903443

research-article2020
CARXXX10.1177/1947603520903443CARTILAGEChao et al.

Clinical Research Article

Cartilage

Effect of Systematic Exercise Rehabilitation

1­–7
© The Author(s) 2020
Article reuse guidelines:
on Patients With Knee Osteoarthritis: A sagepub.com/journals-permissions
DOI: 10.1177/1947603520903443
https://doi.org/10.1177/1947603520903443

Randomized Controlled Trial journals.sagepub.com/home/CAR

Jing Chao1 , Zhang Jing1, Bai Xuehua2, Yang Peilei3,

and Gong Qi4

Abstract
Objectives. We aimed to compare the outcomes of exercise rehabilitation and conventional treatment in patients with
knee osteoarthritis. Methods. This trial included a total of 166 patients diagnosed with knee osteoarthritis; they were
randomly divided into groups. The experimental group underwent systematic exercise rehabilitation, while the control
group received naproxen (n = 28), diclofenac (n = 27), or celecoxib (n = 19). Improvement in symptoms, knee function,
and quality of life were compared. SPSS Statistics 24.0 was used for the data analysis. Results. The mean age of patients
was 56.0 ± 10.5 years, and the average follow-up time was 12 ± 2.3 weeks. No statistically significant differences were
seen in age, body mass index, and sex (P > 0.05) between the groups. The average Western Ontario and MacMaster
Universities (WOMAC) scores after treatment were 84.4 ± 15.2, 108.3 ± 3.9, 107.4 ± 5.4, and 107 ± 6.0 in the exercise
rehabilitation, diclofenac, naproxen, and celecoxib groups, respectively. The mean Lysholm scores were 60.3 ± 14.9, 41.0
± 0.1, 43.5 ± 5.3, and 41.7 ± 3.6 in the exercise rehabilitation, diclofenac, naproxen, and celecoxib groups, respectively.
The mean SF-36 (Short Form-36 Survey) scores were 105.4 ± 21.5, 82.5 ± 3.7, 84.2 ± 3.5, and 83.7 ± 5.0 in the exercise
rehabilitation, naproxen, celecoxib, and diclofenac groups, respectively. The average ranges of knee motion were 125.0
± 6.2°, 116.4 ± 1.4°, 114.7 ± 1.1°, and 115.7 ± 0.8° after exercise rehabilitation, diclofenac, naproxen, and celecoxib
treatments, respectively. These data presented statistical differences between the groups. Conclusion. Exercise better
improved symptoms and quality of life in patients with knee osteoarthritis over a 12-week follow-up period than that
achieved with nonsteroidal anti-inflammatory drugs and COX-2 inhibitors.

Keywords
knee osteoarthritis, rehabilitation, exercise

Introduction under clinical conditions. Furthermore, the specific exercises

The general aim of treatment in patients with knee osteoar-
thritis is to relieve pain, improve joint movement, and find
nontargeted strategies to treat knee osteoarthritis.1 During the
last decade, clinical practices included the use of nonsteroidal
anti-inflammatory drugs (NSAIDs), cyclooxygenase-2
inhibitors (COX-2 inhibitors), and intraarticular injection of
hyaluronic acid to reduce inflammation and relieve pain.2
However, these conventional treatment methods have limita-
tions, such as gastrointestinal side-effects. Moreover, their
effectiveness in protecting the cartilage and delaying disease
progression is controversial.3 Some studies have suggested
that regular exercise may help patients with knee osteoarthri-
tis by reducing articular cartilage breakdown, relieve pain,
and improve knee function and quality of life.4
However, it remains unclear whether exercise rehabilita-
tion can improve outcomes of patients with knee osteoarthritis
that are suitable for patients with knee osteoarthritis are yet to
be determined.
In this study, we hypothesized that exercise rehabilita-
tion is better than treatment with conventional drugs in
patients with knee osteoarthritis. In this study, we com-
pared the outcomes of exercise rehabilitation and conven-
tional treatment in patients with knee osteoarthritis. We
1
The Second Hospital of Hebei Medical University, Shijiazhuang, China
2
Hebei Normal University Sports Rehabilitation Department,
Shijiazhuang, China
3
Peking University Health Science Center, Beijing, China
4
Wuhan Sports University, Wuhan, China
Corresponding Author:
Jing Chao, The Second Hospital of Hebei Medical University, Shijiazhuang
050000, China.
Email: drjingchao1995@foxmail.com
2 Cartilage 00(0)

Table 1. The Kellgren-Lawrence Classification of Osteoarthritis.

Stages Feature
Grade I Formation of osteophytes on joint margin or on the tibial spines
Grade II Periarticular ossicles (primarily with regard to DIP and PIP joints)
Grade III Narrowing of joint cartilage associated with sclerosis of subchondral bone
Grade IV Small pseudocystic areas with sclerotic walls situated usually in the subchondral bone
Grade V Altered shape of bone ends, particularly in the head of the femur

DIP = distal interphalangeal joints; PIP = proximal interphalangeal joints.

Table 2. The Exercise Rehabilitation Training Plan for Patients With Knee Osteoarthritis.

Times Exercise Movement Frequency

Week 1 Quadriceps static-training 10 to 15 times/3 groups
  Ankle pump training 10 to 15 times/3 groups
  The straight leg-raising 10 to 15 times/3 groups
  The straight leg-raising 10 to 15 times/3 groups
  Prone leg flexion 10 to 15 times/3 groups
Weeks 2 and 3 Reclining with the ball 10 to 15 times/3 groups
  Side leg lifts 10 to 15 times/3 groups
  The straight leg-raising 20 to 25 times/3 groups
  Side leg lifts 20 to 25 times/3 groups
Weeks 4 and 5 Reclining with the ball 20 to 25 times/3 groups
  Prone leg flexion 20 to 25 times/3 groups
  Sitting with the ball 10 to 15 times/3 groups

also compared the outcomes achieved with naproxen,
diclofenac, and celecoxib.
Methods
Patients and Study Design
The study was approved by The Second Hospital of Hebei
Medical University Ethics Committee.
The inclusion criteria were as follows: (1) age 50 to 70
years, (2) diagnosis of knee osteoarthritis, (3) classified as
Kellgren-Lawrence grades I to III with obvious symptoms
(Table 1),5 and (4) patients who provided signed informed
consent for inclusion into the clinical trial and agreed to
comply with the protocol requirements of this study.
The exclusion criteria were as follows: (1) rheumatoid
arthritis; (2) previous joint replacement; (3) severe organ
failure, specifically patients with cardiovascular diseases,
classified as New York Heart Association (NYHA) class III
or IV, chronic kidney disease (CKD), classified as stage
≥3, and liver disease, with a Model of End-stage Liver
Disease (MELD) score of ≥20; and (4) patients with severe
mental illness.
Based on the inclusion and exclusion criteria, 185
patients diagnosed with knee osteoarthritis who were
treated at The Second Hospital of Hebei Medical University
between October and December 2018 were included.
Patients were randomly divided into 2 medication groups
and an exercise rehabilitation group. As there were signifi-
cant differences in the treatment among these 3 groups, no
blinding was followed in this trial.
Intervention Methods
Generally, conventional treatment includes the administra-
tion of NSAIDs and COX-2 inhibitors. In this trial, naproxen
and diclofenac were administrated to the patients, respec-
tively. All patients in the conventional treatment group
received the same drug dosage, while patients in the exer-
cise rehabilitation group underwent the same physical ther-
apy by the same physiotherapist.
The systematic exercise rehabilitation program mainly
included lower limb static, dynamic, and flexibility exer-
cises; exercises targeting the gluteus muscles; and core
strength training for 20 minutes per day (Table 2).
The patients were required to attend follow-up visits at
weeks 1, 3, 5, 7, and 12 during the rehabilitation program,
where the effect of the rehabilitation was recorded. No
NSAIDs or other analgesics were used during the study
period in the exercise rehabilitation group.
Assessment of Outcomes
In this study, the outcomes evaluated were improvement in
symptoms, knee function, and quality of life of patients
Chao et al. 3

Figure 1.  Flow diagram of randomized controlled trial. In this study, we assessed for eligibility 195 cases in enrollment, and finally
included 166 cases in analysis; the experiment group included 92 cases, and the control group included 74 cases.

with knee osteoarthritis. All patients were assessed using
the Lysholm Knee Score, Western Ontario and MacMaster
Universities (WOMAC) Osteoarthritis Index Score, and
SF-36 (Short Form-36 Survey) health questionnaire before
and after treatment. Knee range of motion before and after
treatment was evaluated. This study compared the outcome
measures among patients who were administered naproxen,
diclofenac, and celecoxib.
Statistical Analysis
We used SPSS version 24.0 (IBM Corp, Inc., Chicago, IL)
for the statistical analyses. Data were recorded as percent-
age (n). All the measurement data (age, body mass index
[BMI], Lysholm score, WOMAC scores, and SF-36 scores)
and knee range of motion were analyzed using paired
sample t tests. The data from the 3 groups were analyzed
using chi-squared tests. Between-group differences in sex
were evaluated. An alpha level of 0.05 was used. Statistical
significance was considered as P < 0.05.
Results
A total of 166 patients with knee osteoarthritis were included
in this randomized controlled trial. Nineteen patients (11.4%)
were lost to follow-up (Fig. 1). The mean age of patients was
56.0 ± 10.5 years, and 77.7% were women. The average
follow-up was 12 ± 2.3 weeks. There was no significant dif-
ference with respect to age, BMI, and sex between the study
and control groups (P > 0.05), as shown in Table 3.
The average WOMAC score in the exercise rehabilita-
tion and diclofenac groups were 84.4 ± 15.2 and 108.3 ±
4 Cartilage 00(0)

Table 3.  Baseline Characteristics of Patients in This Study.

Exercise (n = 92) Diclofenac (n = 27) Naproxen (n = 28) Celecoxib (n = 19)

Age, mean (SD),years 56.7 ± 10.6 56.7 ± 10.6 55.4 ± 9.3 55.2 ± 8.0
Women, % 76.1% 80.0% 74.2% 63.2%
Men, % 23.9% 20.0% 25.8% 36.8%
BMI, mean (SD) 26.3 ± 2.9 26.2 ± 2.9 25.4 ± 3.4 26.7 ± 4.9
Lysholm score, mean (SD) 38.0 ± 1.3 37.7 ± 1.3 37.4 ± 3.8 38.2 ± 2.2
WOMAC score, mean (SD) 113.6 ± 2.9 112.9 ± 3.0 110.9 ± 4.3 113.9 ± 3.3
SF-36 score, mean (SD) 78.1 ± 1.2 77.9 ± 1.2 76.8 ± 3.2 78.9 ± 1.9
ROM, mean (SD) 114.5 ± 1.2 114.3 ± 1.2 113.1 ± 3.1 114.4 ± 2.1

BMI = body mass index; WOMAC =Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis Index Score; SF-36 = Short Form-36
Survey; ROM = range of motion.

Table 4.  Comparison of the General Condition of Patients in the Exercise Rehabilitation and Diclofenac Groups.

Outcome Sports Rehabilitation, Mean (SD) Diclofenac, Mean (SD) P Value

WOMAC score 84.4 ± 15.2 108.3 ± 3.9 0.009
Lysholm score 60.3 ± 14.9 41.0 ± 3.0 0.024
SF-36 score 105.4 ± 21.5 83.7 ± 5.0 0.043
ROM 125.0 ± 6.2 116.4 ± 1.4 0.017

WOMAC =Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis Index Score; SF-36 = Short Form-36 Survey; ROM = range of
motion.

Table 5.  Comparison of the General Condition of Patients in the Exercise Rehabilitation and Naproxen Groups.

Outcome Sports Rehabilitation, Mean (SD) Naproxen, Mean (SD) P Value

WOMAC score 84.4 ± 15.2 107.4 ± 5.3 0.006
Lysholm score 60.3 ± 14.9 43.1 ± 5.3 0.020
SF-36 score 105.4 ± 21.5 82.5 ± 3.7 0.046
ROM 125.0 ± 6.2 114.7 ± 1.1 0.011

WOMAC =Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis Index Score; SF-36 = Short Form-36 Survey; ROM = range of
motion.

3.9, respectively, after treatment (P = 0.009). The mean
Lysholm score in the exercise rehabilitation and diclofe-
nac groups were 60.3 ± 14.9 and 41.0 ± 0.1, respectively,
after treatment. These results showed a significant differ-
ence in scores between groups, which indicates that exer-
cise rehabilitation can relieve pain and other symptoms
more effectively than diclofenac. In the exercise rehabili-
tation group, the mean SF-36 score was 105.4 ± 21.5, and
the average knee range of motion was 125.0 ± 6.2° after
treatment. The average SF-36 score in the diclofenac
group was 83.7 ± 5.0, and the average knee range of
motion was 116.4 ± 1.4° after treatment. There were
significant between-group differences (P = 0.043 and
0.017, respectively), showing that exercise rehabilitation
achieved a greater improvement in quality of life than that
achieved with diclofenac (Table 4).
In the naproxen group, the average WOMAC score was
107.4 ± 5.4, and the average Lysholm score was 43.5 ± 5.3,
after treatment. The results of the exercise rehabilitation and
naproxen groups were significantly different (P = 0.006 and
0.020, respectively), which indicated that exercise rehabili-
tation was better at treating pain and other related symptoms
than naproxen. Taking into account the quality of life, it was
found that the naproxen group had an average SF-36 score
of 82.5 ± 3.7 and an average knee range of motion of 114.7
± 1.1°, while the exercise rehabilitation group had a score of
105.4 ± 21.5 and range of motion of 125.0 ± 6.2° (P =
0.046 and 0.011, respectively). Thus, exercise rehabilitation
had an advantage over naproxen in improving patients’ qual-
ity of life and recovery (Table 5).
As shown in Table 6, we also compared the outcomes of
the exercise rehabilitation group with that of the celecoxib
group with respect to differences in short-term prognosis of
patients. In the celecoxib group, the average WOMAC score
was 107 ± 6.0, the average Lysholm score was 41.8 ± 3.6,
the average SF-36 score was 84.2 ± 3.5, and the average knee
Chao et al. 5

Table 6.  Comparison of the General Condition of Patients in the Exercise Rehabilitation and Celecoxib Groups.

Outcome Sports Rehabilitation, Mean (SD) Celecoxib, Mean (SD) P Value

WOMAC score 84.4 ± 15.2 107.3 ± 6.0 0.005
Lysholm score 60.3 ± 14.9 41.8 ± 3.6 0.026
SF-36 score 105.4 ± 21.5 84.2 ± 3.5 0.050
ROM 125.0 ± 6.2 115.7 ± 0.8 0.018

WOMAC =Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis Index Score; SF-36 = Short Form-36 Survey; ROM = range of
motion.

Figure 2.  Comparison of outcomes experimental group and control group. (A) To investigate whether exercise rehabilitation could
reduce symptoms in patients with knee osteoarthritis. (B) To study whether exercise could improve daily life function in patients with
knee osteoarthritis. (C) We assessed the life quality of patients with knee osteoarthritis in the short term with exercise rehabilitation
and different NASIDs. (D) We examined the knee range of motion in exercise rehabilitation and NASIDs. WOMAC = Western
Ontario and McMaster Osteoarthritis Index; SF-36 = Short Form-36 Survey; ROM = knee range of motion.

motion range was 115.6 ± 0.8°. The statistically significant
difference between the 2 groups (P < 0.05) validated the
ascendency of exercise rehabilitation on prognosis and quality
of life improvements. Figure 2 shows that there was no statis-
tically significant improvement in the WOMAC, Lysholm, or
SF-36 scores, or knee range of motion in the diclofenac,
naproxen, or celecoxib groups after treatment (P > 0.05).
Discussion
The trial showed that the WOMAC scores, Lysholm scores,
SF-36 scores, and average ranges of motion after treatment
were significantly better for the exercise rehabilitation
group than those for the medication groups.
We still currently lack an effective disease-modifying
therapy for osteoarthritis. Many professional societies sug-
gest the use of NSAIDs for primary pharmacologic man-
agement of knee osteoarthritis. In England, 5.8 million
prescriptions were dispensed for topical NSAIDs in 2014,
mainly including formulations of ibuprofen and diclofenac.
Some studies suggest the use of conservative treatment with
exercise rehabilitation, which is considered to be one of the
important and basic methods for the treatment of knee
osteoarthritis.6-9 However, some studies have expressed
6 Cartilage 00(0)
concern as to whether exercise rehabilitation can surpass
conventional treatment methods.10
A total of 166 patients with knee osteoarthritis were
included in this randomized controlled trial, and the mean
follow-up period of the 2 groups was 12 ± 2.3 weeks.
This study shows that exercise rehabilitation provides
significant improvements in pain, other symptoms, and
quality of life compared to that achieved by conventional
treatments.
A British primary care center and Keele University con-
ducted a systematic review and meta-analysis that showed
that exercise programs that include muscle strength, flexi-
bility, and aerobic training could improve the prognosis of
patients by improving joint function. When compared to the
control group,11 the degree of pain was also significantly
reduced. Japanese researchers conducted an 8-week ran-
domized controlled trial, including patients with knee
osteoarthritis who received home rehabilitation and those
who received NSAIDs. It was found that quadriceps muscle
strength training relieved pain as much as NSAIDs.
Furthermore, it allowed patients to have a normal life, and
even provided patients with a greater ability to perform
social activities in contrast to using NSAIDs.12 This result is
consistent with the conclusion of this study.
In this study, we compared the outcomes of exercise
rehabilitation with that of treatment with naproxen, diclof-
enac, and celecoxib, because these treatments form the
basis of standard treatment recommended by most clinical
practice guidelines for knee osteoarthritis.13,14 Diclofenac
is the most commonly prescribed drug by primary care
physicians. Naproxen is one of the most highly prescribed
drugs worldwide for treatment of knee osteoarthritis15 and
is also the cheapest generic NSAID available to health
insurance providers.16 Celecoxib is a COX-2 inhibitor,
which is widely prescribed in this group of patients.17 A
systematic review and network meta-analysis demon-
strated that naproxen, diclofenac, and celecoxib provided
significantly greater improvement in joint function, stiff-
ness, and pain compared to acetaminophen in patients with
knee osteoarthritis.18
Certain studies have found that some inappropriate exer-
cise patterns can adversely affect the prognosis of patients
with knee osteoarthritis.19 Thorstensson et al. found that
high-intensity knee joint resistance exercise had no effect
on pain relief or functional recovery of patients and even
led to aggravation of pain.20 Therefore, selecting the appro-
priate type of exercise and intensity level play an important
role in the treatment of patients with knee osteoarthritis.
In this study, we evaluated the use of a systematic exer-
cise rehabilitation program to ensure that the suitable type,
intensities, and frequencies of exercise were provided to
patients with knee osteoarthritis. Previous trials only
focused on the effectiveness of muscle strength training or
dynamic balance for patients with knee osteoarthritis.7,20,21
This exercise rehabilitation program includes lower limb
muscle strength training, proprioception training, and core
muscle stability exercises, focusing on the quadriceps and
other peripheral muscles that strengthen the knee. Using
movement, the combination of open-chain training and
closed-chain training was adopted. Each training session
lasted for 20 minutes. During the early stage of training, the
horizontal position was used for open-chain training to min-
imize joint pain caused by excessive knee load, increase
muscle strength of patients, and ensure patient compliance.
During the middle and later stages of training, sitting and
standing positions were used to gradually increase the load
on the knee joint. Finally, a certain amount of heel lift and
core training were provided to increase the lower limb and
core strength of patients.
The limitations of this study include small sample size,
short follow-up time, and the lack of blinding. Because of
significant differences in treatment methods used between
conventional treatment and exercise rehabilitation, a
blinded method could not be used. Thus, there may have
been a placebo effect, as well as a more subjective evalua-
tion in the observation of any improvements, which may
have resulted in evidence bias.
The follow-up period of this trial was 12 weeks, and
thus, the data collected can be used to analyze the short-
term effects of the exercise rehabilitation program in
patients with knee osteoarthritis. This study demonstrated
that the progressive muscle rehabilitation program resulted
in significant improvement in strength, endurance, and
speed of muscle contraction. The improvement seen after 3
months was approximately double that seen after 2 months;
however, some studies suggest that this improvement may
not be significant after more than 4 months of follow-up.22,23
Future studies should focus on long-term follow-up of
patients, larger sample sizes, and increasing the use of func-
tional and serological examinations. Studies should further
explore the effect and mechanism of exercise on patients
with knee osteoarthritis. In addition, the corresponding
training intensity should be tailored for patients with vary-
ing degrees of knee osteoarthritis, and more appropriate
exercise programs should be developed to improve patient
compliance and prognosis.
Acknowledgments and Funding
We thank all participants of this trial. We thank the Lee Yaqian
and Liang Wenjie for helping improve the study. The author(s)
received no financial support for the research, authorship, and/or
publication of this article.
Author Contributions
JC and YPL designed the study; ZJ acquired the data; BXH and
GQ designed the systematic exercise rehabilitation program. All
authors drafted the manuscript and critically revised and approved
the final version of manuscript.
Chao et al. 7
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Ethical Approval
The study was approved by The Second Hospital of Hebei Medical
University Ethics Committee (2017023919).
Informed Consent
Written informed consent was obtained from all subjects before
the study.
Trial Registration
ChiCTR1800019208.
ORCID iD
Jing Chao https://orcid.org/0000-0003-1084-8382
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