Accepted Manuscript

A 12-week Medical Exercise Therapy Program Leads to Significant Improvement inKnee Function after Degenerative Meniscectomy: A randomized Controlled Trial withOne Year Follow-up

Håvard Østerås, MSc

PII: S1360-8592(13)00197-6

DOI: 10.1016/j.jbmt.2013.11.015

Reference: YJBMT 1077

To appear in: Journal of Bodywork & Movement Therapies

Received Date: 18 October 2013

Revised Date: 7 November 2013

Accepted Date: 18 November 2013

Please cite this article as: Østerås, H., A 12-week Medical Exercise Therapy Program Leads toSignificant Improvement in Knee Function after Degenerative Meniscectomy: A randomized ControlledTrial with One Year Follow-up, Journal of Bodywork & Movement Therapies (2014), doi: 10.1016/j.jbmt.2013.11.015.

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A 12-week Medical Exercise Therapy Program Leads to Significant Improvement in

Knee Function after Degenerative Meniscectomy: A randomized Controlled Trial with

One Year Follow-up.

Håvard Østerås, MSc, Ass. Professor, PT, Specialist in Sports Physical Therapy, Sør-

Trøndelag University College, Faculty of Health Education and Social Work, Department of

Physical Therapy, Trondheim, NORWAY

Correspondence:

Address: Håvard Østerås, Sør-Trøndelag University College, Faculty of Health

Education and Social Work, Department of Physical Therapy, Ranheimsv. 10, N-7004

Trondheim, NORWAY

Phone: +47 73 55 93 05

Fax: +47 73 55 93 51

E-mail: havard.osteras@hist.no

Sources of funding: Nil

No conflicts of interests.

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Abstract

There is no consensus in the postoperative rehabilitation regimen for patients who have

undergone surgery for medial meniscus damage. The aim of this study was to examine

whether it is necessary to undergo postoperative physiotherapy treatment these patients.

A prospective randomized controlled clinical trial was performed. 42 participants (26 males,

16 women) were randomly assigned into an exercise group (EG) (n=22) or a control group

(CG) (n=20). Prognostic variables were similar between the groups at baseline. The EG

achieved significantly better outcome effects than the CG at pain (VAS reduced 1.9 in TG and

0.6 in CG, p<0.01) and function (KOOS decreased 18.0 in TG and only 6.5 in CG, p<0.01)

during the 12 week intervention period. The results after a 12-month follow-up indicated the

same results as at posttest 3 months postoperatively. In patients with surgery for degenerative

meniscus damage, postoperative medical exercise therapy – as a model of physiotherapy - is

an efficient treatment alternative compared to no systematic rehabilitation.

Key words: knee, rehabilitation, physical therapy, meniscus

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BACKGROUND

Due to differing clinical practices in the management of postoperative degenerative meniscus

injuries, there are no evidence-based protocols as to what the ideal treatment is for individuals

with a degenerative meniscus injury (e.g. Noyes et al 2012, Østerås et al 2012a). Studies have

shown that quadriceps strength deficits are present after intra-articular knee injuries and

surgeries, and can persist for months (e.g. Østerås et al 2012b). One method employed for

facilitating quadriceps strength is resistive volitional exercises, as progressive resistive

exercises can safely load the muscles in a graduated manner to allow muscle strength

adaptation, while minimizing stress on the damaged tissue (Reinold et al 2006).

Resistance training is one of the major components of rehabilitation after injuries and surgery

in the musculoskeletal system (Morrissey and Goodwin 2007). Despite this importance and

the emphasis of its use in rehabilitation programs, little is known about the factors related to

dose-response that could be useful in devising and monitoring rehabilitation exercises. A

major reason that there exists no scientific consensus regarding a need for postoperative

physical therapy could be the low intervention dosage (in terms of the number of repetitions,

sets, minutes of cycling and total number of weeks of supervised exercises) in patients with

degenerative meniscus surgery.

Middle-aged men and women with degenerative meniscus injuries account for a large group

of patients, with knee pain, swelling and impaired function. Many knee injuries occur without

any trauma in physically active people and older people, and can be part of early osteoarthritis

(Rangger et al 1997). A partial arthroscopic ectomy of the meniscus is a common surgical

procedure in patients with meniscus injury. Postoperatively, many patients report less pain,

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better functioning and a better quality of life (Burks et al 1997). Despite the reduced knee

pain and improved knee function, Roos et al. (2000) showed that three months after knee

surgery, a majority of patients has reduced physical activity and 38% were not physically

active, compared with only 9% before the operation.

The goal of the postoperative rehabilitation period is to reduce knee pain and regain good

knee control, range of motion, strength and knee function. There are many different protocols

for rehabilitation after knee injuries, although no consensus exists. Earlier studies may not

take sufficient account of the fact that pain inhibits force development, thus limiting the

effects of strength training (Brox et al 1997, Fisher and Pendergast 1997). While it has

provided training principles and dosage, it turns out that there are few exercises, high stress

and relatively few repetitions used (Witvrouw et al 2000). Only when pain is reduced, can an

increase in strength, improved coordination and normalization of function be expected

(Torstensen 1999), though it is not known whether this is linked to any specific diagnosis or

part of the muscle-skeletal system.

The aim of this study was to evaluate the mediated effects of medical exercise therapy on

clinical outcomes after arthroscopic surgery in patients with degenerative meniscus, compared

to random treatment.

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METHODS

Design

The present study was a randomized controlled trial with assignment to two groups; an

exercise group (EG) and a control group (CG), with no rehabilitation program (see Figure 1

for flow chart). A computer-generated randomization schedule was used, with annotations for

treatment according to exercise therapy or no postoperative rehabilitation. The same

investigator, who was not involved in the randomization procedure, prepared all the envelopes

in the study. To maintain the blinding of the study, three different experienced physical

therapists did the testing and the exercise intervention, respectively.

Subjects

Patients were recruited from orthopedic surgeons in three hospitals in Norway over a period

of one year. The training was considered not to cause deterioration of the injury or pain, and

was implemented in accordance with the known training principles used by physical

therapists. All participation was based on informed consent, voluntariness and the right to

withdraw from the study without further consequences. Inclusion criteria were subjects with

knee pain for more than two months, who were 35-60 years of age and eligible for

arthroscopic partial meniscectomy, with an MRI – from the radiologist’s description -

showing a degenerative meniscus tear. The exclusion criteria were ACL rupture and those

requiring acute trauma surgeries, including high energy traumas with ligament injuries,

osteoarthritis grade 3-4 (Spector and Cooper 1993), hemarthroses and acute cases of locking

knee, comorbidities excluding physical activities and exercise, and drug abuse.

Insert Table 1 about here

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Sample Size

Sample size calculation based on a predetermined difference between treatment groups of

15% change in pain on a 10 cm visual analogue scale and a standard deviation of 2,0 cm,

showed that 17 participants were required in each group to have 80% power to detect the 20

% difference as statistically significant at the level of p < .05. With an estimated drop-out of

10%, 42 patients were recruited to this trial.

Outcome measures

The primary outcome is pain; a subjective score measured with a visual analog scale (VAS) at

rest was recorded on a 0-100 mm line. The extreme limits were marked by perpendicular

lines, using the verbal descriptors of “no pain” and “worst pain I can imagine,” and the

subjects were not shown their previous markings at follow-ups (Huskisson 1974). The

secondary outcome was a self-reported composite measure:”Knee Injury and Osteoarthritis

Outcome Score” (KOOS) (Roos and Lohmander 2003, Roos et al 1998). The KOOS is a valid

and reliable patient-relevant questionnaire for patients with knee injuries and knee

osteoarthritis (Roos et al 1998). To detect an average difference between individuals and

between groups, a minimal perceptible improvement was set to 10 points, with the KOOS

registered at baseline, three and twelve months postoperatively.

Anxiety and depression were measured with the Hospital Anxiety and Depression Scale

(HADS) (Bjelland et al 2002), which is a self-screening questionnaire for depression and

anxiety consisting of 14 questions, seven for anxiety and seven for depression. The patients

were instructed not to take too long with their replies since as their immediate reaction to each

item would probably be more accurate than a long thought-out response.

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One month postoperatively, after the intervention period (three months postoperatively) and

after 12 months all patients answered the questionnaires and completed the muscle and

functional tests. Prior to the functional- and muscle tests, the subjects warmed up on a

stationary bicycle for approximately 10 minutes. A one-leg jump test for distance was

performed after the warm-up (Noyes et al 1991). Subjects performed two trials each and each

jump test began on the uninjured side, followed by the injured side. Subjects performed two

practice trials, with the best trial being used. The one-leg jump test score was calculated as

(uninjured side score/injured side score) x 100. A leg extension bench for an evaluation of

quadriceps muscle strength deficits was included (Holm 1996), with a five repetition

maximum (RM). The reliability for the muscle test has previously been reported to be

satisfactory (Holm 1996, Drouin et al 2004). The isokinetic test system used for quadriceps

and hamstrings muscles was Biodex (Biodex, Corp., Shirley, NY, USA). The subjects were

tested at peak torque at 60º/sec. and 240º/sec. using 5 and 15 repetitions at 60° per second,

respectively, which is considered adequate for an assessment of muscle strength after knee

injury (Dvir 2004). Isokinetic absolute torque values were measured in newton meters (Nm),

while total work was expressed in joules (J). The isokinetic concentric mode of the Biodex

dynamometer has been shown to be reliable for test-retest measures of both peak torque and

single repetition work (Feiring et al 1990).

A standard arthroscopic partial meniscectomy (NGD 11) was applied as a surgical

intervention, and performed on patients at St. Olav University Hospital and Teres Rosenborg

Clinique in Trondheim, Norway. Normal procedures for this surgery at the respective

hospitals were followed.

Intervention

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An exercise program had been developed and tested in a prior RCT (Østerås et al 2012b), and

was further developed for this particular study, with a focus on high repetitions of pain free

exercises, knee function and strength training. Improved muscle strength and function could

potentially have a positive influence on knee symptoms, function and the progression of

osteoarthritis. The program allowed for individual differences due to performance and

progression. Based on clinical experience the intervention period was three months, and the

subjects performed the exercise program three times per week. Symptoms and clinical

findings were the basis for choosing individual starting positions, range of motion and weight

resistance for each exercise, whereas the treatment goal in the exercise group was to perform

three sets of 30 repetitions. Moreover, the program was a combination of global aerobic

exercises, using a stationary ergometer cycle, treadmill or step machine, in addition to semi-

global and local exercises to modulate pain and increase range of motion, using specially

designed exercise equipment. This included squats, wall pulleys and quadriceps and

hamstrings muscle strength training apparatus.

Each treatment in the exercise group started with 10-20 minutes of aerobic work on a

stationary ergometer cycle (Figure 1). Half way through the exercise program, after four

exercises each of three sets of 30 repetitions (Figures 2-3), the subjects cycled for 10 minutes,

and after the last four exercises (Figures 4-5), the subjects did another 10 minutes on the

stationary ergometer cycle. The intensity during the cycle exercises was moderate to high, i.e.

a heart rate frequency of 70-80% of the maximum heart rate, though the maximum heart rate

was not monitored. For most of the patients this meant an absolute heart rate on 130-160 per

minute. All possible efforts were made to enhance compliance and adherence with the

program, and the subjects had to complete a minimum of 80% of the rehabilitation program,

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monitored by the treating physiotherapists’ journals. The CG did not get any physiotherapy

after the surgery.

INSERT FIGURES 1-5 ABOUT HERE

Statistical Analysis

The statistical analysis was performed using the commercial software package SPSS for

Windows (release 19.0), and descriptive statistics were performed for demographic variables.

Normal distributions of outcome variables were estimated by use of the Kolmogorov-Smirnov

test. Within and between mean group differences were analyzed by using a general linear

model, intervention (group allocation) and time (between pre- and posttest) were main effects.

Baseline values of the primary outcomes were applied as covariates.

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RESULTS

Forty-two individuals with a unilateral degenerative operated meniscus injury, 16 women and

26 men with a mean age of 43.6 years (EG) and 46.8 years (CG), were included in the study.

A total of 91% and 90% of the patients completed the follow-up tests in the EG and CG,

respectively (Figure 6). The patients in the EG, completed on average 82% of the exercise

program.

Insert Figure 6 about here

The adjusted difference between groups were all significant at p<0.01, with all in favor of the

EG from both pre- to posttest and from posttest to follow-up (Tables 2 and 3). Posttest scores

of the primary outcome VAS were adjusted for baseline values, follow-up scores were

adjusted for posttest values of the primary outcomes, and both were applied as covariates in

the analyses.

Insert Table 2 about here

Insert Table 3 about here

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DISCUSSION

The main purpose of this study was to compare the clinical effects of two approaches after

arthroscopic surgery in patients with a degenerative meniscus. The results showed significant

effects in favor of the group that received supervised medical exercise therapy, compared to

no treatment. Ericsson et al. (2006) found that quadriceps strength is reduced in the

meniscectomized leg compared with the non-operated leg four years after surgery. They

suggest that the relative quadriceps weakness significantly affects objective and self-reported

knee function, pain and quality of life, thus indicating the importance of restoring muscle

function after meniscectomy in middle-aged patients. The present trial supports this; hence

high dosage, high repetition medical exercise therapy could be an effective approach.

However, the mechanisms behind the results remain as of yet unknown.

In the present study, 18 patients had an osteoarthritis diagnosis in addition to a degenerative

meniscus, with seven (39%) of these were in the EG and 11 (61%) in the CG. This might have

influenced the results, as osteoarthritis stage 2 is a particularly well-known factor in

decreasing knee function. However, with concern to all included patients, there was no

statistical difference between the groups at baseline. The menisci play a vital role in load

transmission, shock absorption and joint stability, and there is an increasing amount of

evidence that osteoarthritis may not merely be a bystander in the disease process of

osteoarthritis. Sun et al. (2010) suggest that osteoarthritis is a whole joint disease, in which

meniscal cells may play an active role in the development of osteoarthritis. Future studies

with a long follow up period should consider whether postoperative exercises might influence

the risk of osteoarthritis development.

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Criticism has been raised towards the use of isokinetic tests because of its lack of

functionality (Andrade et al 2009). Nevertheless, one may argue in favor of isokinetic testing,

as the open kinetic chain nature of the test allows for an isolation of the muscle of concern, in

the present study for the quadriceps femoris. In order to address a brief description of knee

patients such as in the present study, isokinetic tests may complete the functional tests. There

is a lack of normative data from isokinetic knee muscle strength, particularly among different

patient groups, which needs to be addressed in future studies, as isokinetic testing is an

objective and accurate way of evaluating muscular strength, and one that helps to supplement

other clinical assessments. The present study adds some data, but further research is necessary

to be able to compare absolute values. In clinical trials and daily rehabilitation work with

patients with potentially muscle-skeletal pain, however, one should be aware of a lower

reliability in isokinetic testing than in healthy people. The patient`s pain, or potential fear of

increased pain because of the required maximal effort during isometric testing, is a major bias

that may have affected the present data.

The treatment objective in this trial was to perform approximately 10 exercises, resulting in

more than 1,000 repetitions during each treatment in the EG. The possible mechanisms for

explaining treatment effects was pain modulation by activation of the gate control system in

the poster horn of the spinal cord, an increased release of the endogenous neuropeptides,

improved circulation in the affected structures and a biomechanical stimulus stimulating

tissue regeneration. The high number of repetitions in sets might have stimulated improved

muscular strength and coordination as well as an increased range of motion; thus the grading

of the exercises made it possible and imperative to exercise close to a pain-free threshold

within a comfortable range of motion, with an emphasis on good coordination.

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It has been concluded that exercises for proprioception and balance may improve dynamic

knee stability, and therefore the functional ability of the patients. Furthermore, there is some

evidence to suggest that plyometric exercises will enhance muscular strength and athletic

performance (Dvir 2004), and that rehabilitation programs, including specific perturbation

training, may lead to beneficial neuromuscular adaptations (Reichard et al 2005). Despite the

relatively low number of patients in this study, we suggest that our findings document that the

combined approach of high-repetitive strengthening exercises and endurance training

(cycling) are superior to other exercise programs that emphasize separate elements. Hence, it

is possible to achieve significant and clinically important improvements in both muscle

strength and knee function with an exercise program such as that in the present trial.

It is well chronicled that pain mechanisms of chronic pain sufferers are more complex and

involve sensitisation of the central nervous system, with less relationship between the pain

experience and tissue state than in subacute or acute groups (van Wilgen and Keizer 2012).

Since the primary outcome measured was pain, further trials should investigate a possible

difference between chronic or subacute patients or differentiation between these groups. The

scientific methodology to do this, however, is for the time being not well established. In the

present study, the patients had their pain for as much as 1.9 (EG) and 2,2 (CG) years, where

there might be a considerable central sensitization. Further on, a dominant feature in the pain

experience is the kinesiophobia (Ie Monticone et al 2013). Even though anxiety and

depression were measured I this study, further trials could add fear of movement as an

outcome. The relative distribution between muscle strength, function and psychological

components as contributing factors are yet to be studied.

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Physical activity is well documented as an effective treatment for patients with knee

degeneration to improve function and reduce pain, both in subacute and long-term patients

(Noyes et al 2012). There is strong evidence that physical activity can reduce pain, while

improving the function and quality of life for people with osteoarthritis (Pedersen and Saltin

2006). There are many studies showing a reduced strength in the quadriceps femoris in

connection with knee pain (e.g. Fisher and Pendergast 1997, Eitzen et al 2009). The results

from the present study indicate that pain-free or close to pain-free medical exercise training

could reduce knee pain postoperatively. However, despite the increased muscle strength,

further research is needed to investigate whether muscle strength is the important contributing

factor, or whether activity, together with high dosages of pain free activities, is of more

importance.

A major limitation in the present study is the lack of a blinded assessor. In addition, if the

patients did not go back to their previous physical activity level, they may not give a valid

response on pain assessment since only knee strain had been reduced and the expectations of

knee function had been lower. The population studied may also be very different based on

discrete surgical details. Future studies should include activity level as a separate factor.

ACKNOWLEDGMENTS

I would like to acknowledge the physical therapists Berit Østerås for her assistance in the data

analysis, and Tom Arild Torstensen for inspiring discussions.

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Tables and Figure 6 (figures 1-5 separate file)

Figure 1. -Subject flow diagram of the patients

Eligible patients n = 50 Consented to participate n = 45

Exercise Group n = 22 Withdrew n = 0 Recruited patients n = 22 Patients enrolled n = 22

Control Group n = 20 Withdrew n = 3 Recruited patients n = 23 Patients enrolled n = 20

Month 0 Patients: n = 22 (100%)

Month 0 Patients: n = 20 (100%)

Month 3 Patients: n = 21 (95%) 1 moved away

Month 3 Patients: n = 19 (95%)

1 refused contact

Month 12 Patients: n = 20 (91%) 1 refused contact

Month 12 Patients: n = 18 (90%) 1 refused contact

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Table 1 - Baseline characteristics of the study population. Mean (SD) values, unless otherwise stated.

Exp group Con group Total

(n=22) (n=20) (n = 42)

Age, years 43.6 (8.2) 46.8 (9.5) 45.1 (8.9)

Weight, kg 80.4 (9.3) 79.4 (9.4) 79.9 (9.3)

Height, cm 177.3 (8.2) 175.7 (5.9) 176.5 (7.2)

Duration of symptoms, years 1.9 (2.6) 2.2 (1.8) 2.1 (2.2)

Male (%) 14 (54) 12 (46) 26

Arthritis 1 (%) 5 (50) 5 (50) 10

Arthritis 2 (%) 2 (25) 6 (75) 8

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Table 2 - Mean (SD) pain and function in the groups at pre- and posttest and follow-up, mean (SD) within groups changes and adjusted mean (95% CI) difference between groups after intervention at posttest and follow-up

Outcome Groups

Pretest Posttest (3 months) Follow-up (12 months)

EG (n=22) CG (n=20) EG (n=21) CG (n=19) EG (n=20) CG (n=18)

VAS 3.1 (1.7) 3.5 (1.5) 1.3 (1.4) 2.6 (1.4) 0.6 (0.8) 2.1 (1.2)

FiveRM 11.3 (4.6) 11.4 (5.4) 20.6 (5.4) 13.8 (5.7) 22.3 (5.0) 14.9 (5.3)

KOOS 48.1 (17.7) 47.6 (22.1) 30.7 (16.4) 40.3 (23.1) 20.6 (12.4) 35.4 (17.6)

HAD 6.6 (2.5) 6.8 (4.4) 4.1 (2.1) 6.2 (4.0) 3.8 (1.8) 6.1 (3.4)

Jump 1m 85.9 (7.0) 74.3 (10.0) 92.9 (6.9) 79.3 (9.6) 96.2 (4.8) 82.2 (10.5)

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Difference within groups Adjusted difference between groups†

From pre- to posttest From posttest to follow-up From pre- to posttest From posttest to follow-up

EG CG EG CG

VAS (0 = no

pain, 10 = max) −1.9 (1.6) −0.6 (0.6) -0.8 (1.2) -0.4 (0.7) -1.1* (-1.5 to -0.6) -1.0* (-1.3 to -0.6)

FiveRM 8.6 (3.8) 2.0 (2.3) 2.5 (3.2) 0.1 (2.1) 6.5* (5.0 to 8.0) 4.4* (3.2 to 5.6)

KOOS -18.0 (10.9) -6.5 (6.4) -10.3 (11.2) -4.5 (7.8) -10.7* (-14.7 to -6.7) -8.9* (-11.9 to -5.9)

HADS -2.4 (1.9) -0.4 (0.9) -0.4 (0.7) 0.1 (1.1) -1.7* (-2.3 to -1.2) -0.7* (-1.1 to -0.3)

Jump 1m 7.5 (5.6) 4.9 (3.6) 3.7 (3.5) 3.7 (4.5) 6.2* (3.7 to 8.7) 3.3* (0.6 to 6.1)

Abbreviations: EG, experimental group; CG, control group. One-leg jump test is symmetry index; operated leg/unoperated leg *100.

* The adjusted difference between groups were all significant at p<0.01, all in favor of the EG.

† Posttest scores of the primary outcomes were adjusted for baseline values, and follow-up scores were adjusted for posttest values of the primary outcomes. These were applied as covariates in the analyses.

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Table 3 - Mean (SD) isokinetic biodex-scores (included adjustment for BMI) in the groups at pretest, posttest and follow-up, mean (SD) within groups changes and adjusted mean (95% CI) difference between groups after intervention and between posttest and follow-up

Outcome Groups

Pretest Posttest (3 months) Follow-up (12 months)

EG (n=22) CG (n=20) EG (n=21) CG (n=19) EG (n=20) CG (n=18)

QPT 134.0 (34.5) 118.0 (38.0) 172.1 (40.8) 128.4 (39.9) 182.6 (42.2) 132.5 (38.4)

QTW 527.4 (141.3) 477.9 (147.6) 682.0 (187.6) 514.8 (159.8) 722.2 (202.3) 510.6 (166.0)

HPT 77.4 (22.3) 74.0 (25.8) 103.4 (23.9) 79.3 (25.3) 121.5 (72.0) 87.3 (38.1)

HTW 422.2 (112.6) 358.0 (125.5) 525.0 (123.8) 383.9 (131.3) 551.3 (123.6) 394.9 (132.1)

QPT BMI 5.3 (1.4) 4.7 (1.7) 6.8 (1.7) 5.1 (1.7) 7.2 (1.8) 5.2 (1.7)

QTW BMI 20.7 (5.4) 18.9 (6.3) 26.8 (7.1) 20.3 (6.8) 28.3 (7.7) 20.2 (7.0)

HPT BMI 3.0 (0.9) 2.9 (1.1) 4.1 (1.0) 3.1 (1.1) 4.7 (2.6) 3.5 (1.8)

HTW BMI 16.6 (4.4) 14.1 (4.7) 20.6 (4.9) 15.1 (5.1) 21.7 (5.0) 15.5 (5.0)

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Difference within groups† Adjusted difference between groups‡

Pre- to posttest Posttest to follow-up Pre- to posttest Posttest to follow-up

EG CG EG CG

QPT 38.1 (14.6) 10.4 (6.9) 10.5 (28.7) 4.1 (7.1) 26.8* (19.4 to 34.2) 12.4 (-2.5 to 27.3)

QTW 154.6 (78.5) 36.9 (27.3) 40.2 (59.0) -4.0 (91.1) 110.4* (74.4 to 146.4) 49.1 (-4.3 to 102.5)

HPT 26.0 (7.7) 5.3 (4.6) 18.1 (72.8) 8.0 (20.4) 20.8* (16.7 to 24.9) 13.5 (-25.0 to 52.1)

HTW 102.8 (75.9) 25.9 (23.6) 26.3 (37.3) 11.0 (25.0) 79.6* (42.1 to 117.1) 19.5 (-3.7 to 42.7)

QPT BMI 1.5 (0.6) 0.4 (0.3) 0.4 (1.2) 0.2 (0.3) 1.0* (0.7 to 1.3) 0.5 (-0.1 to 1.0)

QTW BMI 6.0 (3.1) 1.4 (1.0) 1.6 (2.3) -0.1 (3.3) 4.4* (2.9 to 5.8) 1.8 (-0.2 to 3.8)

HPT BMI 1.0 (0.3) 0.2 (0.2) 0.7 (2.6) 0.4 (1.0) 0.8* (0.7 to 1.0) 0.3 (-1.1 to 1.7)

HTW BMI 4.0 (3.0) 1.1 (1.0) 1.1 (1.5) 0.4 (1.0) 3.1* (1.6 to 4.5) 0.8 (-0.1 to 1.8)

Abbreviations: EG, experimental group; CG, control group. QPT=Quadriceps Peak Torque, QTW=Quadriceps Total Work, HPT=Hamstrings Peak Torque, HTW=Hamstrings Total Work. BMI: the same values adjusted for Body Mass Index.

* The adjusted difference between groups were all significant at p<0.01, all in favor of the EG.

† Post minus pre; change scores.

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‡ Posttest scores were adjusted for baseline values of the primary outcomes (used as covariates). Follow-up scores were adjusted for posttest values (used as covariates) of the primary outcomes.

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Figure 1. Bicycling.

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Figure 2A. Deloaded step up, starting position.

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Figure 2B. Deloaded step up, end position.

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Figure 3A. Knee flexion, starting position.

Figure 3B. Knee flexion, starting position.

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Figure 4A. Knee extension, starting position.

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Figure 4B. Knee extension, ending position.

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Figure 5A. Squat, ending position.

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Figure 5B. Squat, starting position.

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Figure 6- Subject flow diagram of the patients

Eligible patients n = 50 Consented to participate n = 45

Exercise Group n = 22 Withdrew n = 0 Recruited patients n = 22 Patients enrolled n = 22

Control Group n = 20 Withdrew n = 3 Recruited patients n = 23 Patients enrolled n = 20

Month 0 Patients: n = 22 (100%)

Month 0 Patients: n = 20 (100%)

Month 3 Patients: n = 21 (95%) 1 moved away

Month 3 Patients: n = 19 (95%)

1 refused contact

Month 12 Patients: n = 20 (91%) 1 refused contact

Month 12 Patients: n = 18 (90%) 1 refused contact