Rheumatol Int
DOI 10.1007/s00296-011-1964-1
ORIGINAL ARTICLE
A comparative analysis of serological parameters and oxidative
stress in osteoarthritis and rheumatoid arthritis
Rachana Mishra • Aastha Singh • Vishal Chandra
Mahendra P. S. Negi • Baishnab C. Tripathy •
Jaya Prakash • Varsha Gupta
Received: 17 May 2010 / Accepted: 22 May 2011
Ó Springer-Verlag 2011
Abstract Progression of Rheumatoid arthritis (RA) and
osteoarthritis (OA) is associated with inflammation and
oxidative stress. Previous studies have shown that there was
no difference between RA and OA patients regarding the
percentages of the different lymphocytes subsets reflecting
the abnormalities in T cells and its subsets that may con-
tribute to the pathogenesis of OA as in RA. Therefore, the
present study was aimed to analyze that whether disease
activity of OA is able to affect a few serological and bio-
chemical parameters in the same way as RA does or dif-
ferently. The study was done on 36 asymptomatic controls
(25 women), 28 patients with OA (20 women), 36 patients
with RA (22 women). Patients with OA were screened
according to radiological and clinical finding of Kellgren
and Lawrence grade and ACR criteria and assessed by VAS
and WOMAC score. Patients with RA were selected who
were fulfilling 4/5 symptoms of ACR criteria, and their
DAS28-CRP, VAS score, and RF positivity were evaluated.
Participants of the groups were matched for sex, age,
weight, and height (body mass index). The BMI of all three
R. Mishra
A. Singh
V. Chandra
V. Gupta (&)
Department of Biotechnology, Institute of Biosciences and
Biotechnology, Chhatrapati Shahu Ji Maharaj University,
Kanpur, Uttar Pradesh, India
e-mail: varsha5@yahoo.co.uk
M. P. S. Negi
Biometry and Statistics Division, Central Drug Research
Institute, Lucknow, India
B. C. Tripathy
School of Life Sciences, Jawaharlal Nehru University,
New Delhi, India
J. Prakash
Vinod Dixit Hospital, Kannauj, Uttar Pradesh, India
•
groups was also found to be the same (P [ 0.05). The mean
level of LDL, Cholesterol, MDA, CRP, and Triglyceride
was significantly (P \ 0.05 or P \ 0.01) higher in both OA
and RA as compared to control. The mean level of total
lipid, cholesterol, MDA, CRP, and triglyceride was found to
be significantly (P \ 0.05 or P \ 0.01) higher in RA as
compared to OA. The pre-treatment CRP level of both
groups of patients showed significant and direct relation
with total lipid (r = 0.27, P \ 0.05) and cholesterol
(r = 0.66, P \ 0.01). Inverse relation was observed
between Uric acid and Creatinine (r = -0.26, P \ 0.05)
and cholesterol and HDL (r = -0.34, P \ 0.01). Our study
shows the similar trend in lipid profile and other parameters
studied in both patients with OA and patients with RA with
more pronounced changes in RA.
Keywords Osteoarthritis
Rheumatoid arthritis

Cardiovascular disease
Dyslipedemia
High density
lipoprotein
Low density lipoprotein
Cholesterol
Abbreviations
OA Osteoarthritis
RA Rheumatoid arthritis
CVD Cardiovascular disease
HDL High density lipoprotein
LDL Low density lipoprotein
CRP C-reactive protein
MDA Malondialdehyde
Introduction
Rheumatoid arthritis (RA) and osteoarthritis (OA) are
chronic diseases associated with joint destruction and
123

mobility impairment. Epidemiological studies have shown
an increased premature mortality in patients with RA com-
pared with general population [17, 22, 42]. RA causes sig-
nificant morbidity as a result of synovial inflammation, joint
destruction, and disability. Patients with RA have abnormal
lipoprotein pattern, principally low levels of high density
lipoprotein (HDL) and high levels of low density lipoprotein
(LDL). The improvement in the lipoprotein profile in RA
appears to be associated with suppression of inflammation
[34]. Dyslipidemia is often associated with normal or
decreased LDL, HDL in a manner comparable to inflam-
matory and infectious diseases [11]. Patients with systemic
inflammation like Rheumatoid arthritis face a significantly
increased risk of CVD compared with general population
[4, 32, 37]. Control of inflammation may have an effect on
modifying cardiovascular risk. More research is needed to
quantify the relationship between systemic inflammation
and lipoprotein levels and to determine the impact of specific
lipoprotein particles, e.g., low density lipoprotein and high
density lipoprotein on long-term risk [34].
Synovial membrane (SM) involvement was established
for RA, but the data for OA are limited, because OA is
usually regarded as noninflammatory disease. Changes in
immune system in RA are not limited to joints, and the
significant role of T cells of peripheral blood (PB) is not
disputable. Although major progress has been made in the
last few years, the etiology, pathogenesis, and progression
of OA and RA are not fully understood. Studies suggest
that osteoarthritis (OA) is induced by mechanical stress
manifested by cartilage destruction with no or minimal
involvement of the immune response as compared to that in
rheumatoid arthritis (RA). But findings of Leheita O et al.
[21] suggest the similarity of immune cell profile in both
RA and OA patients and raised the possibility that abnor-
malities in T cell and its subsets may contribute to the
pathogenesis of OA and predispose to chronic progressive
immune response in the synovial membrane (SM) with
cartilage destruction. Since there are similarities in OA and
RA with local immunological involvement, we were
interested in analyzing whether OA could lead to the
changes similar to RA on lipid profile and thereby
increasing susceptibility of patients for CVD. Therefore,
the present analysis was aimed to evaluate that whether OA
has an effect similar to RA on lipid profile and a few
serological parameters.
Materials and methods
Twenty-eight patients (20 women, 8 men) with knee OA,
36 patients with RA (22 women, 14 men) and 36 asymp-
tomatic independent controls (25 women, 11 men) were
recruited from outdoor patient department of Community
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Rheumatol Int
Health Centre and District Hospital, India. Participants of
all three groups were matched for sex, age, weight, and
height (body mass index). OA patients were screened
according to radiological grading of Kellgren and Law-
rence (K–L) score [19], and clinical evaluation was done
by WOMAC [5, 6] VAS score, and American College of
Rheumatology classification was followed for classification
of OA [1]. All the patients were fulfilling 6 more criteria to
be included in the study. Patients with OA were included
who had knee pain (asymmetrical) of more than 6 months,
stiffness (\30 min), swelling, crepitation, tenderness on
medial side of joint, X-ray had[1/3 decrease in joint space
and/or presence of osteophytes, and decreased range of
motion in their knee joint. Their ligament stability (anterior
cruciate, posterior cruciate) was normal. The participants
who had trauma, any other disease of joint, smokers, and
obese were excluded. None of the controls and patients
were hypertensive.
Controls were asymptomatic (painless, no criptation, no
decrease in joint space on X-ray, nonobese and without any
other systemic disease) and independent of the patients.
Thirty-six patients with active RA and fulfilling 4 or above
criteria of American College of Rheumatology (ACR) [3]
were recruited in the study. Their evaluations included RA
disease activity (DAS28-CRP) (version 1.1 by M. Flendrie,
Pittiman and J. Fransen), pain on visual analog scale
(0–10 cm), inflammatory measures, and sero-positivity for
RF factor. Clinical characteristics of patients with RA
included symmetric arthritis with complaints of severe
multiple joint pain along with morning stiffness ([1 h) of
joint, presence of rheumatoid nodules along with radio-
graphic changes like erosion, swelling ([3 joint especially
phalanges), multiple joint involvement, deformity of
peripheral joint (MCP and PIP), and decreased range of
motion. Out of 36 patients with RA, 19 were tested positive
for RF factor. Nine patients showed decreased joint space
whereas 27 showed increased joint space in the X-ray. All
the patients had normal ligament stability of knee joint.
Their renal disease, ongoing medication, body mass
index (kg/m2) were recorded/measured. Blood was drawn
from overnight fasting patients for all the analysis. The
study was started after approval from Institutional ethical
committee, and written informed consent was obtained
from all the patients.
Lipid profiles
MDA which is an indicator of oxidative stress was mea-
sured by the production of thiobarbituric acid reactive
compounds (TBARS) [25]. Serum creatinine assay was
based on reaction of creatinine with sodium picrate as
described by Vassiliades [39]. Serum uric acid was mea-
sured by the method of Buchanan et al. [9]. Cholesterol,
Rheumatol Int

LDL, HDL, total lipids and CRP estimations were done by
commercial kits from Merck. Quantitative estimation of
C-reactive protein (CRP) was done using the diagnostic kit
(beacon Diagnostics Pvt. Ltd. Navsari, India). Serum
samples were stored at -40°C until analyzed.
Statistical analysis
The values of three independent groups were compared
by one way analysis of variance followed by Newman-
Keuls post hoc test. Before performing ANOVA, the
homogeneity of variance among groups was tested by
Hartley F max, Cochran C, and Bartlett v2 tests. Asso-
ciation among variables of both the patient groups was
done by Pearson correlation analysis. The proportion of
sex (male and female) among three groups was compared
by v2 test. A two-tailed (a = 2) P \ 0.05 was considered
to be statistically significant. Graphpad Prism (version
3.0) and STATISTICA (version 6.0) were used for the
analysis.
Results
The aim of study was to compare serological changes
occurring in OA and RA. The demographic characteristics
of three groups were summarized in Table 1. On compar-
ing, sex (male and female) proportion (v2 = 0.25,
P [ 0.05), mean age (F = 0.05, P [ 0.05), and BMI
(F = 0.22, P [ 0.05) of three groups were found to be the
same.
Out of 28 patients with OA, 25 patients had grade II
changes and 3 had grade III changes according to K and L
score. Their WOMAC score ranged from 31.8 to 64.4
having the median value of 51.19 (0–100 scale with 0 as
the worst and 100 as the best). Patients with OA had
median VAS score of 5.5 (3–8 on 10 cm scale) whereas it
was 7.5 (6–9 on 10 cm scale) in patients with RA. The
median disease activity score DAS28-CRP of patients with
RA was 5.3 (4.8–6.5).
The levels of serological parameters of three groups
were summarized in Table 2. The mean level of Uric acid
and HDL in both OA and RA patient groups were lower
while LDL, total lipid, cholesterol, MDA, CRP, and tri-
glyceride were higher as compared to respective control
groups. Further, as compared to control, the difference was
more evident in RA than OA. Patients with OA had sig-
nificantly increased but normal level of serum creatinine
(P \ 0.05) (Table 2). On comparing, the mean level of
LDL, HDL, cholesterol, MDA, CRP, and triglyceride in
both OA and RA patient groups, they were found to be
significantly (either P \ 0.05 or P \ 0.01) different as
compared to respective control groups. The mean level of
HDL, total lipid, cholesterol, MDA, and CRP in RA patient
group was also found to be significantly (either P \ 0.05 or
P \ 0.01) different as compared to respective OA groups.
The mean level of Uric acid in all three groups did not
differed significantly (P [ 0.05), i.e., it was statistically
similar.
The inter-correlation between clinical variables of both
patients with OA and patients with RA were summarized in
Table 3. Both the groups of patients showed significant
negative correlation between cholesterol and HDL (r =

Table 1 Demographic
Characteristics Control (n = 36) OA (n = 28) RA (n = 36)
characteristic of participants of
three groups Sex: (male/female) 11/25 8/20 14/22
Age (years) 49.62 ± 1.32 49.14 ± 1.37 49.72 ± 1.29
BMI (kg/m2) 22.89 ± 0.58 23.42 ± 0.55 23.21 ± 0.51

Table 2 Serological variables

Variables Control (n = 36) OA (n = 28) RA (n = 36)
(mean ± SE) of three groups
Creatinine (lmoles/L) 69.42 ± 3.95 78.16 ± 3.72a 65.74 ± 3.96
Uric acid (mg/dL) 5.05 ± 0.29 4.70 ± 0.28 4.40 ± 0.21
a LDL (mg/dL) 54.81 ± 4.27 96.39 ± 4.93b 99.92 ± 4.61b
p \ 0.05 in comparison with
Control HDL (mg/dL) 67.10 ± 1.61 52.93 ± 1.58b 46.52 ± 1.50b,c
b
p \ 0.01 in comparison with Total lipid (mg/dL) 900.31 ± 53.20 959.80 ± 54.59 1,145.58 ± 53.24a,c
a
Control Cholesterol (mmol/L) 3.45 ± 0.13 4.25 ± 0.16 6.56 ± 0.14b,d
c a
p \ 0.05 in comparison with MDA (nmoles/mg protein) 0.76 ± 0.11 1.21 ± 0.11 2.87 ± 0.13b,c
OA CRP (mg/L) 0.41 ± 0.04 2.62 ± 0.05 b
4.25 ± 0.04b,d
d
p \ 0.01 in comparison with Triglyceride (mg/dL) 86.48 ± 4.26 135.82 ± 5.38b 142.53 ± 5.01b
OA

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 Rheumatol Int

Table 3 Inter-correlation (n = 64) of all serological variables of patients with OA and RA

Variables Creatinine Uric acid LDL HDL Total lipid Cholesterol MDA CRP Triglyceride

Creatinine 1.00
Uric acid -0.26* 1.00
LDL -0.13ns 0.30* 1.00
ns ns
HDL -0.10 0.19 0.13ns 1.00
ns ns
Total lipid -0.01 -0.09 0.07ns -0.03ns 1.00
Cholesterol -0.11ns -0.17ns -0.01ns -0.34** 0.22ns 1.00
MDA -0.13ns 0.02ns 0.17ns 0.22ns 0.05ns 0.25* 1.00
CRP -0.06ns -0.04ns 0.05ns -0.20ns 0.27* 0.66** 0.19ns 1.00
Triglyceride 0.18ns -0.07ns -0.09ns 0.05ns 0.24ns 0.10ns -0.01ns 0.10ns 1.00
ns P [ 0.05
* P \ 0.05; ** P \ 0.01

-0.34, P \ 0.01), while significant positive correlation
between MDA and cholesterol (r = 0.25, P \ 0.05), CRP
and total lipid (r = 0.27, P \ 0.05), and CRP and choles-
terol (r = 0.66, P \ 0.01). The study shows that in patients
with OA, the changes in the parameters analyzed followed
a pattern similar to RA though were less pronounced.
Discussion
Our aim was to compare the lipid profile, inflammation,
and oxidative stress in patients with OA and RA. In con-
trast to the traditional view of OA disease being degener-
ative and noninflammatory, our results support that OA is
associated with inflammation, oxidative stress, and dysl-
ipedemia-like RA but to a lesser extent.
On comparing serum uric acid, we could not find any
significant difference in serum uric acid levels in the three
groups studied suggesting that uric acid metabolism is not
affected in patients with knee OA or RA. Serum uric acid
levels vary with sex and age. The previous studies have
found positive association between serum uric acid and
generalized OA [16, 35] but not among patients with knee
OA [35]. Serum creatinine is the indicative of kidney
function. As compared to control group, the levels were
significantly higher (P \ 0.05) but within normal range
(\133 lmolesl-1) in patients with OA suggesting some
effect on kidney function, but long-term studies would be
required to evaluate association between creatinine
metabolism and OA. The levels were comparable in control
and patients with RA.
The CRP levels were significantly elevated in patients
with OA and RA. CRP gene haplotype is associated with
severity of hand OA and may influence onset of OA [8]. In
patients with RA, the CRP levels were higher than those in
patients with OA. Both OA and RA were marked with high
inflammation.
Lipids might modulate the susceptibility to the devel-
opment of inflammatory diseases such as OA and RA. In
our study, total cholesterol, triglycerides, and LDL were
significantly increased (P \ 0.05) in patients with OA.
There is an association between high serum cholesterol and
both knee and generalized OA [2, 16]. The accumulation of
HDL was significantly reduced in patients with OA as
compared to control. In osteoarthritis, a higher disease
activity might be associated with lower HDL and higher
triglycerides and cholesterol levels.
Patients with RA were marked by significantly higher
levels of cholesterol, triglycerides, LDL, and reduced HDL
as compared to control and OA showing dyslipedemia and
therefore risk of cardiovascular disease. But the evidences
in patients with RA with regard to total cholesterol and
LDL cholesterol are mixed with some studies showing
significant elevations in these parameters relative to control
[14] but others do not [10, 12]. Studies have shown that in
established RA, total cholesterol levels were only slightly
raised, irrespective of disease activity [24].
High cholesterol induces oxidative stress leading to free
radical generation that promotes lipid peroxidation [29]. In
hypercholesterolemia, high levels of lipids and phospho-
lipids are accumulated resulting in increased production of
arachidonic acid and prostaglandins with the help of
phospholipase A2 and cyclooxygenase enzymes [20]. MDA
is the end product of lipid peroxidation; therefore, its
measurement gives an indirect evidence of LDL oxidation.
Under intense oxidative stress, aldehyde levels increase
and take part in numerous pathological conditions such as
cancer, arthritis, arthrosclerosis, and cardiac diseases [38].
MDA concentration was significantly increased in patients
with OA (P \ 0.05) as compared to control. Formation of
4-Hydroxy-2-nonenal (HNE) and MDA is enhanced in
synoviocytes from patients with OA [15]. However,
patients with RA showed higher accumulation of MDA
when compared with control or OA (P \ 0.05).

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Rheumatol Int
Rheumatoid patients generally are described as having high
levels of oxidative stress that appears to exacerbate or
modify risk in patients with RA [31].
MDA and CRP correlated positively with cholesterol
showing that oxidative stress and inflammation might
augment dyslipedemia in patients with RA. Inflammation is
clearly a risk factor for cardiovascular disease (CVD) in
patients with RA, and lipoprotein abnormalities may con-
tribute to increased risk. The increase in CVD is suggested
to be related to the effects of the chronic inflammation on
the vascular endothelium, mainly through dysregulation of
lipid metabolism. Growing evidence points to inflamma-
tion in RA being associated with a worsening of the lipid
profile, [7, 27] a factor already present early in the disease
[14]. The adverse lipid profile may be associated with an
accelerated prognosis of atherosclerosis [40]. In RA, a
higher disease activity is associated with lower HDL-cho-
lesterol levels and higher oxidative stress [34]. These may
be the result of excessive ongoing systemic inflammation
resulting in cytokine overflow from the inflamed joint into
the circulation [13, 36]. Cytokines are crucial in trafficking
of mononuclear cells into synovium, leading to the initia-
tion and progression of the disease.
It appears that this dyslipidemia is already present long
before the clinical onset of rheumatoid arthritis. Patients
with RA may have any of the traditional risk factors for
cardiovascular disease, but evidence suggests that the
prevalence of these risk factors is no higher than in general
population [18, 41]. Studies have shown that patients with
RA were at increased risk for multi-vessel coronary artery
disease (CAD), although the risk of cardio-vascular (CV)
events was not found to be increased; however, there was a
trend for increased CV death in patients with RA [23].
Data show that abdominal adiposity is a strong predictor
of CRP level [30]. Chronic inflammation is an important
factor for increasing susceptibility to CVD in patients with
RA. BMI, hypertensiveness, and elevated CRP are strong
risk factor for RA and result in worsening of lipid profile
[26, 33].
Our study is supporting the findings of Pawlowska J
et al. [28] that OA may also like RA is a disease with
immunological process and both OA and RA are marked
with oxidative stress, inflammation, and dyslipedemia.
Guidelines should be included not only for RA but for OA
also for the better management of rheumatic diseases.
Acknowledgments The work was supported by grant of Depart-
ment of Science and Technology, Govt. of India (FT/L-101/2006).
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