1272

ORIGINAL ARTICLE
Effects of glucosamine and chondroitin sulfate supplementation in addition to
resistance exercise training and manual therapy in patients with knee
osteoarthritis: A randomized controlled trial
Muhammad Osama1, Muhammad Naveed Babur2, Furqan Ahmed Siddiqi3, Naureen Tassadaq4, Muhammad Ali Arshad Tareen5

Abstract
Objective: To determine the added benefits of short-term glucosamine and chondroitin sulfate supplementation in
combination with manual therapy and resistance exercise training in the management of knee osteoarthritis.
Method: A parallel-design, double-blind randomised controlled trial was conducted from January to September 2020 at
the Foundation University Institute of Rehabilitation Sciences and Fauji Foundation Hospital, Rawalpindi, Pakistan, and
comprised of knee osteoarthritis patients of either gender having radiological evidence of grade III or less on Kellgren
classification. The subjects were randomly allocated to active comparator group A and experimental group B. Both the
groups received manual therapy and resistance exercise training, while group B additionally received glucosamine and
chondroitin sulfate supplementation for 4 weeks. Study outcomes included pain, function, quality of life, range of motion,
strength, fall risk, skeletal muscle mass, visceral fat area, body fat, intracellular water ratio, and segmental lean and fat mass.
Data was analysed using SPSS 21.
Results: Of the 24 subjects, there were 12(50%) in each of the two groups. Each group had 9(75%) males and
3(25%) females. In terms knee osteoarthritis grade, there was no significant difference between the groups (p=1.00).
No significant differences were observed in any of the outcome measures neither at 2 weeks, nor at 4 weeks post-
intervention between the groups (p>0.05) except for percentage change in segmental lean mass of the right leg at
2nd week and of the left leg at 4th week (p<0.05).
Conclusion: Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis,
however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits.
Clinical Trial Number: NCT04654871. https://www.clinicaltrials.gov/ct2/show/NCT04654871
Keywords: Chondroitin sulfate, Glucosamine, Knee osteoarthritis, Physiotherapy, Resistance exercise, Manual therapy.
(JPMA 72: 1272; 2022) DOI: https://doi.org/10.47391/JPMA.2444

Introduction known cure for KOA and symptom management is the

Half of the world’s population over the age of 65 years mainstay of the treatment.3 Prolonged use of
suffers from osteoarthritis,1,2 making it the most common pharmacological treatments is associated with numerous
cause of joint pain and disability.3-6 Knee joint is the most side-effects3 and for this reason there is an increasing
common site of osteoarthritis, comprising 80% of the total interest in the use of non-pharmacological alternatives for
disease burden,4 being the 4th and 8th leading cause of the management of KOA, including dietary supplements,
disability in females and males respectively.6 The exercise and manual therapy.3,5,7 The most commonly used
prevalence of knee osteoarthritis (KOA) has been shown to supplements for the management of KOA include
continually increase in the elderly population3,4 and a 2.1 glucosamine and chondroitin sulfate3,8-15 and some studies
fold increase has been observed in its prevalence since the have shown the two to be slightly more effective when
mid 20th century.4 This is perhaps in accordance with the administered in combination.10-12 However, it is imperative
general trend of increase in non-communicable diseases to point out that the evidence regarding the effectiveness
related to advancements in medical field and increase in of glucosamine and chondroitin sulfate is contradictory,
life expectancy, as well as sedentary lifestyle contributing with some studies supporting, and others negating their
to obesity and eventually KOA.3,4 Unfortunately, there is no effectiveness in KOA management.3 On the other hand, in
terms of therapeutic exercises for the management of KOA,
1,3Foundation University Institute of Rehabilitation Sciences, Foundation progressive resistance training has been found to exert
University Islamabad, Pakistan; 2Isra Institute of Rehabilitation Sciences, Isra positive effects.16,17 Literature has shown muscular
University Islamabad Campus, Islamabad, Pakistan & Superior University Lahore, atrophy,18 especially weakness of quadriceps femoris being
Pakistan.; 4,5Department of Physical Medicine and Rehabilitation, Fauji a significant contributor in terms of knee pain and related
Foundation Hospital and Foundation University Institute of Rehabilitation disability in persons with KOA,16,19 advocating the
Sciences, Foundation University Islamabad, Pakistan. importance of resistance exercise training in KOA
Correspondence: Muhammad Osama. e-mail: [email protected] management.

Vol. 72, No. 7, July 2022

1273 M. Osama, M.N. Babur, F.A. Siddiqi, et al.

The current study was planned to determine the additional delivering the treatment was different from the one
benefits of short-term supplementation of glucosamine responsible for outcome assessment. Participants and the
and chondroitin sulfate in combination with resistance outcome assessor were both blinded, and were not aware
exercise and manual therapy in the management of KOA. of the treatment group allocation to minimise bias.

Patients and Methods Outcome measurement tools included VAS for pain
A parallel-design, double-blind randomised controlled trial (intraclass correlation ICC=0.97)22 and the Knee Injury and
(RCT) was conducted at the Foundation University Institute Osteoarthritis Outcome Score (KOOS) (ICC=0.83-0.89),26
of Rehabilitation Sciences (FUIRS), Islamabad, and Fauji modified sphygmomanometer test for isometric muscle
Foundation Hospital (FFH), Rawalpindi, Pakistan, from strength in knee flexion and extension (ICC>0.83),27 5
January to September 2020. After approval from the FUIRS repetition sit to stand test (5XRSS) (ICC=0.982-0.998),26
ethics review committee, the sample was acquired using knee range of motion (ROM) in flexion and extension
purposive sampling technique. Those included were (ICC=0.96),27 fall risk score via Biodex balance system
individuals of either gender aged 40-70 years, having KOA (ICC=0.80)28 and body composition analysis using multi-
history of no less than 3 months, with knee pain no more frequency direct segmental bio-electrical impedance
than 8/10 cm on the visual analogue scale (VAS)20 and analysis (In-Body 720) (ICC>0.8).31,32
radiological evidence of grade III or less on Kellgren Data was analysed using SPSS 21 at a confidence interval
classification.23,24 Those with signs of serious pathology, (CI) of 95%. Normality was assessed using Shapiro Wilk
such as malignancy, inflammatory disorder or infection, test of normality. Since all data was not normally
history of trauma or fractures in lower extremity, signs of distributed, Mann Whitney U and Friedman tests were used
lumbar radiculopathy or myelopathy, history of knee for inter- and intra-group comparison. The sample size was
surgery or replacement and/or receiving intra-articular calculated to be 8 using the Harvard sample size
steroid therapy in the preceding two months were calculator,33 considering VAS as the primary outcome
excluded. Those meeting the inclusion criteria were variable with a minimal detectable change of 2.8 cm,32
assessed and diagnosed by a physiatrist and then referred power of 0.8 and a two-sided significance level of 0.05. The
to FUIRS research lab for final inclusion. sample was inflated to cover up for potential dropouts.
After taking consent from the subjects, they were randomly
allocated to active comparator group A and experimental
Results
group B using the lottery method. Both the groups Of the 50 individuals assessed, 24(48%) were included;
received manual therapy and resistance exercise training, 12(50%) in each of the two groups (Figure). Both groups
including interferential therapy and heat therapy using a had 9(75%) males and 3(25%) females. In terms KOA grade,
hot pack for 20 minutes prior to manual therapy, followed Enrollment Assessed for eligibility
by joint mobilisation, consisting of tibio-femoral anterior (n=50)
and posterior glide and patello-femoral joint mobilisation, Excluded (n=26)
3 times a week. Resistance exercise training was carried out • Not meeting inclusion criteria (n=8)
as supervised exercise training 3 times a week and as home • Declined to participate (n=8)
exercise programme for the remaining 4 days. The exercise • Could not follow up treatment (n=10)
session was started with 5-10 minutes of pain-free self- Randomized (n= 24)
paced walking, followed by resistance exercise training,
including leg press, concentric and isometric knee
extension and flexion in sitting, isometric terminal knee Allocation
extension in lying and mini-squats.16 Three sets of 8 Allocated to Active Comparator Group Allocated to Experimental Group (n=12)
repetitions were carried out for each individual exercise, (n=12) • Received allocated intervention (n=12)
• Received allocated intervention (n=12) • Did not receive allocated intervention
allowing 1-2 minute rest between the sets.18,25 For • Did not receive allocated intervention (give reasons) (n=0)
equipment-based supervised resistance training 80% of 8 (give reasons) (n=0)
repetition maximum was used as training intensity, which
Follow-Up
was reassessed every week.16,23 The participants in the Lost to follow-up (n=0) Lost to follow-up (n=0)
experimental group also received film-coated tablets of Discontinued intervention (n=0) Discontinued intervention (n=0)
glucosamine 500mg and chondroitin sulfate sodium
Analysis
400mg, thrice a day for 4 weeks. The active comparator Analyzed (n=12) Analyzed (n=12)
group received empty capsules during the research process • Excluded from analysis (n=0) • Excluded from analysis (n=0)
to ensure blinding. The physical therapist responsible for
Figure: Consolidated Standards of Reporting Trials (CONSORT) flow-chart.

J Pak Med Assoc

Effects of glucosamine and chondroitin sulfate supplementation in addition to …….. 1274

Table-1: Comparison of participant characteristics, visual analogue scale (VAS), knee osteoarthritis and outcome there was no significant difference
score (KOOS), range of motion (ROM), isometric muscle strength, 5 repetition sit to stand test (5XSST) and between the groups (p=1.00). There were
fall risk scores between the two groups at baseline, 2-week and 4-week post-intervention follow-up.
no significant intergroup differences at
Variable Median (IQR) p-value
Active Comparator Experimental
baseline (p<0.05) in terms individual
Group Group factors or outcome variables either
Age (years) 57.00 (9.00) 57 (11.00) 0.932 (Table 1).
Weight (kg) 72.00 (13.25) 72.00 (10.50) 0.932
Height (cm) 162.00 (14.75) 162.50 (9.25) 0.843 No significant differences were observed in
BMI (kg/m2) 27.39 (3.95) 27.37 (1.89) 0.887 any of the outcome measures neither at 2
Visual Analogue Scale (cm) Baseline 6.00 (1.50) 6.00 (1.00) 0.630 weeks, nor at 4 weeks post-intervention
2nd Week 3.5 (1.00) 3.5 (1.00) 0.887 between the two groups (p>0.05) except
4th Week 3.00 (1.00) 2.50 (1.00) 0.443
Knee Osteoarthritis & Total Baseline 38.00 (3.00) 38.00 (4.00) 0.799 for percentage change in segmental lean
Outcome Score (KOOS) 2nd Week 50.00 (6.00) 53.00 (6.00) 0.755 mass of the right leg at the 2nd week and
4th Week 60.50 (15.00) 68.00 (15.00) 0.630 of the left leg at the 4th week (p<0.05)
Symptoms Baseline 50.00 (8.25) 50.00 (8.25) 1.000 (Table 2).
2nd Week 69.50 (3.00) 71.00 (3.00) 0.755
4th Week 78.50 (15.00) 86.00 (15.00) 0.630
Pain Baseline 42.00 (0.00) 42.00 (0.00) 1.000
Discussion
2nd Week 57.00 (8.00) 61.00 (8.00) 0.755 The current study looked into the effects of
4th Week 71.00 (20.00) 81.00 (20.00) 0.630 resistance exercise training and manual
ADL Baseline 51.00 (0.75) 51.00 (0.75) 1.000 therapy with and without short-term
2nd Week 62.00 (6.00) 65.00 (6.00) 0.755
4th Week 73.00 (16.00) 81.00 (16.00) 0.630 glucosamine and chondroitin sulfate
Sports Baseline 10.00 (0.00) 10.00 (0.00) 1.000 supplementation on pain, KOOS, ROM,
2nd Week 10.00 (0.00) 10.00 (0.00) 1.000 5XSST, fall risk, phase angle, impedance,
4th Week 25.00 (0.00) 25.00 (0.00) 1.000 intracellular water (ICW) ratio, visceral fat
QOL Baseline 38.00 (5.25) 38.00 (5.25) 1.000
2nd Week 50.00 (12.00) 56.00 (12.00) 0.755 area, percentage body fat, skeletal muscle
4th Week 69.00 (0.00) 69.00 (0.00) 0.755 mass, segmental lean mass and segmental
Range of Motion (°) Flexion (Symptomatic Side) Baseline 88.00 (8.75) 90.50 (8.75) 0.799 fat mass in KOA patients, with positive
2nd Week 113.00 (8.75) 115.50 (8.75) 0.799 effects of treatment on all outcomes in
4th Week 128.00 (8.75) 133.00 (8.75) 0.410
Flexion (Asymptomatic Side) Baseline 125.00 (8.75) 130.00 (8.75) 0.410 both groups, except for fall risk. In vitro and
2nd Week 128.00 (8.75) 133.00 (8.75) 0.410 in vivo studies have shown beneficial
4th Week 132.50 (4.50) 135.00 (4.50) 0.410 effects of both glucosamine and
Extension (Symptomatic Side) Baseline -10.00 (3.75) -10.00 (3.35) 1.000 chondroitin sulfate on injured cartilage,
2nd Week -5.00 (3.75) -5.00 (3.75) 0.932
4th Week 0.00 (4.00) 0.00 (3.75) 0.630 and are found to reduce pain and
Extension (Asymptomatic Side) Baseline -3.00 (1.5) -3.00 (1.5) 1.000 inflammation.3 Because both the
2nd Week -1.00 (1.50) -1.00 (1.50) 1.000 supplements produce similar effects, they
4th Week 0.00 (1.75) 0.00 (1.50) 1.000 are commonly used in combination in KOA
Isometric Muscle Flexion (Symptomatic Side) Baseline 85.00 (7.50) 85.00 (10.00) 0.671
Strength (mmHg) 2nd Week 95.00 (7.75) 95.00 (11.50) 0.514 management3 and are among the highest-
4th Week 120.00 (7.50) 120.00 (10.00) 0.887 selling dietary supplements.14 However,
Flexion (Asymptomatic Side) Baseline 105.00 (3.75) 105.00 (9.00) 0.887 conflicting and inconclusive results have
2nd Week 125.00 (8.75) 125.00 (7.50) 0.551 been reported regarding the therapeutic
4th Week 145 (10.00) 145 (7.50) 0.443
Extension (Symptomatic Side) Baseline 92.5 (8.75) 90.00 (10.00) 0.932 effectiveness of glucosamine and
2nd Week 100.00 (12.50) 102.50 (10.00) 0.630 chondroitin sulfate in the management of
4th Week 126.50 (8.75) 127.50 (10.00) 0.843 KOA, and thus their treatments effects
Extension (Asymptomatic Side) Baseline 114.50 (10.00) 111.0 (13.75) 0.887 need to be clarified.3.10 For this reason, the
2nd Week 133.50 (10.00) 131.75 (13.75) 0.977
4th Week 157.00 (10.00) 155.00 (10.00) 0.843 current study determined the additive
5 repetition sit to Baseline 50.00 (6.36) 50.00 (6.11) 0.887 benefits of glucosamine and chondroitin
stand test (seconds) 2nd Week 21.21 (1.86) 21.00 (1.48) 0.755 sulfate supplementation in the
4th Week 18.50 (2.01) 18.00 (1.75) 0.843 management of KOA in addition to
Fall Risk Score (Eyes Open) Baseline 3.3 (0.73) 3.25 (0.73) 0.843
2nd Week 3.29 (0.60) 3.23 (0.56) 0.887 resistance exercise and manual therapy,
4th Week 3.30 (0.75) 3.24 (0.72) 0.755 both of which are found to be effective in
(Eyes Closed) Baseline 4.28 (0.52) 4.23 (0.41) 0.843 the management of KOA.5,16,33
2nd Week 4.30 (0.54) 4.25 (0.71) 0.977
4th Week 4.21 (0.63) 4.26 (0.64) 0.755 A systematic review in 2018 suggested that
p<0.05 is considered significant. IQR: Interquartile range, BMI: Body mass index, ADL: Activities of daily living, QOL: Quality of life.

Vol. 72, No. 7, July 2022

1275 M. Osama, M.N. Babur, F.A. Siddiqi, et al.

Table-2: Comparison of body composition parameters between the two groups at baseline, and recreation subscales. These findings are in accordance
2-week follow-up and post-intervention at 4th week. with earlier findings.8,10,34 Another systematic review in
Variable Median (IQR) p-value 2018 also reported no additional benefits of glucosamine
Active Comparator Experimental
Group Group
and chondroitin sulfate supplementation on Western
Ontario and McMaster Universities Osteoarthritis Index
Phase angle (°) Baseline 5.6 (0.63) 5.6 (0.59) 0.799
2nd Week 5.8 (0.62) 5.8 (0.60) 0.443 (WOMAC) and its subscales, based on the summary of 29
4th Week 5.9 (0.63) 5.9 (0.60) 0.443 RCTs.35 However, a study has shown beneficial effects of
Impedance (Rt.) (Ω) Baseline 308.12 (51.11) 308.10 (78.18) 0.410 glucosamine and chondroitin sulfate supplementation on
2nd Week 303.11 (51.13) 302.90 (78.20) 0.319 pain, but only in the moderate to severe subgroup when
4th Week 300.67 (51.09) 300.50 (78.19) 0.319
Impedance (Lt.) (Ω) Baseline 307.37 (45.28) 307.38 (63.34) 0.977 observed after 6 months.8
2nd Week 306.16 (45.27) 306.18 (63.36) 0.755
4th Week 305.05 (45.28) 305.08 (63.35) 0.977 Another study showed glucosamine supplementation in
Visceral fat area (cm2) Baseline 147.48 (18.51) 147.48 (18.44) 1.000 combination with strength training to be more effective
2nd Week 144.18 (18.52) 144.18 (18.48) 0.887 than exercise only in terms of pain and concentric work,
4th Week 142.98 (18.50) 142.98 (18.45) 0.977 but no significant differences were observed in terms of
Percentage body fat (%) Baseline 40.20 (7.33) 40.20 (9.33) 0.755
2nd Week 39.80 (7.33) 39.80 (9.18) 0.887 muscle cross-sectional area, eccentric work, muscle
4th Week 39.45 (6.55) 39.50 (9.33) 0.932 strength, muscle power or 5XSST after 12 weeks of
ICW ratio (%) Baseline 61.80 (0.10) 61.90 (0.175) 0.630 training.17 These findings are comparable to the current
2nd Week 62.65 (0.10) 62.75 (0.075) 0.128 study.
4th Week 63.05 (0.175) 63.10 (0.175) 0.478
ICW ratio (Rt. Leg) (%) Baseline 61.90 (0.10) 61.90 (0.175) 0.799 It is also imperative to point out that glucosamine and
2nd Week 62.80 (0.038) 62.80 (0.080) 0.932
4th Week 63.20 (0.075) 63.20 (0.183) 0.843 chondroitin sulfate are considered dietary supplements,
ICW ratio (Lt. leg) (%) Baseline 61.66 (0.0825) 61.64 (0.14) 0.713 and are thus exempted from the United States Food and
2nd Week 62.54 (0.06) 62.54 (0.1175) 0.887 Drug Administration (FDA) rigorous regulations required
4th Week 62.93 (0.1325) 62.93 (0.2025) 0.887 for prescription and non-prescription drugs, and are
Skeletal Muscle Mass (kg) Baseline 17.60 (4.24) 17.60 (5.75) 0.977
2nd Week 18.06 (4.35) 18.06 (5.84) 0.887 generally recognised as safe.38.39 For this reason the
4th Week 18.10 (4.03) 18.10 (5.48) 0.799 duration of supplementation has not been established by
Segmental Lean (Rt. leg) (kg) Baseline 6.25 (1.18) 6.20 (1.15) 0.671 FDA. However, reported improvements have been
2nd Week 6.41 (1.22) 6.48 (1.65) 0.266 observed as early as three weeks, with a steady state
4th Week 6.64 (1.26) 6.66 (1.64) 0.378
Segmental Lean 2nd Week 3.35 (0.63) 3.66 (0.69) 0.010 achieved in 3-4 days and 50% of maximal efficacy (Emax)
% change (Rt. leg) 4th Week 6.41 (0.18) 6.45 (1.08) 0.068 accomplished in 35 days.37,38 Previous studies have
Segmental Lean (Lt. leg) (kg Baseline 6.13 (1.17) 6.13 (1.20) 0.551 administered glucosamine and chondroitin sulfate
2nd Week 6.34 (1.16) 6.34 (1.16) 0.266 supplementation ranging from 42 days to 3 years35 but due
4th Week 6.52 (1.14) 6.53 (1.15) 0.114
Segmental Lean 2nd Week 3.43 (0.10) 3.43 (1.10) 0.514 to increased risk of participant dropout in long-term follow-
% change (Lt. leg) (kg) 4th Week 6.36 (0.15) 6.52 (2.56) 0.010 up and lack of funding, the treatment was administered for
Segmental fat (Rt. Leg) (kg) Baseline 4.10 (0.54) 4.10 (0.51) 0.713 4 weeks only in the current study. Even though, the
2nd Week 3.81 (0.50) 3.81 (0.48) 0.932 findings of the current study showed no statistically
4th Week 3.69 (0.49) 3.69 (0.46) 0.713
Segmental fat (Lt. Leg) (kg) Baseline 4.10 (0.54) 4.10 (0.62) 0.977 significant additional benefit of glucosamine and
2nd Week 3.82 (0.48) 3.82 (0.59) 0.932 chondroitin sulfate on disability and function when
4th Week 3.69 (0.49) 3.69 (0.46) 0.799 combined with manual therapy and exercise, which is in
p<0.05 is considered significant; IQR: Interquartile range, ICW: Intracellular water. accordance with the findings of the previous studies
glucosamine and chondroitin sulfate in combination are concluding that there is no significant effect of
found to reduce KOA pain,3 which is in accordance with the glucosamine and chondroitin sulfate on WOMAC and its
findings of the current study showing that glucosamine subscales,35 careful interpretation of the findings is
and chondroitin sulfate group demonstrated lower levels essential as the treatment duration was only 4 weeks.
of pain after 4 weeks of treatment compared to physical Furthermore, greater improvement was noted in terms of
therapy and exercise only group even though the pain in the supplementation group, which is also in
differences were not significant. Furthermore, in terms of accordance with the findings of the previous studies35 but
KOOS scores, manual therapy and exercise was found to be the difference was not significant, and it is suggested that
effective, but no added benefit of glucosamine and future studies with a longer treatment duration should be
chondroitin sulfate supplementation was observed neither carried out to determine if the difference is statistically
in the overall KOOS scores nor in the pain, symptoms, significant.
activities of daily living (ADLs), quality of life (QOL) or sports
The biggest threat to the internal and external validity of

J Pak Med Assoc

Effects of glucosamine and chondroitin sulfate supplementation in addition to …….. 1276

the current study was the coronovirus disease 2019 11. Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E. Effects
(COVID-19) pandemic and recurring lockdowns, because of of oral chondroitin sulfate on the progression of knee osteoarthritis:
a pilot study. Osteoarthritis Cartilage 1998; 6: 39-46.
which the current study was done at a single centre with a 12. Bauerova K, Ponist S, Kuncirova V, Mihalova D, Paulovicova E, Volpi
small sample size and short treatment duration with a N. Chondroitin sulfate effect on induced arthritis in rats.
short-term follow-up. Another limitation was a wide age Osteoarthritis Cartilage 2011; 19: 1373-9.
range. Multi-centre studies with larger samples and longer 13. Henrotin Y, Marty M, Mobasheri A. What is the current status of
treatment durations along with longer follow-up periods chondroitin sulfate and glucosamine for the treatment of knee
osteoarthritis? Maturitas 2014; 78: 184-7.
are recommended.
14. Sherman AL, Ojeda-Correal G, Mena J. Use of glucosamine and
chondroitin in persons with osteoarthritis. PM&R 2012; 4: S110-6.
Conclusion 15. Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, et
Physical therapy and resistance exercise training is effective al. Nonsteroidal anti-inflammatory drug or glucosamine reduced
in KOA management, short-term supplementation of pain and improved muscle strength with resistance training in a
glucosamine and chondroitin sulfate showed no additional randomized controlled trial of knee osteoarthritis patients. Arch Phys
Med Rehabil 2011; 92: 1185-93.
benefits after 4 weeks of treatment.
16. Minshull C, Gleeson N. Considerations of the principles of resistance
Limitation: The current study was retrospectively training in exercise studies for the management of knee
osteoarthritis: a systematic review. Arch Phys Med Rehabil 2017; 98:
registered at clinicaltrials.gov (NCT04654871). 1842-51.
Disclaimer: This manuscript is a part of Muhammad 17. Latham N, Liu CJ. Strength training in older adults: the benefits for
Osama's PhD in Rehabilitation Sciences. osteoarthritis. Clin Geriatric Med 2010; 26: 445-59.
18. Hurley BF, Roth SM. Strength training in the elderly. effects on risk
Conflict of interest: None. factors for age-related diseases. Sports Med 2000; 30: 249-68.
Source of Funding: None. 19. O’Reilly SC, Jones A, Muir KR, Doherty M. Quadriceps weakness in
knee osteoarthritis: the effect on pain and disability. Ann Rheum Dis
1998; 57: 588-94.
References
20. Alghadir AH, Anwer S, Iqbal A, Iqbal ZA. Test–retest reliability, validity,
1. Xing D, Xu Y, Liu Q, Ke Y, Wang B, Li Z, et al. Osteoarthritis and all- and minimum detectable change of visual analog, numerical rating,
cause mortality in worldwide populations: grading the evidence and verbal rating scales for measurement of osteoarthritic knee pain.
from a meta-analysis. Sci Rep 2016; 6: 24393. J Pain Res 2018; 11: 851-6.
2. Sacks JJ, Luo YH, Helmick CG. Prevalence of specific types of arthritis 21. Wing N, Van Zyl N, Wing M, Corrigan R, Loch A, Wall C. Reliability of
and other rheumatic conditions in the ambulatory health care three radiographic classification systems for knee osteoarthritis
system in the United States, 2001-2005. Arthritis Care Res (Hoboken) among observers of different experience levels. Skeletal Radiol 2021;
2010; 62: 460-4. 50: 399-405.
3. Simental-Mendía M, Sanchez-Garcia A, Vilchez-Cavazos F, Acosta- 22. Kurniawati WS, Ilyas M, Muis M, Faridin F, Asriyani S. Correlation
Olivo CA, Pena-Martinez VM, Simental-Mendía LE. Effect of between Osteoarthritis Knee Damage Based on Ultrasound with
glucosamine and chondroitin sulfate in symptomatic knee Kellgren-Lawrence Classification. Mutiara Medika: Jurnal Kedokteran
osteoarthritis: a systematic review and meta-analysis of randomized dan Kesehatan 2021; 21: 50-8.
placebo-controlled trials. Rheumatol Int 2018; 38: 1413-28.
23. Foroughi N, Smith RM, Lange AK, Singh MAF, Vanwanseele B.
4. Wallace IJ, Worthington S, Felson DT, Jurmain RD, Wren KT, Maijanen Progressive resistance training and dynamic alignment in
H, et al. Knee osteoarthritis has doubled in prevalence since the mid- osteoarthritis: a single-blind randomised controlled trial. Clin Biomec
20th century. Proc Natl Acad Sci 2017; 114: 9332-6. 2011; 26: 71-7.
5. Li Y, Su Y, Chen S, Zhang Y, Zhang Z, Liu C, et al. The effects of 24. Collins N, Prinsen CA, Christensen R, Bartels E, Terwee CB, Roos EM.
resistance exercise in patients with knee osteoarthritis: a systematic Knee Injury and Osteoarthritis Outcome Score (KOOS): systematic
review and meta-analysis. Clin Rehabil 2016; 30: 947-59. review and meta-analysis of measurement properties. Osteoarthritis
6. Osama M, Babur MN, Siddiqi FA. Walking related performance Cartilage 2016; 24: 1317-29.
fatigability in persons with knee osteoarthritis; an important yet 25. Silva BBC, Venturato ACT, Aguiar LT, Filho LFRM, Faria CDCM, Polese
neglected outcome. J Pak Med Assoc 2021; 71: 1513-4. JC. Validity and reliability of the Modified Sphygmomanometer Test
7. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell with fixed stabilization for clinical measurement of muscle strength.
KL. Exercise for osteoarthritis of the knee. Cochrane database of Journal Bodyw Mov Ther 2019; 23: 844-9.
systematic reviews. Br J Sports Med 2015; 49: 1554-7. 26. Medina-Mirapeix F, Vivo-Fernández I, López-Cañizares J, García-Vidal
8. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. JA, Benítez-Martínez JC, del Baño-Aledo ME. Five times sit-to-stand
Glucosamine, chondroitin sulfate, and the two in combination for test in subjects with total knee replacement: Reliability and
painful knee osteoarthritis. N Eng J Med 2006; 354: 795-808. relationship with functional mobility tests. Gait Posture 2018; 59:
9. Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, et al. 258-60.
Glucosamine and chondroitin for knee osteoarthritis: a double blind 27. Rodriguez E, Carolina R, Yannely S. No. 377 Intrarater Reliability and
randomised controlled clinical trial evaluating single and Level of Agreement of the Visual Analogue Scale, Goniometry,
combination regimens. Ann Rheum Dis 2015; 74: 851-8. Hand‐Held Dynamometry and the Six-Minute Walk Test in Persons
10. Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, et al. With Knee Osteoarthritis. PM&R 2014; 6: S166.
Glucosamine and chondroitin for knee osteoarthritis: a double-blind 28. Parraca JA, Olivares Sánchez-Toledo PR, Carbonell Baeza A, Aparicio
randomised placebo-controlled clinical trial evaluating single and García-Molina VA, Adsuar Sala JC, Gusi Fuertes N. Test-Retest
combination regimens. Ann Rheum Dis 2015;74: 851-8. reliability of Biodex Balance SD on physically active old people. J

Vol. 72, No. 7, July 2022

1277 M. Osama, M.N. Babur, F.A. Siddiqi, et al.

Human Sports Exercise 2011; 6: 444-51. 34. Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, Largo R, Herrero-
29. Ling CH, de Craen AJ, Slagboom PE, Gunn DA, Stokkel MP, Beaumont G; CS/GS Combined Therapy Study Group. Combined
Westendorp RG, et al. Accuracy of direct segmental multi-frequency Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows
bioimpedance analysis in the assessment of total body and No Superiority Over Placebo for Reduction of Joint Pain and
segmental body composition in middle-aged adult population. Clin Functional Impairment in Patients With Knee Osteoarthritis: A Six-
Nutr 2011; 30: 610-5. Month Multicenter, Randomized, Double-Blind, Placebo-Controlled
30. Bedogni G, Malavolti M, Severi S, Poli M, Mussi C, Fantuzzi A, et al. Clinical Trial. Arthritis Rheumatol 2017; 69: 77-85.
Accuracy of an eight-point tactile-electrode impedance method in 35. Simental-Mendia M, Sanchez-Garcia A, Vilchez-Cavazos F, Acosta-
the assessment of total body water. Eur J Clin Nutr 2002; 56: 1143-8. Olivo CA, Pena-Martinez VM, Simental-Mendia LE. Effect of
31. Schoenfeld D. Statistical considerations for a parallel trial where the glucosamine and chondroitin sulfate in symptomatic knee
outcome is a measurement MGH Mallinckrodt General Clinical osteoarthritis: a systematic review and meta-analysis of randomized
Research Center: Harvard University. [Online] [Cited 2021 Sep 30]. placebo-controlled trials. Rheumatology Int 2018; 38: 1413-28.
Available from: URL: http://hedwig.mgh.harvard.edu/sample_size/ 36. (FDA) FFaDA. Generally Recognized as Safe (GRAS) Notification for
js/js_parallel_quant.html. Chondroitin Sodium Sulfate. 2016.
32. Naylor JM, Hayen A, Davidson E, Hackett D, Harris IA, Kamalasena G, 37. Associates O. The Truth About Glucosamine and Chondroitin Sulfate.
et al. Minimal detectable change for mobility and patient-reported [Online] [Cited 2021 June 8]. Available from: URL:
tools in people with osteoarthritis awaiting arthroplasty. BMC https://www.oaph.com/patient-resources/education/truth-about-
Musculoskeletal Disord 2014; 15: 235. glucosamine-and-chondroitin-sulfate.
33. Xu Q, Chen B, Wang Y, Wang X, Han D, Ding D. The effectiveness of 38. Henrotin Y, Mathy M, Sanchez C, Lambert C. Chondroitin sulfate in
manual therapy for relieving pain, stiffness, and dysfunction in knee the treatment of osteoarthritis: from in vitro studies to clinical
osteoarthritis: A systematic review and metaanalysis. Pain Physician recommendations. Ther Adv Musculoskeletal Dis 2010; 2: 335-48.
2017; 20: 229-43.

J Pak Med Assoc