data (25,37,42). Deluzio and Astephen (32) re- 2011 (62) * Values are theCollege mean of Rheumatology; HSS † Unless otherwise stated, radiographic changes are based on Kellgren/Lawrence grades: mild Zeni et al, 2010 (28) Moderate: n Zeni and Higginson, ported that individuals with severe KOA exhibited an increased average knee adduction moment throughout 1654 Mills et al

Table 3. Results of nonpooled data*

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Temporospatial Butler et al, 2011 Walking speed, Lateral Control Ϫ0.1 (Ϫ0.26, 0.06) 0.44 (21) m/second Medial Lateral 0.00 (Ϫ0.72, 0.72) 0.0 Creaby et al, 2012 Walking speed, Unilateral Control Ϫ0.27 (Ϫ0.37, 0.17) 1.59 (42) m/second Bilateral Control Ϫ0.22 (Ϫ0.30, Ϫ0.14) 1.3 Unilateral pain, Control Ϫ0.14 (Ϫ0.25, Ϫ0.03) 0.7 bilateral OA Unilateral Bilateral Ϫ0.05 (Ϫ0.13, 0.03) 0.32 Unilateral pain, Bilateral 0.08 (Ϫ0.02, 0.18) 0.44 bilateral OA Unilateral Unilateral pain, Ϫ0.13 (Ϫ0.25, 0.01) 0.66 bilateral OA Go¨k et al, 2002 (38) Stride duration, Mild Control 0.1 (Ϫ0.2, 0.22) 0.61 seconds Huang et al, 2008 Cadence, Mild Severe 4.3 (Ϫ4.20, 12.80) 0.35 (18) steps/minute Stride length, Mild Severe 0.03 (Ϫ0.11, 0.17) 0.15 % leg length Walking speed, Mild Severe 0.11 (Ϫ0.01, 0.23) 0.65 % height Hunt et al, 2010 Walking speed, Mild (varus) Control Ϫ0.1 (Ϫ0.2, 0.0) 0.6 (19) m/second Mild (varus) Severe (varus) 0.11 (0.02, 0.2) 0.68 Moderate (varus) Severe (varus) 0.04 (Ϫ0.05, 0.13) 0.24 Kaufman et al, 2001 Walking speed, Females Males Ϫ0.09 (Ϫ0.18, Ϫ0.52) 0.17 (45) m/second Ko et al, 2011 (44) Walking speed, Symptomatic OA Control P ϭ 0.153 m/second Asymptomatic Control P ϭ 0.076 Symptomatic OA Asymptomatic P ϭ 0.99† Krackow et al, 2011 Walking speed, Severe (tibial torsion) Control Ϫ0.36 (Ϫ0.57, Ϫ0.15) 1.54 (59) m/second Severe Severe 0.1 (Ϫ0.11, 0.31) 0.46 (tibial torsion) Landry et al, 2007 Stance duration (FW), Mild Control 0.02 (Ϫ0.01, 0.05) 0.3 (34) seconds Stride duration (FW), 0.01 (Ϫ0.03, 0.05) 0.1 seconds Stride length (FW), m 0.0 (Ϫ0.06, 0.06) 0.0 Walking speed (FW), Ϫ0.03 (Ϫ0.13, 0.07) 0.12 m/second Levinger et al, 2012 Stride length OA Control Ϫ0.2 (Ϫ0.25, Ϫ0.15) 1.98 (23) Liikavainio et al, Stride length OA (varus) Control 0.02 (Ϫ0.01, 0.05) 0.28 2010 (60) (1.2 m/second) Stride length OA (varus) Control 0.0 (Ϫ0.03, 0.03) 0.0 (1.5 m/second) Stride length OA (varus) Control 0.01 (Ϫ0.02, 0.04) 0.11 (1.7 m/second) Mu¨ ndermann et al, Walking speed, Mild Severe (varus) 0.01 (Ϫ0.13, 0.15) 0.04 2005 (33) m/second Rutherford et al, Walking speed, Mild to moderate Control Ϫ0.07 (Ϫ0.15, 0.01) 0.35 2008 (25) m/second Mild to moderate Severe 0.37 (0.27, 0.47) 1.6 Sahai et al, 2003 Walking speed, OA Control Ϫ0.34 (Ϫ0.53, Ϫ0.15) 1.29 (46) m/second Sims et al, 2009 (4) Stride length, % Females Males 0.03 (Ϫ0.03, 0.05) 0.26 height Walking speed, Females Males 0.06 (Ϫ0.05, 0.17) 0.28 m/second (continued) Biomechanical Changes Associated With Knee OA 1655

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Weidow et al, 2006 Cadence, strides/ Lateral Control Ϫ23.1 (Ϫ34.41, Ϫ11.79) 1.42 (5) minute Medial Lateral 6.4 (Ϫ6.13, 18.93) 0.36 Stride length, m Lateral Control Ϫ0.18 (Ϫ0.30, Ϫ0.06) 1.02 Medial Lateral 0.00 (Ϫ0.13, 0.13) 0.00 Walking speed, Lateral Control Ϫ0.43 (Ϫ0.60, Ϫ0.26) 1.78 m/second Medial Lateral 0.12 (Ϫ0.02, 0.26) 0.6 Zeni and Higginson, Cadence (FW), steps/ Moderate Control Ϫ9.45 (Ϫ17.86, Ϫ1.04) 0.65 2009 (3) minute Severe Control Ϫ10.09 (Ϫ22.92, 2.74) 0.58 Moderate Severe 0.64 (Ϫ11.67, 12.95) 0.04 Cadence (SS), Moderate Control Ϫ4.83 (Ϫ11.87, 2.21) 0.4 steps/minute Moderate Severe 3.1 (Ϫ9.72, 15.92) 0.19 Cadence (1.0 m/second), Moderate Control Ϫ1.28 (Ϫ6.36, 3.80) 0.15 steps/minute Severe Control 4.01 (Ϫ2.23, 10.25) 0.41 Moderate Severe Ϫ5.29 (Ϫ10.95, 0.37) 0.54 Stride duration (FW), Moderate Control 0.04 (Ϫ0.01, 0.09) 0.49 seconds Severe Control 0.1 (0.05, 0.15) 1.32 Moderate Severe Ϫ0.06 (Ϫ0.11, Ϫ0.01) 0.79 Stride duration (1.0 m/ Moderate Control Ϫ0.02 (Ϫ0.07, 0.03) 0.23 second), seconds Severe Control Ϫ0.01 (Ϫ0.07, 0.05) 0.12 Moderate Severe Ϫ0.01 (Ϫ0.07, 0.05) 0.11 Stride length (FW), Moderate Control Ϫ19.57 (Ϫ30.38, Ϫ8.76) 1.05 seconds Severe Control Ϫ25.19 (Ϫ40.73, Ϫ9.65) 1.19 Moderate Severe 5.62 (Ϫ9.6, 20.84) 0.28 Stride length (1.0 m/ Moderate Control Ϫ6.18 (Ϫ12.00, Ϫ0.36) 0.62 second), cm Severe Control 0.51 (Ϫ9.51, 10.53) 0.04 Moderate Severe Ϫ6.69 (Ϫ16.12, 2.74) 0.58 Walking speed (FW), Moderate Control Ϫ0.22 (Ϫ0.34, Ϫ0.1) 1.05 m/second Severe Control Ϫ0.32 (Ϫ0.47, Ϫ0.17) 1.49 Moderate Severe 0.1 (Ϫ0.05, 0.25) 0.48 Zeni et al, 2010 (28) Walking speed (FW), Moderate Control Ϫ0.22 (Ϫ0.36, Ϫ0.08) 1.02 m/second Severe Control Ϫ0.35 (Ϫ0.53, Ϫ0.17) 1.56 Moderate Severe 0.13 (Ϫ0.05, 0.31) 0.62 Zeni and Higginson, Walking speed (FW), Moderate Control Ϫ0.33 (Ϫ0.47, Ϫ0.19) 1.47 2011 (62) m/second Kinematics† Astephen et al, 2008 Knee flexion peak Severe Control Ϫ10.68 (Ϫ13.09, Ϫ8.27) 1.57 (16) during stance Moderate Severe 5.98 (3.6, 8.36) 0.89 Knee flexion excursion Moderate Control Ϫ2.5 (Ϫ4.91, Ϫ0.09) 0.37 Severe Control Ϫ18.6 (Ϫ22.92, Ϫ14.28) 1.52 Moderate Severe 16.1 (11.65, 20.55) 1.28 Knee peak flexion Moderate Control Ϫ2.7 (Ϫ5.2, Ϫ0.2) 0.38 Severe Control Ϫ18.1 (Ϫ22.25, Ϫ13.95) 1.53 Moderate Severe 15.4 (11.05, 19.75) 1.25 Baliunas et al, 2002 Knee extension OA (varus) Control Ϫ3.0 (Ϫ5.25, Ϫ0.75) 0.65 (41) Knee range of motion Ϫ6.0 (Ϫ9.03, Ϫ2.97) 0.97 Knee peak flexion Ϫ3.0 (Ϫ6.25, 0.25) 0.45 Bejek et al, 2005 Knee extension (1.0 m/ Severe Control Ϫ7.4 (Ϫ8.35, 6.45) 4.74 (31) second) Knee extension (2.0 m/ Ϫ8.5 (Ϫ9.38, Ϫ7.62) 5.89 second) Knee extension (3.0 m/ Ϫ8.7 (Ϫ9.38, Ϫ7.62) 4.87 second) Knee peak flexion Ϫ18.0 (Ϫ22.70, Ϫ13.3) 2.33 (1.0 m/second) Knee peak flexion Ϫ23.1 (Ϫ26.42, Ϫ19.78) 4.22 (2.0 m/second) Knee peak flexion Ϫ28.0 (Ϫ31.57, Ϫ24.43) 4.77 (3.0 m/second) (continued) 1656 Mills et al

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Knee range of motion Ϫ25.4 (Ϫ30.95, Ϫ19.85) 2.78 (1.0 m/second) Knee range of motion Ϫ31.5 (Ϫ36.75, Ϫ26.25) 3.64 (2.0 m/second) Knee range of motion Ϫ37.0 (Ϫ42.35, Ϫ31.65) 4.87 (3.0 m/second) Butler et al, 2011 Hip peak adduction Medial Control Ϫ1.5 (Ϫ3.60, 0.60) 0.5 (21) Lateral Control 1.4 (Ϫ1.0, 3.8) 0.41 Medial Lateral Ϫ2.9 (Ϫ5.04, Ϫ0.76) 0.95 Creaby et al, 2012 Lateral trunk lean Unilateral Control 3.0 (2.53, 3.47) 5.29 (42) (average) Unilateral pain, Control 2.20 (1.85, 2.55) 4.46 bilateral OA Bilateral Control 2.14 (1.88, 2.4) 5.11 Unilateral Bilateral 0.86 (0.41, 1.31) 1.99 Unilateral pain, Bilateral 0.06 (Ϫ1.17, 1.29) 0.15 bilateral OA Unilateral Unilateral pain, 0.8 (0.31, 1.29) 1.31 bilateral OA Knee peak flexion Unilateral Control Ϫ4.61 (Ϫ5.91, Ϫ3.31) 2.94 Unilateral pain, Control Ϫ6.71 (Ϫ7.67, Ϫ5.75) 4.88 bilateral OA Bilateral Control Ϫ6.44 (Ϫ6.96, Ϫ5.92) 5.89 Unilateral Bilateral 1.83 (0.59, 3.07) 1.54 Unilateral pain, Bilateral Ϫ0.27 (Ϫ0.92, 0.38) 0.24 bilateral OA Unilateral Unilateral pain, 1.23 (0.44, 2.02) 0.21 bilateral OA Go¨k et al, 2002 Knee flexion peak Mild Control Ϫ4.0 (Ϫ7.73, Ϫ0.27) 0.8 (38) during stance Deluzio and Knee range of motion Severe Control PCA: OA patients had Astephen, 2007 Knee peak flexion less range of motion (32) PCA: of OA patients were less flexed throughout the gait cycle Huang et al, 2008 Hip peak adduction Mild Control Ϫ1.55 (Ϫ4.96, 1.86) 0.32 (18) Mild Severe 1.48 (Ϫ1.65, 4.61) 0.33 Knee flexion during Mild Control Ϫ2.21 (Ϫ8.18, 3.76) 0.26 loading (excursion) Severe Control Ϫ7.48 (Ϫ13.08, Ϫ1.88) 0.93 Mild Severe 5.27 (0.22, 10.32) 0.73 Hunt et al, 2010 Lateral trunk lean Mild (varus) Control 0.7 (Ϫ0.61, 2.01) 0.31 (19) (peak) Moderate (varus) Control 1.5 (0.19, 2.81) 0.67 Severe (varus) Control 3.4 (2.04, 4.76) 1.46 Mild (varus) Moderate (varus) Ϫ0.8 (Ϫ1.91, 0.31) 0.39 Mild (varus) Severe (varus) Ϫ2.7 (Ϫ3.87, Ϫ1.53) 1.26 Moderate (varus) Severe (varus) Ϫ1.9 (Ϫ3.07, Ϫ0.73) 0.89 Hip peak adduction Mild (varus) Control Ϫ0.8 (Ϫ2.79, 1.19) 0.23 Moderate (varus) Control Ϫ3.0 (Ϫ5.07, Ϫ0.93) 0.81 Severe (varus) Control Ϫ4.4 (Ϫ6.45, Ϫ2.35) 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 (Ϫ0.79, 3.59) 0.35 Ko et al, 2011 (44) Knee range of motion Symptomatic OA Control P ϭ 0.403 Asymptomatic Control P ϭ 0.207 Symptomatic OA Asymptomatic P ϭ 0.987§ (continued) Biomechanical Changes Associated With Knee OA 1657

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Landry et al, 2007 Knee range of motion Mild Control PCA: walking faster (34) (FW) increased knee range Knee range of motion of motion and phase- (SS) shifted angles throughout the stride in both groups. No difference between groups Linley et al, 2010 Lateral trunk lean Mild Control 0.0 (Ϫ0.79, 0.79) 0.00 (35) (peak) Manetta et al, 2002 Knee flexion during OA Control Ϫ3.1 (Ϫ8.8, 2.6) 0.46 (24) loading (peak) McGibbon and Knee range of motion OA Control PCA: OA patients Krebs, 2002 (61) extended knee in mid to late stance and flexed knee less in swing McKean et al, 2007 Knee flexion Mild to moderate Control PCA: OA patients (36) excursion exhibited smaller knee flexion angles throughout the entire gait cycle Knee range of motion Females Controls and PCA: females with OA males exhibited less range of motion during stance phase than controls and males with OA Mu¨ ndermann et al, Knee extension Mild Control Ϫ4.09 (Ϫ6.48, Ϫ1.70) 1.07 2005 (33) Severe (varus) Control 2.32 (Ϫ3.91, 8.55) 0.21 Mild Severe (varus) Ϫ4.66 (Ϫ7.72, Ϫ1.60) 0.87 Knee flexion at initial Mild Control Ϫ7.08 (Ϫ11.93, Ϫ2.23) 0.91 contact Severe (varus) Control Ϫ3.75 (Ϫ9.61, 2.09) 0.5 Mild Severe (varus) Ϫ2.68 (Ϫ4.83, Ϫ0.53) 0.74 Rudolph et al, Knee flexion at initial Moderate (varus) Control 1.09 (Ϫ2.6, 4.78) 0.21 2007 (6) contact Schmitt and Knee flexion Mild (varus) Control Ϫ2.6 (Ϫ4.98, Ϫ0.22) 0.57 Rudolph, 2007 excursion (39) Sims et al, 2009 (4) Knee range of motion Females Males 0.94 (Ϫ2.37, 4.25) 0.15 Weidow et al, Hip peak adduction Lateral Control 3.46 (2.15, 4.77) 1.83 2006 (5) Medial Lateral Ϫ9.53 (Ϫ10.78, Ϫ8.28) 5.29 Knee peak extension Medial Control 5.67 (Ϫ8.3, Ϫ3.04) 1.5 Lateral Control Ϫ5.0 (Ϫ7.39, Ϫ2.61) 1.46 Medial Lateral Ϫ0.67 (Ϫ3.19, 1.85) 0.19 Knee peak flexion Medial Control Ϫ9.4 (Ϫ12.79, Ϫ6.01) 1.93 Lateral Control Ϫ10.87 (Ϫ14.18, Ϫ7.56) 2.29 Medial Lateral 1.47 (Ϫ3.00, 5.94) 0.23 Joint moments‡ Astephen et al, Hip peak adduction Moderate Control Ϫ0.18 (Ϫ0.28, Ϫ0.08) 0.66 2008 (16) moment stance, Moderate Severe 0.03 (Ϫ0.08, 0.14) 0.1 Nm/kg Hip peak internal Moderate Control Ϫ0.04 (Ϫ0.07, 0.00) 0.4 rotation moment, Moderate Severe 0.04 (0.02, 0.07) 0.62 Nm/kg Knee peak flexion Moderate Control Ϫ0.12 (Ϫ0.21, Ϫ0.03) 0.46 moment, Nm/kg Moderate Severe 0.07 (Ϫ0.00, 0.14) 0.33 Knee peak internal Moderate Control Ϫ0.02 (Ϫ0.04, 0.00) 0.32 rotation moment, Moderate Severe 0.07 (0.04, 0.1) 0.92 Nm/kg (continued) 1658 Mills et al

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Baliunas et al, Knee peak adduction OA (varus) Control OA group was 2002 (41) moment, Nm/kg significantly higher and m (P ϭ 0.003) Butler et al, 2011 Hip peak adduction Medial Control 0.00 (Ϫ0.72, 0.72) 0.00 (21) moment, Nm/kg Lateral Control 0.03 (Ϫ0.05, 0.11) 0.25 and m Medial Lateral Ϫ0.03 (Ϫ0.12, 0.06) 0.24 Knee peak adduction Lateral Control Ϫ0.14 (Ϫ0.21, Ϫ0.07) 1.42 moment, Nm/kg Medial Lateral 0.23 (0.16, 0.3) 2.33 and m Creaby et al, 2012 Knee peak adduction Unilateral Control Ϫ0.19 (Ϫ0.38, 0.0) 0.84 (42) moment, Nm/kg Unilateral pain, Control Ϫ0.1 (Ϫ0.21, 0.0) 0.5 and m bilateral OA Bilateral Control Ϫ0.26 (Ϫ0.34, Ϫ0.18) 1.67 Unilateral Bilateral 0.07 (Ϫ0.11, 0.25) 0.41 Unilateral pain, Bilateral 0.16 (Ϫ0.07, 0.25) 1.01 bilateral OA Unilateral Unilateral pain, Ϫ0.09 (Ϫ0.29, 0.11) 0.36 bilateral OA Knee peak flexion Unilateral pain, Control Ϫ1.97 (Ϫ2.11, Ϫ1.83) 7.51 moment, Nm/kg bilateral OA and m Bilateral Control Ϫ2.09 (Ϫ2.19, Ϫ1.99) 10.26 Unilateral Bilateral 0.51 (Ϫ0.28, 0.74) 2.33 Unilateral pain, Bilateral 0.12 (0.0, 0.24) 0.59 bilateral OA Unilateral Unilateral pain, 0.39 (0.14, 0.64) 1.23 bilateral OA Go¨k et al, 2002 Knee peak flexion Mild Control Ϫ0.21 (Ϫ0.38, Ϫ0.04) 0.9 (38) moment, Nm/kg Deluzio and Knee peak adduction Severe Control PCA: OA patients Astephen, 2007 moment, Nm/kg exhibited a higher (32) average moment, but a lower moment during early stance Knee peak flexion PCA: OA patients moment, Nm/kg 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 Hip peak adduction Mild (varus) Control Ϫ0.43 (Ϫ0.94, 0.08) 0.46 (19) moment, Nm/kg Moderate (varus) Control Ϫ0.71 (Ϫ1.26, Ϫ0.16) 0.70 and m Mild (varus) Moderate (varus) 0.28 (Ϫ0.3, 0.86) 0.26 Mild (varus) Severe (varus) 0.69 (0.16, 1.22) 0.71 Moderate (varus) Severe (varus) 0.41 (Ϫ0.16, 0.98) 0.39 Hip peak abduction Mild (varus) Control 0.28 (Ϫ0.39, 0.95) 0.23 moment, Nm/kg Moderate (varus) Control 0.37 (Ϫ0.34, 1.08) 0.28 and m Mild (varus) Moderate (varus) Ϫ0.09 (Ϫ0.8, 0.62) 0.07 Mild (varus) Severe (varus) Ϫ0.62 (Ϫ1.48, 0.24) 0.39 Moderate (varus) Severe (varus) Ϫ0.53 (Ϫ1.42, 0.36) 0.32 Knee peak adduction Mild (varus) Moderate (varus) Ϫ0.04 (Ϫ0.61, 0.53) 0.04 moment, Nm/kg Moderate (varus) Severe (varus) Ϫ0.14 (Ϫ0.7, 0.42) 0.14 and m (continued) Biomechanical Changes Associated With Knee OA 1659

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Hurwitz et al, 2002 Knee peak adduction OA (varus) Control OA group was (40) moment, Nm/kg significantly higher and m (P ϭ 0.027) Kaufman et al, Knee peak adduction Females Males Ϫ0.08 (Ϫ0.2, 0.36) 0.1 2001 (45) moment, Nm/kg and m Knee peak flexion Ϫ0.16 (Ϫ0.42, 0.1) 0.22 moment, Nm/kg and m Knee peak internal 0.09 (Ϫ0.02, 0.2) 0.3 rotation moment, Nm/kg and m Landry et al, 2007 Knee peak adduction Mild Control PCA: OA patients (34) moment, Nm/kg exhibited larger overall adduction moments during stance in both fast walking and preferred speeds Knee peak flexion PCA: OA patients moment, Nm/kg exhibited smaller flexion moments at both fast and preferred speeds Linley et al, 2010 Hip peak adduction Mild Control 0.02 (Ϫ0.03, 0.07) 0.17 (35) moment, Nm/kg McKean et al, 2007 Hip peak internal Moderate Control PCA: OA patients (36) rotation moment, walked with a Nm/kg smaller internal/external rotation moment and more internally rotated hip Knee peak adduction Females Controls and PCA: OA females moment, Nm/kg males exhibited lower magnitude than controls and OA males Knee peak flexion Females Controls and PCA: OA females moment, Nm/kg males exhibited lower moment than controls and OA males Knee internal rotation Females Controls and PCA: OA females moment, Nm/kg males exhibited lower knee internal rotation moment during stance than controls and OA males Messier et al, 2005 Knee peak internal OA Control Ϫ0.03 (Ϫ0.05, 0.01) 1.44 (47) rotation moment Mu¨ ndermann et al, Hip peak adduction Mild Control Ϫ0.13 (Ϫ0.66, 0.40) 0.15 2005 (33) moment, Nm/kg Mild Severe (varus) 0.52 (Ϫ0.06, 1.10) 0.54 and m Hip peak abduction Mild Control 0.97 (0.14, 1.81) 0.73 moment, Nm/kg Mild Severe (varus) Ϫ0.57 (Ϫ1.45, 0.31) 0.41 and m Knee peak adduction Mild Severe (varus) Ϫ0.79 (Ϫ1.28, Ϫ0.40) 1.17 moment, Nm/kg and m (continued) 1660 Mills et al

Table 3. (Cont’d)

Mean difference Authors Outcome Study group Comparator (95% CI) ES

Rutherford et al, Knee peak adduction Mild to moderate Control PCA: the mild to 2008 (25) moment, Nm/kg Severe Control 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 Knee peak flexion Mild (varus) Control 0.00 (Ϫ0.53, 0.53) 0.00 Rudolph, 2007 moment, Nm/kg (39) and m Sims et al, 2009 (4) Hip peak abduction Females Males 0.04 (Ϫ0.08, 0.17) 0.18 moment, Nm/kg Knee peak adduction Ϫ0.13 (Ϫ0.22, Ϫ0.03) 0.7 moment, Nm/kg Weidow et al, 2006 Hip peak adduction Lateral Control Ϫ0.18 (Ϫ0.28, Ϫ0.08) 1.29 (5) moment, Nm/kg Medial Lateral 0.05 (Ϫ0.05, 0.15) 0.34 Hip peak abduction Medial Control 0.02 (Ϫ0.06, 0.1) 0.17 moment, Nm/kg Lateral Control 0.13 (0.07, 0.19) 1.45 Medial Lateral Ϫ0.11 (Ϫ0.17, Ϫ0.05) 1.33 Hip peak internal Lateral Control 0.03 (Ϫ0.02, 0.08) 0.45 rotation moment, Medial Lateral Ϫ0.05 (Ϫ0.1, 0.00) 0.65 Nm/kg Knee peak adduction Medial Control 0.18 (0.06, 0.30) 1.09 moment, Nm/kg Lateral Control Ϫ0.32 (Ϫ0.42, Ϫ0.21) 2.32 Medial Lateral 0.50 (0.42, 0.58) 4.52 Knee peak flexion Lateral Control Ϫ0.21 (Ϫ0.34, Ϫ0.08) 1.14 moment, Nm/kg Medial Lateral Ϫ0.08 (Ϫ0.20, 0.04) 0.46 Knee peak internal Lateral Control Ϫ0.01 (Ϫ0.02, 0.00) 0.49 rotation moment, Medial Lateral 0.0 (Ϫ0.02, 0.02) 0.0 Nm/kg Zeni and Knee peak adduction Moderate Control No difference reported Higginson, moment, Nm/kg Severe No difference reported 2011 (62) Knee peak flexion Moderate At SS, there was moment, Nm/kg significant reduction Severe At both SS and FW, there were significant reductions

* 95% CI ϭ 95% confidence interval; ES ϭ effect size; OA ϭ osteoarthritis; FW ϭ fast walking; SS ϭ self-selected speed; PCA ϭ principle components analysis. † Authors did not provide estimates of variability. ‡ All kinematic measurements are in degrees. All joint moments are external moments. § Authors did not provide measures of variance.

stance, but this was reduced (compared with controls) ment between individuals with mild and severe KOA with during early stance. Rutherford et al (25) reported a change varus malalignment (19,43) (Figure 3). Similar findings in shape of the knee adduction moment waveform in in- have been reported when comparing individuals with dividuals with severe KOA compared with controls and mild KOA and varus malalignment with those with mod- those with moderate KOA, but reported no change in am- erate KOA and varus malalignment as well as those with plitude. moderate and severe disease and varus malalignment (19). Between KOA subgroups. The only data meeting criteria Significant increases in knee adduction moment were re- for pooling indicated no difference in knee adduction mo- ported in individuals with primarily medial compartment Biomechanical Changes Associated With Knee OA 1661

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 ϭ osteoarthritis; %BH ϭ percentage of body height. involvement compared with those with lateral KOA (5,21) dial compartment KOA was larger than those with lateral and in males with KOA compared with females (4,36) compartment involvement (5). (Table 3). Of the remaining comparisons between KOA cohorts, DISCUSSION there was a moderately increased hip internal rotation moment and knee internal rotation moment in individuals A comprehensive search of the literature revealed that with moderate KOA when compared with severe KOA individuals with KOA exhibited a variety of biomechani- (16). Hunt et al (19) reported that individuals with mild cal alterations during gait compared with their healthy KOA and varus malalignment exhibited a moderate in- counterparts. However, the only gait alteration with strong crease in hip adduction moment compared with individ- and consistent evidence was increased stride duration for uals with severe KOA and varus malalignment. However, those with severe KOA compared with healthy controls. this was not supported by the findings of Mu¨ ndermann et Moderate evidence indicated that individuals with mod- al (33), whose mild KOA group exhibited normal align- erate KOA (varus malalignment only) exhibited reduced ment. The hip abduction moment in individuals with me- knee flexion excursion during loading, peak knee flexion, 1662 Mills et al

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 ϭ osteoarthritis; Nm/kg*m ϭ Nm/kg and meters; IC ϭ initial contact. and walking speed, while individuals with severe KOA horts, some studies considered radiographic and clinical (varus malalignment only) reduced their cadence and hip findings (3,26,30,32,37), while other studies solely refer- adduction moment. Those with severe KOA also increased enced radiographic changes (19,33) and others used radio- their stride duration compared with those with moderate graphs to confirm the presence of KOA but only reported disease. There was limited evidence for general KOA co- clinical findings (44–47). The lack of homogeneity in KOA horts exhibiting reduced knee flexion excursion during description and classification schemes highlights the need loading and increased knee flexion at IC compared with for standard classification systems to be used and reported healthy controls. Similarly, limited evidence indicated in future studies. that individuals with moderate (nonvarus) KOA exhib- The key findings from nonpooled data indicated that ited reduced walking speed (although faster than those temporospatial and kinematic gait alterations associated with severe KOA) and individuals with severe KOA and with KOA increased in magnitude with increasing disease varus malalignment exhibited increased hip abduction severity. Therefore, individuals with severe KOA exhib- moments. The remaining pooled data resulted in conflict- ited the greatest alterations, while there were few differ- ing or no evidence of biomechanical alterations. ences observed between those with mild KOA and con- A likely cause of conflicting evidence was the high trols. There was insufficient evidence to support or refute amount of heterogeneity between pooled publications. the influence of mechanical alignment, the involved com- While K/L grade was primarily used to determine disease partment, sex, and symptoms on most of the biomechani- severity, the Ahlback scale (5,17,38) and magnetic reso- cal variables examined. However, in joint moment com- nance imaging (20,29) were also utilized. Furthermore, not parisons, larger moments were observed in milder KOA all studies described the mechanical axis alignment of severities, except for knee adduction moment, where there their cohorts. When classifying the severity of KOA co- were no differences between KOA subgroups. For knee Biomechanical Changes Associated With Knee OA 1663 adduction moment, those with medial compartment in- adverse effects are speculated. Longitudinal data are re- volvement and males were reported to exhibit larger mo- quired to make a causative statement regarding gait adap- ments. tions and KOA progression, which is beyond the scope of It has been suggested that individuals with KOA adopt this review. gait strategies that result in immediate reduction in knee Along with the lack of homogeneity in disease severity joint load, particularly medial compartment load (33,48). classification and dearth of long-term studies, several This is particularly pertinent for individuals with primar- other methodologic factors influenced and limited the ily medial compartment KOA, who constitute the majority findings of this review. The external and internal validity of individuals examined in the studies included in this of the included publications was limited because the pub- review. The present data support this hypothesis because lications did not provide sufficient information regarding there was no evidence of increased knee adduction mo- participant recruitment and did not blind assessors to ment, which is a proxy for medial knee joint load (49). group allocation/KOA diagnosis. It must be acknowledged Likewise, although pooled evidence was conflicting, knee that such limitations affect the validity of the findings of flexion and internal rotation moments were also reduced this review; however, this should be counterbalanced by (more so in those with severe KOA). These moments have the increased precision gained from data synthesis. An- been correlated with the magnitude of adduction moment other limitation is that there is currently no consensus and compressive knee load in KOA (50,51). regarding an accepted standard reference frame for calcu- The lack of evidence of alterations in knee adduction lating joint moments and no consensus on whether walk- moment is surprising (although similar to findings from a ing speed is considered a confounding factor in publica- previous systematic review examining knee adduction tions where participants set their own speed. Both of these moment [52]), given the importance of this variable in the factors have been shown to influence the magnitude of progression of KOA (53) and the large number of studies joint moments (16,57) and make comparisons across pub- that have utilized knee adduction moment as a primary lications difficult. Similarly, there is no standard for nor- outcome. It is likely that alterations in knee adduction malizing external joint moments. Normalizing moments moment are driven by alterations of known moment-mod- by height and body weight has the smallest residual effect ifying gait characteristics. A recent systematic review re- on joint moments, but may also overcorrect data relative to ported that increased lateral trunk lean demonstrated the normalizing by body weight only due to the correlation largest reductions in early stance knee adduction moment between height and body weight (58). However, by choos- (54), with other kinematic alterations such as foot progres- ing to pool data based on point estimates of effect rather sion angle and walking speed also affecting knee adduc- than mean differences, such comparisons were possible tion moment magnitudes. In the current study, the magni- regardless of joint reference frame, walking speed, and tude of trunk lean and resultant alterations at the hip normalization protocol. (reduced hip adduction moment and increased hip abduc- In summary, there is a range of evidence indicating that tion moment and peak abduction) was greatest in those individuals with KOA exhibit altered gait biomechanics with severe KOA. Similarly, changes in temporospatial during gait compared with those without KOA. The ma- characteristics (i.e., walking speed, cadence, and stride jority of strong and moderate evidence is for adaptations length) were also greatest in those with severe KOA. Such occurring in the temporospatial domain, whereas evidence changes potentially decrease the ground reaction forces, for kinematic and joint moment change is primarily lim- moment , and cumulative load acting on the knee joint ited or conflicting. An interesting finding from the present (55) and potentially explain why, unlike Foroughi et al data synthesis is the lack of evidence from pooled and (52), we did not find that the knee adduction moment discrete data for alterations in knee external adduction increased with severity of KOA. In contrast, those with moment. This was likely due to changes in known mo- mild KOA demonstrated the smallest number and magni- ment-modifying gait characteristics such as lateral trunk tude of kinematic and temporospatial alterations while lean and temporospatial characteristics, all of which were demonstrating small increases in the knee adduction mo- more altered in those with more severe KOA. However, ment. Therefore, this review demonstrates that differences some gait adaptations such as decreased knee motion are in knee adduction moment between individuals with KOA theorized to have long-term adverse effects on the joint. and healthy controls are not guaranteed and can poten- Therefore, further research into the long-term effects of tially be explained by kinematic and temporospatial dif- consistently occurring biomechanical gait adaptations, as ferences. identified by this review, is needed. Such research would While some observed gait alterations might reflect at- benefit from a standardized KOA classification system that tempts to reduce pain and protect the knee in the short encompasses radiographic and clinical findings and in- term, they may have long-term adverse effects. Specifi- cludes measurement of mechanical axis alignment. cally, it has been postulated that gait modification strate- gies that are successful in reducing joint loading and/or pain are attenuated by increased knee flexion excursion/ AUTHOR CONTRIBUTIONS angles (51). Childs et al (56) hypothesized that reduced knee motion stiffens the knee, making it less capable of All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors ap- dissipating potentially harmful localized impact loads. A proved the final version to be published. Dr. Ferber had full access caveat to these long-term effects is that this review was to all of the data in the study and takes responsibility for the limited to cross-sectional studies, meaning that the above integrity of the data and the accuracy of the data analysis. 1664 Mills et al

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