* * Emerging Prevention and Intervention Strategies for Knee Osteoarthritis that Target Mechanical Factors. Disclosure. Pathogenesis of knee OA

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Emerging Prevention and Intervention Strategies for Knee Osteoarthritis that Target Mechanical Factors Disclosure Nothing to disclose Alison H. Chang, PT, DPT, MS Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University Objectives Discuss clinical evidence of modifying mechanical factors in management of knee OA (1) Global approach weight loss, slow walking speed (2) Proximal approach minimize contra-lateral pelvic drop, unilateral trunk lean (3) Local approach quads strengthening, medial thrust gait, medial collapse gait, neuro-muscular training, elliptical training, knee unloading brace (4) Distal approach toe-out gait, lateral wedge insole, footwear Pathogenesis of knee OA Impaired knee local neuromechanical environment Previous knee injuries Muscle weakness Malalignment Laxity & Instability Proprioception Vibratory perception threshold Systemic vulnerability Genetic factors Obesity Aging External knee adduction moment (KAM) 70% of the knee joint load passes thru the medial compartment due to the ground reaction force passing medial to the joint axis External knee adduction moment (KAM) * * Torque closing medial compartment in stance phase of gait Strongly relates to medial load and medial compartment disease progression (Hurwitz et al., 1998; Miyazaki et al., 2002; Bennell et al., 2011) Often used as an indirect measure of medial joint loading in many biomechanical studies and load-modifying trials 1

G Global approach weight loss slow walking speed G Global approach weight loss slow walking speed Proximal approach control pelvic drop trunk lean Distal approach toe-out gait lateral wedge insole footwear Local approach quads strengthening medial thrust & collapse gait neuro-muscular training elliptical training knee brace Proximal approach control pelvic drop trunk lean Distal approach toe-out gait lateral wedge insole footwear Local approach quads strengthening medial thrust & collapse gait neuro-muscular training elliptical training knee brace Weight loss Design: assessor-blinded RCT Participants: overweight or obese elderly with radiographic knee OA (n=76) Intervention: any of 4 interventions of exercise, diet, exercise + diet, healthy lifestyle (control) Outcome: peak knee compressive force, KAM Follow-up time: 18 months high weight loss group (10% change) had decreased peak knee compressive force, but no change in KAM (Messier et al., 2011) Weight loss Design: single group pre- and post-intervention comparison Participants: obese persons with knee OA (n=157) Intervention: diet Outcome: peak knee compressive force, KAM Follow-up time: 16 weeks - average wt loss: 13.5% - decreased peak knee compressive force and KAM - decreased pain and increased walking speed (Aaboe et al., 2011) Weight loss - Caveat Other studies have shown that weight loss may reduce pain and improve function, however the mechanisms may not be completely related to reduced joint load Weight loss > 10% appears to be beneficial Knee malalignment may mediate the effect of weight loss on medial knee load (Sharma et al., 2000; Christensen et al., 2005; Jenkinson et al., 2009; Bliddal et al., 2011) Walking speed Participants: persons with medial knee OA (n=44) Intervention: walking at self-selected vs. slow vs. fast speed Outcome: KAM (1 st and 2 nd peak) - Positive correlation between gait speed and 1 st KAM, especially in knees with mild disease (Mundermann et al., 2004) 2

Walking speed Participants: persons with knee OA (n=34) Intervention: fast vs. self-selected vs. slow walking speed on treadmill - In severe OA (K/L=4), slow speed resulted in a small KAM reduction; fast speed did not change KAM - In moderate OA (K/L=2-3), slow speed did not change KAM; fast speed resulted in a small KAM increase (Zeni & Higginson, 2009) Walking speed Participants: persons with knee OA (n=41) Intervention: increase gait speed to 150% of natural pace - no change in overall KAM magnitude - Increased 1 st peak KAM and decreased 2 nd peak KAM (Landry et al, 2009) Walking speed - Caveat The effects of walking speed on KAM are inconsistent G Global approach weight loss slow gait speed More severe knee OA may not respond to gait speed change To cover the same distance, slower walking speed may require more gait cycles and may yield similar cumulative knee load Physical function may be affected with significantly lower walking speed Proximal approach control pelvic drop trunk lean Distal approach toe-out gait lateral wedge insole footwear Local approach quads strengthening medial thrust & collapse gait neuro-muscular training elliptical training knee brace Hip abductor strengthening Hip abductor strengthening Participants: persons with medial knee OA (n=6) Intervention: strengthening ex. on hip abductors, quads, and hamstrings in both weight-bearing (WB) and non WB Frequency: 1:1 training session with a PT 3x/wk for 2 wks, then 1x/wk for 2 wks; home ex. on other days, pain, and function Follow-up time: 4 wks - 9% mean reduction of KAM - decreased pain and improved WOMAC function (Thorp et al., 2010) 3

Hip abductor strengthening Design: non-equivalent control group (no knee OA or pain), within subject comparison Participants: with medial knee OA & controls (n=40 each) Intervention: home exercise programs of hip abductor strengthening in both WB and non-wb positions Controls: continue daily activities Frequency: home ex. 3-4x/wk for 8 wks, pain, and function Follow-up time: 8 wks - no change of peak KAM in both groups - decreased pain and improved chair-stand function in intervention group (Sled et al., 2010) Hip abductor strengthening Design: assessor-blinded RCT Participants: medial knee OA (n=39 in strengthening, n=37 in control) Intervention: supervised home exercise programs of hip abductor & adductor strengthening in both WB and non-wb Controls: no intervention Frequency: home ex. 5x/wk for 12 wks, pain, and function Follow-up time: 12 wks - no change of peak KAM in both groups - intervention group had contral-lateral pelvic drop - decreased pain and improved function (Bennell et al., 2010) Femoral brace Participants: persons with medial knee OA (n=15) Intervention: use SERF (stability through ER of the femur) strap to promote hip ER and abduction during walking, pelvic drop angle, and pain - 28% reduction of peak KAM - 35% reduction of pain on VAS - decreased contra-lateral pelvis drop by 2 - increased ipsi-lateral hip abduction angle by 3 (Wallace et al., 2010) Hip control - Caveat Hip abductor strengthening ex. program decreased pain and improved function, but it s role in KAM reduction may be limited Other LE muscles were also strengthening in WB exercises Minimizing contra-lateral pelvic drop during gait significantly reduced medial knee load Gait training and motor control of hip movement during walking may be more beneficial than muscle strengthening alone Ipsi-lateral trunk lean A compensatory gait strategy of rapid shift of body weight to the stance limb and lateral trunk sway to reduce external knee adduction moment (KAM) (Mundermann et al., 2005; Briem et al., 2009; Hunt et al., 2008 & 2010) Ipsi-lateral trunk lean Participants: young healthy (n=19) Intervention: instructed to move their trunk from side to side to self-selected amount during walking - mean lateral trunk lean angle = 10-64% reduction of 1 st peak KAM - no change of 2 nd peak KAM (Mundermann et al., 2008) 4

Ipsi-lateral trunk lean Design: single group within subject comparison Participants: young healthy (n=9) Intervention: practiced to walk with 3 conditions of trunk lean (4, 8, and 12 ), using real-time biofeedback of the actual trunk lean angle (Hunt et al., 2011) Ipsi-lateral trunk lean - 7%, 21%, and 25% KAM reduction in 4, 8, and 12 trunk lean conditions respectively - 33% participants reported discomfort, mainly in ipsilateral hip, knee, and spine - 8 trunk lean may be optimal, balancing the load reduction and reported discomfort (Hunt et al., 2011) Lpsi-lateral trunk lean - Caveat Ipsi-lateral trunk lean during walking can significantly reduce KAM No trials on elderly persons with knee OA This movement pattern may help to reduce KAM, but may also perpetuate hip abductor weakness and adversely affect spinal mechanics Need to closely monitor adverse effects on other joints G Proximal approach control pelvic drop trunk lean Distal approach toe-out gait lateral wedge insole footwear Global approach weight loss slow gait speed Local approach quads strengthening medial thrust & collapse gait neuro-muscular training elliptical training knee brace Quadriceps strengthening Design: assessor-blinded RCT Participants: medial knee OA (n=49 in strengthening, n=48 in control) Intervention: supervised home exercise programs of quad strengthening in non-wb positions Controls: no intervention Frequency: home ex. 5x/wk for 12 wks, pain, and function Follow-up time: 12 wks - no change of peak KAM in both groups - pain reduction only in intervention group with neutrallyaligned knees - no change of physical function (Lim et al., 2010) Quadriceps strengthening Design: assessor-blinded RCT Participants: older adults with or without knee OA (n=113 in strengthening, n=108 in control) Intervention: quads strengthening ex. in both WB and non WB Controls: ROM exercises Frequency: 3x/wk for 12 wks, then taper to 3x/wk at home over 12 months Outcome: quads isokinetic strength, radiographic disease progression Follow-up time: 30 months (Mikesky et al., 2006) 5

Quadriceps strengthening - In OA knees, quad strengthening group had nonsignificant lower rate of OA progression than ROM group (18% vs. 28%, p = 0.094) - In knees that were radiographically normal at baseline, quad strengthening group had greater rate of joint space narrowing > 0.5mm than ROM group (34% vs. 19%, p = 0.038) - Both groups lost quads strength at 30 months, though strengthening group had less strength loss (Mikesky et al., 2006) Quadriceps strengthening - Caveat Focusing on quad strengthening alone may not beneficial Strengthening program should be tailored to knee subsets with different mechanical characteristics, such as varus/valgus mal-alignment or laxity Emphasize on proper knee dynamic alignment during all exercises and functional activities, i.e. maintaining neutral dynamic frontal and transverse alignment through motor control, foot orthotics, and bracing, or taping Factors contributing to varus mal-alignment or instability Decreased passive tissue stiffness Loss of cartilage & meniscus Poor active muscular stabilization Impaired sensory input Frontal plane instability/mal-alignment Medial thrust gait Design: single subject Participants: 37 y/o male with medial knee OA (K/L=2) Intervention: based on computer optimization, he was instructed to practice medial thrust gait Follow-up time: learning the new gait over 9 months - 50% reduction of KAM (Fregly et al., 2007) Medial collapse gait Participants: young healthy individuals with varus alignment (n=8) Intervention: treadmill walking with hip IR and adduction, using real-time biofeedback of the knee varus angle info Follow-up time: 8 sessions of training over 1 month - 19% reduction of KAM - knee varus angle by 2 (Barrios et al., 2007) Gait modification for varus thrust Design: single subject Participants: 64 y/o female with medial knee OA and varus thrust during gait Intervention: gait modifications of ipsi-lateral trunk lean, toe-out angle (self-selected magnitude), lateral wedged insole, and custom-made foot orthotics - variable performance from trial to trial - both trunk lean and toe-out reduced KAM - only trunk lean varus thrust angle by 38% (Hunt et al., 2011) 6

Gait modification with real-time feedback of KAM Participants: young healthy (n=16) Intervention: real-time visual or vibratory feedback of the magnitude of peak KAM provided while walking on treadmill, awkwardness scale (0-10) - mean reduction of peak KAM = 21%, ranging from 3 to 50% - common strategies: toe-in (n=14), loading medial side of foot (n=6), increased trunk sway (n=4) - average awkwardness = 5.3 (Wheeler et al., 2011) Gait modification - Caveat Modifying gait appears to be a promising approach to reduce medial knee load and dynamic varus instability, and may ultimately alter disease course Need to monitor kinematic and kinetic changes at other regions of body Medial thrust or collapse gait may harm PFJ Current research are very limited; studies on elderly with knee OA and larger-scale RCTs are needed Long-term effects and retention of the modified gait patterns are unknown Neuro-muscular training Participants: women with early radiographic knee OA (K/L I or II) (n=11) Intervention: LE strengthening and neuromuscular training in WB Frequency: 2x/wk (during one-leg rise from stool and during gait) Follow-up time: 8 wks - reduction of KAM observed during lone-leg rise, but not during gait (Thorstensson et al., 2007) Neuro-muscular training Design: assessor-blinded RCT Participants: knee OA (n=91 in treatment, n=92 in control) Intervention: agility and perturbation training + standard ex. therapy Controls: arm bike activity + standard ex. therapy Frequency: 12 supervised sessions in 6-8 wks, continue ex. 2x/wk Outcome: function and pain Follow-up time: 2-, 6, and 12-month follow-up periods - improved self-reported function in both groups - no change in pain or performance-based function in either group (Fitzgerald et al., 2011) Examples Examples Courtesy of Dr. Kelly Fitzgerald Courtesy of Dr. Kelly Fitzgerald 7

Elliptical neuromuscular trainer Sliding (with or without rotation) - Locked - Free - Perturbed Elliptical neuromuscular training Design: single subject Participants: 43 y/o male with medial knee OA and varus thrust during gait Intervention: training on the modified elliptical exerciser, responding to frontal plane perturbation by the footplate Frequency: 3x/wk Outcome: function, pain, and subjective report of instability Follow-up time: 6 weeks - 25% and 18% improvement in pain and function respectively - resolution of complaints of instability - frontal plane stability improved from 2.05 to 1.08cm (Chang et al., 2011) Neuromuscular training - Caveat Neuromuscular training targeting knee frontal and transverse plane motor control during functional weight bearing activities may be beneficial Frontal plane stability may be improved via programmed external varus-valgus perturbation Unloading knee brace Previous studies have shown that knee valgus unloading brace reduced peak KAM by 13% to 25% during the stance phase of gait (Pollo et al., 2002; Self et al., 2000) Clinical trials showed variable and inconsistent improvement in pain and function (Brouwer et al., 2005; Krohn, 2005) Unloading knee brace Participants: persons with medial knee OA (n=16) Intervention: knee unloading brace in neutral for 2 wks 2-wk washout period in 4 valgus alignment for 2 wks Outcome: pain, function, and muscle co-contraction Follow-up time: 2wks - reduction of muscle co-contraction in both bracing settings - knee varus angle excursion with both bracing settings - pain and function improved in both - neutral alignment setting is as good as the 4 valgus one (Ramsey et al., 2007) Unloading knee brace - caveat Knee unloading brace Reduce KAM + Diminish abnormal quad/hamstrings cocontraction Decrease knee compressive load Relieve pain Neoprene or hinged brace may also be beneficial for reducing muscle co-contraction Unloading knee brace may be used only in more intense physical activities, such as tennis or jogging Women tend to have compliance issue = 8

G Proximal approach control pelvic drop trunk lean Distal approach toe-out gait lateral wedge insole footwear Global approach weight loss slow gait speed Local approach strengthening medial thrust & collapse gait neuro-muscular training elliptical training knee brace GRF Adduction moment Toe-out Adapted from Wang et al., 1990 Toe-out gait GRF Greater toe-out angle: shifts ground reaction force (GRF) vector closer to knee joint center reduces KAM Toe-out gait Participants: persons with mild to moderate knee OA (n=9) Intervention: increase toe-out angle by 15 during gait, using visual cues of lines drawn on the force place Outcome: 1 st and 2 nd peak KAM - 55% reduction of 2 nd peak KAM - no change of 1 st peak KAM (Guo et al, 2007) Toe-out gait Participants: persons with knee OA (n=12) Intervention: three walking conditions (1) natural foot angle (2) toe-out (3) toe-in Outcome: 1 st and 2 nd peak KAM - toe-out gait 2 nd peak KAM, did not change the 1 st peak KAM - toe-in gait did not change KAM values (Lynn and Costigan, 2008) Toe-out gait - Caveat Walking with toe-out may help to reduce 2 nd peak KAM Potential sources of out-toeing (1) tibial ER (2) hip ER (3) combination of both Caution: not to compromise the normal function of the foot, knee, and hip Lateral wedged insole Lateral wedged insole moves the center of pressure laterally reduce the moment arm of ground reaction force acting at the knee joint decrease KAM and lessen the medial joint load A 2-year RCT demonstrated reduced intake of NSAIDS, but no change of pain/function or slow disease progression (Pham et al., 2004) Another 6-wk double-blinded randomized crossover trial showed no clinically meaningful improvement in pain (Baker et al., 2007) MA GRF GRF MA 9

Lateral wedged insole Design: participant-blinded RCT Participants: medial knee OA (n=20 in treatment, n=25 in control) Intervention: 5-15 full length insole worn daily for 12 months Posting determine by pain response during 8 lateral step down, non-responders eliminated from the study * participants wore standardized walking shoes Controls: neutral insole without wedging Outcome: WOMAC pain, function Follow-up time: insole worn daily for 12 months - both groups improved in pain and function - neutral insole did as well as the lateral wedged one - standardized footwear may contribute to favorable outcomes in both groups (Barrios et al., 2009) Lateral wedged insole Design: double-blind RCT Participants: medial knee OA (n=89 in treatment, n=90 in control) Intervention: 5 full length insole worn bilaterally, replaced every 4 months Controls: neutral insole without wedging Outcome: medial tibial cartilage volume, pain, function, physical activity Follow-up time: insole worn daily for 12 months - small pain reduction did not differ between groups - no difference in cartilage volume change between groups - no differences in all other secondary measures - lateral wedge group is less compliant than controls (worn 6.8 vs. 9.1 hrs daily (Bennell et al., 2011) Lateral wedged insole - Caveat Variations in shoe types or ankle/foot characteristics may mediate the biomechanical effects of wedge insole Classify patients into subgroups of responders vs. non Use a wedge at about 5 and full length Daily use of 5-10 hours Persons with less severe disease, younger age, and less obesity tend to benefit more Patients with immediate favorable responses tend to have greatest long-term functional gain and pain reduction Monitor potential problems with ankle/foot with use of wedges Footwear Gait studies showed that barefoot walking had lower KAM than walking with shoes in persons with medial knee OA ranging from 7.4-11.9% (Shakoor et al., 2006; Kemp et al., 2008) Mechanism of why barefoot walking reduce knee load is unclear, possibly due to: - reduce peak ground reaction force - promote mid-foot strike and minimize impact transient - increase foot intrinsic muscle activity - enhance proprioceptive inputs Shoes that simulate barefoot walking may be beneficial Footwear mobility shoe Design: single group within group comparison Participants: persons with medial knee OA; n=28 and 20 in groups A and B respectively Intervention: Group A: mobility shoe vs. self-selected walking shoe vs. barefoot Group B: mobility shoe vs. control stability shoe vs. barefoot Mobility shoe plantar view Mobility shoe side view Control stability shoe Footwear mobility shoe and KAM impulse - Group A - the specialized mobility shoe reduced KAM by 8% when comparing with self-selected walking shoe - Group B - the specialized mobility shoe reduced KAM by 12% when comparing with control stability shoe - long-term disease modifying effect of this novel mobility shoe is unknown (Shakoor et al., 2008) 10

Footwear variable stiffness shoe Design: participant-blinded RCT Participants: medial knee OA (n=32 in treatment, n=23 in control) Intervention: variable-stiffness sole worn daily Lateral sole is 1.3-1.5 x stiffer than the medial sole lateral medial Controls: shoe with constant stiffness on both sides Outcome: within-day peak KAM, WOMAC pain, function Follow-up time: one year - both groups improved in pain and function - when compared to personal shoe, 4.7 % of KAM in variable stiffness shoe, 3% in control shoes (Erhart-Hledik et al., 2011) Footwear APOS shoe Participants: women with medial knee OA (n=25) Intervention: as a biomechanical treatment device, wearing APOS shoe to change center of pressure location and provide perturbation during walking Outcome: barefoot peak KAM and KAM impulse WOMAC pain, function Follow-up time: 3 and 9 months - improved in pain and function at both 3 and 9 months - 13%, 8.4%, and 12.7% reduction in KAM impulse, 1 st peak KAM and 2 nd peak KAM (Haim et al., 2011) Footwear - Caveat The role of footwear in management of knee OA is complex; more evidence and RCT with structural outcomes are needed for sound recommendations Flat-heel shoes may be worn in preference to > 1.5 inch heels Flexible/mobility shoes may provide mobility needed to mimic barefoot walking and reduce knee load Variable-stiffness sole with stiffer lateral side may help to reduce medial knee load and improve symptoms Patients with pathologies associated with pronatory foot type may not benefit from flexible/mobile shoes and lateral wedge Summary Variability in individual neuro-mechanical characteristics and adaptation classify into different sub-groups responders vs. non-responders Each intervention approach may have its pros and cons single vs. combination intervention approach Limited RCT on these approaches need for RCT with structural outcomes 11