Effectiveness of therapeutic exercise and platelet-rich plasma in the case of knee osteoarthritis

Abstract

[Purpose] Osteoarthritis is the most common form of arthritis worldwide and has detrimental effects on an individual’s quality of life. We compared two interventions—an exercise program alone and an exercise program combined with the intra-articular platelet-rich plasma (PRP) injection—focusing on pain and functionality in patients with mild knee osteoarthritis. [Participants and Methods] A total of 76 patients (41 men and 35 women) participated in the study. They were divided equally into the control and intervention groups. To assess knee functionality in both groups, we used state-of-the-art assessment tools, namely the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). [Results] The results revealed that following the eight-week exercise program, the intervention group showed significantly better values in the WOMAC scale and in three of the four components of the KOOS scale (pain, symptoms, and activities of daily living). Additionally, we observed that the improvement in WOMAC and KOOS scores was significantly better in the intervention group than in the control group. [Conclusion] Combining PRP and exercise therapy can help improve patients’ quality of life. However, PRP preparation protocols and exercise prescriptions must be optimized and tailored to individual patient needs.

INTRODUCTION

Knee osteoarthritis (OA) is an articular cartilage pathology characterized by complex biological processes that recruit inflammatory, mechanical, and metabolic factors, eventually leading to knee joint failure. The primary symptoms of knee OA are pain, stiffness, and joint dysfunction. Advanced age, increased body mass index, a sedentary lifestyle, and trauma are among the most important factors that cause knee OA. Owing to its significant disability, especially in the advanced stages, OA has a substantial social and economic impact¹⁾. Knee OA management strategies focus on joint function improvement, reduction of disability, and pain relief that ultimately result in the improvement of the patient’s quality of life (QOL)²⁾.

With the development of less invasive procedures, existing therapeutic approaches have focused on preventing or delaying disease progression³⁾. Current research is focused on developing new methods for stimulating or replacing damaged cartilage. Treatments such as nonsteroidal anti-inflammatory drugs, hyaluronic acid, chondroid sulfate glucocorticoids, platelet-rich plasma (PRP), physical therapy, and exercise are the mainstay of the nonsurgical management of knee OA^{4, 5)}

Recently, PRP therapy has gained attention as a potential treatment for knee OA. Platelet-rich plasma injections have been shown to influence the entire joint environment, leading to short-term clinical improvements. Moreover, PRP injections are considered a safe procedure with favorable clinical outcomes, including pain relief and stiffness reduction, compared with alternative treatments⁶⁾. Notably, PRP is relatively easy to use because of its simple and rapid preparation and minimally invasive administration. The related clinical trials seem promising; however, this therapeutic approach requires further investigation to fully demonstrate its benefits and effectiveness⁷⁾. Additionally, PRP therapy and exercise programs have demonstrated potential benefits in the management of knee OA⁸⁾. Therefore, combining these two therapeutic approaches as adjuvant therapies may be valuable in the management of knee OA⁹⁾.

This study compared the effectiveness of a well-established exercise regimen alone against the same regimen combined with an intra-articular PRP injection in terms of pain and functional outcomes in patients with knee OA.

PARTICIPANTS AND METHODS

This controlled study involved two groups receiving different treatments. The study protocol was approved by the Ethics Committee of the Technological Educational Institute of Western Greece (reference number: 335750/10/10/2017). Participants were recruited from a private Orthopedic Medical Clinic in Patras, Greece. All the clinical assessments and treatments were performed at the same clinic. Before recruitment, each participant was screened for eligibility. Eligible participants were older than 18 years and diagnosed with mild knee OA grade II, “definite osteophytes and possible narrowing of joint space” according to the criteria established by the American College of Rheumatology and the staged Kellgren–Lawrence radiological classification¹⁰⁾.

Written informed consent was obtained from the participants upon their acceptance, and their demographic and clinical characteristics were recorded via face-to-face interviews. The exclusion criteria included an inability to obtain informed consent; intra-articular injection of steroids, anesthetics, or hyaluronic acid in the past year; arthroscopic surgery in the past three months; compromised bone metabolism (excluding osteoporosis); fibromyalgia; chronic fatigue syndrome; cancer; neuromuscular disease; severe cardiovascular disease; and pregnancy.

The final sample comprised 76 patients, of which 41 were men and 35 were women. All the patients were Caucasian. The participants were aged (Mean ± SD) 64.12 ± 12.35, while their BMI was (Mean ± SD) 30.80 ± 6.23. The control and intervention groups included 38 people each. Specifically, the control group consisted by 21 males and 17 females while the intervention group consisted by 20 males and 18 females. The individuals in each group had the same age and body type characteristics based on the body mass index. To assess knee functionality in both groups, we used the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire²⁾. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was assessed twice—at the initial evaluation and upon completion of the eight-week exercise program¹¹⁾.

The patients were treated with a single PRP intra-articular injection at the beginning of the study. After 15 minutes of rest, the patients were asked to flex and extend their knees to spread the PRP throughout the joint. Mild pain occasionally occurred during the injection. During the initial evaluation, all exercises were conducted under the supervision of a physiotherapist (C. F.). All patients received supervised exercise therapy once a week at the medical center and continued therapy exercises at home. The participants were given oral instructions and an eight-week exercise program (exercise protocol).

To ensure adequate and consistent performance of the exercises, the patients reported their progress with smartphone video-call communication. Subsequently, they were asked to continue the exercises at home for six months without supervision but with smartphone coaching. Each exercise session began with warm-up activities lasting five minutes, followed by a circuit training program focusing on knee strength and flexibility. The exercises were performed with the weight of the body and elastic rubber bands and ended with ice packs being applied to the affected areas for 20 minutes to relieve pain. The level of exercise, including the number of repetitions or duration, was recorded for each patient in a personal electronic diary.

The normality of the quantitative variables was checked by a visual observation of the patient’s histograms and Q-Q plots and evaluated by statistical analyses (Kolmogorov–Smirnov statistical test). In addition to the variables describing the WOMAC scale and the four components of the KOOS scale (pain, symptoms, activities of daily living [ADL], and quality of life related to the knee), the differences in these variables between the initial and final evaluations were also assessed, aiming to investigate whether statistically significant differences existed between the control and intervention groups. An independent samples t-test was performed for the variables that followed the normal distribution, and a non-parametric Mann–Whitney U test was performed for the variables that were not normally distributed. Similarly, to check for any significant difference in the scores of the KOOS and WOMAC scales after the completion of the eight-week exercise program, a samples t-test was performed for the variables that followed a normal distribution, whereas for those that did not follow a normal distribution, the Wilcoxon test was applied.

RESULTS

The results of the inductive statistical analysis are presented in Tables 1 and 2.

Table 1. Results of inductive statistics (t-test).

	Control group	Intervention group	Mean difference
	Mean ± SD	Mean ± SD
KOOS pain initial	64.34 ± 13.88	65.63 ± 13.52	–1.29
KOOS symptom initial	71.58 ± 12.38	65.63 ± 13.52	–0.58
KOOS ADL initial	68.45 ± 8.53	70.29 ± 7.31	–1.84
KOOS QOL initial	53.34 ± 9.14	52.05 ± 7.68	1.29
WOMAC initial	40.24 ± 11.66	39.11 ± 10.94	1.13
KOOS pain final	65.21 ± 13.62	71.76 ± 12.77	6.55
KOOS symptom final	72.34 ± 12.10	77.79 ± 10.97	5.45*
KOOS ADL final	65.21 ± 13.62	74.13 ± 7.05	–4.63*
KOOS QOL final	53.26 ± 9.59	52.24 ± 7.73	1.03
WOMAC final	39.11 ± 11.28	33.74 ± 9.47	5.37*

*p-value <0.05.

KOOS: Knee Injury and Osteoarthritis Outcome Score; ADL: activities of daily living; QOL: quality of life; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

Table 2. Results of inductive statistics (Mann–Whitney).

	Control group	Intervention group	Mean difference
Δ (KOOS pain)	0.87 ± 1.29	4.47 ± 3.86	3.6**
Δ (KOOS symptom)	0.76 ± 1.53	3.34 ± 1.45	2.58**
Δ (KOOS ADL)	1.05 ± 1.39	3.84 ± 1.51	2.79**
Δ (KOOS QOL)	0.08 ± 1.61	0.18 ± 1.43	0.49
Δ (WOMAC)	1.13 ± 0.70	−4.53 ± 1.95	−5.66**

**p-value <0.01.

KOOS: Knee Injury and Osteoarthritis Outcome Score; ADL: activities of daily living; QOL: quality of life; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

The statistical analyses revealed that during the initial evaluation, no significant differences existed in the somatotype characteristics of the participants or between the KOOS and WOMAC scores of the two groups (p>0.05). Nevertheless, after completing the eight-week exercise program, the intervention group showed statistically better values on the WOMAC scale and three of the four components of the KOOS (pain, symptoms, and ADL; p<0.001.

DISCUSSION

This study compared the efficacy of intra-articular PRP injections combined with therapeutic exercises and therapeutic exercises alone in patients with knee OA. A key strength of our study was the inclusion of a control group that underwent exercise therapy, ensuring that all patients received effective treatments known to reduce pain and improve function in knee OA¹²⁾. This design allowed for a clear comparison of PRP and exercise with exercise therapy alone.

At baseline, no significant differences were observed between the control and intervention groups in terms of the somatotype characteristics or between the KOOS and WOMAC scales. However, after completing the eight-week exercise program, the intervention group demonstrated statistically significant improvements in the WOMAC scores and three of the four KOOS scale components (pain, symptoms, and ADL) compared with the control group. Although the control group also showed improvements in these areas, these were less pronounced. This suggests that the addition of PRP injections may offer enhanced benefits in managing OA symptoms compared with exercise therapy alone.

The biological mechanism of the combination of PRP and exercise therapy involves PRP-derived grown factors that reduces inflammation, promotes tissue repair and enhance natural body healing process. Concurrently exercise improves muscle strength and joint function contributing to pain relief targeting the complex pathology of Knee OA, which affects the cartilage and the entire joint. The observed improvements in pain and inflammation may lead to a reduction in medical interventions, thereby lowering the risk of surgery and supporting the cost-effectiveness of this combined approach¹³⁾. By empowering patients to control their condition through non-invasive therapies, the long-term outcomes of OA management can be improved, offering a more sustainable approach to pain relief and the long-term preservation of joint function. Our findings align with those of previous studies demonstrating the efficacy of PRP in treating OA symptoms and achieving better WOMAC parameters, particularly in the early stages of cartilage degradation^{14, 15)}. Unsurprisingly, better outcomes were observed in younger patients with lower body mass index and low-grade OA¹⁶⁾.

Despite these promising results, this study has several limitations. More specifically, the small sample size may have reduced the statistical power, and the lack of a PRP classification¹⁷⁾ may have prevented a more thorough understanding of the treatment effects. Additionally, the short follow-up period limited our ability to assess the long-term sustainability of the observed improvements. Moreover, exercise therapy is associated with compliance challenges, which may have influenced the results in both groups. Further multicenter studies are required to address these limitations. Increasing the sample size, stratifying patients based on PRP type, and extending the follow-up period could provide a more comprehensive evaluation of the effectiveness of the proposed treatment.

The present study suggested that the combination of PRP and exercise therapy has the potential to improve the quality of life of patients with mild OA. However, further research is necessary to optimize PRP preparation protocols and refine exercise prescriptions tailored to individual patient needs. Establishing a unified PRP classification system is crucial before this treatment approach can be widely adopted in clinical practice.

Conflict of interest

The authors have no conflicts of interest to declare.