This document provides an overview of biomechanical factors related to clinical progression versus structural progression of knee osteoarthritis. It summarizes several gait studies that investigated relationships between joint moments, muscle activation patterns, and structural or clinical progression of OA as measured by imaging or joint replacement. Key findings included that higher knee adduction moment magnitude and less unloading were related to clinical progression, while structural progression was more linked to higher medial compartment loading ratios and prolonged muscle activity. The document discusses implications for developing personalized interventions targeting gait biomechanics to manage clinical progression of knee OA.

1. 1
Cheryl Hubley-Kozey, PhD
Schools of Physiotherapy and Biomedical Engineering
Biomechanical Factors Related to
Clinical vs. Structural Progression of
Knee OA
Kozey-Hubley 2019

2. 2
I have no conflicts to declare.
Non-disclosure
Kozey-Hubley 2019

3. IMPACT TEAM
Innovation in Musculoskeletal Health and
Physical Activity Team
3
Principal Investigators:
Dr. Janie Astephen Wilson, BME
Dr. Cheryl Kozey, Physiotherapy/BME
Dr. Michael Dunbar, Surgery/BME
Dr. William Stanish, Surgery/BME
Dr. Derek Rutherford, Physiotherapy
Dr. Rebecca Moyer, Physiotherapy
Dr. Jason McDougall, Phamacology
Dr. Scott Grandy, Kinesiology
Former grad students:
Dr. Gillian Hatfield
Dr. Kerry Costello
Research Personnel:
Dianne Ikeda
Kozey-Hubley 2019

4. Purpose
• To provide an overview of the in vivo human gait
studies investigating biomechanical factors related to
clinical (i.e. evidence of structural damage and
symptoms) versus structural severity/progression in
knee osteoarthritis (OA).
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Kozey-Hubley 2019

5. KNEE OSTEOARTHRITIS (OA)
• Degenerative Joint Disorder
• Not a normal aging process
• Hallmark is articular cartilage degradation
• But bone,muscle, nerves etc. (Brandt, 2006)
• OAdiagnosis (Altman, 1986)
• Clinicalevidence (pain, stiffnessetc.)
• Structural damage(Imaging)
• Structural progression
• Disease component(Lane et al, 2011)
• Imaging (Radiographs,MRI)
• Clinical progression
• Illness and disease component(Laneet al, 2011)
• Totaljoint replacement (Gossec et al, 2011)
• Biomechanical insults trigger biochemical responses
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6. STRUCTURE/
FUNCTIONAL
IMPAIRMENT
ACTIVITY
LIMITATIONS/
ALTERATIONSImpacts Movement
Impacts Pathology
KNEE OSTEOARTHRITIS
Hubley-Kozey & Astephen Wilson, Handbook of Human Motion, 2017 6
Kozey-Hubley 2019

7. Gait model of biomechanical factors
Muscle responses
Reflex or learned
Co-activation
KAM magnitudeKFM magnitude
Stresses on tissues
Distribution
Lateral ligaments
Capsule
+
effusion
and pain
7Modified Andriacchi and Favre, 2014
Kozey-Hubley 2019

8. .
Gait Metrics of Knee OA Severity
Sagittal plane moments
KFM – peak
KEM – peaks
KFM-KEM range
KFM patterns
Fontal plane moments
KAM peaks
KAM impulse
KAM mid stance amplitudes
KAM patterns
Musculature
Quadriceps/ hamstrings –
Systematic amplitude increases
site specific
generalized
Prolonged activation
site specific not systematic
general
Altered patterns
Structural severity based on imaging
8
+
Astephen Wilson, 2008, 2011, 2016; Childs’s 2004; Hubley-Kozey, 2006, 2009;
Lewek, 2004; Rutherford, 2011,2013: Thorp, 2006, 2007; Zeni, 2009, 2010;
Clinical severity based on function and treatment
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9. 9
Structural severity based on imaging KL I-IV
Metrics of Knee OA SEVERITY
Asymptomatic Moderate OA Severe OA
Sagittal plane moments
KFM – peak
KEM – late stance
KFM-KEM range
KFM patterns
Fontal plane moments
KAM peaks
KAM impulse
KAM mid stance amplitudes
KAM patterns
Astephen Wilson, 2008, 2011, 2016; Childs’s 2004; Hubley-Kozey, 2006, 2009;
Lewek, 2004; Rutherford, 2011,2013: Thorp, 2006, 2007; Zeni, 2009, 2010;
Musculature
Quadriceps/ hamstrings –
Systematic amplitude increases
site specific
generalized
Prolonged activation
site specific not systematic
general
Altered patterns
Blue- ASYM
Dashed-Mod
Dotted Severe
Kozey-Hubley 2019

10. STRUCTURE/
FUNCTIONAL
IMPAIRMENT
ACTIVITY
LIMITATIONS/
ALTERATIONSImpacts Movement
Impacts Pathology
KNEE OSTEOARTHRITIS
Hubley-Kozey & Astephen Wilson, Handbook of Human Motion, 2017 10
Kozey-Hubley 2019

11. Study KAM
(PG)
KFM
(PG)
KRM
(PG)
EMG
(PG)
Progression
metric
Follow-up
(years)
Bennell et al. 2011 • Peak not different
• Impulse higher
MRI 1
Brisson et al. 2017 • Peak higher
(in higher BMI)
• Impulse higher
(in higher BMI)
Peak NSD MRI 2.5
Chang et al. 2007 • Peaks higher MRI 1.5
Chang et al. 2015 • Peak higher
• Impulse higher
• Peak NSD MRI 2
Chehab et al. 2014 • Peak higher • Peak higher MRI 5
Miyazaki et al. 2002 • Peak higher Radiographs 6
Woollard et al. 2011 • Peak higher MRI 1
Davis et al., 2019 • Peak higher
• Lower early to mid
stance difference
• Peak NSD Greater range LH higher
LH prolonged
activity
Radiographs 3.0
Hodges et al., 2015 Medial sites
longer co-
activation
duration
MRI 1
Gait studies: joint load & structural OA progression
11Modified from Costello 2018
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12. 12
Gait metrics and Clinical OA progression
Moments
KAM magnitude
KAM early to mid stance
KFM–KEM difference
Total joint replacement outcome
No differences in demographics, radiographic features or muscle strength
Hatfield et al., ACR 2015; Clin Biomech, 2015
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13. 13
Gait metrics and Clinical OA progression
Moments
KAM magnitude
KAM early to mid stance
KFM–KEM difference
Total joint replacement outcome
No differences in demographics, radiographic features or muscle strength
Hatfield et al., ACR 2015; Clin Biomech, 2015
74% CCR, odds ratio 5.8
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14. 14
Muscle activation
Higher overall hamstring
magnitude
Prolonged quadriceps &
Hamstrings activity
Higher lateral site
Co-activation
Blk- ASYM
Blue- No TKA
Red- TKA
Total joint replacement outcome
No differences in demographics, radiographic features or muscle strength
Gait metrics and Clinical OA progression
Hubley-Kozey et al., OAC 2013; Hatfield ACR (under review)
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15. Data types
in model
CCR Odds Ratio (OR)
for clinical
progression
Moments 70.5 % 2.8
EMG 69.2 % 2.0
Covariates 67.9 % 2.4
Moments
+ EMG
79.5 % 4.1
Moments
+ EMG
+ Covariates
80.8 % 4.8
15
Clinical Progression Models
Costello Dissertation 2018
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16. Structural progression
• KAM higher ratio of medial to lateral loading
• KFM equivocal
• Longer duration of medial site activity
• More prolonged LH activity
Clinical progression
• KAM higher magnitude and less unloading
• KFM less unloading
• Muscle activation: both magnitude and patterns
• Higher overall amplitudes in hamstrings
• More prolonged quadriceps and hamstrings activity
Structural vs Clinical Progression
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17. 17
Overall KAM or KFM
magnitude features (PC1)
are not well correlated with
overall amplitude (PC1) or
prolonged (PC2) muscle
activity
Muscle Activation and Joint Moment Patterns
Hubley-Kozey et al.,OARSI 2018 (O&C v26, s1, pp19-s20)
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18. 18
0 20 40 60 80 100
Percent Gait Cycle
-0.5
0
0.5
1
Moment(Nm/kg)
KAM of High/Low KAMPC2
High
Low
0 20 40 60 80 100
Percent Gait Cycle
-1
-0.5
0
0.5
1
Moment(Nm/kg)
KFM of High/Low KFMPC2
High
Low
0 20 40 60 80 100
Percent Gait Cycle
0
20
40
60
80
100
MuscleActivity(%MVIC)
Muscle Activity of High/Low LHPC2
High
Low
0 20 40 60 80 100
Percent Gait Cycle
0
20
40
60
80
MuscleActivity(%MVIC)
Muscle Activity of High/Low VLPC2
High
Low
-150 -100 -50 0 50 100 150
LHPC2 (Prolonged Activity)
-1
0
1
2
KAMPC2
(Early-midStanceDiff)
KAMPC2 and LHPC2 Correlation (r = -0.41)
-150 -100 -50 0 50 100
VLPC2 (Prolonged Activity)
-2
0
2
4
6
KFMPC2
(Flex-ExtMomentDiff)
KFMPC2 and VLPC2 Correlation (r = -0.65)
KFM and KAM unloading
(PC2) and Prolonged
activation (PC2) of quads
and hamstrings correlated
73% variance in KFM and
44% in KAM unloading
explained by muscle
activation patterns
Muscle Activation and Joint Moment Patterns
Hubley-Kozey et al., OARSI 2018 (O&C v26, s1, pp19-s20)
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19. • Explant and animal models:
• loading magnitude, duration, frequency and patterns trigger
biochemical and structural changes (Brandt, 2003, Griffin&Guilak, 2005,
Moyer et al, 2014)
• Sustained loading leads to
• Disruption in cartilage synthesis (Chen, 1999; Femor, 2001,Kim, 2012,
Abusara, 2013)
• Increased expression of inflammatory biomarkers (Sakai , 1997,
Chen, 1999)
• Worsening of knee pain (Stannus, 2013; Wang, 2007)
• Static low level muscle activation
• chondrocyte death versus cyclic loading (Horizberger, 2012, 2013)
Mechanistic Study and Loading
19
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20. Gait Studies: Biochemical Biomarkers
• Human studies of joint loading and biochemical
biomarkers (Cattano et al., 2017)
• Loading and COMP (cartilage oligomeric matrix protein)
• 30 Minutes of walking increase COMP in knee OA (6.3%) and age-
matched controls (5.2%) (Mündermann et al., 2009)
• Subset cohort: COMP at 5.5 hr post walk predicted medial compartment
cartilage loss at 5-year follow-up (Erhart-Hledik et al., 2012)
• Cartilage synthesis versus cartilage degradation markers (Chu et al, 2017)
• Loading and inflammatory cytokines
• Pre-OA group asymptomatic but evidence of cartilage damage (n=52)
versus Controls (n=26) (Edd et al., 2017)
• Pre OA group: lower late stance knee extension moment
• Pre OA group: had higher TNFα concentrations
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21. 21
Control
(n=18)
LR OA
(n=9)
HR OA
(n=11)
Sex (male/female) 9M/9F 6M/3F 4M/7F
Age (years) 63.1 (8.4) 66.3 (4.2) 63.6 (6.0)
Mass (kg) 79.2 (13.7) 81.7 (10.9) 78.3 (17.0)
Height (m) 1.66 (0.12) 1.69 (0.11) 1.63 (0.09)
BMI (kg/m2) 28.9 (4.4) 28.4 (2.5) 29.5 (7.5)
Median KL (range) 2 (1-3) 3 (2-4) 3 (2-4)
Treadmill Walking
Speed (m/s)
1.08 (0.17) 1.18 (0.30) 1.00 (0.28)
No. of steps in 30 min 3281 (304) 3261 (456) 3151 (378)
Profiles different
COMP Con<LR OA< HR OA
IL-10 HR OA< Con<LR OA
BE Con< HR OA < LR OA
High Risk Gait Patterns: 30min Walking
Kozey-Hubley 2019
Hubley-Kozey et. al., OARSI, 2018 (O&C V25, S1, P135)

22. • High Tibial Osteotomy (HTO) pre-12Mo post
IMPLICATIONS: Management
Moyer, Birmingham et al., MAGMA, accepted 22
MFTC and cMFC thickness
Lateral no change
Change in mechanical axis
Decrease KAM
Increase KFM-KEM Range
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23. • Exercise: Findings equivocal for change in KAM magnitude
surrogates with exercise (Bennell et al., 2010, 2014, Holsgaard Larson et
al, 2017, Kunz et al, 2018, Brenneman and Maly, 2018)
• Neuromuscular exercises versus strengthening NSD KAM
• NMEX versus pain meds: NSD Knee index or KAM
• Strengthening and neuromuscular control exercise
• Showed increase in KFM-KEM range (Brenneman and Maly 2018)
IMPLICATIONS: Management
23
Clinical Progression
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24. • Aerobic exercise (McAlidon et al. 2014, Fransen 2015)
• Step count did not explain structural progression (Brisson et al., 2017)
• POSTER #159 Low level Physical activity levels in Knee OA associated with “at
Risk” gait patterns (Costello et al.)
• POSTER #145 Pain response on neuromuscular function after 30 minutes of
physical activity in individuals with knee OA (Moyer et al.)
• Effusion
• OARSI POSTER # 159 Effusion explain differences between asymptomatic and
symptomatic knee (Rutherford et al.)
IMPLICATIONS: Management
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25. • Clinical progression includes structural and/or symptom worsening
• TKA is an end point, how can we monitor clinical progression?
• New conservative intervention targets for clinical progression
• magnitude and patterns
• non-frontal plane moments
• muscle activation patterns
Person-specific
interventions
25
Take Home
+
Kozey-Hubley 2019

26. Thank you
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Kozey-Hubley 2019