COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL …

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i COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL OUTCOME BETWEEN THE EFFICACY OF PLATELET RICH PLASMA AND HYALURONIC ACID INJECTION IN OSTEOARTHRITIS OF KNEE JOINT By Dr. VIGNESH KUMAR.V Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, in partial fulfilment of the requirements for the degree of MASTER OF SURGERY IN ORTHOPAEDICS Under the guidance of Dr. MURALIDHAR.N MS Professor & HOD DEPARTMENT OF ORTHOPAEDICS VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE BANGALORE 2016

Transcript of COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL …

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COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL

OUTCOME BETWEEN THE EFFICACY OF PLATELET

RICH PLASMA AND HYALURONIC ACID INJECTION IN

OSTEOARTHRITIS OF KNEE JOINT

By

Dr. VIGNESH KUMAR.V

Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bangalore,

Karnataka, in partial fulfilment of the requirements for the degree of

MASTER OF SURGERY IN ORTHOPAEDICS

Under the guidance of

Dr. MURALIDHAR.N MS

Professor & HOD

DEPARTMENT OF ORTHOPAEDICS

VYDEHI INSTITUTE OF MEDICAL SCIENCES

AND RESEARCH CENTRE

BANGALORE

2016

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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

DECLARATION BY THE CANDIDATE I hereby declare that this dissertation titled “COMPARATIVE STUDY OF

CLINICAL AND FUNCTIONAL OUTCOME BETWEEN THE

EFFICACY OF PLATELET RICH PLASMA AND HYALURONIC ACID

INJECTION IN OSTEOARTHRITIS OF KNEE JOINT” is a bonafide and genuine

research work carried out by me under the guidance and supervision of

Dr.MURALIDHAR.N, Professor & HOD, Department of orthopaedics, Vydehi Institute

of Medical Sciences and Research Centre, Bangalore in partial fulfilment of the regulations

of Rajiv Gandhi University of Health Sciences for the award of M. S. Degree in

ORTHOPAEDICS.

This work has not formed the basis for the award of any Degree or Diploma to me

previously, by any other university.

Date: Signature of the Candidate

Place: Dr. VIGNESH KUMAR.V

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CERTIFICATE BY THE GUIDE This is to certify that the dissertation titled “COMPARATIVE STUDY OF CLINICAL

AND FUNCTIONAL OUTCOME BETWEEN THE EFFICACY OF

PLATELET RICH PLASMA AND HYALURONIC ACID INJECTION IN

OSTEOARTHRITIS OF KNEE JOINT” is a bonafide research work done by

postgraduate student Dr. VIGNESH KUMAR V, at Vydehi Institute of Medical

Sciences and Research Centre, Bangalore, under my guidance and supervision, in partial

fulfilment of the regulations of the Rajiv Gandhi University of Health Sciences for the award

of M. S. Degree in ORTHOPAEDICS.

Date: Signature of the Guide

Place: Dr. MURALIDHAR N MS Professor & HOD,

Department of orthopaedics Vydehi Institute of Medical Sciences and

Research Centre,Bangalore

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ENDORSEMENT BY THE HOD/PRINCIPAL

HEAD OF THE INSTITUTION This is to certify that the dissertation titled “COMPARATIVE STUDY OF

CLINICAL AND FUNCTIONAL OUTCOME BETWEEN THE

EFFICACY OF PLATELET RICH PLASMA AND HYALURONIC ACID

INJECTION IN OSTEOARTHRITIS OF KNEE JOINT” is a bonafide and

genuine research work carried out by Dr. VIGNESH KUMAR V under the guidance and

supervision of Dr. MURALIDHAR N MS, Professor, Department of orthopaedics, Vydehi

Institute of Medical Sciences and Research Centre, Bangalore in partial fulfilment of the

regulations of Rajiv Gandhi University of Health Sciences for the award of M. S. Degree

in ORTHOPAEDICS.

Seal and Signature of the HOD Seal and Signature of the Principal

Dr. MURALIDHAR N MS Dr. PRABHAKAR G MS

Professor & HOD, Principal,

Department of orthopaedics, Vydehi Institute of Medical

Vydehi Institute of Sciences and Research Centre,

Medical Sciences and Research Centre Bangalore

Bangalore

Date: Date:

Place: Place:

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COPYRIGHT

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Sciences, Karnataka

shall have the rights to preserve, use and disseminate this dissertation/thesis in print or

electronic format for academic/research purpose.

Date: Signature of the Candidate

Place: Dr. VIGNESH KUMAR.V

© Rajiv Gandhi University of Health Sciences, Karnataka

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ACKNOWLEDGEMENT

I take this opportunity to thank a number of people who have been an integral part

in the completion of my dissertation.

I am grateful to our Honorable Director Mrs. KALPAJA D A and the management

of Vydehi Institute of Medical Sciences and Research Centre, Bangalore, for providing me

support and help.

It gives me an immense pleasure to express my deep sense of gratitude to the

Professor and HOD, Department of orthopedics, Vydehi Institute of Medical Sciences and

Research Centre, Bangalore, Dr. MURALIDHAR.N, for providing all the support in

completion of my dissertation work successfully.

I owe utmost and heart-felt thanks and respect to our Honorable Principal Dr. PRABHAKAR for his constant encouragement and support throughout the course of

this dissertation work.

I am forever grateful to my guide Dr.MURALIDHAR.N, Professor & HOD,

Department of orthopaedics, Vydehi Institute of Medical Sciences and Research

Centre, Bangalore, for his guidance, timely advices and immense help to complete my

dissertation. His constant motivation and drive were key factors for construction of the

study.

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I am also grateful to all the staff and my colleagues from the Department of

Anaesthesiology for their help and valuable advice whenever I approached them.

I would like to extend my gratitude to Dr. Rama R, Statistician, for all her efforts

involved in completing this thesis.

I also thank the operation theater staff members for their invaluable support during

my study.

Lastly, I thank all the patients who have given consent to be a part of this study and

without whom it would not have been possible.

Date: Signature of the Candidate

Place: Dr. VIGNESH KUMAR V

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LIST OF ABBREVIATIONS

OA

Osteoarthritis

HA

Hyaluronic acid

PRP

Platelet rich plasma

JSN

Joint space narrowing

PDGF

Platelet derived growth factor

IGF

Insulin like growth factor

DJD

Degenerative joint disease

BMP

Bone morphogenetic protein

WOMAC

Western Ontario mcmaster universities osteoarthritis

index

KL

Kellgren & Lawrence

VAS

Visual analog scale

HGF

Hepatocyte growth factor

SD

Standard deviation

PRGF

Platelet rich growth factors

VEGF

Vascular endothelial growth factor

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ABSTRACT

Background: Platelet Rich Plasma a blood-derived product rich in growth factors, is a

treatment for cartilage defects but there is still a lack of clinical evidence. Various study

suggests Hyaluronic acid injection gives better results in early osteoarthritis. So the aim of

this study is to show, through a randomized prospective trial, To compare clinical and

functional outcome between platelet rich plasma(PRP) and hyaluronic acid in terms of

treatment of osteoarthritis of knee joint.

Methods: 60 patients (30 treated with HA and 30 with PRP) were treated and evaluated at 6

months of follow-up.

The patients were enrolled according to the following inclusion criteria: age > 45 years,

history of chronic pain or swelling of the knee and imaging findings of degenerative

changes of the joint - Kellgren-Lawrence Score up to 2. All patients were prospectively

evaluated before and at 6 weeks, 12 weeks,24 weeks after the treatment by: VAS, WOMAC

scores. Range of motion were measured over time. Adverse events and patient satisfaction

were also recorded.

Results: Both groups presented a clinical improvement but the comparison between the two

groups showed a Statistically significantly better results in the WOMAC Index and VAS

scores were recorded in a group of patients who received PRP injections after a 12 weeks

and 24 weeks follow-up. No severe adverse events were observed. Mild pain and effusion

after the injections were seen in PRP group.

Conclusions: Our preliminary findings support the application of autologous PRP as an

effective and safe method in the treatment of the initial stages of knee osteoarthritis and

significant clinical improvement up to 6 months of follow-up. More promising results are

shown for its use in low grade degeneration in short term followup, but they still have to be

confirmed.

Key words

Osteoarthritis of knee; hyaluronic acid injection; platelet rich plasma

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TABLE OF CONTENTS

Sl.

No. CONTENTS Page No.

1. INTRODUCTION 14

2. AIM AND OBJECTIVES 17

3. REVIEW OF LITERATURE 19

3.1 RELEVANT ANATOMY 20

3.2 PATHOLOGY 24

3.3 HYALURONIC ACID 30

3.4 PLATELET RICH PLASMA 31

4. MATERIALS & METHODS 33

5. RESULTS 45

6. DISCUSSION 55

7. CONCLUSION 58

8. SUMMARY 62

9. BIBLIOGRAPHY 64

10

ANNEXURES

CONSENT FORM

PATIENT PROFORMA

MASTER CHART

ABBREVIATIONS USED IN MASTER CHART

69

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LIST OF TABLES

S.NO TABLES PAGE NO

1. Background particulars of the study participants 46

2. Mean scores of VAS and WOMAC for Hyaluronic Acid

group 47

3. Mean scores of VAS and WOMAC for PRP group 47

4. Percentage of scores for VAS for Hyaluronic Acid group 50

5. Percentage of scores for VAS for PRP group 50

6. Comparison of means for Hyaluronic Acid group between

pre and post intervention for VAS 51

7. Comparison of means form PRP group between pre and post

intervention for VAS 51

8. Comparison of means for Hyaluronic acid group between

pre and post intervention for WOMAC 52

9. Comparison of means for PRP group between pre and post

intervention for WOMAC 53

10. Comparison of VAS score between Hyaluronic Acid group

and PRP group 54

11. Comparison of difference in scores over the period of

intervention for WOMAC score and VA Score between

Hyaluronic Acid group and PRP group

54

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LIST OF IMAGES

S.NO IMAGES PAGE NO

1. Human knee joint

21

2. Synovial membrane of knee joint

21

3. Patellofemoral joint

22

4. Tibiofemoral joint

23

5. Kellgren and Lawrence criteria of OA knee

28

6. Visual analogue score

29

7. Painting of parts

38

8. Hyaluronic acid injection

38

9. Injection hyaluronic acid

39

10. Palpation of knee joint line

39

11. Administration of hyaluronic acid injection into knee joint

40

12. 30ml of venous blood collection

41

13. Instruments used for procedure

41

14. Collected blood instilled into special container

42

15. Container placed in centrifuge machine

42

16. PRP collected at the right side of the container post

centrifuge

43

17. PRP collected in a syringe

43

18. Administration of PRP injection

44

.

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.

LIST OF GRAPHS

S.NO GRAPH PAGE NO

1

Comparison of mean VAS scores between HA &

PRP group.

48

2

Comparison of mean WOMAC scores between

HA group and PRP group

49

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INTRODUCTION

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INTRODUCTION

Osteoarthritis is a chronic degenerative illness of modern era. It is often associated with pain,

disability and reduction in the quality of life. It is a common disorder, affecting more than 10%

of the population1. The condition is characterized by degeneration of articular cartilage and

subsequent chondral bone changes2. The management of chondral disease is challenging, due to

its low regenerative potential and healing ability. Conservative therapies include oral

administration of Non Steroidal Anti Inflammatory Drugs (NSAIDs) and Disease Modifying OA

Drugs (DMOADs). The existing pharmacological therapies are non curative and have their own

limitations. As a result, the disease not only imposes a physical disability but also a financial

burden to the individuals, family and society at large. Therefore, there is a growing need for

alternate, cost effective, non invasive treatment modalities.

The underlying pathophysiology of osteoarthritis remains largely unknown; it has been proposed

that glycosaminoglycan-proteoglycan matrix plays a major role. Therefore, HA (HA), a large

viscoelastic glycosaminoglycan has been in use in recent times, for therapeutic management. It is

said to possess a number of protective properties, which include shock absorption, traumatic

energy dissipation, protective coating of the articular cartilage surface and lubrication3. HA

injections have brought about reduction in the perception of pain by inhibiting inflammatory

mediators and act by decreasing the cartilage degeneration and promoting cartilage matrix

synthesis. However, therapeutic benefits in the long run were dependent on the variability of HA

in terms of its molecular weight and duration of treatment1. Meta analyses showed that HA

therapies for durations greater than 4 weeks very small effect size. Several studies have shown

little significant improvement in clinical outcomes3.

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More recently, Platelet Rich Plasma (PRP) have been used in treatment of Osteoarthritis. PRP

contains high concentration of platelets in small volume of plasma, and also autologous growth

factors including PDGF, TGF-β1 and IGF4. Apart from several wound healing properties, it is

said to stimulate proliferation and extracellular matrix metabolism in chondrocytes. Studies have

shown that clinical outcomes were better with PRP in comparison to HA, especially in long term

managements5. There are several extraneous factors involved in the clinical outcome;

nevertheless, very few studies have been done in India in this line.

With the increasing burden of osteoarthritis, and need for alternative management techniques, we

aimed to compare the clinical outcomes and therapeutic benefits of HA and PRP in patients with

Osteoarthritis.

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AIM & OBJECTIVES

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OBJECTIVES

1. To assess the clinical and functional outcomes of early Osteoarthritis in HA and PRP

group over time.

2. To compare the treatment efficacy between both the therapeutic groups.

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REVIEW OF LITERATURE

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REVIEW OF LITERATURE

Osteoarthritis

Osteoarthritis (OA) or Degenerative Joint Disease (DJD) is a form of arthritis characterized by

the loss of joint smoothness and range of motion without major joint inflammation. The disease

is slowly progressive and results in long term disability. Though it affects both weight bearing

and non weight bearing joints, the disability and discomfort is higher with the knee joints. It is

most often manifested in the medial compartment of the knee, as an inflammatory disease of the

cartilage. The incidence of the disease sharply increases with increase in age; the other risk

factors being obesity, heredity, malalignment of the articulating surfaces, metabolic disease and

joint trauma6.

Relevant Anatomy:

The knee joint is the largest synovial joint in the body. It consists of three distinct nd partially

seprated comprtment which form a complex hinge joint. This arrangement forms the fulcrum for

propulsive muscles, and allows the limb to be folded away in confined spaces and to get closer to

ground. The price of its mobility is a tendency to instability. To counter this instability a complex

ligament arrangement, vulnerable to injury has evolved.

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Fig 1: HUMAN KNEE JOINT

Fig 2: SYNOVIAL MEMBRANE OF KNEE JOINT

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Joints around knee:

Patellofemoral joint:

The patellofemoral joint, which ia prt of the knee joint, is a synovial joint.the articular surface of

the patella is adopted to that of the femur, which extends onto the anterior surfaces of both

condyles like an inverted U. since the whole area is concave transversly and convex in the

saggital plane, it is a asymmetrical seller surface. The ‘odd’ facet contacts the lateral anterior end

of the medial femoral condyle in full flexion, when the highest lateral patellar facet contacts the

anterior part of the lateral condyle. As the knee extends, the middle patellar facets contact the

lower half of the femoral surface. In full extension only the lowest patellar facets are in contact

with the femur.

Fig 3 : PATELLOFEMORAL JOINT

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Tibiofemoral joint:

The tibiofemoral joint is a complex synovil joint. In proximal tibial articular surface slopes

posteriorly and downwards relative to the long axis of the shaft. The tilt which is maximal at

birth, decreases with age, and is more marked with habitual squatters. The posterior surface

distal to the articular margin, displays a horizontal, rough groove to which the capsular and

posterior parts of the medial collateral ligaments are attached. The antero medial surface of the

tibia is rough strip, separated from the medial surface of the shaft by an inconspicuous ridge. The

medial patellar retinacullum is attached to the medial and anterior condylar surface. Which is

marked by vascular formina.

The medial articular surface is longer than the lateral tibial condyle. Around its anterior, medial,

posterior margins its related to the medial meniscus and the meniscal imprint, wider behind,

narrower anteromedially, is often discernible. The surface is flat in the posterior half with the

more anterior surface sloping upwards. Most of the posterior surface of the tibia is covered by

the meniscus so that a concave surface is presented to the medial femoral condyle.

Fig 4 : TIBIOFEMORAL JOINT

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Pathology

The knee joint is lined by hyaline cartilage which is whitish yellowish in colour.

Microscopically, the cartilage consists of evenly stained collagen and proteoglycan rich

extracellular matrix with sparsely distributed chondrocytes. In OA, the cartilage is often

yellowish or brownish macroscopically, and is soft and swollen. In later stages, there is

fibrillation and matrix loss and in severe cases, the subchondral bone plate is visible.

Microscopically, there are surface undulations, along with degradation of matrix molecules

which is evidenced as loss of proteoglycans. Following this there are cartilaginous outgrowths at

the margins of the joins. This process is referred to as secondary chondroneogensis. The

osteophytes derived from mesenchymal precursor cells within periosteal tissue and merge with

the original cartilage. This measenchymal multipotential stem cells undergo chondrogenic

differentiation. Formation of osteophytes is considered as endogenous repair attempt. Though

they are mainly found in non weight bearing joints the underlying molecular mechanism is

largely unknown. It is more likely that growth factors like transforming growth factor (TGF) and

bone morphogenetic protein – 2 (BMP -2) play a dominant role in the induction and promotion

of osteophyte formation7.

Mechanical aspects of OA

The initiation and progression of OA knee involves mechanical structural genetic and

environmental factors. The knee cartilage thickens in the areas of greatest loading in both

anterior to posterior and medial to lateral regions. Therefore tibiofemoral mechanics and loading

patterns has significant influence. Disruption of normal weight mechanics with trauma, acute

injury, ligamental laxity, weight gain and improper footwear can shift the loading patterns on the

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weight bearing cartilage. Increased internal tibiofemoral rotation and peak knee adduction

movement during load bearing are two important factors involved in OA. The thickness maps of

cartilage reveal that the cartilage regions are thickest at the lateral facet of the tibia and thinnest

on the medial facet. Aberrant loading of these areas causes fibrillation of the collagen network,

loss of matrix proteoglycans, increase surface fiction, increased shear stress, upregulation of

catabolic factors and ultimately cartilage degradation. Compared to patients with healthy knees

patients with knee OA demonstrate greater femoral internal rotation. Over time, the repeated

daily loading with an increase in internal rotation will adversely wear and induce symptomatic

OA.

During normal ambulation in the healthy knees, the medial compartment experiences 60% to

80% of weight bearing load. Peak knee adduction movement is produced when the foot is in

contact with the drum. This has been associated with initiation and progression of OA. It results

in varus alignment which causes the knee joint to move laterally related to the position of foot in

the ground. This is reflected as change in pattern and speed of the gate in patients with OA

knee8.

Biochemical aspects of OA

The classic morphologic changes of osteoarthritic articular cartilage begin with fibrillation, and

with disease progression synovial hyperplasia and adjacent osteophyte formation occurs.

Cartilage matrix is a gel like substance composed of water and macro molecular polyanionic

substances, proteoglycan and collagen. Proteoglycans are elastic molecules that expand in

solution and strongly resist compression into a small volume. In the matrix the proteoglycan is

arranged in high molecular weight aggregates formed by noncovalent association between

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proteoglycan sub units, hyaluronic acid and linkage protein. The water content of normal

articular cartilage is between 70% to 78%. Owing to proteoglycan depletion large amounts of

water bind to the collagen. This affects chondrocyte nutrition, cartilage elasticity and joint

lubrication.

The joint is lined with synovial membrane which is composed of synoviocytes. With the onset

of OA Knee, a slight to moderate synoviocyte hypertrophy is noted. There is also a synoviocyte

hyperplasia and thickening of inner synovial membrane layer. There is also marked

hypercellularity of fibroblast in the subsynoviocytic layer9.

Burden of Osteoarthritis of Knee:

Osteoarthritis is the common debilitating disease associated with a large societal and economic

burden. Several risk factors have been identified which include age, gender, heredity and obesity.

A study done in Malmo, Sweden showed the prevalence of radiographic osteoarthritis of 25.4%

among age 56-84 years. The prevalence of osteoarthritis analyzed in Dutch population showed a

steady increase in the prevalence from 2% to more than 20% as age increased. For men, and for

Women it went as high as 18%. The female to male ratio is often between 1.5: to 4:1. In

Framingham study, the prevalence of radiographic knee OA was 19.2%. The prevalence of the

same was 12.1% in NHANES III and 16.3% in Johnston county Osteoarthritis project. As far as

Asia was concerned the prevalence was found to be 19.3% in rural Iran while the COPCORD

studies conducted in India showed a prevalence of 5.5%10

.

The severity of disease is directly proportional to the duration in years. When the baseline

Kellegren and Lawrence score is 0, the progression of the disease to scores 2+ was only 22% in

fifteen years as against 70% with a baseline score of 1 for the same duration11

. A study done in

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New Delhi by AK Singh et al in 2010 showed a prevalence of 41.1% using the American

College of Rheumatology Criteria for Osteoarthritis12

. A study done in Uttar Pradesh by Chandra

Prakash Pal showed a prevalence of 28.7% all over India, with highest prevalence in Agra

(35.5%)13

.

Clinical manifestations of Osteoarthritis:

Osteoarthritis is a debilitating illness affecting the knee joint most commonly. It is a chronic

degenerative joint disease, progressing in severity with years. The symptoms of osteoarthritis

include pain, stiffness, joint swelling and deformity occurs in rare cases. Pain is often due to the

stimulation of capsular pain fibres, mechanoreceptors, periosteal nerve fibres and by perception

of subchondral microfractures. Stiffness is a sequel of pain, due to lack of activity, especially

initiating movement. The signs include coarse crepitus, bony enlargement due to remodelling

and osteophytes, deformity, instability, restricted ability and stress pain14

.

The debilitating factors in osteoarthritis knee are pain and disability. In 2009, it was the 4th

most

common reason for hospitalization in the United States of America15

. A study done by MS

Radha in Mysore showed that 63.3% of patients with OA suffered with pain, while 51.3% with

stiffness and 67.3% with disability in performing physical functions based on WOMAC scores16

.

These manifestations have a direct impact on the Quality Of Life in terms of social interactions,

mental functioning and sleep quality. For this reason, it is essential to assess Health Related

Quality of Life (HRQoL). A study reported by Desmeules et al reported a HRQoL score below

the 25th

percentile among patients with OA knee awaiting Total Knee Arthroplasty17

.

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Assessment of Osteoarthritis:

The assessment of OA Knee is based on clinical, and radiological methods. The clinical

diagnosis uses various criteria and scores, of which American College of Rheumatology (ACR)

criteria is quite popular. The ACR criteria evaluates based on pain, age, morning stiffness,

crepitus on active motion, bony enlargement/ tenderness and palpable warmth as criteria for

assessment clinically18

. The Kellgren & Lawrence (K&L) criteria19

is used for radiographic

diagnosis which is graded in the following manner –

Grade 0 – no Radiographic features of OA are present

Grade 1 – doubtful joint space narrowing (JSN) and possible osteophytic lipping

Grade 2 – Definite osteophytes and positive JSN on anterio posterior weight bearing

radiograph

Grade 3 – multiple osteophytes, definite JSN, sclerosis, possible bony deformity

Grade 4 – large osteophytes, marked JSN, severe sclerosis, definite bony deformity.

GRADE : O I II III IV

IMAGE V : KELLGREN AND LAWRENCE CRITERIA OF OA KNEE

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Assessment of clinical and functional outcomes:

The clinical and functional outcomes of OA are usually assessed as patient reported outcomes. It

was decided that the assessment be made based on pain, disability and patient’s global

assessment in the 3rd

Outcome Measures in Rheumatology (OMERACT) Conference in 199620

.

This is achieved using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC)

and Visual Analog Scale (VAS). The interpretation of the score is based on calculating mean

scores.

The Visual Analog Scale score21

tool is used as a self assessment tool for pain with a score

ranging from 0 – 10

Interpretation of the score:

0- no pain

1-3 – low pain distress score

4-6 – moderate pain distress score

7-10 – high pain distress score.

IMAGE VI : VISUAL ANALOGUE SCORE

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Western Ontario and McMaster Universities Arthritis score (WOMAC)22

: This tool consists of

evaluating pain, stiffness and physical function by rating over a scale of 5, where 0 is none and 4

is extremely difficult. The final score is computed by the formula total score/ 96 (in %).

Management of Osteoarthritis:

The management of OA knee is a comprehensive concept involving pharmacological, social,

psychological, surgical and supportive methods. Nevertheless, a curative therapy is not yet found

and constant research is underway. The therapeutic management involves administration of Non

Steroidal Anti Inflammatory Drugs (NSAIDs), Disease Modifying OA Drugs (DMOADs) which

include administration of corticosteroids. The surgical technique involves Total Knee

Arthroplasty which has its own advantages and disadvantages23

. Some of the newer, non

pharmacological therapies include intra-articular administration of hyaluronic acid (HA) and

platelet rich plasma (PRP).

Hyaluronic Acid:

Infiltration of Hyaluronic Acid (HA) for therapeutic purposes has been in vogue since 1970.

Intra articular injections of HA was first approved in 1987, following which many patients have

been treated with HA, showing marked improvements1. HA, is a large viscoelastic

glycosaminoglycan that is naturally present in the synovial fluid. It provides shock absorption,

lubrication and traumatic energy dissipation to the joints. Administration of HA into the joints

increased the viscosity of the synovial fluid. A metanalysis done by Raveendhara examined the

efficacy of HA in OA3. Several studies compared corticosteroid with HA, and in the initial

period of therapy, HA did not show any positive results, while it showed positive outcomes,

when given for a period longer than 4 weeks. A systematic review done by Jasmin Arrich

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examined the trials on HA. There was a significant improvement in VAS scores following HA

infiltration when the mean scores were pooled (p=0.046); but individual scores measured at

various time frames did not show statistical significance. The results of various trials were

inconclusive of a definitive therapeutic efficacy of HA for OA2. Going by the molecular

mechanisms, study done by Grigorij Kogan demonstrate that therapeutic efficacy may be

indirectly linked with the molar mass of HA. A higher molar mass may require smaller doses,

while low molar mass HA required infiltrations at repeated time periods in order to sustain the

therapeutic effect24

.

Platelet Rich Plasma:

In recent years, autologous Platelet Rich Growth Factors (PRGF) in the form of Platelet Rich

Plasma (PRP) has been considered as a regenerative treatment for OA. It has been proposed that

PRGF stimulate growth factors which help in stimulating chondrocytes to produce cartilage.

Apart from this, there has been an observed increase in proteoglycan and collagen synthesis.

Growth Factors GFs are soluble, diffusible, polypeptidic macromolecules which have potent

specific actions on the growth, differentiation and the genotype of numerous cell types, including

chondrocytes. They consist of anabolic factors for the growth of cartilage, namely Transforming

Growth Factor β1 (TGF-β1), Platelet Derived Growth Factor (PDGF), Vascular Endothelial

Growth Factor (VEGF), IGF-1 and Hepatocyte Growth Factor (HGF). A study done by Saito M

et al showed increase in the concentration of Glycosaminoglycans in the PRP cultures to upto

106% as compared to control groups. The improvement was marked with increase in the days,

demonstrating long term benefits of PRP4. Study done by Ana Wang et al showed marked

improvements in WOMAC scores following infiltration of PRP (p<0.0001). There was also a

significant improvement in VAS scores (p<0.0001)25

. Study done by Guisseppe Filardo showed

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32

significant improvement in EQ-VAS scores with PRP infiltration at 2, 6 and 12 months

(p<0.0005)26

. A study done by Sandep Patel showed improvement in WOMAC scores following

PRP infiltration (p<0.005) while VAS scores did not show this improvement. A study done by

Seyed also showed similar results, with an overall improvement in means WOMAC scores

(p,0.001)27

.

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MATERIALS & METHODS

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MATERIALS & METHOD

Study Design: Randomized before and after comparative interventional study.

Study Area: Teaching hospital facility of Vydehi Institute of Medical Sciences and Research

Centre, Bangalore.

Study population: Patients admitted in Orthopaedics ward of Vydehi Institute of Medical

Sciences and Research with degenerative lesions of cartilage and early OA changes of knee joint.

Study period: January 2015 to July 2016.

Inclusion criteria:

1. Age between 40- 60 years

2. Degenerative changes in cartilage

3. Osteoarthritis of knee joint in grade I &II as diagnosed using Kellegren & Lawrence

grading.

4. Patients who have consented for the study.

Exclusion criteria:

1. Neurological disease

2. Severe degenerative bone disease

3. Presence of infection at the site

4. Current tobacco use

5. Active cancer

6. Endocrine disorders

7. Inflammatory disorders

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8. Severe vascular diseases

9. Traumatic knee arthritis

10. Unicompartmental arthritis

Operational definition: Osteoarthritis (OA) or Degenerative Joint Disease (DJD) is a form of

arthritis characterized by the loss of joint smoothness and range of motion without major joint

inflamation6.

Sample Size: A total of 60 participants were taken up for the study. In intervention group, 30

participants were included and in control group, 30 participants were included.

Sampling technique: Randomization was carried out between the two groups. In our study,

block randomization was done by generating a random sequential block, consisting of

BABABA. Any participant who was enrolled into the study were allocated into B (HA) group

and A (PRP) group alternatively, in order to achieve allocation concealment.

Data collection tools: An initial screening was carried out to assess the grading of osteoarthritis

using Kellgren & Lawrence OA grading. There are four grades for classification of

Osteoarthritis:

Grade 0 – no Radiographic features of OA are present

Grade 1 – doubtful joint space narrowing (JSN) and possible osteophytic lipping

Grade 2 – Definite osteophytes and positive JSN on anterio posterior weight bearing

radiograph

Grade 3 – multiple osteophytes, definite JSN, sclerosis, possible bony deformity

Grade 4 – large osteophytes, marked JSN, severe sclerosis, definite bony deformity.

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Participants who fell in grade I and II were included in the study. Following this grading, an

interview schedule was used to collect the data in our study. It comprised of two components-

1. Questions related to the background characteristics:

This section included questions on age, gender and side of the diseased knee joint.

2. Questions related to assessment of clinical and functional outcomes:

a. using Visual Analog Scale score: This tool was used as a self assessment tool for pain

with a score ranging from 0 – 10.

Interpretation of the score:

1- no pain

1-3 – low pain distress score

4-6 – moderate pain distress score

7-10 – high pain distress score.

This score was measured for both HA and PRP groups prior to intervention, 6th

, 12th

and 24th

week following intervention.

using Western Ontario and McMaster Universities Arthritis score (WOMAC): This

tool consists of evaluating pain, stiffness and physical function by rating over a scale

of 5, where 0 is none and 4 is extremely difficult. The final score is computed by the

formula total score/ 96 (in %). This score was measured for both HA and PRP groups

prior to intervention, 6th

, 12th

and 24th

week following intervention.

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Ethical Committee Approval:

Approval from Institutional Ethics Committee was obtained prior to the commencement of data

collection.

Informed Consent:

All the participants were explained in detail about the purpose of the study, advantages and

disadvantages of being a participant in the study. Informed Consent was obtained prior to the

data collection in the format prescribed by Indian Council of Medical Research (ICMR).

Pilot testing:

A pilot test was carried out among 10 participants with 5 in each group prior to the data

collection. The results of the pilot study were not included in the actual study results.

Data collection:

This study was carried out in the Orthopaedics Department of Vydehi Institute of Medical

Sciences. This study was carried out as a single blind trial with two intervention groups, namely

HA and PRP. It was done as a randomized before and after comparative interventional study

among a total of 60 participants, with 30 in each group. Any patient with clinical symptoms of

osteoarthritis was screened based on inclusion and exclusion criteria. Patients with grade I or II

Osteoarthritis based on Kellegren & Lawrence grading were taken up for the study. They were

randomly allocated into either HA group or PRP group using block randomization technique.

After obtaining informed consent, a structured interview schedule was administered to both the

groups to obtain information on their background characteristics, clinical and functional outcome

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38

of Osteoarthritis using VAS and WOMAC tools. Following this, the intervention was done. The

intervention procedure for both the groups is given below:

a. HA group: The participant was made to lie down supine on the examination couch, with

the affected knee flexed at the joint. The knee was scrubbed with Povidone-iodine

solution. After this, 5 ml of Hyaluronic Acid was injected in either lateral or medial joint

line. This was followed by performing of active range of movement exercise on that knee

joint. Same procedure is repeated after 1 weeks in the same knee.

IMAGE VII : Painting of parts

IMAGE VIII: Hyaluronic acid injection

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39

IMAGE IX: Injection hyaluronic acid

IMAGE X: Palpation of knee joint line

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IMAGE XI: Administration of hyaluronic acid injection

b. PRP group: Initially, 30 ml of venous blood was drawn from the participant’s median

cubital vein. This was centrifuged at 2100 rotations for the first 9 minutes followed by

1500 rotations for the next 6 minutes, totalling to 15 minutes of centrifuge. After this, the

Plasma Rich Platelets were separated in a special container. The participant was made to

lie down supine on the examination couch, with the affected knee flexed at the joint. The

knee was scrubbed with Povidone-iodine solution. After this, 5 ml of Platelet Rich

Plasma was injected in either lateral or medial joint line. This was followed by

performing of active range of movement exercise on that knee joint.

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IMAGE XII : 30ml of venous blood collection

IMAGE XIII: Instruments used for procedure

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IMAGE XIV: Collected blood instilled into special container

IMAGE XV: Container placed in centrifuge machine

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IMAGE XVI: PRP collected at the right side of the container post centrifuge

IMAGE XVII: PRP collected in a syringe

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IMAGE XVIII: Administration of PRP injection

The clinical and functional outcomes of the interventions were assessed at 6th

, 12th

& 24th

weeks using VAS and WOMAC scores.

Statistical analysis:

Data was entered in Microsoft Excel Spreadsheet. Statistical analysis was carried out using SPSS

software ver.15. The background characteristics were expressed in percentages. Mean and SD

were computed for VAS and WOMAC scores at different durations of assessment namely prior

to intervention, 6th

, 12th

& 24th

week. Paired t test was used to compare the treatment outcomes at

each period, for each group separately. Independent t test was used to compare the outcome

mean scores between both the groups. Chi square test was used to compare the percentages of

VAS scores between both the groups.

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RESULTS

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RESULTS

This study was carried out among 60 participants, of which 30 were in HA group and 30

were in Platelet Rich Plasma (PRP) group. Table 1 shows the background particulars of the study

population. In our study, 13 (43.4%) of the participants in HA group belonged to 35- 40 years of

age, while in PRP group, 11 (36.6%) belonged to the same age group. Moreover, 18 (60 %) in

PRP group and 14 (46.7%) in HA group were males. According to Kellegren and Lawrence

grading of Osteoarthritis, 66.7% in HA group belonged to grade I while in PRP group, the

participants were equal in both the grades.

Table -1: Background particulars of the study participants:

S. no Particulars HA group PRP group

Frequency Percentage Frequency Percentage

1. Age (in years)

35-40 13 43.4 11 36.6

40-45 7 23.3 7 23.3

45-50 10 33.3 10 33.3

50-55 0 0 2 0.06

2. Sex

Male 14 46.7 18 60.0

Female 16 53.3 12 40.0

3. Side of the limb

Left 15 50.0 13 43.3

Right 15 50.0 17 56.7

4. Grading of Osteoarthritis (Kellgren and Lawrence)

Grade I 20 66.7 15 50.0

Grade II 10 33.3 15 50.0

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47

Table 2 shows the mean scores for VAS and WOMAC in HA group. The mean VAS score was

5.03±0.615 prior to intervention, while at 24th

week it was 3.10±0.923. Similarly, prior to

intervention, WOMAC score was 29.83±2.069 and the same at 24th

week was 25.57±2.528.

Table – 2: Mean scores of VAS and WOMAC for HA group

S.

No

Duration N VAS WOMAC

Mean SD Mean SD

1. Prior to intervention 30 5.03 0.615 29.83 2.069

2. 6th

Week 30 3.70 1.119 27.67 2.090

3. 12th

Week 30 3.33 .884 26.57 2.300

4. 24th

Week 30 3.10 .923 25.57 2.528

Table 3 shows the mean scores for VAS and WOMAC in PRP group. The mean VAS score was

4.87±0.860 prior to intervention, while at 24th

week it was 3.00±0.643. Similarly, prior to

intervention, WOMAC score was 31.67±2.963 and the same at 24th

week was 23.63±1.217.

Table – 3: Mean scores of VAS and WOMAC for PRP group

S. No Duration N VAS WOMAC

Mean SD Mean SD

1. Prior to intervention 30 4.87 0.860 31.67 2.963

2. 6th

Week 30 3.70 .651 29.23 2.223

3. 12th

Week 30 3.00 .830 26.77 1.960

4. 24th

Week 30 3.00 .643 23.63 1.217

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48

The comparison of VAS scores between HA & PRP group is given in figure graph- 1.

Figure graph 1: Comparison of mean VAS scores between HA & PRP group.

0

1

2

3

4

5

6

prior to intervention 6th week 12th week 24th week

HA group

PRP group

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49

Comparison of WOMAC scores between HA group and PRP group depicted in Figure graph 2:

Figure graph 2: Comparison of mean WOMAC scores between HA group and PRP group

The VAS Score was graded as high (7-10), moderate (4-6) and low (1-3). The score for HA

group is given in table 4. It was found that prior to the intervention, 100% of the study

population belonged to moderate score, while at the 24th

week, 80% of the study population have

progressed to low score, which shows the effect of treatment.

0

5

10

15

20

25

30

35

Prior to intervention 6th week 12th week 24th week

HA group

PRP group

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50

Table -4: Percentage of scores for VAS for HA group:

S.

No

Duration of

intervention

High Moderate Low

N % N % N %

1. Prior to intervention 0 0 30 100 0 0

2. 6th

week 0 0 17 56.7 13 43.3

3. 12th

week 0 0 14 46.7 16 53.3

4. 24th

week 0 0 6 20.0 24 80.0

The VAS Score was graded as high (7-10), moderate (4-6) and low (1-3). The scores for PRP

group is given in table 5. It was found that prior to the intervention, 93.3% of the study

population belonged to moderate score, while at the 24th

week, 80% of the study population have

progressed to low score, which shows the effect of treatment.

Table – 5: Percentage of scores for VAS for PRP group:

S.

No

Duration of

intervention

High Moderate Low

N % N % N %

1. Prior to intervention 0 0 28 93.3 2 6.7

2. 6th

week 0 0 18 60.0 12 40.0

3. 12th

week 0 0 8 26.7 22 73.3

4. 24th

week 0 0 6 20.0 24 80.0

The mean VAS scores between prior and post intervention in HA group were compared in table

6. There was a significant difference in the means as the duration increased. A statistically

significant difference was seen between prior to the intervention and at 6th

week (t=8.651,

p<0.0005), 12th

week (t=8.562; p<0.0005) and 24th

week (t=12.195; p<0.0005).

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Table – 6: Comparison of means for HA group between pre and post intervention for VAS:

S. no Factor Mean

Difference

Standard

Error

t value 95% CI p

value lower Upper

1. Prior to

intervention Vs.

6th

week

1.333 .154 8.651 1.018 1.649 .0001

2. Prior to

intervention Vs.

12th

Week

1.700 .199 8.562 1.294 2.106 .0001

3. Prior to

intervention Vs.

24th

week

1.933 .159 12.195 1.609 2.258 .0001

The mean VAS scores between prior and post intervention in PRP group were compared in table

7. There was a significant difference in the means as the duration increased. A statistically

significant difference was seen between prior to the intervention and at 6th

week (t=7.663,

p<0.0005), 12th

week (t=8.165; p<0.0005) and 24th

week (t=10.143; p<0.0005).

Table – 7: Comparison of means form PRP group between pre and post intervention for

VAS:

S. no Factor Mean

Difference

Standard

Error

t value 95% CI p

value lower Upper

1. Prior to

intervention Vs.

6th

week

1.167 .152 7.663 .855 1.478 .0001

2. Prior to

intervention Vs.

12th

Week

1.867 .229 8.165 1.399 2.334 .0001

3. Prior to

intervention Vs.

24th

week

1.867 .184 10.143 1.490 2.243 .0001

The mean WOMAC scores between prior and post intervention in HA group were compared in

table 8. There was a significant difference in the means as the duration increased. A statistically

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52

significant difference was seen between prior to the intervention and at 6th

week (t=4.563,

p<0.0005), 12th

week (t=6; p<0.0005) and 24th

week (t=6.579; p<0.0005).

Table – 8: Comparison of means for HA group between pre and post intervention for

WOMAC:

S. no Factor Mean

Difference

Standard

Error

t value 95% CI p

value lower Upper

1. Prior to

intervention Vs.

6th

week

2.167 .475 4.563 1.195 3.138 .0001

2. Prior to

intervention Vs.

12th

Week

3.267 .544 6.000 2.153 4.380 .0001

3. Prior to

intervention Vs.

24th

week

4.267 .648 6.579 2.940 5.593 .0001

The mean WOMAC scores between prior and post intervention in PRP group were compared in

table 9. There was a significant difference in the means as the duration increased. A statistically

significant difference was seen between prior to the intervention and at 6th

week (t=10.656,

p<0.0005), 12th

week (t=13.266; p<0.0005) and 24th

week (t=19.680; p<0.0005).

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Table – 9: Comparison of means for PRP group between pre and post intervention for

WOMAC:

S. no Factor Mean

Difference

Standard

Error

t value 95% CI p

value lower Upper

1. Prior to

intervention Vs.

6th

week

2.433 .228 10.656 1.966 2.900 0.001

2. Prior to

intervention Vs.

12th

Week

4.900 .369 13.266 4.145 5.655 0.001

3. Prior to

intervention Vs.

24th

week

8.033 .408 19.680 7.198 8.868 0.001

The VA score between HA group and PRP group is compared in table 10. It was observed that

there was no statistically significant difference between the HA group and PRP group at any

period of time (p >0.05).

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Table – 10: Comparison of VAS score between HA group and PRP group :

S.

No

Grading of scores

in HA group

N Grading of scores in PRP

group at respective duration

of intervention

χ2 value p value

Moderate Low

1. 6th

week

Moderate 17 10

58.8%

7

41.2%

0.023 0.880

Low 13 8

61.5%

5

38.5%

2. 12th

week

Moderate 14 5

35.7%

9

64.3%

1.099 0.295

Low 16 3

18.8%

13

81.3%

3. 24th

week

Moderate 6 1

16.7%

5

83.3%

0.052 0.819

Low 24 5

20.8%

19

79.2%

The comparison between effect of treatment in terms of duration of intervention for WOMAC

score and VAS between HA group and PRP group is compared in table 11. It was observed that

the mean difference scores between PRP and HA group is statistically significant for WOMAC

score (p<0.01).

Table – 11: Comparison of difference in scores over the period of intervention for

WOMAC score and VA Score between HA group and PRP group:

S. no Factor Mean

Difference

Standard

Error

t value 95% CI p

value lower Upper

1. WOMAC 1.81 0.55 3.3 0.6 3.01 0.006

2. VAS -0.73 0.42 -1.74 -1.6 0.2 0.113

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DISCUSSION

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DISCUSSION

This study was carried out as a comparative study between HA and PRP. In our study, majority

of the study population belonged to 35-40 years of age, in both HA & PRP groups (43.4% and

36.6% respectively). In most of the studies, the mean age of the participants was over 50 years.

Females were higher in HA group (53.3%) while males were higher in PRP group (60%). In a

study done by Sandeep Patel et al females were higher than males in all the groups, with a male

female ration of 11:16, 5:20 and 6:1727

.

Prior to intervention the mean VAS scores were 5.03± 0.615 and WOMAC scores were 29.83±

0.06, In a study done by Sandeep Patel, the mean VAS score was 4.6 ±0.62, which comparable

with our study, while WOMAC score was 45.5 ± 17.327

. There was a significant reduction in

WOMAC scores at the end of 24th

week for HA group with a mean difference of 4.27 (p=

0.0001) and PRP group at 24th

week 8.03 (p = 0.001). There was a significant reduction in VAS

scores at 6th

week with mean difference 1.33 (p=0.0001), at 12th

week with mean difference of

1.7 (p=0.0001)the end of 24th

week for HA group with a mean difference of 1.933 (p= 0.0001).

For the PRP group, the mean difference was statistically significant (p<0.001). In our study it

was evident that as the duration increased the mean difference rose higher for PRP group in

comparison to the HA group, which proves the long term efficacy of a single administration of

PRP.

Our study showed a significant difference in WOMAC scores, when a comparison is made

between both the groups, concluding that PRP is better than HA (p = 0.006). There are very few

studies which have compared both the interventions in a single trial. As far as VAS score is

concernced, our study did not show conclusive results. As the PRP injection was like a day care

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procedure hospital admission was nor required for patients. Patients were allowed to carry out

their day to day activities post procedure.

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CONCLUSION

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CONCLUSION

This study has highlighted the advantages of using PRP over HA in the treatment of grade I and

grade II OA knee. The benefits are witnessed with a remarkable improvement in WOMAC

scores, and moreover, the effect of the intervention has been documented even at 24th

week. This

study has focused on the key benefits of PRP in reducing the physical, social and economic

burden of OA knee.

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SUMMARY

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SUMMARY:

The present study was done in vydehi institute of medical science and research center, whitefield

from January 2015 to July 2016 cases of grade I and grade II OA knee treated with HA for 30

patients and PRP for 30 patients

13(43.4%) in HA group belonged to 35 – 40 years of age

11(36.6%) in PRP group belonged to 35 – 40 years of age

14(46.7%) in HA are male patients

18(60%) in PRP group are male patients

16(53.3%) in HA are female patients

12(40%) in PRP are female patients

20(66.7%) in HA are grade I patients

15(50%) in PRP are grade I patients

10(33.3%) in HA are grade II patients

15(50%) in PRP are grade II patients

In HA group the mean VAS score - 5.03±0.615 prior to intervention,

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VAS score - 3.10±0.923at 24th

week.

WOMAC score - 29.83±2.069 prior to intervention

WOMAC score - 25.57±2.528 at 24th

week.

In PRP group the mean VAS score - 4.87±0.860 prior to intervention,

VAS score - 3.00±0.643 at 24th

week.

WOMAC score - 31.67±2.963 prior to intervention

WOMAC score - 23.63±1.217 at 24th

week.

In HA group VAS score - 100% - moderate score at prior to intervention.

80% - low score at 24th

week of the study population.

In PRP group VAS score - 93.3% - moderate score at prior to intervention.

80% - low score at 24th

week of the study population.

In HA group the mean VAS scores between prior and post intervention

6th

week (t=8.651, p<0.0005),

12th

week (t=8.562; p<0.0005)

24th

week (t=12.195; p<0.0005).

In PRP group the mean VAS scores between prior and postintervention

6th

week (t=7.663, p<0.0005),

12th

week (t=8.165; p<0.0005)

24th

week (t=10.143; p<0.0005).

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63

In HA group the mean WOMAC scores between prior and post intervention

6th

week (t=4.563, p<0.0005),

12th

week (t=6; p<0.0005)

24th

week (t=6.579; p<0.0005).

In PRP group the mean WOMAC scores between prior and post intervention

6th

week (t=10.656, p<0.0005)

12th

week (t=13.266; p<0.0005)

24th

week (t=19.680; p<0.0005).

The VA score between HA group and PRP group was observed that there was no statistically

significant difference between the HA group and PRP group at any period of time (p >0.05).

The comparison between effect of treatment in terms of duration of intervention for WOMAC

score and VAS between HA group and PRP group was observed that the mean difference scores

between PRP and HA group is statistically significant for WOMAC score (p<0.01).

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BIBLIOGRAPHY

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REFERENCES

1. Anita Aggarwal, Ian P. Sempowski. Hyaluronic acid injections for knee osteoarthritis.

Systematic Review of the literature. Can Fam Physician 2004;50:249-256.

2. Arrich J. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee:

systematic review and meta-analysis. Canadian Medical Association Journal.

2005;172(8):1039-1043.

3. Bannuru R, Natov N, Obadan I, Price L, Schmid C, McAlindon T. Therapeutic trajectory

of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: A

systematic review and meta-analysis. Arthritis Rheum. 2009;61(12):1704-1711.

4. Saito M, Takahashi KA, Arai Y, Inoue A, Sakao K, Tonomura H et al. Intraarticular

administration of Platelet Rich Plasma with biodegradable gelatine hydrogel

microspheres prevents osteoarthritis progression in the rabbit knee. Clinical and

Experimental Rheumatology 2009; 27: 201-207

5. S.A.Raeissadat; S.M.Rayegani; M.Babaee and E.Ghorbani; ( 2013) – The Effect of

Platelet-Rich Plasma on Pain, Function, and Quality of Life of Patients with Knee

Osteoarthritis: Hindawi Publishing Corporation,Pain Research and Treatment,Volume

2013, Article ID 165967, 7 pages.

6. UW Medicine. Orthopaedics and Sports Medicine [Internet]. Seattle. University of

Washington, Osteoarthritis.. University of Washington. Available from

http://www.orthop.washington.edu/?q=patient-care/articles/arthritis/osteoarthritis.html

Page 66: COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL …

66

7. Thomas Aigner, Nicole Schmitz. Osteoarthritis and related disorders. Pathogenesis and

pathology of Osteoarthritis. Pg 1741-1759. Available from

https://www.med.unc.edu/tarc/events/event-files/Hichberg%20text.%20OA%20path..pdf

8. Vincent K, Conrad B, Fregly B, Vincent H. The Pathophysiology of Osteoarthritis: A

Mechanical Perspective on the Knee Joint. PM&R. 2012;4(5):S3-S9.

9. Treppo S, Koepp H, Quan E, Cole A, Kuettner K, Grodzinsky A. Comparison of

biomechanical and biochemical properties of cartilage from human knee and ankle pairs.

Journal of Orthopaedic Research. 2000;18(5):739-748.

10. Allen KGolightly Y. State of the evidence. Current Opinion in Rheumatology.

2015;27(3):276-283.

11. Litwic A, Edwards M, Dennison E, Cooper C. Epidemiology and burden of

osteoarthritis. British Medical Bulletin. 2013;105(1):185-199.

12. Gupta S. Prevalence of Osteoarthritis of Knee Among Elderly Persons in Urban Slums

Using American College of Rheumatology (ACR) Criteria. JCDR. 2014;.

13. Chandra Prakash Pal. Study to Find the Prevalence of Knee Osteoarthritis In the Indian

Population and Factors Associated with it. Indian Orthopedics Association

Conference.2013. Agra.

14. Mahajan A, Verma S, Tandon V. Osteoarthritis. Journal of the Association of Physicians

of India. 2005; 53:634-653.

15. Murphy LHelmick C. The Impact of Osteoarthritis in the United States. AJN, American

Journal of Nursing. 2012;112:S13-S19.

Page 67: COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL …

67

16. M.S. Radha et al, Serum Enzyme Of Matrix Metalloproteinase-3 In Patients With Knee

Osteoarthritis. International Journal of Recent Scientific Research Vol. 6, Issue, 6,

pp.4457-4460, June, 2015

17. Farr J. Quality of Life in Patients with Knee Osteoarthritis: A Commentary on

Nonsurgical and Surgical Treatments. The Open Orthopaedics Journal. 2013;7(1):619-

623.

18. Johns Hopkins Arthritis Center [Internet]. Baltimore. Johns Hopkins Medicine. ACR

Diagnostic Guidelines. Available from www.hopkinsarthritis.org/physician-

corner/education/arthritis-education-diagnostic-guidelines/#class_knee

19. Radiopedia.org. Dr. Vivek Pai et al. Kellgren & Lawrence System of Classification of

Osteoarthritis. Available from http://radiopaedia.org/articles/kellgren-and-lawrence-

system-for-classification-of-osteoarthritis-of-knee

20. Carsten Juhl, Hans Lund, Ewa M Roos, Weiya Zhang, Robin Christnen. A hierarchy of

patient reported outcomes for meta analysis of knee osteoarthritis trials: Empirical

Evidence from a survey of high impact journals. Arthritis. 2012. Article ID 136245, 17

pages. Available from https://www.hindawi.com/journals/arthritis/2012/136245/

21. Hawker G, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog

Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain

Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain

Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF. Arthritis Care Res.

2011;63(S11):S240-S252.

22. Salaffi F, Leardini G, Canesi B, Mannoni A, Fioravanti A, Caporali R et al. Reliability

and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis

Page 68: COMPARATIVE STUDY OF CLINICAL AND FUNCTIONAL …

68

Index in Italian patients with osteoarthritis of the knee. Osteoarthritis and Cartilage.

2003;11(8):551-560.

23. Feeley BT e. Management of osteoarthritis of the knee in the active patient. - PubMed -

NCBI [Internet]. Ncbi.nlm.nih.gov. 2016 [cited 10 September 2016]. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/20595133

24. Kogan G, Šoltés L, Stern R, Gemeiner P. Hyaluronic acid: a natural biopolymer with a

broad range of biomedical and industrial applications. Biotechnology Letters.

2006;29(1):17-25.

25. A.W.Saegusa; R.Cugat; O.Ares; R.Seijas; X.cusco; M.G.Balletbo; (2011)- Infltration of

plasma rich in growth factors for osteoarthritis of the knee short-term effects on function

and quality of life. Arch Orthop Trauma Surg 131:311–317.

26. G.Filardo; E.Kon; R.Buda; A.Timoncini; A.D.Martino; A.Cenacchi; P.M.Fornasari;

S.Giannini; M.Marcacci; (2011)- Platelet-rich plasma intra-articular knee injections for

the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports

Traumatol Arthrosc 19:528–535.

27. Sandeep.P, MS; Mandeep.S.D MS, FAMS; S.Aggarwal; N.Marwaha.z MD, FAMS; and

A.Jain. MD; (2013)- Treatment With Platelet-Rich Plasma Is More Effective Than

Placebo for Knee Osteoarthritis:. The American Journal of Sports Medicine, Vol. 41, No.

2.

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ANNEXURE

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70

INFORMED CONSENT FORM

I, do hereby give my informed consent for the research program as a part of M.S

Orthopaedics dissertation being carried out at Dept of orthopaedics, vydehi institute of medical

sciences & research centre, Bangalore.

I have been explained about the details of the research program in the language I

understand. I have voluntarily given the informed consent for the publication of research data

and I will not make any claim what so ever against any individual or the institution in the process

of this research program, if anything untoward happens in the process. I have also been

explained that at any time I can withdraw myself from this research program

Signature of doctor Signature of patient

Name of Doctor: Name:

Date: Date:

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71

PROFORMA

STUDY:

NAME:

AGE:

SEX:

IP NUMBER:

HEIGHT:

WEIGHT:

DIAGNOSIS:

DATE OF PROCEDURE:

PROCEDURE TIME:

METHOD USED:

PLATELET RICH PLASMA

HYALURONIC ACID

Kellgren & Lawrence system of OA grading:

GRADE 1 GRADE 2

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72

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

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73

Visual analogue score:

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74

MASTER CHART ABBREVATION

S.NO Serial number

M Male

F Female

RT Right

LT Left

WOMAC Western Ontario and McMaster Universities Arthritis score

VAS Visual analogue score

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75

PLATELET RICH PLASMA MASTER CHART

S.N

O

NAME AGE SEX SIDE GRAD

E

DATE OF

INJECTION

SCORE

PRIOR TO

INTERVENTION

6TH WEEK 12TH WEEK 24TH

WEEK

WOMA

C

VAS WOMAC VAS WO

MAC

VAS WO

MAC

VAS

1 Amera

begum

39 F RT I 02/01/15 30 5 30 4 28 2 25 2

2 Prasad 38 M LT I 02/01/15 32 6 30 4 29 2 24 2

3 Shikha

acharjee

49 F LT II 05/01/15 34 5 32 5 32 3 25 2

4 Anith saha 49 F RT II 05/01/1 33 4 30 3 29 3 25 4

5 Sakuntala

devi

48 F RT I 09/01/15 30 4 27 3 26 3 23 3

6 Abu taher sk 43 M RT I 09/01/15 32 4 30 4 28 3 23 2

7 Shishu

paddhan

42 M RT I 16/01/15 30 5 28 3 26 2 23 3

8 padmavathi 46 F LT II 16/01/15 34 5 31 3 29 2 25 2

9 Cham 39 M RT II 16/01/15 33 5 30 3 27 2 23 3

10 Revanna 46 M RT II 20/01/15 35 5 32 4 29 2 24 4

11 Kumari 49 F LT I 20/01/15 28 3 27 3 25 3 22 2

12 Polash das 36 M RT I 20/01/15 30 4 30 3 27 3 23 3

13 Mujafar 41 M LT II 28/01/15 34 6 30 4 26 2 26 3

14 suresh 43 M LT I 03/02/15 29 5 27 4 25 2 24 3

15 Raghava rao 52 M RT II 03/02/15 36 6 31 4 29 3 25 4

16 Krishna

ghosh

46 M LT I 17/02/15 29 3 26 3 24 2 22 3

17 Gowri saha 47 F RT II 17/02/15 35 6 31 5 27 3 25 4

18 Sahul 42 M LT II 10/03/15 33 5 30 4 27 3 23 3

19 Muniyappa 45 M RT II 17/03/15 35 5 32 3 28 3 24 3

20 Urmila devi 38 F LT II 31/03/15 34 6 30 4 26 4 23 3

21 Prabu 37 M RT I 07/04/15 27 5 25 3 24 4 23 4

22 Seethamma 48 F LT I 21/04/15 27 4 27 3 25 4 22 3

23 Kala 40 F RT II 21/04/15 35 5 32 3 28 3 25 3

24 Lilly donel 47 F LT II 05/05/15 33 6 30 4 27 3 24 3

25 Rajendra ram 38 M RT I 19/05/15 29 5 28 4 26 3 23 3

26 Prabhu

thakoor

40 M LT I 02/06/15 28 4 26 5 24 5 21 4

27 Srinivas 39 M RT II 09/06/15 34 5 30 4 26 4 24 3

28 MD

sikhander ali

41 M RT II 16/06/15 36 6 33 4 28 4 25 3

29 Thomas 53 M LT I 16/06/15 27 5 26 4 24 4 23 3

30 Subhra roy 40 F RT I 30/06/15 28 4 26 4 24 4 22 3

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76

HYALURONIC ACID INJECTION MASTER CHART

S.NO NAME HOSPIT

AL NO

A

G

E

S

E

X

SID

E

GR

AD

E

DATE

OF

INJECTI

ON

SCORE

PRIOR TO

INTERVENTI

ON

6TH WEEK

12TH WEEK

24TH WEEK

WOM

AC

VAS WO

MAC

VAS WOM

AC

VAS WOM

AC

VAS

1 Madhu 3349812 42 M RT I 01/01/14 30 5 26 4 25 4 24 3

2 Azan

molla

3589446 38 M LT II 01/01/14 30 5 29 3 28 4 24 4

3 Poornima 3550811 38 F RT II 01/01/14 34 4 29 2 28 2 26 2

4 Gopa das 3691518 46 F RT I 05/01/14 27 5 28 2 28 2 27 3

5 Meena 3086647 44 F RT II 05/01/14 31 5 29 3 27 3 25 3

6 Feroj 3557908 40 M LT I 09/01/14 28 5 27 4 27 3 26 3

7 Lakshmi 2993362 42 F LT II 09/01/15 28 5 24 3 23 3 23 3

8 Kokila 3138182 45 F RT I 14/01/15 27 5 30 5 30 5 30 5

9 Narashima 2154972 47 M LT I 14/01/15 32 4 26 3 25 3 24 2

10 Siddesh 2654642 49 M RT I 19/01/15 31 5 27 2 25 3 24 2

11 shabana 3706561 43 F LT I 19/01/15 30 5 24 3 24 2 23 2

12 Rupa

nandi

3686214 46 F LT I 26/01/15 30 5 25 5 23 3 23 3

13 Jibon bani 3538392 47 M RT I 26/01/15 30 4 27 2 24 4 24 3

14 Nagesh 3596687 44 M RT I 26/01/15 30 6 26 5 26 2 24 2

15 kanthamm

a

3537807 40 F LT I 09/02/15 30 6 26 5 25 4 24 4

16 Rukmini 3573883 49 F LT II 09/02/15 30 5 24 4 23 3 23 3

17 Manjunath 3596643 49 M RT II 23/02/15 34 4 28 2 29 2 27 2

18 Jareena 1972071 41 F RT I 23/02/15 27 5 28 3 30 4 30 5

19 Amulya

kumar

3220822 40 M RT I 02/03/15 31 5 29 4 27 4 25 3

20 Sandramar

y

1958746 40 F LT I 02/03/15 28 5 28 3 27 2 27 2

21 Babu 3465320 40 M LT II 23/03/15 28 5 27 4 24 3 25 3

22 Radhamm

a

3194796 40 F RT II 23/03/15 28 5 27 5 25 3 23 3

23 Srinivas 1768983 40 M LT II 06/04/15 34 5 32 5 28 4 23 3

24 Tapas

ranjan

3217111 39 M LT I 06/04/15 31 5 29 4 27 4 25 3

25 Syed kai 3535935 49 M RT I 20/04/15 27 4 30 3 30 3 25 3

26 Ravi 2723550 49 M RT I 20/04/15 28 6 27 4 26 4 30 3

27 Baghyam

ma

3598210 39 F LT I 04/05/15 28 6 27 4 26 4 26 3

28 Kala 2573157 39 F LT I 04/05/15 31 5 29 4 27 4 25 3

29 Amuda 3044225 40 F LT I 25/05/15 30 6 32 5 28 5 30 5

30 sonalinag 3545126 49 F RT II 25/05/15 32 6 30 6 32 5 32 5