PROFORMA FOR THESIS OF MASTER OF SURGERY

(ORTHOPAEDICS)
ATAL BIHARI VAJPAYEE UNIVERSITY, LUCKNOW U.P (2022-25)

HOSPITAL-BASED PROSPECTIVE AND COMPARATIVE STUDY OF THE

EFFECTIVENESS OF INTRA-ARTICULAR INJECTION OF PLATELET-RICH
PLASMA VERSUS HYALURONIC ACID FOR OSTEOARTHRITIS OF KNEE
JOINT

HEAD OF Dr. C.P.PAL

DEPARTMENT (M.S. ORTHOPAEDICS)
PROFESSOR AND HEAD
DEPARTMENT OF ORTHOPAEDICS
S.N. MEDICAL COLLEGE, AGRA
GUIDE Dr. VIVEK MITTAL
(M.S. ORTHOPAEDICS)
ASSOCIATE PROFESSOR
DEPARTMENT OF ORTHOPAEDICS
S.N. MEDICAL COLLEGE, AGRA
CO GUIDE Dr. AMRIT GOYAL
(M.S. ORTHOPAEDICS)
PROFESSOR
DEPARTMENT OF ORTHOPAEDICS
S.N. MEDICAL COLLEGE, AGRA
CO GUIDE Dr. K S DINKAR
(M.S. ORTHOPAEDICS)
ASSOCIATE PROFESSOR
DEPARTMENT OF ORTHOPAEDICS
S.N. MEDICAL COLLEGE, AGRA
STUDENT Dr. SUMIT KUMAR GUPTA
PLACE OF STUDY S.N MEDICAL COLLEGE, AGRA
CERTIFICATE CERTIFIED THAT AIMS, OBJECTIVES, MATERIAL AND METHODS
HAVE BEEN CHECKED AND APPROVED. THE WORK IS FEASIBLE
AND STATISTICIAN HAS BEEN CONSULTED
 INTRODUCTION

Knee osteoarthritis is a common degenerative joint disease characterized by loss

of articular cartilage, subchondral bone changes, and inflammation of synovial
tissue. The hallmark symptom of Osteoarthritis is pain. The early stages of
Osteoarthritis is characterized by activity related pain, thereafter, with the
advancing disease, the pain gets the chronicity character and converts to a more
constant nature with accompanying intense pain attacks. Other symptoms are loss
of function, and swelling. It mostly affects older adults (age ≥ 65 years), and it
affects women (incidence: 18%) more than men (incidence: 9.6%), according to a
2004 study involving patients ≥60 years of age.
Risk factors related to knee Osteoarthritis include obesity, older age, previous knee
trauma, hand Osteoarthritis, and female sex. Surgical interventions including
arthroscopic surgery, osteotomy, and arthroplasty are considered the next steps
for treating knee Osteoarthritis, after other nonsurgical treatments have been
attempted, such as physical therapy, oral non-steroidal anti-inflammatory drugs
(NSAIDs), and intra-articular injections of platelet-rich plasma, hyaluronic acid and
corticosteroids.
1 PLATELET RICH PLASMA
Platelet-rich plasma is autologous conditioned plasma containing a high
concentration of platelets. Platelets are a natural source of growth factors, such as
insulin-like growth factor, platelet-derived growth factor, vascular endothelial
growth factor, transforming growth factor beta, and platelet-derived angiogenic
factor. Growth factors play a vital role in regenerative processes and wound
healing.
The platelets undergo degranulation to release growth factors. The plasma is the
acellular portion of mixture including cytokines, thrombin, and other Growth
Factors. The platelet concentrate is activated by addition of calcium chloride, and
this results in the formation of platelet gel and the release of growth factors and
bioactive molecules. Thereby, platelets actively participate in healing processes by
delivering a broad spectrum of Growth Factors (insulin-like growth factor,
transforming growth factor b-I, platelet derived growth factor, and many others)
and other active molecules (e.g., cytokines, chemokines, arachidonic acid
metabolites, extracellular matrix proteins, nucleotides, ascorbic acid) to the injured
site. These factors altogether contribute to comprehensive roles of Platelet Rich
Plasma; including chondrogenesis, bone remodeling, proliferation, angiogenesis,
anti-inflammation, coagulation and cell differentiation.

2 HYALURONIC ACID INJECTION (VISCOSUPPLEMENTATION)

Hyaluronic acid is a naturally occurring glycosaminoglycan and a component of
Synovial fluid and cartilage matrix. Synovial cells, fibroblasts and chondrocytes
synthesize Hyaluronic Acid and secrete into the joint. Hyaluronic Acid enhances
viscosity and elastic nature of Synovial fluid which with normal Hyaluronic Acid
concentration acts as a viscous lubricant during slow joint movements and as an
elastic shock absorber during rapid joint movements. The adaptive ability reduces
stress and friction on cartilage. In individuals with knee Osteoarthritis, Hyaluronic
Acid synthesis and degradation are abnormal, resulting in reduced concentration
and molecular weight of Hyaluronic Acid at the joint. These pathological changes
reduce synovial fluid viscoelasticity, leading to cartilage damage; thus, intra-
articular Hyaluronic Acid injection is a common therapy to treat Osteoarthritis of
knee joint.
Hyaluronic Acid is produced either from harvested rooster combs or via bacterial
fermentation in vitro. The injectable hyaluronan products that are approved by
FDA are sodium hyaluronate, Hylan G-F 20, and high-molecular weight hyaluronan.
It also forms the backbone for the proteoglycans of the extracellular matrix.
Hyaluronic Acid functions through anti-inflammatory, anabolic, analgesic, and
chondroprotective mechanisms. In the osteoarthritic joint, synovial inflammation
leads to increased permeability of the synovial membrane for Hyaluronic Acid. Also,
the elevated Synovial fluid levels of free radicals, inflammatory cytokines, and
proteolytic enzymes in osteoarthritic knees impair Hyaluronic Acid function and
contribute to the progression of Osteoarthritis.
 STAGES OF OSTEOARTHRITIS (KNEE JOINT)

Kellgren-Lawrence scale for radiographic classification of osteoarthritis

Grade
0: Normal
1: Questionable
Doubtful narrowing of joint space and possible osteophytic lipping
2: Mild
Definite osteophytes and possible narrowing of joint space
3: Moderate
Moderate multiple osteophytes, definite narrowing of joint space, some
sclerosis, and possible deformity of bone ends
4: Severe
Large osteophytes, marked narrowing of joint space, severe sclerosis, and
definite deformity of bone ends
 AIMS AND OBJECTIVES

AIM: TO STUDY THE COMPARISON OF EFFECTIVENESS BETWEEN INTRA-

ARTICULAR INJECTION OF PLATELET-RICH PLASMA VERSUS HYALURONIC

ACID IN OSTEOARTHRITIS OF KNEE JOINT

OBJECTIVES
• TO EVALUATE THE ALLEVIATION OF PAIN IN INTRA-ARTICULAR
INJECTION OF PLATELET RICH PLASMA AND HYALURONIC ACID
TO COMPARE BOTH IN OSTEOARTHRITIS.
• TO ASSESS THE IMPROVEMENT IN RANGE OF MOTION OF
KNEE JOINT.
• TO EVALUATE THE EFFICACY OF INJECTABLE PLATELET RICH

PLASMA AND HYALURONIC ACID TO COMPARE BOTH IN

OSTEOARTHRITIS.
 REVIEW OF LITERATURE

1. Kon et al(2011)[1] studied Platelet Rich Plasma versus Hyaluronic

Acid injections in 150 patients, with Platelet Rich Plasma treatment
giving better results than Hyaluronic Acid in reducing pain and
symptoms and recovering articular function up to 6 mo. In this
study, Platelet Rich Plasma showed a better performance
compared with Hyaluronic Acid in younger patients affected by
cartilage lesions or early Osteoarthritis. However, Platelet Rich
Plasma and Hyaluronic Acid treatments offered similar results in
patients aged over 50 years and in the treatment of advanced
Osteoarthritis.
2. Spakova et al[2] compared 120 patients receiving IA injection of
either Hyaluronic Acid or Platelet Rich Plasma. The authors
reported that statistically significantly better results in the scores
were recorded in a group of patients who received Platelet Rich
Plasma injections after a 3- and 6-mo of follow-up.
3. Say et al[3] compared IA Hyaluronic Acid and Platelet Rich Plasma
injections in their prospective study and concluded that the
application of single dose Platelet Rich Plasma to be a safe,
effective and low-cost method for treating Osteoarthritis.
4. Duymus et al.[4] compared the efficacy of intra-articular injections
of Platelet Rich Plasma with Hyaluronic Acid for Osteoarthritis
 treatment. They found that Platelet Rich Plasma injection was more
successful than Hyaluronic Acid injection in the treatment of mild–
moderate osteoarthritis of knee joint. Platelet Rich Plasma
application could provide at least 12 months of pain-free daily
living activities.
5. Lin et al[5] investigated the discrepancy between Platelet Rich
Plasma and Hyaluronic Acid in therapy of Osteoarthritis and
suggested that intra-articular injections of leukocyte-poor Platelet
Rich Plasma (LP-Platelet Rich Plasma) improved function recovery
for at least 1 year in patients with mild-to moderate osteoarthritis
of the knee.
6. Ahmad et al.[6] explored the clinical outcomes of Platelet Rich
Plasma injection with changes in the ultrasonography structural
appearance. They observed that intra-articular injections of
Platelet Rich Plasma were associated with improved synovial
hypertrophy and vascularity scores and less effusion.
7. Filardo et al.[7] found that the patients with Platelet Rich Plasma
injection could not obtain a better clinical outcome than those
treated with Hyaluronic Acid injection.
8. Di Martino et al.[8] concluded that Platelet Rich Plasma injection
did not provide an overall superior clinical improvement compared
 with Hyaluronic Acid injection in terms of functional improvement
at any follow-up point.
9. Laudy et al.[9] enrolled 10 trials and found that Platelet Rich Plasma
injection performed better clinical outcomes than Hyaluronic Acid
injection on pain reduction at 6 months post injection.

In very recent three Level 1 studies, two randomized Hyaluronic Acid

controlled clinical trials and one placebo controlled trial, Platelet Rich
Plasma decreased pain and improved function in all three trials better
than Hyaluronic Acid or placebo.

However, there is no extensive research comparing Platelet Rich Plasma

versus Hyaluronic Acid in patients having osteoarthritis of knee joint in
this region of our country. Hence, the present study will be conducted
with an aim to evaluate and compare the effectiveness of platelet-rich
plasma versus hyaluronic acid in osteoarthritis of knee joint.
 MATERIALS AND METHOD

STUDY AREA

The study will be conducted in Department of Orthopaedics, S.N. Medical College,

Agra.

STUDY POPULATION

Individuals with a clinical diagnosis of Osteoarthritis presenting to the OPD and

Emergency Department of Department of Orthopaedics, S.N. Medical College,
Agra.

STUDY PERIOD

From October 2022 to September 2024. Total duration of study is 24 months.

STUDY DESIGN

It will be a prospective and comparative interventional study.

INCLUSION CRITERIA
1. Age 35-80 years
2. A diagnosis of primary osteoarthritis of knee joint
3. Kellgren–Lawrence (K–L) grade ≤ 3

EXCLUSION CRITERIA
1. Age< 35 years or > 80 years
2. K–L grade > 3
3. History or active presence of clinically significant
inflammatory articular or rheumatic disease other than OA
4. Recent history of trauma
5. Excessive mechanical axis deviation
6. History or presence of malignant disorders
7. Systemic disorders, such as severe cardiovascular diseases,
hematologic diseases, immune-deficiencies, and infections
8. Systematic or intra-articular corticosteroid therapy in the
previous 3 months
9. Anti-coagulants or antiaggregant therapy in the preceding 30
days
SAMPLE SIZE
Patients who fulfill the inclusion criteria of the study during the survey period will
be selected as a sample of the study.

SAMPLING TECHNIQUE
Randomized sampling

ETHICAL CONSIDERATION
Ethical clearance will be obtained by the Institutional Ethical Committee.

CONSENT
Written and informed consent will be taken from the patient and the procedure
will be explained to the patient in a language they best understand.
 METHODOLOGY
Individuals between the age group of 35-80 years with a clinical diagnosis of
osteoarthritis that fulfil the inclusion and exclusion criteria will be selected.
Detailed history and examination will be carried out according to the case
proforma. The patient selected will be divided into two groups randomly.
GROUP A – with intra-articular injection of platelet rich plasma
GROUP B – with intra-articular injection of hyaluronic acid
The patients will be categorized into one of the two groups randomly.
A single unit of 10 mL of peripheral venous blood will be harvested from all
participants in the Platelet Rich Plasma group. Whole blood will be centrifuged at
3200 rpm for 10 min, and an approximate volume of 4 mL Platelet Rich Plasma will
be obtained for use in a single-dose treatment.
In the Hyaluronic Acid group, 60 mg of purified sodium hyaluronate will be used
for single-dose treatment.
Both Platelet Rich Plasma and Hyaluronic Acid will be injected from the
anterolateral portal of the affected knee, flexed to about 90 degrees, just lateral to
the patellar tendon, with 5cc syringe and 21G needle without the guidance from
ultrasound or other imaging techniques.

OUTCOME ASSESSMENT
The Western Ontario and McMaster Universities Index (WOMAC) score will be used
to assess patients’ clinical outcomes at baseline and 1-, 3-, and 6-month follow-ups.
The WOMAC is a self-reported measure and contains three subscales, including the
pain (5 items), stiffness (2 items), and physical function (17 items) subscales. The
primary outcome is the change of WOMAC score at 1-, 3-, and 6-month follow-ups
compared to baseline.

STATISTICAL ANALYSIS
Statistical analysis will be done after data collection with unpaired student t test
using WOMAC Scores during the course of study and the change of WOMAC score
at 1-, 3-, and 6-month follow-ups compared to baseline.
WOMAC SCALE
 REFERENCES

1. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A,

Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular
injection versus hyaluronic acid visco-supplementation as treatments for
cartilage pathology: from early degeneration to osteoarthritis.
Arthroscopy2011; 27: 1490-1501
[PMID: 21831567 DOI: 10.1016/j.arthro.2011.05.011]
2. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of
knee joint osteoarthritis with autologous platelet-rich plasma in
comparison with hyaluronic acid. Am J Phys Med Rehabil 2012; 91: 411-417
[PMID: 22513879 DOI: 10.1097/PHM.0b013e3182aab72]
3. Say F, Gürler D, Yener K, Bülbül M, Malkoc M. Platelet-rich plasma injection
is more effective than hyaluronic acid in the treatment of OSTEOARTHRITIS
OF KNEE JOINT. Acta Chir Orthop Traumatol Cech 2013; 80: 278-283
[PMID: 24119476]
4. Duymus TM, Mutlu S, Dernek B, et al. Choice of intra-articular injection in
treatment of OSTEOARTHRITIS OF KNEE JOINT: platelet-rich plasma,
hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc.
2017;25:485–92. https://doi.org/10.1007/s00167-016-4110-5.
5. Lin KY, Yang CC, Hsu CJ, et al. Intra-articular injection of platelet-rich
plasma is superior to hyaluronic acid or saline solution in the treatment of
mild to moderate OSTEOARTHRITIS OF KNEE JOINT: a randomized, double-
blind, triple-parallel,
 placebo-controlled clinical trial. Arthroscopy. 2019;35:106–17.
https://doi.org/10.1016/j.arthro.2018.06.035.
6. Ahmad HS, Farrag SE, Okasha AE, et al. Clinical outcomes are associated
with changes in ultrasonographic structural appearance after platelet-rich
plasma treatment for osteoarthritis of knee joint. Int J Rheum Dis.
2018;21:960–6. https://doi.org/10.1111/1756-185x.13315.
7. Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, Fornasari
PM, Marcacci M. Platelet-rich plasma vs hyaluronic acid to treat knee
degenerative pathology: study design and preliminary results of a
randomized controlled trial. BMC Musculoskelet Disord 2012; 13: 229
[PMID: 23176112 DOI: 10.1186/1471-2474-13-229]
8. Di Martino A, Di Matteo B, Papio T, et al. Platelet-rich plasma versus
hyaluronic acid injections for the treatment of osteoarthritis of kmee joint:
results at
5 years of a double-blind, randomized controlled trial. Am J Sports Med.
2019;47:347–54.
https://doi.org/10.1177/0363546518814532
9. Laudy AB, Bakker EW, Rekers M, et al. Efficacy of platelet-rich plasma
injections in osteoarthritis of the knee: a systematic review and
metaanalysis.
Br J Sports Med. 2015;49:657–72.
https://doi.org/10.1136/bjsports-2014-094036.
 CASE PROFORMA

1. NAME

2. AGE

3. SEX

4. UHID NO

5. ADDRESS

6. OCCUPATION

7. CONTACT NO

8. RELEVANT CLINICAL HISTORY

EXAMINATION

DURATION OF DISEASE:

PROGRESSION OF DISEASE:

9. PERSONAL HISTORY :

10.EXAMINATION :

11.ADVERSE EFFECTS REPORTED