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doi: 10.1136/ard.2010.134015
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Extended report
Paris 7, UFR
mdicale, Assistance PubliqueHpitaux de Paris, Hpital
Lariboisire, Fdration de
Rhumatologie, Paris Cedex,
France
2Assistance Publique-Hpitaux
de Paris, Piti-Salptrire
Hospital, Nutrition and
Endocrinology Department,
Paris, France
3Center of Research on Human
Nutrition Ile de France, Paris,
France
4INSERM, U872, Nutriomique
Team 7, Paris, France
5Universit Pierre et Marie
Curie-Paris 6, Centre de
Recherche des Cordeliers,
UMRS 872, Paris, France
6INSERM Research Unit 664
and Cisbio Bioassays, Lyon,
France
7Synarc, Lyon, France (past
affiliation)
8Universit Paris 7, UFR
mdicale, Assistance Publique
Hpitaux de Paris, Hpital
Fernand Widal, Unit de
Recherche Clinique, Paris
Cedex, France
9Assistance Publique-Hopitaux
de Paris, Htel-Dieu Hospital,
Surgery Department, Paris,
France
10Assistance Publique-Hpitaux
de Paris, Piti-Salptrire
Hospital, Endocrinology
and Oncology Biochemistry
Department, Paris, France
11Assistance Publique-Hpitaux
de Paris, Hpital Henri-Mondor,
Crteil, France
Correspondence to
Dr Pascal Richette, Fdration
de Rhumatologie, Hpital
Lariboisire, 2 Rue Ambroise
Par, 75475 Paris cedex 10,
France;
pascal.richette@lrb.aphp.fr
The first two authors
contributed equally to this work.
Accepted 11 August 2010
Published Online First
26 October 2010
ABSTRACT
Objective To investigate the effect of massive
weight loss on (1) knee pain and disability, (2) lowgrade inflammation and metabolic status and (3) joint
biomarkers in obese patients with knee osteoarthritis
(OA).
Methods 140 patients involved in a gastric surgery
programme were screened for painful knee OA, and 44
were included (age 44 10.3 years, body mass index
(BMI) 50.7 7.2 kg/m2). Clinical data and biological
samples were collected before and 6 months after
surgery.
Results Before surgery, interleukin 6 (IL-6) levels were
correlated with levels of high-sensitivity C reactive protein
(hsCRP) (p=0.006) and Helix-II (p=0.01), a biomarker
of cartilage turnover, and the Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC)
function score (p=0.03). Surgery resulted in substantial
decrease in BMI (20%). Levels of insulin and insulin
resistance were decreased at 6 months. Knee pain
decreased after surgery (24.5 21 mm vs 50 26.6
mm; p<0.001), and scores on all WOMAC subscales
were improved. Levels of IL-6 (p<0.0001), hsCRP
(p<0.0001), orosomucoid (p<0.0001) and fibrinogen
(p=0.04) were decreased after surgery. Weight loss
resulted in a significant increase in N-terminal propeptide
of type IIA collagen levels (+32%; p=0.002), a biomarker
of cartilage synthesis, and a significant decrease in
cartilage oligomeric matrix protein (COMP) (36%;
p<0.001), a biomarker of cartilage degradation. Changes
in COMP concentration were correlated with changes in
insulin levels (p=0.02) and insulin resistance (p=0.05).
Conclusion Massive weight loss improves pain and
function and decreases low-grade inflammation. Change
in levels of joint biomarkers with weight loss suggests a
structural effect on cartilage.
INTRODUCTION
Obesity is the main modiable risk factor for the
onset of knee osteoarthritis (OA).13 The strong
association between body mass index (BMI) and
OA of the knee is thought to be mainly due to an
increase in mechanical loads to the tibiofemoral
cartilage.4
The observation that obesity is also a risk factor for OA of non-weightbearing joints such as
the hand5 has suggested that the link between
overweight and OA might also occur through systemic inammation. Adipose tissue may act as
an endocrine organ, releasing several proinammatory mediators and adipokines in blood that
Extended report
gave their written informed consent before their inclusion in the
study.
Statistical analysis
140
Extended report
analysis was used to assess the independent association and
contributions of changes in BMI, insulin and HOMA-IR with the
dependant variable COMP. A two-sided signicance level was
xed at 5%. All analyses involved use of SAS v9.2 (SAS Institute,
Cary, North Carolina, USA). A two-tailed p value <0.05 was
considered statistically signicant.
RESULTS
Demographic characteristics of patients and effects of
weight loss on metabolic status
Baseline
6 Months
p Value
44 10.3
8/36
50.7 7.2
138.8 23.5
59.6 10.0
64.0 9.9
4.8 1.2
1.2 0.3
1.2 0.6
6.7 3.3
15.4 9.6
2.2 1.6
NA
NA
40.4 6.8
110.2 20.6
47.2 11.5
58.3 10.9
4.1 0.7
1.2 0.3
1.0 0.4
4.8 0.8
8.7 6.6
1.1 0.9
NA
NA
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.1
0.001
<0.0001
<0.0001
<0.0001
Baseline
6 Months
p Value
5026.6
51.626.5
24.521
25.320.9
<0.0001
<0.0001
187.3124.4
68.253.8
643.9424.2
94.193.9
36.441.9
272.6289
<0.0001
<0.0001
<0.0001
Baseline
6 Months
p Value
63.224.4
7.94.6
5.02.5
1.10.8
1.00.2
4.10.8
3316.7
9.97.7
3.72.0
0.60.5
0.80.2
3.90.9
<0.0001
0.03
<0.0001
<0.0001
0.0001
0.04
141
Extended report
Table 4
Serum levels of joint biomarkers at baseline and 6 months after bariatric surgery
Baseline
PIIANP, ng/ml
Helix-II, ng/ml
COMP, UI/l
HA, ng/ml
6 Months
MeanSD
MedianIQR
MeanSD
MedianIQR
p Value
443.6257.5
5.94.6
10.53.5
31.326.8
377.4220.2
3.95.0
10.44.9
20.438.0
586.4239.4
6.36.5
6.72.2
36.234.0
538.4242.6
3.85.5
6.12.9
27.735.3
0.002
0.98
<0.001
0.41
DISCUSSION
Our study shows that a surgically induced mean weight loss of
20% in patients with severe obesity and knee OA can improve
pain and function, decrease levels of metabolic parameters and
low-grade inammation, and result in a change in cartilage turnover as assessed by systemic biochemical markers.
Behavioural and pharmacological treatments of obesity usually result in short-term weight loss of approximately 510%
body weight.33 According to a recent meta-analysis, the pooled
effect sizes for improvement in pain and physical disability in
patients with knee OA who lost an average of 6.1 kg were 0.2
(95% CI 0 to 0.39) and 0.23 (95% CI 0.04 to 0.42), respectively.
Weight loss alone of <5% seems ineffective or poorly effective in alleviating OA knee pain in obese patients.34 Trials that
have assessed the efcacy of surgically induced massive weight
loss on knee OA symptoms are scarce and have not specically
included patients with well-dened radiographic evidence of
knee OA, as in our study.35 36 Hooper et al, using a single-arm
open study design, found that obese patients with knee OA
who lost 29% of body weight between 6 and 12 months after
bariatric surgery showed improved WOMAC pain, function
and stiffness scores, by 51%, 74% and 64%, respectively.36 In
142
Extended report
Table 5 Correlation between change in biochemical parameters and
change in COMP and PIIANP levels
Change in
BMI, kg/m2
Total cholesterol (mmol/l)
Triglycerides (mmol/l)
Glucose (mmol/l)
Insulin (IU/l)
HOMA-IR
Leptin, ng/ml
Adiponectin, g/ml
IL-6, pg/ml
hsCRP, mg/dl
Orosomucoid (g/l)
Fibrinogen (g/l)
R
0.48
0.14
0.09
0.2
0.36
0.31
0.17
0.04
0.19
0.09
0.24
0.006
Ethics approval The ethics committee of the Htel-Dieu Hospital approved the
clinical investigations.
Provenance and peer review Not commissioned; externally peer reviewed.
COMP
Change in
PIIANP
p Value
0.001
0.35
0.58
0.20
0.02
0.05
0.27
0.79
0.22
0.54
0.16
0.97
r
0.13
0.12
0.10
0.03
0.04
0.01
0.10
0.17
0.21
0.14
0.20
0.04
p Value
0.390
0.44
0.53
0.81
0.79
0.90
0.53
0.29
0.20
0.36
0.25
0.81
BMI, body mass index; COMP, cartilage oligomeric matrix protein; HOMA-IR,
homoeostasis model assessment estimate of insulin resistance; hsCRP, high-sensitivity
C reactive protein; IL-6, interleukin 6; PIIANP, N-terminal propeptide of type IIA collagen;
r, Spearman rank correlation coefficient.
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