Serum Cartilage Oligomeric Matrix Protein (COMP) in Knee
Osteoarthritis: A Novel Diagnostic and Prognostic Biomarker
Priyanka Verma, Krishna Dalal
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
Received 4 October 2012; accepted 23 January 2013
Published online 19 February 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jor.22324
ABSTRACT: A case–control study was conducted to estimate the association of cartilage oligomeric matrix protein (COMP) with knee
osteoarthritis (OA) and to examine the potential utility of COMP as a diagnostic and prognostic biomarker in early knee OA. The
COMP levels were estimated in the blood sera of 150 subjects belonging to study group (n ¼ 100) and control one (n ¼ 50). Patients
with confirmed clinical isolated knee OA diagnosed through American College of Rheumatology criteria were included and were
without any other cause of knee pain. ELISA was used to determine the levels of COMP, interleukin-1b (IL-1b) and tumor necrosis
factor-a (TNF-a). The median (range) serum COMP levels were observed to be 1117.21 ng/ml (125.03–4209.75 ng/ml) in OA patients
and 338.62 ng/ml (118–589 ng/ml) in control subjects with p < 0.001. The COMP levels of study group were negatively correlated
(correlation factor 0.88) with disease duration and positively correlated with age, BMI, pain score and IL-1b with correlation factors
0.86, 0.63, 0.76, and 0.79, respectively with p < 0.001. Gender differentiation was found in study group with 52% higher COMP level in
males as compared to that of females. There was no significant correlation of COMP levels with radiological grading, erythrocyte
sedimentation rate (ESR), hemoglobin (Hb), and TNF-a. The serum COMP levels may be used as a diagnostic OA marker along with
prognostic value in determining the patients at risk of rapidly progressing this debilitating joint disease. The serum COMP level
remains significantly high in first 3 years of disease duration. # 2013 Orthopaedic Research Society. Published by Wiley Periodicals,
Inc. J Orthop Res 31:999–1006, 2013.
Keywords: COMP; prognosis; diagnosis; knee osteoarthritis; biomarker
Osteoarthritis (OA) is currently defined by the American College of Rheumatology1 as a “heterogeneous
group of conditions that leads to joint symptoms and
signs which are associated with defective integrity of
articular cartilage, in addition to related changes in
the underlying bone at the joint margins.” The aetiology of OA is based on various factors such as
inflammation, mechanical and physical injury, and
other metabolic causes. A number of environmental
risk factors like obesity, occupation, and trauma, can
also initiate various pathological pathways which may
lead to OA. OA is mainly characterized by the
degeneration of articular cartilage. Articular cartilage
is made up of extracellular matrix and collagen fibrils.
The extracellular matrix provides this tissue with its
great strength in order to dissipate the load and
handle the forces generated within the joint.2 It also
provides the resistance against deformation. The colla-
Abbreviations: COMP, cartilage oligomeric matrix protein; OA,
osteoarthritis; BMI, body mass index; ESR, erythrocyte sedimentation rate; ECM, extra cellular matrix; Hb, hemoglobin; JSN,
joint space narrowing; MMP, matrix metalloproteinases; VAS,
visual analog scale
Authors’ contribution: K.D. and P.V. designed the study. P.V.
conducted the study. P.V. performed data collection. K.D. and P.
V. analyzed the data. K.D. performed data interpretation. P.V.
drafted the manuscript. K.D. and P.V. revised the manuscript
content: K.D. and P.V. K.D. approved the final version of
manuscript. P.V. take the responsibility for the integrity of the
data analyses.
All authors state that they have no conflicts of interest.
Grant sponsor: Council of Scientific and Industrial Research.
Correspondence to: Priyanka Verma (T: 91-11-26593215 ext. 919818795588; F: 91-11-26588641 ext. 91-11-26588663; E-mail:
[email protected])
# 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
gen fibrillar network provides tensile strength, and
the aggregate of water-laden proteoglycan aggrecan
contributes to its compressive stiffness.3 As there is no
vascularity in articular cartilage, it is not able to
recruit the chondroprogenitor stem cells which can do
the effective repair once growth ceases. Therefore, in
knee OA, the amount of cartilage matrix synthesis in
relation to its degradation may prove of great importance in determining the disease progression.4 The
degenerative process are found to be more apparent
with aging, and in a majority of the population over
age 60 years, this process may result in OA.4 Since the
earliest pathological changes in OA take place periarticularly, they are not captured well by radiographs
but are evident only through the costly MRI. Therefore, the field of OA study is in desperate need of
biomarkers which can change the process of OA prediction, OA management, and the efficacy of drug therapies
and our understanding of disease pathogenesis. The
possibility to objectively determine the OA status
through serum would significantly increase the possibilities of diagnosing the disease with greater ease and with
much cost-effective method than radiographic methods.
It has been studied that in the course of the disease,
when the erosion of the cartilage is taking place, it is
possible that immune reactions to other cartilage
proteins are initiated and contribute to the disease
course. The pro-inflammatory cytokines like interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a) are
known to play important roles in the development and
progression of OA.5–7 It has been documented that
they stimulate the production of MMPs8 by regulating
the collagenases and aggrecanase production, and are
known to suppress chondrocyte synthesis of aggrecan
and type II collagen which is required to restore the
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
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VERMA AND DALAL
ECM.7,9–11 It thus results in the degradation of cartilage matrix. However, the development and progression
of OA is affected by multiple active mediators but still it
is essential to elucidate the effect of these two cytokines
in progression of OA and to find if there is any
correlation between them and studied biomarker level.
It has also been observed that during turnover of
cartilage matrix in normal and diseased joints, fragments of extracellular matrix molecules, and other
degradation products of cartilage metabolism are
released into the synovial fluid12–14 and thereafter into
the blood serum.15 One such biomarker which was
most investigated till date to predict knee OA progression is cartilage oligomeric matrix protein (COMP).
COMP is an important degradation product of articular cartilage16 and it may prove to be a promising
diagnostic and prognostic marker in serum for diagnosis of knee OA.
COMP is a pentameric non-collagenous glycoprotein
belonging to the heterogeneous family of thrombospondin which can bind type to collagen type I, II, and IX.17
COMP pentamer bound up to five collagen molecules
thereby retaining them in close proximity. By this
process, COMP facilitates the collagen–collagen interactions and microfibril formation. Several studies conducted in past suggested that COMP is mainly
produced by articular chondrocytes18,19 and reached
the consensus that COMP levels in synovial fluid and
serum might be related to cartilage damage.20–22
It was also reported that COMP level elevates in the
knee joint synovial fluids of patients with reactive
rheumatoid arthritis and in serum of patients with
juvenile chronic arthritis compared to healthy
children.23 Despite these results, the role of COMP as
a marker of a disease process remained to be determined.
The use of serum COMP to disclose disease status
is not yet thoroughly studied in knee OA as the
elevated serum COMP levels correlated with a more
rapid disease course in RA.24,25 There is also evidence
that an increase in serum COMP may serve as an
indicator of radiographic OA progression.26,27 Therefore, this study has been devoted to evaluate the
COMP in serum for assessing the knee OA disease
progression, and to find out its association with
duration of disease, patient’s gender, BMI, radiological
grading, visual analog scale (VAS) score, erythrocyte
sedimentation rate (ESR), hemoglobin (Hb), and levels
of cytokines.
MATERIALS AND METHODS
Participants
This case control study was carried out in a tertiary care
medical institute located in New Delhi, India with the
permission of the institute ethics committee and was conducted among the populations of the plain lands of India.
The study was comprised of two groups: control group
(n ¼ 50) and study group (n ¼ 100). The data was collected
in person with the submission of the signed individual’s
informed consent form of one’s participation prior to the
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
initiation of the study. The details of both the group subjects
are stated in the sub-sections to follow.
Study Group
This group consisted of patients with primary OA of the knee
joint with effusions, screened in the outpatients Department
of Medicine and other medical specialty services of the study
institute for their confirmed knee OA as per the definition of
American College of Rheumatology criteria for diagnosis of
primary knee OA.1 The medical visits of the patients were
prompted by the acute onset of pain, swelling, and stiffness
in the affected region. Patients with primary knee OA
unilateral or bilateral and with chronic knee pain of more
than 3 months and radiological evidence of early OA were
included in the study group. The grading of knee severity on
knee X-ray was done according to Kellgren/Lawrence scale.28
The study group was consisted of 100 patients with the age
group 40–80 years and disease duration of 4 months to
12 years. The patients were excluded if they presented with
secondary OA, previous knee injury, or intra-articular fracture, steroid injection into the affected knee joint within
3 months of recruitment for the study, OA in joints other
than the knee joint, osteoporosis, and other rheumatic
diseases. Also, the patients with inflammed joints other than
knee joint were excluded. The process of OA evaluation also
included VAS scores for pain.
Control Group
Fifty individuals without any history of knee pain were
chosen from the Casualty Department of the study institute
and from patient’s allies to serve as a control group. The
control group did not report any evidence of fracture or
meniscal injury in past. They were matched for genders and
age with the OA group but there was no subject with age
more than 60 years who could be defined as controls as per
the inclusion criteria.
Outcome Variables
The potential determinants of the outcome measures explored included the following: demographic data together
with the BMI, radiological grading, VAS score, and serum
levels of COMP, ESR, and Hb. Every patient prior to blood
sampling procedure was asked to take a rest of 30 min. In a
subject 5 ml of blood sample was withdrawn for estimating
serum COMP and for carrying out other relevant investigations. Each blood sample was dispensed in 1.5 ml micro
centrifuge tube (MCT). Blood was allowed to clot for 1–2 h at
room temperature (25–26˚C). The clotted blood was rimmed
(so as to detach fibrin from the walls of the tube) and
centrifuged at 2,000–3,000 rpm for 10 min. Serum was
separated using a micropipette and aliquoted in triplicates
to a fresh set of MCTs. The tubes were labeled and stored
at 20˚C until use for investigative purposes.
Biochemical Analysis
The quantitative measurement of overall COMP level was
performed on the serum samples using an immunoassay
ELISA. The kit was manufactured by BioVendor Laboratory
Medicine, Inc., BioVendor GmbH, Heidelberg, Germany; Cat.
no. RD 194080200R (Cat. No.: RD194080200R). The detection limit of the assay was 0.4 ng/ml, and the intra-assay and
inter-assay coefficients of variation were 4% and 3.1%,
respectively. In case of TNF-a, the quantitative measurement was performed on the serum samples using an
immunoassay by RayBio Human TNF-alpha ELISA Kit
SERUM COMP IN KNEE OA
(U.S.; Cat#: ELH-TNF-a-001) having detection limit of
0.03 ng/ml, and the intra-assay and inter-assay coefficients
of variation were <10% and <12%, respectively. IL-1b
immunoassay was performed using RayBio Human IL-1b
ELISA Kit (U.S.) (Cat#: ELH-IL-1b-001) having detection
limit of 0.0003 ng/ml, and the intra-assay and inter-assay
coefficients of variation were <10% and <12%, respectively.
Differences due to inter-assay variations were eliminated by
comparing concentrations within subjects and by testing all
samples of any subject on the same plate. The following
procedure was used with each ELISA kit.
The sample was diluted 50 with dilution buffer supplied
in above-mentioned ELISA kits. The total quantity of 100 ml
of standards, quality controls, dilution buffer (as blank) and
samples in duplicates was pipetted into the appropriate wells
of ELISA plate. The plate was incubated at room temperature (ca. 25˚C) for 1 h. Washing of the wells was done three
times with 0.35 ml of wash solution per well (supplied). After
final wash, plate was inverted and tapped strongly against
paper towel. Then 100 ml of biotin labeled antibody was
added into each well and the plate was again incubated at
room temperature (ca. 25˚C) for 1 h. Washing step was
repeated as above and then 100 ml of streptavidin-HRP
conjugate was added into each well. The plate was again
incubated at 25˚C for 30 min. Washing step was once again
repeated as described earlier and then 100 ml of substrate
solution was added into each well. The plate was covered
with aluminum foil to avoid exposure to sunlight and it was
incubated again for 10 min at 25˚C. The color development
was stopped by adding 100 ml of stop solution. The absorbance of each well was determined using a micro plate
reader set to 450 nm (Bio-Rad 550; Bio-Rad Laboratories,
Hercules, CA). The standard curve was constructed by
plotting the mean absorbance (Y) of standards against the
known concentration (X) of standards in logarithmic scale,
using the four-parameter algorithm. Results are reported as
concentration of COMP ng/ml in samples. The measured
concentration of samples calculated from the standard curve
was multiplied by their respective dilution factor, that is,
50, because samples had been diluted prior to the assay.
Measurement of Knee Pain
The severity of OA pain (OAP) was measured on VAS scores
ranging from “0 to 10” (“0” indicating “no pain” and “10”
indicating “unbearable pain”). Pain was assessed by the
individual patient herself/himself by marking “no pain” (0 <
OAP 0.5), “mild pain” (0.5 < OAP 3), “moderate pain”
(3 < OAP 6) or “severe pain”(6 < OAP 9) on the pain
chart each day for a period of 2 weeks and the average VAS
score was recorded as the reported pain score for an
individual. There was no subject reported with “unbearable
OAP” (9 < OAP 10). The data was collected in person or
over the telephonic conversation.
Radiological Evaluation
Radiological evaluation was done to all patients by Kellgren–
Lawrence grading scale, 1957. Radiographs with no osteophytes and normal joint space were defined as K/L “grade 0”
(normal findings). A minute radiographic osteophyte of doubtful pathologic significance was assigned a K/L “grade of 1”
(doubtful). Radiographs showing an osteophyte without joint
space narrow were assigned a K/L “grade of 2” (mild). A
moderate decrease of the joint space was assigned a K/L “grade
of 3” (moderate). K/L “grade of 4” (severe) was defined as severe
joint space narrowing with subchondral bone sclerosis.28
1001
Statistical Analysis
The recorded data were statistically analyzed using the
statistical software package STATA 11.1 for Windows,
STATA Corporation, USA. Continuous variables were summarized as mean SD or median (range) as applicable and
categorical variables as proportions, n (n %). Comparison
between groups for parametric and non-parametric variables
was done by independent Student’s t-test and Mann–Whitney test, respectively. Chi-square (x2) test was used for
categorical variables. The relationship between serum COMP
and various variables (age, BMI, VAS, K/L grades and
duration of disease, IL-1b and TNF-a) in knee OA patients
were accessed by one-way analysis of variance (ANOVA).
Spearman’s correlation test was performed to study linear/
nonlinear correlation between variables. The significance
level was set at p-value <0.05.
RESULTS
The average concentrations of COMP in serum of
study group with primary OA were found to be
elevated over that of the reference group with statistical significance (p < 0.0001). It was estimated that the
serum COMP levels of the study individuals ranged
from 125.03 to 4209.75 ng/ml with median level of
1117.21 ng/ml whereas these values of the control
ones were found to be 338.62 ng/ml (118–589 ng/ml).
Table 1 presents the comparative statements of the
observables in which the median COMP levels were
found to be explicitly different in both groups as well
as within the study group with respective to the
different parameters. No significant correlations were
observed between serum COMP levels and K/L X-rays
score (p ¼ 0.37).
The data records reveal that the median COMP
levels in the study subjects were found to be raised in
comparison with that of the control ones irrespective of
age and gender. The graphical variations of COMP
levels are shown in Figures 1A–D and 2A–D, respectively. The variations depict that there was nonlinear
and negative variation of the COMP level with the
duration of OA (Fig. 1A) exhibiting a residual COMP
level of 200 ng/ml approximately. It was found to have
the linear but positive variations of the COMP levels
with age, BMI, VAS score, and level of IL-1b (Figs. 1B–
D and 2A), respectively). Using Table 1, it was revealed
that there was manifold increase in serum COMP level
in OA affected persons with age more than 60 years
compared with those in the age group 45–60 years.
This result is statistically significant with p-value
<0.0001. For the age group 40–60 years, there was
97.6% increase in serum COMP level among the OAaffected persons compared with that of the reference
subjects (p < 0.001). There was a positive and linear
increase of median serum COMP level with age for
both the control and OA-affected groups (Fig. 1B) with
markedly different correlation factors in between these
two groups. Figure 1B and C also exhibits the comparative variations of COMP levels with age and BMI in
between the groups. A cross-over relation of COMP
level with age was observed in the age group 44–48
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
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VERMA AND DALAL
Table 1. Comparison of Serum COMP Levels Under Various Studied Parameters
COMP Level (ng/ml)
Variables
Group
Group
Study
Control
Age (years): 40–60
Study
Control
Age (years): >60
Study
Controla
Gender (M)
Study
Control
Gender (F)
Study
Control
Disease duration (D) in months
4 D 36
Study
36 < D 60
Above 60
n (n%)
Mean ± SD/Median (Range)
p-Value
100
50
56 (56%)
50 (100%)
44 (44%)
—
40 (40%)
25 (50%)
60 (60%)
25 (50%)
1117.21 (125.02–4209.74)
338.62 (118–589)
668.08 (125.02–2194.40)
338.62 (118–589)
1822.91 (1031.82–4209.74)
—
1516.55 (178.60–4209.74)
335.30 (118.80–584.97)
997.76 (125.02–3436.28)
370.17 (117.90–588.84)
<0.001
13 (13%)
35 (35%)
52 (52%)
2561.56 ± 683.67
1639.43 ± 404.67
624.62 (125.03–1461.55)
<0.001
<0.001
<0.001
<0.001
a
No individual was encountered in age group >60 years fulfilling the inclusion criteria.
Figure 1. The variations of COMP levels with (A) disease duration in the study group: correlation factor ¼ 0.8783, p < 0.001. (B)
Age representing the comparison between the study and control subjects study group: correlation factor ¼ 0.8580 and control group:
correlation factor ¼ 0.1146; p < 0.001. (C) BMI presenting a comparison in COMP levels between study and control groups. Study
group: correlation factor ¼ 0.6310 and control group: correlation factor ¼ 0.016; p < 0.001. (D) Pain score (VAS) in the study group:
correlation factor ¼ 0.7619, p < 0.001.
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
SERUM COMP IN KNEE OA
1003
Figure 2. The variations of COMP levels in the study group with (A) IL-1b (correlation factor ¼ 0.7882; p < 0.001), (B) TNF-a
(correlation factor ¼ 0.1420; p < 0.0831), (C) Hb (correlation factor ¼ 0.1315; p < 0.1922), (D) ESR (correlation factor ¼ 0.0177;
p < 0.8610).
years (Fig. 1B). The patients of age more than 48years
showed prominent elevated COMP level at a rate of 26fold higher than the reference group.
There was a positive correlation of COMP level
(0.6310) with the BMI (p < 0.001) and the variations
are shown in Figure 1C. The body mass index in OA
patients (25.10 4.89 kg/m2) was significantly higher
than controls (22.06 3.66 kg/m2; p < 0.001). Hence
it was observed that the COMP levels increased with
BMI (for BMI > 17) and were found to be 3.2-fold
higher in study group than that of the control one
(Fig. 1C).
This study did not show any specific nature of
variations of COMP levels with radiological grading,
Hb (Fig. 2B), TNF-a (Fig. 2C), and ESR (Fig. 2D).
DISCUSSION
Till date, the diagnosis of knee OA is traditionally done
by radiographs and by pain intensity caused due to
joint tissue degeneration. It is therefore, realised that
attention must be focused on developing assays for
molecular markers which are derived from cartilage
and its degradation. It has been reported that pentameric COMP binds to collagen I/collagen II29 and collagen
IX30 with high affinity via the C-terminal globular
domains. Indeed, COMP appears to function as a
catalyst in collagen fibril formation.31 The utility of
COMP as a diagnostic biomarker is less well examined
than its role in prognosis or progression monitoring.
The increased release of fragments of COMP, into
serum in rheumatoid23,24 and reactive arthritis has
already been reported.31,32 This study was thus
designed to evaluate diagnostic and prognostic value of
COMP as biochemical markers in the included patients
of OA and its relation to disease severity and progression and the results thereby obtained are presented in
Table 1 and in Figures 1 and 2, respectively.
This study reports that the concentrations of COMP
in primary OA were found to be increased over
reference levels in the early stages of knee OA
development (Fig. 1A). The increased release of COMP
into serum during primary early OA is presumably
due to series of catabolic events undergoing in articular cartilage which results in high turnover rate by
the chondrocytes in order to repair the cartilage
matrix. This process led first to dismantling of cartilage matrix and then a net loss of tissue. In the later
stages of disease (more than a period of 51 =2 years),
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
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VERMA AND DALAL
there remains the saturation level of COMP fragments
indicating the destruction of cartilage matrix to an
extent beyond repair mechanism.
It may be inferred that the serum COMP level
declines with increase in disease duration (Fig. 1A).
The serum COMP level decreases in advanced stages of
OA as in prolong course of these pathologic remodelling
events, the number of chondrocytes declines and they
fail in their function to restore the matrix, which
culminates into a mode favoring degradation over
synthesis of ECM. Another study corroborates this
observation to the fact that there are proteinases active
in the affected cartilage matrix which has the capability
to degrade molecules of the matrix including COMP.33
Moreover, it has been observed that the range of
serum COMP for majority (83%) of OA-affected individuals did not overlap with that of unaffected individuals (age >48 years) and a cross over region was
observed in the age group of 44–48 years (Fig. 1B).
This observation is similar to the works of Mansson B
et al.34 in which it was reported that serum COMP
levels remain stable until 50 years of age. These
observations suggested that the changes in serum
COMP levels might have prognostic significance and
were consistent with a model of OA in which early
signs of episodic clinical progression might have been
found in the cartilage.
The observation on the positive correlation between
COMP level and BMI may be explained with the fact
that with increase in BMI, the resulted body weight
exerts more body mass load on the knee joint and
causes further damage to the cartilage matrix and
hence enhances the COMP level.
The observations as presented in Table 1 reveal
that males had 52% higher COMP levels (1516.55 ng/
ml) in comparison to females (997.76 ng/ml) for the
patients suffered from OA. The observation on the low
level of COMP in females with OA may be attributed
to the fact that they have small size skeleton, narrow
joint space, low cartilage mass, and lower bone density
in relation to those of the males.35 Most of the study
participants were female (60%) and the rest were 40%
males. The mismatch of the sample size was due to
higher number of the female subjects seeking for the
clinical advice in the study institute. This finding is
corroborative with the Hart et al.36 finding that
females are at higher risk of OA.
In general, the results of this study report that there
were a few cases (i.e., 17/100) in study group subjects
whose serum COMP levels were detected to be low
belonging to range of (125–497 ng/ml) which overlaps
with that of the control group subjects (118–589 ng/ml).
The anomalous observation in these cases were with the
following parameters (i) 82% of the subjects (n ¼ 17)
were females with age group 44–48 years (ii) the disease
duration of these 17 cases was more than 61 =2 years. The
effects of these two parameters are discussed individually in the above sub-sections.
JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2013
Table 1 reveals statistically significant (p < 0.0001)
increase in serum COMP levels in study group with
age more than 60 years compared with those in the
age group 40–60 years. An increase in mean serum
COMP level with age was noted for both the control
and the OA-affected groups. This could be attributed
to the increased bone and cartilage metabolism with
age. This study was not adjusted with age because at
age >60 years, we had 44 patients in study group but
in control group, we hardly got any individual who
was not suffering from any knee trauma/pain/OA.
Therefore the comparative data between the control
and the study groups in the age group >60 years was
not available. The age group >60 in this study was
limited to the study group patients only and needs
further research work to conclude the comparative
COMP level with that of control group.
This study showed that the COMP level had
positive and significant correlation with IL-1b (corelation factor ¼ 0.7882; p < 0.001). This could be
attributed to the association of IL-1b with OA which
had been identified as a catabolic cytokine implicated
in the pathogenesis of cartilage matrix degradation in
OA.37,38 The COMP level was found to be negatively
correlated with TNF-a (0.142), a pleiotropic cytokine
modulating the inflammatory and immune reactions
in response to infection or injury. This result was not
statistically insignificant (p ¼ 0.0831). This observation may be due to a small size and demands for
another study with larger population. Our observation
reconfirmed the findings of another study39 which
stated that the serum COMP level decreased with
anti-IL-1a and IL-1b treatment and neutralization of
IL-1a and IL-1b after onset of disease reduces the joint
inflammation, cartilage damage, loss of matrix proteoglycan, and bone erosions.
No significant correlation was observed between
serum COMP level and K/L X ray score (p ¼ 0.37,
data not shown) since in early disease there is damage
in joint tissue which cannot be seen on a regular Xrays; but serum COMP level was very much high
during early disease duration, signifying the cartilage
erosion has already been started. This result is in
agreement with Belcher et al.40 who could not detect
any significant correlation between the markers and
radiological findings.
In contrast, this study did not show any statistically
significant correlation (p > 0.05) between serum
COMP level with Hb (p ¼ 0.28), ESR (p ¼ 0.86), or
TNF-a (p ¼ 0.08) levels. This suggests that COMP
appears to have a pathogenetic role that is independent of the mechanism regulating the inflammatory
process pathways. Further investigations need to be
carried out in this direction.
In our study, the range of serum COMP levels for
majority (83%) of OA-affected persons did not overlap
with that of the unaffected individuals (Table 1). It is
thus to conclude that the serum COMP levels may be
SERUM COMP IN KNEE OA
used as a diagnostic marker of OA marker along with
prognostic value.
The main focus of the study was how to use the
information on the serum COMP level in early detection and disease prognosis of OA. For these purposes
patients with clinical symptoms of OA with minimum
and maximum durations were selected and this process led to recruit patients with duration as low as
4 months and as high as 12 years. The findings of the
present work may be extended to classify the state of
OA with duration by the use of the serum COMP
level.
With all these observations, it seems probable that
in order to determine patients’ risk for developing OA
by serum COMP level, his/her clinical profile should
also be assessed which includes family history, joint
injury, other visible symptoms, radiographs. The clinical profile along with serum COMP level will help the
physician in better diagnosing the OA and may also
contribute in managing the knee OA at the earliest
stage possible.
ACKNOWLEDGMENTS
The authors acknowledge the grant from the Council of
Scientific and Industrial Research, New Delhi. We gratefully
acknowledge the patients for their trust and participation.
We are also thankful to Professor A. B. Dey, MD, Department of Medicine, AIIMS and Dr. Harish Kumar, MD,
Radiology for providing with diagnosed primary knee OA
patients and to the Department of Biostatistics, AIIMS for
analyzing the data statistically.
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