Beruflich Dokumente
Kultur Dokumente
2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.joca.2009.07.004
reduced quadriceps strength is a risk factor as well as a consequence of OA in the knee2e5. It has repeatedly been
shown, that exercise reduces pain and improves function in
subjects with OA of the knee6e9. These benecial effects
are seen in protocols including both strength and endurance
training10e17. To our knowledge, it is not known whether
physical training affects cartilage homeostasis in these
patients.
Cartilage oligomeric matrix protein (COMP) is a prominent
component of cartilage matrix18. This glycoprotein has
a role in governing assembly of type II collagen bres in cartilage, and in cooperation with other matrix proteins it stabilizes the collagen network19,20. Patients with knee OA have
increased serum concentrations of COMP21e27. Furthermore, studies suggest that increased levels of serum
COMP are related to progressive joint damage in knee
OA measured by radiography over a 5-year period28,29.
COMP levels are also modied in response to acute exercise; an acute bout of exercise elevates serum COMP in
Introduction
Approximately 8e10% of all men and women have osteoarthritis (OA) in one or more of their joints, which causes disability, pain and reduced quality of life1. The disease
affects the cartilage, synovium, subchondral bone, tendons
and muscles surrounding the joint. There are a number of
established risk factors for OA in the knee such as age, increased body mass index (BMI), previous injury or surgery
of the knee, and genetic factors. Studies also suggest that
1
34
35
the study. The experimental protocol was approved by the local Ethical Committee for Copenhagen and Frederiksberg Communities (KF 01-189/04). All
procedures followed were in accordance with the ethical standards of the
Helsinki Declaration of 1975, as revised in 2000.
MEDICATION
Four patients from each group were previously treated with NSAID. Seven
patients from the glucosamine-group and ve from both the ibuprofen and
placebo-group had previously taken glucosamine. They were instructed to
stop the intake at least 1 month before the study began. Patients were randomly assigned to one of three medication groups. They were administered
glucosamine (n 12), NSAID (n 12) or placebo (n 12). The administration of placebo and glucosamine was started 4 weeks before the training,
but active NSAID treatment was initiated only 1 week before (Fig. 1). We
chose to initiate the administration of glucosamine 4 weeks before training
in order to ensure that glucosamine levels were adequate. Furthermore, it
has been shown that ibuprofen works more quickly than glucosamine, which
has to be given at least 2 weeks before you can expect a potential effect on
OA symptoms54,55. Subjects in the glucosamine-group were given glucosamine sulphate tablets (Ferrosan) of 500 mg three times a day and subjects
in the NSAID group were given tablets of 600 mg of ibuprofen (Nycomed)
twice a day. Placebo tablets were identically supplied and formulated as
the glucosamine or ibuprofen tablets except that they contained no medicine.
The treatment was blinded to the patients, so that all subjects were supplied
the same amount of pills (ve a day) that had similar appearance. To ensure
compliance, the subjects returned the empty packages every week to a lab
technician not involved in other parts of the study. For further control, NSAID
levels in the blood were traced in the beginning of the training period, as well
as after 6 and 12 weeks. If any of the patients experienced severe pain during the training period, they were allowed to take rescue medicine 50 mg
tramadol (synthetic, monoagonistic opioid), which unlike NSAID does not inuence prostaglandin synthesis. Alternatively the subjects were offered
acupuncture.
Fig. 1. Time-schedule.
36
physical activity before sampling. No formal training was carried out for a minimum of 48 h prior to blood and urine sampling. On the day of the sampling
the subjects met in the laboratory after having consumed a standardized,
regular breakfast. Venous blood samples were drawn and serum prepared
in a standard way and stored at 80 C until analysis. The subjects themselves collected the urine in the morning (rst morning void), before they
met in the laboratory. The urine samples were stored at 20 C until
measurement.
Results
The total number of persons prescreened via telephone
or face-to-face interview during the recruitment period was
181 (Fig. 2). Of these, 36 were randomized, and 145 were
STATISTICAL ANALYSIS
Statistical Analysis System (SAS, Version 9.2, SAS Institute, Cary, NC)
was used to analyze the data. Analyses were performed on the log-transformed dependent variable (marker-level) to improve approximation of the
Table I
Baseline characteristics of participants in the three groups
Glucosamine
Ibuprofen
Placebo
Sample size
12
11
12
Gender
7F/5 M
7F/4 M
7F/5 M
Age (years)
62.2 3.4
61.7 5.2
63.1 4.7
Body weight (kg)
78 14
83 17
82 14
Height (cm)
168 11
172 9
169 9
2
27.3 3.3
27.9 3.9
28.3 3.2
BMI (kg m )
X-ray (KL-score)
2.5 0.8
2.3 1.0
2.2 1.0
COMP baseline 13.6 /O 1.3
14.3 /O 1.3
13.8 /O 1.4
(U/L)
CTX-II baseline
514.3 /O 2.2 327.2 /O 1.6 304.6 /O 1.6
(ng/mmol)
Data for continuous measures are mean SD. Data for biomarkers are backtransformed factor means /O factor SD.
37
BIOMARKERS
Discussion
The present experiment demonstrated that in response to
a period of muscle strength training (12 weeks) muscle
Fig. 5. Levels of serum COMP (on a logarithmic scale) pre and post 12-week of strength training. Each line represents an individual patient.
We observed a statistical signicant decrease in serum COMP levels in the glucosamine-group (P 0.012).
38
Table II
Mean effects of treatments, with the log-transformed pre-treatment
value of the dependent marker as a covariate
Glucosamine vs
placebo
Ibuprofen vs
placebo
Glucosamine vs
ibuprofen
17 (28 to 4)*
1 (42 to 69)
Fig. 6. Urine CTX-II levels (on a logarithmic scale) pre and post 12-weeks strength training. Each line represents an individual patient. No
signicant alterations in CTX levels were observed in any of the groups.
Conict of interest
DH and TS are cofounders and minor shareholders in
AnaMar Medical.
Acknowledgements
We thank all the patients for their time and devotion to the
study. Additionally, we thank the laboratory at Lund University for analyzing the serum samples for COMP, Ann Christina R. Reimann and Ann-Marie Sedstrom for their
technical assistance, and Katja Heinegaard and Abigail
Mackey for writing assistance. Finally we thank Nina Beyer
for advises on patient testing and training protocols, and Sren Reitelseder, Troels Gravers Pedersen, Trine Honnens de
Lichtenberg, Lone Hrdum Larsen, Signe :stergaard, Ina
Wieland for their assistance with exercising the patients.
This was work was supported by the Danish Rheumatism Association, Danish Ministry of Health, Nordea Foundation and
IMK (Ib Mogens Kristiansen) Almene Fond.
Supplementary material
Supplementary material associated with this article can
be found, in the online version, at doi:10.1016/j.joca.
2009.07.004.
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