Does the Combination of Platelet-rich Plasma and Supervised Exercise Yield Better Pain Relief and Enhanced Function in Knee Osteoarthritis? A Randomized Controlled Trial

Abstract

Background

Knee osteoarthritis is a leading cause of disability with substantial healthcare costs, and efficient nonsurgical treatment methods are still needed. Platelet-rich plasma (PRP) injections and exercise therapy are used frequently in clinical practice. Whether PRP or PRP combined with exercise is more effective than exercise alone is unclear.

Questions/purposes

(1) Which treatment relieves knee osteoarthritis pain better: PRP alone, exercise, or PRP combined with exercise? (2) Does PRP alone, exercise, or PRP combined with exercise yield better results in terms of the WOMAC score, performance on the 40-m fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score?

Methods

In this randomized, controlled, three-arm clinical trial, we recruited patients with mild-to-moderate (Kellgren-Lawrence Grade II or III) knee osteoarthritis with a minimum of 3 points on the 11-point numeric rating scale for pain. During the study period, 157 patients with a diagnosis of knee osteoarthritis were screened and 84 eligible volunteers were enrolled in the study. Patients were randomly allocated (1:1:1) into either the exercise group (28), PRP group (28), or PRP + exercise group (28). Follow-up proportions were similar between the groups (exercise: 89% [25], PRP: 86% [24], PRP + exercise: 89% [25]; p = 0.79). All patients were analyzed in an intention-to-treat manner. There were no between-group differences in age, gender, arthritis severity, and baseline clinical scores (pain, WOMAC, functional performance tests, and health-related quality of life). The exercise group underwent a 6-week structured program consisting of 12 supervised individual sessions focused on strengthening and functional exercises. Meanwhile, the PRP group received three weekly injections of fresh, leukocyte-poor PRP. The PRP + exercise group received a combined treatment with both interventions. The primary outcome was knee pain over 24 weeks, measured on an 11-point numeric rating scale for pain (ranging from 0 to 10, where 0 represents no pain and 10 represents the worst pain, with a minimum clinically important difference [MCID] of 2). The secondary outcome measures included the WOMAC index (ranging from 0 to 100, with lower scores indicating a lower level of disability and an MCID of 12), the durations of the 40-meter fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score. For the a priori sample size calculation, we used the numeric rating scale score for pain at 24 weeks as the primary outcome variable. The MCID for the numeric rating scale was deemed to be 2 points, with an estimated standard deviation of 2.4. Based on sample size calculations, a sample of 24 patients per group would provide 80% power to detect an effect of this size between the groups at the significance level of p = 0.05.

Results

We found no clinically important differences in improvements in pain—defined as ≥ 2 points of 10—at 24 weeks when comparing exercise alone to PRP alone to PRP + exercise (1.9 ± 0.7 versus 3.8 ± 1.8 versus 1.4 ± 0.6; mean difference between PRP + exercise group and exercise group -0.5 [95% confidence interval -1.2 to 0.4]; p = 0.69). Likewise, we found no differences in WOMAC scores at 24 weeks of follow-up when comparing exercise alone to PRP alone to PRP + exercise (10 ± 9 versus 26 ± 20 versus 7 ± 6; mean difference between PRP + exercise group and exercise group -3 [95% CI -12 to -5]; p = 0.97). There were no differences in any of the other secondary outcome metrics among the PRP + exercise and exercise groups.

Conclusion

PRP did not improve pain at 24 weeks of follow-up in patients with mild-to-moderate knee osteoarthritis compared with exercise alone. Moreover, exercise alone was clinically superior to PRP alone, considering function and the physical component of health-related quality of life. Despite the additional costs and endeavors related to PRP products, the combination of PRP and exercise did not differ from exercise alone. The results of this randomized controlled trial do not support the use of PRP injections in the treatment of patients diagnosed with mild-to-moderate knee osteoarthritis. Consequently, exercise alone is the recommended treatment for reducing pain and enhancing function throughout this timeframe.

Level of Evidence

Level I, therapeutic study.

Introduction

Osteoarthritis will affect as many as 10% of men and 20% of women [9, 12], and it is a cause of serious pain, disability, and burden on healthcare systems [12, 34]. Current treatment options for knee osteoarthritis focus on pain relief and improvements in function and health-related quality of life. Exercise is one of the safe and recommended methods, according to clinical guidelines [3, 18, 22]. However, it is often challenging for patients to maintain regular exercise, resulting in a lack of long-term benefit. Although the pharmacologic treatment options vary, they generally have small-to-moderate effects in the short term and may have several side effects [3,7,22]. It is obvious that safe and efficient treatment techniques supported by evidence are needed [6,7]. Platelet-rich plasma (PRP) is one such potential treatment, and its use is increasing [38].

However, serious questions have been raised about whether PRP is efficacious in patients with osteoarthritis [6, 11, 22, 25, 28, 29]. Osteoarthritis clinical practice guidelines have suggested that more high-quality evidence is needed to make a recommendation about the clinical efficacy of PRP [3, 18, 22]. There remains a relative paucity of reports characterizing the injected material, and heterogeneity is considered a major limitation [23], as is the lack of high-quality randomized trials comparing PRP with reasonable alternatives, including exercise. PRP injections and exercise therapy are commonly prescribed for patients with knee osteoarthritis, but whether PRP injection or PRP combined with exercise therapy is associated with better improvements in pain and function than exercise alone is unclear.

We therefore asked: (1) Which treatment relieves knee osteoarthritis pain better: PRP alone, exercise, or PRP combined with exercise? (2) Does PRP alone, exercise, or PRP combined with exercise yield better results in terms of the WOMAC score, performance on the 40-m fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score?

Patients and Methods

Trial Design and Setting

We conducted a three-group, randomized, controlled clinical trial at the orthopedics and traumatology department of Istanbul Medical Faculty Hospital. Patients with suspected knee osteoarthritis were recruited at the university hospital, which serves as a central healthcare hub for a diverse patient population from the surrounding metropolitan area. The hospital provides essential healthcare services to individuals from various socioeconomic backgrounds. Referrals from general practitioners directed patients to their initial specialist consultation with an orthopaedic surgeon at the general orthopaedic outpatient clinic, specifically for the assessment of knee osteoarthritis.

Participants

Volunteers were assessed for eligibility if they were 40 to 70 years old and reported knee pain on most days of the previous month (a minimum of 3 points on an 11-point numeric pain rating scale). Eligible patients met the criteria of the American College of Rheumatology classification [1] and had Kellgren-Lawrence Grade II (demonstrating possible narrowing with definite osteophyte formation) to Grade III (definite narrowing, moderate osteophyte formation, some sclerosis, and possible deformity) knee osteoarthritis [21]. Patients were excluded if they met one of the following criteria: previous invasive procedure, intra-articluar injections, or physiotherapy in the past 3 months; platelet count lower than 150 × 10³/μL; BMI greater than 30 kg/m²; ongoing anticoagulation therapy; an active infection, malignancy, or systemic disorder limiting functional abilities; and impaired cognition that impacted the patient’s ability to give informed consent.

Study Procedure and Randomization

Before patient enrollment, a computer-based random-number generator was used to create a random sequence to allocate treatment groups. An independent assistant who was uninvolved in the study managed the concealed allocation process, ensuring that the sequence remained unknown to the investigators. Then, sequentially numbered, sealed, opaque envelopes were used. After acquiring written consent from patients, we randomly assigned eligible participants to one of three treatment groups in a 1:1:1 ratio, without any restrictions such as blocking. The assessor and statistician involved in the study remained blinded to the group allocation. However, because of the nature of the study design, it was not possible to blind the patients to their respective treatment groups. An intention-to-treat analysis was performed, where all participants were analyzed in the groups to which they were assigned.

In this three-arm randomized controlled study, patients received one of the following interventions based on group allocation: supervised exercise program (exercise group), intra-articular PRP injections (PRP group), or a combination of both treatments (PRP + exercise group). Regardless of group allocation, patients were not allowed to use NSAIDs from 3 weeks before the first assessment until 24 weeks after treatment.

Study Flow and Completeness of Follow-up

One hundred fifty-seven patients were screened for eligibility. A total of 84 patients who satisfied the eligibility criteria and agreed to participate were enrolled. Patients were randomly allocated into the exercise group (28), PRP group (28), or PRP + exercise group (28). Follow-up proportions between the groups were similar (exercise: 89% [25], PRP: 86% [24], PRP + exercise: 89% [25]; p = 0.79) at 24 weeks. Four patients (exercise: 7% [2], PRP: 4% [1], PRP + exercise: 4% [1]) did not complete their allocated interventions; nonetheless, all patients received at least one exercise session or one dose of PRP (Fig. 1). In accordance with the intention-to-treat principle, all participants were involved in the analysis regardless of whether they discontinued treatment or were lost to follow-up. The groups did not differ at baseline in terms of scores on outcome instruments, arthritis severity, or outcomes scores before treatment (Table 1).

Fig. 1.

This Consolidated Standard of Reporting Trials flow diagram depicts the trial enrolment and follow-up.

Table 1.

Demographic and baseline characteristics of the participants by group

Characteristic	Exercise (n = 28)	PRP (n = 28)	PRP + exercise (n = 28)
Age in years	58 ± 7	55 ± 7	54 ± 7
Women	79 (22)	71 (20)	71 (20)
Height in cm	162 ± 8	165 ± 9	163 ± 7
Body mass in kg	72 ± 10	81 ± 9	75 ± 11
BMI in kg/m2	27 ± 4	29 ± 4	28 ± 4
Radiographic disease severity  KL Grade II  KL Grade III	43 (12) 57 (16)	46 (13) 54 (15)	36 (10) 64 (18)
Knee flexion range of motion, degrees	133 ± 6	131 ± 6	131 ± 9
Pain, 0-10	6.7 ± 1.0	6.5 ± 1.2	6.8 ± 0.9
WOMAC score	42 ± 12	45 ± 14	42 ± 17
40-m fast-paced walk test, m/s	0.9 ± 0.1	0.9 ± 0.2	0.9 ± 0.2
Stair climbing test, s	27 ± 7	30 ± 10	29 ± 6
SF-12 physical component score	35 ± 7	34 ± 8	39 ± 9
SF-12 mental component score	38 ± 11	38 ± 11	38 ± 10

Data are presented as % (n) or mean ± SD. There was no difference between groups (p > 0.05). KL = Kellgren-Lawrence classification.

Interventions

Three injections of fresh leukocyte-poor PRP were administered at weekly intervals in the PRP group and PRP + exercise group. For the PRP preparation procedure, a commercially available kit (T Lab, T-Biotechnology Laboratory) was used, with a single centrifugation at 830 g for 5 minutes (Fig. 2). In a sterile manner, 26 mL of the whole blood sample was harvested from the antecubital vein using a 16-gauge needle. The tubes were placed in a swing-out rotor centrifuge (Supplemental Table 1; http://links.lww.com/CORR/B310). This procedure yields leukocyte-poor PRP with a platelet concentration that is 3.4 times higher than whole blood values and 76% platelet recovery (Supplemental Table 2; http://links.lww.com/CORR/B310). Therefore, in accordance with the PRP classification and coding system proposed by Kon et al. [23] and Magalon et al. [26], the PRP code used in this study was 23-00-00 and B-B-A, respectively. An experienced orthopaedic surgeon (ONE) with 18 years of clinical experience injected 6 mL of fresh PRP using a 22-gauge needle with a medial patellofemoral approach under ultrasound guidance. The PRP-injected knee was passively flexed and extended three times, and the patient rested for 10 minutes. The patient was sent home, and active rest—especially avoiding high-impact activities on the treated leg—was recommended for 48 hours.

Fig. 2.

This photograph depicts the injected fresh leukocyte-poor PRP.

In both the exercise and PRP + exercise groups, patients received the same exercise program and individual sessions supervised by the same experienced physiotherapist (SKA) who had 12 years of clinical experience. Therapeutic exercises were performed twice per week for 6 weeks, for a total of 12 sessions. Exercises were performed in three sets of 10 repetitions, and each exercise session lasted approximately 40 minutes. Exercise was progressed by increasing resistance or weight [20] (Table 2).

Table 2.

Details of the structured exercise program^a

0 to 3 weeks	Dose
Quadriceps isometric set exercise	10 repetitions/2 sets
Active assisstive/active knee mobility exercises (heel slide)	10 repetitions/2 sets
Terminal knee extension	10 repetitions/2 sets
Prone knee bends	10 repetitions/2 sets
Gluteal strengthening exercises  Straight leg raises (flexion with   external rotation, abduction)  Bridging exercise  Clamshell exercise	10 repetitions/2 sets
Hamstring and gastrocnemius stretching (in sitting)	30 seconds/3 repetitions
Patellar mobilization	2 minutes

3-6 weeks	Dose
Resistive knee mobility exercises (heel slide with theraband)	10 repetitions/2 sets
Resistive knee extension	10 repetitions/2 sets
Resistive terminal knee extension	10 repetitions/2 sets
Wall squats	10 repetitions/2 sets
Chair stands	10 repetitions/2 sets
Sliding exercises  Forward/backward  Sideways	10 repetitions/2 sets
Step ups (forward/sideways)	10 repetitions/2 sets
Hamstring and gastrocnemius stretching (standing)	30 seconds/3 repetitions

^aIndividual sessions were supervised by physical therapist; total of 12 sessions: two sessions per week for 6 weeks. Sessions began after a 5-minute warmup, and the amount of resistance was determined by the patient's 10-repetition maximum weight [20].

Adverse Events

During the study and follow-up periods, minor and transient adverse events were reported. Injection site pain was reported in the PRP group (14% [4 of 28]) and PRP + exercise group (11% [3 of 28]). Knee stiffness (disappearing within 24 hours) was reported by more participants in the PRP group (18% [5 of 28]) than in the PRP + exercise group (7% [2 of 28]). Two participants in the PRP + exercise group (7% [2 of 28]) experienced knee swelling. There were no serious related adverse events.

Primary and Secondary Study Outcomes

The primary outcome was knee pain over 24 weeks. Pain severity was measured using an 11-point numeric pain rating scale, with 0 indicating no pain and 10 indicating the worst pain conceivable. Patients were asked to rate their knee pain’s severity with a number between 0 and 10 using this scale. The minimum clinically important difference (MCID) of this validated pain scale is accepted as ≥ 2 [17].

Secondary outcome measures were function and health-related quality of life. The assessment of functional difficulty included the WOMAC index and performance tests measured over time. The total score of the WOMAC ranges from 0 to 100 (lower scores representing lower level of disability), and the MCID was reported as 12 points [39]. Furthermore, the Osteoarthritis Research Society International–recommended performance-based tests including 40-m fast-paced walk and stair climbing were used [14]. The Osteoarthritis Research Society International recommendations are a 10-m marked walkway and 20-cm step height, which are preferred for the 40-m fast-paced walk test and stair climbing test, respectively [14]. Patients performed the tests twice against time, and the average score of three performances was recorded for both tests. The SF-12 physical and mental scores (range 0 to 100, representing worst to best; MCID of 5) was used to evaluate health-related quality of life [10, 15, 37].

A blinded researcher (DC) performed all assessments at baseline, after treatment, and at the 12-week and 24-week follow-up intervals (Supplemental Table 3; http://links.lww.com/CORR/B310). Adverse events were monitored during the study.

Ethical Approval and Trial Registration

The study protocol was approved by the Research Ethics Committee at Istanbul University-Cerrahpasa (IRB: 59491012-604.01.02). As a doctoral thesis endeavor, this study adhered to university protocol by first securing ethics committee endorsement for its methodology. Approval from the ethics committee was obtained in April 2020, marking the commencement of logistical arrangements, including equipment and material procurement for the project. The patient randomization into study groups occurred on January 25, 2021. This trial was registered at ClinicalTrials.gov (NCT04697667) and adhered to the principles outlined in the Declaration of Helsinki.

Statistical Analysis

For the a priori sample size calculation, we used the numeric rating scale score for pain at 24 weeks as the primary outcome variable. To detect an effect size of 0.82 (MCID 1.74 ± 2.1 points) with a power of 80% (alpha level = 0.05), a sample of 72 patients (24 in each group) would be needed [17]. We targeted a final enrollment of 84 patients by adding approximately 15% more patients to compensate for potential participants who may withdraw from the study or may be lost to follow-up.

To assess between-group differences, we evaluated improvements in the numerical pain rating score, WOMAC score, durations of functional performance tests, and SF-12 physical and mental scores from baseline to the 6-, 12-, and 24-week follow-up intervals. These improvements were compared using one-way analysis of variance. We present between-group differences in improvement from baseline with 95% confidence intervals (exercise group versus PRP + exercise group; exercise group versus PRP group) and conducted Bonferroni-adjusted pairwise comparisons. All statistical analyses were performed using IBM SPSS Version 29 for Mac OS, with the significance level set at p < 0.05.

Results

Knee Pain

We found no clinically important differences in improvements in pain—defined as ≥ 2 points of 10—at 24 weeks when comparing exercise alone with PRP alone with PRP + exercise (1.9 ± 0.7 versus 3.8 ± 1.8 versus 1.4 ± 0.6; p < 0.001). Exercise alone showed superiority over PRP alone, with a mean difference of 1.9 (95% CI 1.2 to 2.7), approaching the MCID of 2 (p < 0.001). However, incorporating three-dose PRP injections into the exercise regimen did not alter the pain score compared with exercise alone (24-week mean difference: -0.5 [95% CI -1.2 to 0.4]; p = 0.69). Throughout the study, the pain scores diminished across all treatment groups (Fig. 3).

Fig. 3.

These graphs depict the progression of primary and secondary outcome measures throughout the study. (A) The baseline to 24-week changes on overall knee pain, (B) the total WOMAC score, (C) the 40-m fast-paced walk test, (D) the stair climbing test, (E) the SF-12 physical component score, and (F) the SF-12 mental component score are presented by randomized treatment assignment.

WOMAC, Physical Function Metrics, and Health-related Quality of Life

We found clinically important differences in improvements on the WOMAC score—defined as ≥ 12 points of 100—at 24 weeks when comparing exercise alone to PRP alone to PRP + exercise (10 ± 9 versus 26 ± 20 versus 7 ± 6, respectively; p < 0.001). Exercise alone was clinically superior to PRP alone, with a mean difference of 16 (95% CI 5 to 22; p < 0.001), whereas PRP + exercise did not differ from exercise alone (mean difference: -3 [95% CI -12 to 5]; p = 0.97). Similarly, PRP alone was inferior to exercise alone regarding the 40-m fast-paced walk test and stair climbing test (0.1 [95% CI 0.2 to 1.2] and 6 [95% CI 2 to 10], respectively; p = 0.01).

There were clinically important differences in improvements in the SF-12 physical function score—defined as ≥ 5 points of 100—at 24 weeks when comparing exercise alone to PRP alone (46 ± 8 versus 40 ± 10, respectively; mean difference -6 [95% CI -10 to 1]; p = 0.04). There were no differences in any of other comparisons among the groups (Table 3).

Table 3.

Improvements in outcome measures between baseline and 24 weeks

	Exercise (n = 28)	PRP (n = 28)	PRP versus exercise		PRP + exercise (n = 28)	PRP + exercise versus exercise
Outcome	Mean ± SD	Mean ± SD	Mean difference (95% CI)	p value	Mean ± SD	Mean difference (95% CI)	p value
10-point pain scorea	1.9 ± 0.7	3.8 ± 1.8	1.9 (1.2 to 2.7)	< 0.001	1.4 ± 0.6	-0.5 (-1.2 to 0.4)	0.69
WOMAC scoreb	10 ± 9	26± 20	16 (5 to 22)	< 0.001	7 ± 6	-3 (-12 to 5)	0.97
40-m fast-paced walk test, m/sc	1.0 ± 0.1	0.9 ± 0.1	0.1 (0.2 to 1.2)	0.01	1.0 ± 0.1	-0.1 (-0.1 to 0.9)	0.99
Stair climbing test, sc	22 ± 8	28± 7	6 (2 to 10)	0.01	23 ± 4	1 (-3 to 5)	0.99
SF-12 physical component scored	46 ± 8	40 ± 10	-6 (-10 to 1)	0.04	50 ± 8	4 (2 to 13)	0.05
SF-12 mental component scored	45 ± 9	43 ± 8	-2 (-6 to 4)	0.97	44 ± 9	1 (-4 to 5)	0.99

^aPain was measured with the 11-point numeric pain rating scale (ranging from 0 to 10, where 0 represents no pain and 10 represents the worst pain; minimum clinically important difference [MCID] of 2).

^bWOMAC: MCID of 12.

^cFunctional performance was assessed with the Osteoarthritis Research Society International–recommended performance-based tests. To our knowledge, there is no reported MCID for this population.

^dHealth-related quality of life was measured with the SF-12 physical and mental scores (ranging from 0 to 100, representing worst to best; MCID of 5).

Discussion

Despite its widespread application in osteoarthritis treatment, the efficacy of PRP remains to be definitively established, casting uncertainty on its clinical effectiveness. Substantial questions persist regarding the therapeutic efficacy of PRP [6, 11, 22, 25]. It is unclear whether PRP provides benefits to patients with knee osteoarthritis when injected alone or combined with exercise, which is a recommended treatment [3, 22]. In this randomized controlled trial, we aimed to ascertain the superior treatment for reducing pain or enhancing function in patients with knee osteoarthritis among three interventions: PRP + exercise, PRP alone, or exercise alone. Our investigation yielded no substantiating evidence suggesting the superiority of PRP or PRP combined with exercise over exercise alone. Notably, no discernible variations were observed between groups concerning pain alleviation or functional improvement throughout the 24 weeks of this study. This contributes to the accumulating body of evidence implying that PRP interventions have limited efficacy. Consequently, considering these findings, we advocate refraining from using PRP injections in patients with a diagnosis of knee osteoarthritis.

Limitations

The trial included individuals diagnosed with mild-to-moderate radiographic knee osteoarthritis. The decision to limit the trial to this specific group was informed by prior evidence indicating that the interventions evaluated may not be suitable for individuals with severe arthritis [30]. Consequently, the findings presented may not be generalizable to more advanced stages of osteoarthritis. Secondly, PRP preparations demonstrate variability and a lack of standardization. Hence, the findings from this trial might not be universally applicable to other PRP formulations. Nevertheless, our trial specifically used a commercially available PRP product administered in a manner that was previously stated to enhance efficacy for osteoarthritis (as three injections at weekly intervals) [36]. Moreover, our study reported the characteristics of the administered PRP product, along with the associated preparation and application procedures, in accordance with described classification and coding systems [23, 26].

Another limitation is the lack of a placebo in the control group. However, according to the Declaration of Helsinki, the use of a placebo or no treatment in the control group is inappropriate when there is an existing effective intervention to seek benefit. Moreover, the clinically relevant question should be whether this potential treatment is better than the recommended treatment [8]. In the current study, the control group underwent exercise therapy, a treatment endorsed by clinical guidelines for its safety and efficacy in addressing knee osteoarthritis [3, 18, 22]. Finally, the 24-week follow-up duration in this study was relatively short for assessing osteoarthritis; further investigations should consider using more protracted follow-up intervals. Considering the findings of this study, indications suggest that if a treatment does not demonstrate efficacy or ceases to be effective within 24 weeks, the likelihood it will exhibit effectiveness over 1 year or longer appears improbable.

Knee Pain

The current guidelines regarding the application of PRP have predominantly offered an inconclusive recommendation because of the dearth of robust evidence [3, 22, 32]. Despite an array of studies delving into the purported benefits of PRP injections for managing pain, the actual effectiveness of PRP remains contentious in osteoarthritis. Although some systematic reviews have reported positive alterations in pain linked to PRP [19, 24, 35], there is a notable level of variability among these studies, often exacerbated by insufficient statistical power. A recent meta-analysis examining injectables in knee osteoarthritis revealed markedly wide CIs concerning the efficacy of PRP, casting uncertainty on its application [31]. Conversely, high-quality clinical trials indicated that PRP did not demonstrate superiority over saline or hyaluronic acid injections at the 12-month mark or beyond [6, 13, 25].

Our findings imply that PRP may not yield clinically important benefits in alleviating pain for individuals with knee osteoarthritis. Exercise was as effective as exercise + PRP, and PRP was less effective than exercise alone. Thus, we recommend against the use of PRP in patients with mild to moderate osteoarthritis, and we favor an exercise program similar to the one we used here (Table 2). Based on these findings, exercise is the optimal choice for managing pain over the 24-week follow-up period. In instances where a patient cannot engage in exercise because of severe pain, recommendations outlined in osteoarthritis guidelines, such as corticosteroid injections or oral NSAIDs, may offer potential benefits [3, 22]. Corticosteroids have substantial evidence supporting their efficacy in treating symptomatic knee osteoarthritis among intra-articular injections; however, the duration of their beneficial effects typically spans up to 3 months [7]. In patients for whom exercise alone is not feasible, intra-articular corticosteroids or oral NSAIDs provide short-term relief.

WOMAC, Physical Function Metrics, and Health-related Quality of Life

Likewise, there is ongoing debate regarding the efficacy of PRP in treating knee osteoarthritis concerning functional improvement and quality of life. Remarkably, there has been considerable underreporting of crucial PRP-related factors in previous research. However, the specifics regarding the injected product and procedural details, encompassing preparation and application, are pivotal in contributing to the scientific evidence [16, 23]. Although some favorable results were reported by systematic reviews and meta-analyses [27, 35], improvements were modest and effect sizes were small [2, 24] and unfavorable results have also been reported [5, 19]. Randomized controlled trials have yielded inconsistent evidence concerning the impact of PRP on function and quality of life. Although trials indicated potential benefits [27, 33], others observed no discernible difference compared with control groups [6, 13, 25].

Our findings indicated that exercise alone was clinically superior to PRP alone in terms of WOMAC score and SF-12 physical component score. The differences between exercise alone and PRP alone were also greater for the 40-m fast-paced walking and stair climbing tests (Table 3), yet the clinical superiority was not defined because the MCID values were not reported [4]. Our findings indicated that adding three doses of PRP injections to the supervised exercise program did not lead to any additional improvement. Given its associated costs, invasive nature, and procedural complexities, we advise against opting for PRP injections in this context. Instead, we advocate for prioritizing supervised exercise therapy because it offers a more beneficial approach.

Conclusion

The results of this randomized controlled trial do not support the use of PRP injections in the treatment of patients with a diagnosis of mild-to-moderate knee osteoarthritis. There was no clinically meaningful evidence regarding PRP, either alone or in conjunction with exercise, compared with exercise alone. Moreover, exercise alone was clinically superior to PRP alone, considering function and the physical component of health-related quality of life. In light of these findings, exercise was the best treatment in terms of pain relief or functional enhancement over the 24-week period of our study, especially when considering the additional costs of PRP injections. Therefore, we advise against using PRP injections for individuals with mild-to-moderate knee osteoarthritis.