Efficacy and clinical outcomes of intra-articular injection of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis

INTRODUCTION

Osteoarthritis (OA) of the knee joint is by far the most prevalent rheumatic disorder, and it is a primary cause of functional impairment in the elderly ^1,2. The characteristic abnormalities include articular cartilage degeneration and whole-joint failure ^3,4. As a result, cartilage begins to deteriorate and deep clefts are formed. At the same time, the subchondral bone undergoes pathological changes, including the formation of subarticular cysts and osteophytes development ⁵. These abnormalities cause joint dysfunction and pain, making standing, walking, and performing daily tasks difficult. They also have a significant negative impact on one's quality of life and psychological well-being. ^6,7

Despite the fact that there are various therapeutic available options, conservative treatment measures such as weight reduction, exercise, and nonsteroidal anti-inflammatory medications are only beneficial for individuals with early knee OA; advanced knee OA patients, on the other hand, are more likely to require a total knee replacement. ^8,9

Intra-articular injections of hyaluronic acid (HA) or corticosteroids (CS) have been used as conservative therapies for mild KOA for many years. ¹⁰

 Earlier studies have shown that HA improves the viscoelasticity and mechanical properties of synovial fluid or promotes endogenous HA production in both chondrocytes and synoviocytes. ^11-13

Fresh leukocyte-poor PRP is a promising new growth factor created by centrifuging autologous whole blood and separating plasma with a high platelet count (14–16). PRP has long been used to treat bone, cartilage, and soft tissue ¹⁷, and it is now increasingly being employed in orthopaedics and sports medicine ¹⁸. However, there is disagreement on whether PRP injections should be used ⁶. As a result, we are conducting this research to assess the short-term effects and clinical outcomes of PRP and HA intra-articular injections for the treatment of knee OA.

PATIENTS AND METHODS

This prospective randomised clinical study included 45 patients with knee OA, of whom 40 were eventually enrolled and 5 did not fit the requirements for inclusion. Figure 1 displays a flowchart of the study. Patients were recruited from rheumatology and rehabilitation outpatient clinics at Al-Azhar University Hospitals. This study was approved by the Research Ethics Committee of the Rheumatology and Rehabilitation Department at Al-Azhar University Hospitals, and all patients signed a written informed consent before entering the study. It is in accordance with the Helsinki Declaration's legal principles. The privacy of all details of patients was granted, as each medical file containing all inquiries contained a code number.

Fig. 1: Flow chart of the study subjects.

The participants were separated into two groups: 20 had intra-articular injections of autologous fresh leukocyte-poor PRP at various concentrations, whereas 20 received low molecular weight HA intra-articular injections (Hylans).

The inclusion criteria were age 40–70 years old, a history of knee pain for at least one month, a requirement for analgesics, and radiographic evidence of knee osteoarthritis (Kellgren-Lawrencegrade 1–3) (19) in which Grade 1 shows questionable narrowing of the joint space , Grade 2 shows  definite osteophyte formation, and Grade 3 shows definite narrowing of the joint space with some sclerosis. Exclusion criteria included a history of diabetes or connective tissue disorders, neoplasms, platelet abnormalities, coagulation disorders, and intra-articular steroid injection within the previous six months.

Method of PRP Preparation

8.5 mL of the patient's venous blood was taken by venipuncture and mixed with 1.5 mL of anticoagulant citrate dextrose solution in a sterile vacationer. A unit (3ml) of PRP was produced after two centrifugations (one at 1200 rpm for 15 minutes to separate erythrocytes and one at 1200 rpm for 10 minutes to concentrate platelets). All of the operations were carried out at the same appointment (20)

Within half an hour, one unit of PRP was transferred to the laboratory for platelet concentration determination, while the remaining two units were used for injection. The total number of platelets per mL in PRP can be up to ten times greater than in whole blood. The skin was sterilely prepared before infiltration with an 18-gauge needle in a typical lateral approach. Following the operation, the patient was instructed to repeatedly flex and extend the leg to allow the PRP to disperse all over joint before changing into a gel (21). Patients were instructed to contact their referring physician if they experienced any side effects from the treatment. The injections, however, were safe, with no adverse reactions reported after the injection.

Hyaluronic acid

Hylans are hyaluronan (sodium hyaluronate) derivatives made up of repeating disaccharide units of N-acetylglucosamine and sodium glucuronate. Synvisc (Hylans) comes in prefilled 2-mL syringes containing hylan A with an average molecular weight of 6 million daltons. The suggested injection regimen is one injection per week for three weeks, using a syringe with a gauge of 18 to 22.

There are several methods for injecting a knee joint. One approach is to inject the knee in an extended position with the needle directed beneath the patella. In individuals who are sensitive to iodine derivatives, a topical antiseptic such as povidone-iodine is given to the region and allowed to dry before wiping away the excess with an alcohol swab. For local anaesthetic, an ethyl chloride spray was used. For the knee injection, a 1.5-inch, 22-gauge needle was utilised. If there was any resistance, the needle might need to be redirected.Following the procedure, the injected knee joint should be rested for one to two days.

Outcome Measures

At baseline, we collected demographic data, clinical features, and the Kellgren-Lawrence grading of knee OA. Further measurements were taken at the beginning and four weeks following the third injection including the subjective VAS, which is self-rated pain intensity at the time of the assessment expressed on a 10-cm horizontal scale, with 0 cm indicating "no pain" and 10 cm indicating "worst pain" (22).The Western Ontario and McMaster Universities (WOMAC) OA index is a multidimensional self-assessment questionnaire that assesses 17 functional activities, 5 pain-related activities, and 2 joint stiffness categories in three distinct subscales (23). The degree of knee flexion was determined by measuring the active range of motion of the knee with a goniometer. The standard ROM is 135° (24).

Statistical Analysis:

The sample size was calculated using data from a previous study conducted by Raeissadat et al.(25), who reported a success rate defined as a WOMAC total score reduction of more than 30% at the 12th month compared to the baseline. The total score reduction of WOMAC values in the PRP and HA groups was 72.5% and 22.4%, respectively. A minimum sample size of 36 patients was required for a power of 0.80 and an alpha error of 0.05.  The sample size was calculated using G*Power, Version 3.1.9.2 for Windows. 

A blinded medical statistics specialist input the pre/post-treatment data into the computer and then analysed it using Epi-info software, version 6.04.

RESULTS

Our study comprised 40 people who had knee osteoarthritis (20 injected with PRP and 20 with HA). There was no difference between the two groups in terms of age, gender, or affected side. The characteristics of the research subjects were shown in Table 1.

Table 1: The initial characteristics of the study subjects.

The knee range of motion was measured by a goniometer, the VAS for pain, and WOMAC scores were assessed in our patients at baseline and 4 weeks after the intra-articular injection.

The Knee ROM  measured in degrees by a goniometer shown in Table 2 revealed no statistically significant difference between the two groups either at baseline or the 4 weeks post-injection follow up (P>0.05) as.

Table 2: Knee ROM in degrees before and after injection for cases in the PRP & HA groups.

There were highly statistically significant differences regarding knee ROM in each group. In the PRP group, ROM increased from 93 ± 9.67 to 102.25 ± 7.34 at 4 weeks with a difference of 9.25±5.2 (95 % CI, 9.25±2.279; P<0005). In the HA group, a significant increase in knee ROM from 90 ± 9.32 to 97.5 ± 9.8 was also noted with a difference of 7.5±7.35 (95 % CI, 7. 5±3.3; P<0001).

Despite the difference in knee ROM between the 4 weeks’ follow-up and baseline injection in each group being highly significant, comparing these differences between the two groups showed no statistical significance (P>0.05).

A similar pattern was seen in the VAS score as shown in Table 3, which revealed a significant reduction from (8.7 ± 1.92 and 8 ± 1.03) at baseline to (4.1 ± 1.71 and 4.55 ± 1.64) at 4 weeks of follow-up in the PRP and HA groups, respectively.

Table 3: VAS scale before and after injection for cases in PRP and HA groups.

The difference in VAS score between the two groups was still statistically significant ( PRP vs. HA,-4.6 ± 1.79:-3.45 ±1.54) (t test = 2.18, P < 0.05) showing that the PRP injection group had a higher mean.

There were no statistically significant differences between the two groups at baseline and after 4 weeks post-injection in terms of pain, stiffness, and function subscales of the WOMAC index (Tables 4 - 6). By considering P values of mean difference (4 weeks follow-up and baseline evaluation) within each group, there were considerably better success rates in pain, knee stiffness, and physical function scores. However, the differences in WOMAC subscales between the two groups were not significant (P < 0.05).

Table 4: Pain scale of WOMAC index before and after injection for cases in PRP and HA groups.

Table 5: Stiffness subscale of WOMAC index before and after injection for cases in PRP and HA groups.

Table 6: Physical function subscale of WOMAC index before and after injection for cases in HA and PRP groups: