Comparison of C-Reactive Protein Levels and Erythrocyte

Sedimentation Rates to Osteoarthritis Patients with Sidaguri Extract

Treatment within 1 Month and 2 Month

Blondina Marpaung

, J. Siregar



Division of Rheumatology, Department of Internal Medicine, Universitas Sumatera Utara/ Adam Malik Hospital, Jl.Bunga

Lau, Medan, Indonesia

Clinical Pathology Department, Universitas Sumatera Utara/ Adam Malik Hospital, Jl.Bunga Lau Medan Indonesia

Keywords: Sidaguri, CRP, ESR

Abstract: Osteoarthritis (OA) is defined as a heterogeneous condition that leads to joint sign and symptoms caused by

defective integrity of articular cartilage and inflammation. CRP is a sensitive acute phase reactant with

levels rapidly rising in many inflammation conditions. ESR is an indirect measure of the level of

inflammation in the body. The management of OA limited in the pain and inflammation control with any

NSAID. Meloxicam is one of NSAID that inhibits the synthesis of prostaglandins by inhibiting at least 2

cyclo-oxygenases (COX) isoenzymes. Sidaguri plant (Sida rhombifolia L.) is one of the most important

species of the medicinal part in Indonesia as anti-inflammation, by inhibition of nitric oxide and protein

denaturation inhibitions. Our study recruited 50 patients with OA divided into two groups, patients who get

Meloxicam and Sidaguri (n = 25) and patients with Meloxicam and placebo (n = 25). There were significant

differences before, one month, and two months after therapy with p-value <0.001, and the Sidaguri

combination with meloxicam is better in reducing CRP and ESR levels.

1 INTRODUCTION

According to the American College of

Rheumatology (ACR), osteoarthritis (OA) is defined

as a heterogeneous condition that leads to joint sign

and symptoms which are caused by defective

integrity of articular cartilage. (Sarzi-Puttini et al.,

2005)

OA is one of the most common chronic disorder

among the elderly. WHO Scientiﬁc Group on

Rheumatic Diseases data found that approximately

40% of people over the age of 70 years developed

this disease. More than 65 years of age are at risk of

having OA. The prevalence of OA was 80% and

have some degree of limitation of movement.

(Organization, 2003) The disease is characterized by

degenerative process and mechanical disturbance

with the gradual erosion of joint cartilage.

Prevalence of OA was found to increase with age

and enzymatic sequence that triggers a response

which ended in the destruction of joints.

(Dahaghin

et al., 2005)

Assessment of pain usually used in OA is the

visual analog scale (VAS). The pain VAS is self-

completed by the respondent. The score is classiﬁed

as 1 to 4 (on a 0-10 scale). The mild pain is treated

with non-opioid analgesics with or without adjuvant

therapy, 5 to 6 scale as moderate pain treated with

non-opioid analgesics, weak opioid analgesics with

or without adjuvant therapy, and 7 to 10 as severe

pain treated with strong opioids analgesics with or

without adjuvant therapy. (Jensen et al., 2003)

The ACR use non-steroidal anti inﬂammatory

drugs (NSAIDs) as the main drug of OA. The

Agency for Healthcare Research and Quality

(AHRQ) reported the use of non-opioid analgesics

for OA as primary and secondary treatment. The

European League Against Rheumatism (EULAR)

recommendations for the management of OA

recommend paracetamol as the first line treatment,

with topical agents such as topical NSAID and

capsaicin. The American Heart Association

Scientiﬁc Statement on the use of NSAIDs and the

American College of Cardiology Foundation

consensus recommend reducing the risk of

gastrointestinal (GI) adverse events in patients using

antiplatelet and NSAID therapy. (Hochberg et al.,

2012)

Marpaung, B. and Siregar, J.

Comparison of C-Reactive Protein Levels and Erythrocyte Sedimentation Rates to Osteoarthritis Patients with Sidaguri Extract Treatment within 1 Month and 2 Month.

DOI: 10.5220/0009855600330037

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 33-37

ISBN: 978-989-758-469-5

Meloxicam is one of NSAID member of oxicam

class that inhibits the synthesis of prostaglandins in

cells settle in a specially designated tube of

anticoagulated blood, an effect that is altered by

proteins associated with an inflammatory response

(Assasi et al., 2015)

CRP is merely an indicator or biomarker of a

disease process that is caused by cell death due to

inflammation. C-reactive protein (CRP) is a protein

produced by the liver as a response of inflammation

and infection. It is an extremely sensitive acute

phase reactant with levels rapidly rising 1000 times

or more in many disease condition. ESR is an

indirect measure of the level of inflammation in the

body. ESR measures the rate at which red blood

body tissue by inhibiting at least 2 cyclo-oxygenases

(COX) isoenzymes. (Davies and Skjodt, 1999) From

an international perspective, WHO has agreed to

promote the use of traditional medicine,

complementary medicine for health that focuses on

people centered on health services and encourages

the use of security and the efficacy of the traditional

medicines related to licensing and products, training

and practitioners. (Aditama, 2014)

Sidaguri plant (Sida rhombifolia L.) is one of the

most important species of the medicinal part in

Indonesia as anti-inflammation. The anti-

inflammatory activity effects by inhibition of nitric

oxide and protein denaturation inhibitions. Potent

anti-inflammatory effect of root of Sidaguri on rat

periapical lesion model caused by β-sitosterol, a

sterol isolated of different species of Sidaguri, which

is reported to have anti-inflammatory properties,

similar to hydrocortisone and oxyphenbutazone.

(Khalil et al., 2006)

2 METHODS

2.1 Patient Selection

This randomized, independently and a double-blind

controlled clinical trial was performed from April

2017 until November 2017 in Haji Adam Malik

Hospital and Prof. Dr. Boloni Hospital in Medan.

This Study enrolled patients diagnosed with

osteoarthritis. CRP, ESR, RFT, LFT levels were

measured from blood samples collected from the

cubital fossa area at one day before treatment, 30

days and 60 days later. The patients were randomly

divided into two groups: one group with sidaguri

extract and meloxicam and the other group with

meloxicam and placebo, in simple random sampling

with some sealed envelope that was not transparent

and given odd and even numbers on the rolled of

paper in it.

2.2 Inclusion and Exclusion Criteria

In inclusion criteria, all the subjects aged over 40

years of both men and women with OA, with VAS ≥

4, no impaired liver and kidney function and other

causes of inflammatory reaction.

2.3 Statistical Methods

To display epidemiological data of the subject of the

research, we used tabulation to show the descriptive

picture. Data were processed and analyzed using

SPSS Version-24 program with p <0.05

significance.

3 RESULT

This study involved 50 patients who fulfilled the

inclusion criteria, the patients were equally divided

into two groups: patients who received Meloxicam

with Sidaguri ( n=25) and the other group who

received Meloxicam with placebo (n=25). The

patients were monitored before treatment, one month

and two months after treatment. Nine patients

(69,2%) who received Meloxicam therapy and

placebo were male. Meanwhile, 21 patients (56,8%)

who received meloxicam and sidaguri were female.

The baseline characteristics showed no significant

differences between the two groups (p-value =0,017)

Table 1. Basic characteristics

Characteristics

Therapy

P-Value

Meloxicam&

Placebo (MP)

Meloxicam&Sidaguri (MS)

Gender Male 9 (69.2%) 4 (30.8%) 0.107

Female 16 (43.2%) 21 (56.8%)

Age

58.92 േ10.43 59.64 േ 11.39

0.817

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

Table 2: Significance Test Differences in laboratory results based on Meloxicam and Placebo Therapy

Variable Mean n Standard Deviation P-Value

ESR-PRE 22.88 25 2.205

<0.001

ESR-1 month

ESR- 2 months

22.40

21.44

2.217

1.873

CRP-PRE 0.876 25 0.2437

<0.001

CRP-1 month

CRP- 2 months

0.836

0.764

0.2515

0.2079

SGOT-PRE 19.45 25 4.342

<0.001

SGOT-1 month

SGOT-2 months

22.76

23.67

4.560

4.628

SGPT-PRE 21.05 25 7.239

<0.001

SGPT-1 month

SGPT- 2 months

23.87

22.96

7.538

7.760

UREUM-PRE 30.786 25 17.875

<0.001

UREUM-1 month

UREUM-2 months

36.709

38.912

18.786

19.074

CREATININ-PRE 0.876 25 0.265

<0.001

CREATININ-1 month

CREATININ-2 months

1.120

1.368

0.298

0.321

Table 3: Significance Test Differences in laboratory results based on Meloxicam and Sidaguri Therapy

Variable Mean n Standard Deviation P-Value

ESR-PRE 23.89 25 1.689

<0.001

ESR-1 month

ESR- 2 months

12.98

11.32

3.309

3.867

CRP-PRE 1.309 25 0.245

<0.001

CRP-1 month

CRP- 2 months

0.762

0.639

0.158

0.142

SGOT-PRE 19.59 25 7.987

<0.001

SGOT-1 month

SGOT-2 months

25.68

27.52

8.142

9.043

SGPT-PRE 22.81 25 14.986

<0.001

SGPT-1 month

SGPT- 2 months

27.47

29.56

13.782

12.908

UREUM-PRE 23.90 25 11.703

<0.001

UREUM-1 month

UREUM-2 months

27.51

30.91

10.678

10.002

CREATININ-PRE 0.79 25 0.156

<0.001

CREATININ-1 month

CREATININ-2 months

0.83

0.98

0.179

0.190

Our study revealed a statistically significant

improvement based on laboratory results include

CRP, liver function, renal function, and ESR

before, after 1 month and 2-month Meloxicam and

placebo treatment with p-value <0.001. (Table 2 )

A statistically significant improvement

laboratory results include CRP, liver function,

renal function, and ESR before, after 1 month and

2 months after Meloxicam and Sidaguri treatment

also revealed p-value < 0.001. (Table 3)

The mean ESR after 2 months Meloxicam and

Placebo therapy was 66.72, while the mean ESR

after 2 months Meloxicam and Sidaguri therapy

were 16.06. There is a statistically significant

Comparison of C-Reactive Protein Levels and Erythrocyte Sedimentation Rates to Osteoarthritis Patients with Sidaguri Extract Treatment

within 1 Month and 2 Month

difference between ESR-2 months treatment with

MP and ESR-2 months treatment with MS with p-

value <0.001.

The mean CRP after 2 months with MP

therapy was 0.825, while the mean CRP after 2

months with MS therapy was 0.903. There is a

statistically significant difference between CRP-2

months treatment with MP and CRP-2 months

treatment with MS with p-value 0.003.

Table 4: Significance Test of difference between post-therapy ESR and post-therapy CRP in both groups and VAS score

Variable Therapy N Mean Standard Deviation P-Value

ESR

Meloxicam& Placebo 25 66.72 2.098

˂0.0001

Meloxicam&Sidaguri 25 16.06 2.855

CRP

Meloxicam& Placebo 25 0.825 0.234

0.003

Meloxicam&Sidaguri 25 0.903 0.182

4 DISCUSSION

This study included 50 samples, divided into two

groups. It was found that OA was predominantly in

women (43.2% and 56.8%). Subject’s age in both

groups were not significantly different (58.92 ±

10.43 and 59.64 ± 11.39) with p-value 0.817. The

prevalence of OA is rising along with the age due to

its irreversibility. Therefore, age has a major role as

an important risk factor in osteoarthritis and it is

much more common in women than men. (Glyn-

Jones et al., 2015)

Increased level of CRP and ESR was found in

both groups before therapy with either meloxicam

and Sidaguri or meloxicam with placebo. On the

other hand, CRP and ESR levels after 30 days and

60 days are lower, and statistically significant with

p-value <.0.001. According to Mishra et al. there is a

significantly increased CRP level in patients with

OA (Mishra et al., 2012).

A significant improvement was found in the

meloxicam group compared to placebo while

comparing meloxicam with placebo and meloxicam

with Sidaguri resulted in a statistically different

outcome in CRP and ESR. Systemic inflammation is

reflected by CRP, even it is not specific for OA. Its

level can reach up to 100 times of normal range.

CRP levels will diminish rapidly when tissue

damage and inflammation recede and return to

baseline in 24-48 hours. CRP levels are steady in

plasma and are not influenced by diurnal variation.

(Kandy, 2016)

Meanwhile, ESR could rise in the following

condition: acute inflammatory processes, acute and

chronic infections, tissue damage (necrosis),

rheumatoid, collagen disease, malignancy and

physiological stress conditions (e.g. pregnancy), thus

it is not a specific indicator. ( Kee, 2008)

From the study results, it can be concluded that

mean ESR in patients receiving meloxicam and

placebo treatment group was 66,72 while in

meloxicam and sidaguri-treated patient, the mean

ESR was 16.06 with p-value ˂0.0001. This implied

that meloxicam and sidaguri treatment was

preferable in decreasing ESR over meloxicam and

placebo treatment. Moreover, mean CRP levels

found in meloxicam and placebo group was 0.825

while in meloxicam and the sidaguri group was

0.903 with p-value 0.003, succeeded by clinical

improvement observed from decreasing VAS (p

=0,003).

Several studies found the anti-inflammatory

effect in Sidaguri. It contains an alkaloid,

ecdysteroid, flavonoids, and saponins, which is

believed can inhibit the production of prostaglandin

(as cyclooxygenase blockers). Moreover, it is also

found that β-sitosterol in the Sidaguri also has anti-

inflammatory properties. (Mah et al., 2017)

The author acknowledges the limitation of this

study. The study had a smaller sample size. We

recommend further study with larger samples to

confirm this finding.

5 CONCLUSIONS

There were significant differences before, one

month, and two months after therapy with p-value

<0.001 in both group and the Sidaguri combination

with meloxicam is better in reducing CRP and ESR

levels.

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

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Comparison of C-Reactive Protein Levels and Erythrocyte Sedimentation Rates to Osteoarthritis Patients with Sidaguri Extract Treatment

within 1 Month and 2 Month