CMPH

Introduction

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of lower extremity disability among older adults [1]. It is associated with progressive joint degeneration and the inflammation of synovial spaces [2]. The prevalence of OA increases with advancing age and higher Body Mass Index (BMI) [3]. Approximately 12.1% of the US population between the ages of 25 and 74 has OA in one or more joints [4]. Recent data estimate that the prevalence of OA in the Middle East and North Africa is 24,604,611 (95% UI: 22,080,960–27,327,135), with 399,351 cases in Jordan (95% UI: 357,424-447,816); higher rates are observed among females, with knee OA accounting for the majority of cases [5].

OA causes a substantial loss of mobility and independence, contributing significantly to increased years lived with disability. The limitations resulting from OA impose a considerable economic burden on both patients and healthcare systems due to the need for ongoing management, including pharmacological therapy, physical rehabilitation, and, in advanced cases, joint replacement surgery. In this regard, Jordan—among other countries—experiences a higher-than-expected burden [5]. Since surgical intervention remains limited by accessibility and cost in many regions, and there is no definitive cure or proven structure-modifying interventions for OA, early diagnosis and effective non-surgical interventions are essential for managing OA and improving patients’ quality of life [5,6].

Many therapeutic agents, such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), opioids, and Intra-Articular (IA) injections (including platelet-rich plasma, corticosteroids, and hyaluronic acid), are used to manage OA. Due to contraindications or the risk of addiction, NSAIDs and opioids are not prescribed for all patients or for chronic use [7]. Patients who receive plateletrich plasma (PRP) injections are typically advised to discontinue NSAIDs during the treatment period. Previous studies, including one conducted by Schippinger et al., highlight the negative impact of NSAIDs on platelet function in individuals receiving PRP injections [8].

Non-pharmacological approaches such as exercise, lifestyle modification, and weight loss have been investigated, with some being strongly suggested as core interventions for managing OA; however, they are often not implemented in clinical practice. If conservative management fails and joint symptoms substantially impact patients’ quality of life, they are referred for surgical options [9].

PRP is a biological product derived from autologous blood obtained after centrifugation, which contains a higher-thanbaseline concentration of platelets suspended in a portion of the plasma fraction [10]. Platelets serve as a natural reservoir of growth factors, including platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor, plateletderived angiogenesis factor, insulin-like growth factor-1, platelet factor 4, platelet-derived angiogenic factor, and Transforming Growth Factor-beta (TGF-β) [10].

The average platelet count in healthy individuals’ blood is approximately 200,000/μl. Scientific evidence has demonstrated that platelet concentrations of approximately 1,000,000 platelets/ μl can enhance bone and soft tissue healing. Therefore, this concentration within a 5-ml volume of plasma is now considered the practical working definition of PRP [11]. Intra-articular plateletrich plasma (IA-PRP) injection has been shown to be beneficial for both early and advanced stages of knee osteoarthritis (KOA) [1214]. A single injection of PRP is reported to be as effective as two injections in early KOA [12]. When compared to corticosteroid and hyaluronic acid injections, IA-PRP injection has been reported to produce superior outcomes for the management of KOA [1517].

Aim

This retrospective study aims to evaluate the short-term effects of a single IA-PRP injection in patients with KOA. Despite growing international evidence regarding the potential benefits of PRP, findings across studies remain inconsistent, and data from Jordan are limited. The Jordanian population was chosen as a representative cohort of the Middle East, where such research is scarce. Clinical and psychological outcomes were evaluated three weeks post-injection using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Patient Health Questionnaire-9 (PHQ-9).

Methods

Study Design and Ethical Approval

This retrospective cohort study was conducted after obtaining approval from the Royal Medical Services Human Research Ethics Committee. The electronic medical database of the institution was reviewed to identify patients diagnosed with KOA who received their first IA-PRP injections between June 2024 and June 2025.

Patient Selection

Radiographic classification of KOA severity was done based on the Kellgren-Lawrence (K&L) grading system. Those with a K&L Grade of 2, 3, or 4 were included in the study, corresponding to mild, moderate, and severe KOA, respectively.

Patients with Grade 1 KOA were excluded because most of them declined the IA-PRP injection, preferring conservative pharmacological (NSAIDs or opioids) or non-pharmacological management. To minimize confounding, only patients who did not use NSAIDs, opioids, or any other medications apart from paracetamol during the study period were included, as these drugs may interfere with the healing process, pain assessment, and evaluation of treatment outcomes.

Eligible participants were required to complete both pre- and postinjection assessments, receive a single ultrasound-guided IA-PRP injection, and have no prior IA injections.

PRP Preparation and Injection Procedure

PRP was prepared from each patient’s autologous blood sample on the day of the procedure. The resulting PRP contained a platelet concentration at least five times higher than the patient’s baseline value. All injections were administered under ultrasound guidance by an experienced anaesthesiologist to ensure accurate IA delivery.

Outcome Measures

Patient outcomes were assessed before treatment and three weeks after IA-PRP injection using validated tools. The WOMAC questionnaire was used to evaluate the key outcomes of KOA. WOMAC is a standardized tool used to assess three main complications associated with KOA: pain (maximum score = 20), stiffness (maximum score = 8), and physical functions (maximum score = 68). The results of these three categories are summed to give a total WOMAC score out of 96. The WOMAC questionnaire is a copyrighted instrument; therefore, no individual items or questions are reproduced in this manuscript, and only aggregated subscale and total scores were analyzed [18]. PHQ-9 was used to assess psychological and depressive symptoms [19,20].

Patients’ data were collected only once—at the end of the third week following IA-PRP injection (first follow-up)—because beyond this period, nearly all participants began using additional analgesics other than paracetamol, introducing a confounding variable. Consequently, data collection beyond three weeks was rendered inconsistent and insufficient for meaningful analysis.

A one-way multivariate analysis of variance (MANCOVA) was used with a statistical power of 0.8, medium effect size, and alpha level set at 0.05. The required sample size was estimated at 40 patients per group.

This study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Statistics

Categorical data were expressed as mean, standard deviation, or median based on normality test; the frequency and percentage were used to represent categorical data. The Wilcoxon signedrank test was used to compare median differences in WOMAC pain, stiffness, function, total score, and depression score (PHQ-9) before and after IA-PRP injection. MANCOVA was used to assess mean differences in all outcome parameters during the post-test phase after controlling for baseline differences, age, and BMI. Cohen’s r and partial eta-squared effect sizes were reported for clinical importance. A p-value < 0.05 was deemed statistically significant. SPSS IBM software Version 28 was used to analyze the data.

Results

As shown in Table 1, 130 patients were included in the study, with a mean age of 64.21 (±11.66) and a BMI of 30.54 (±4.06). The majority of patients were female (53.8%) compared to male (46.2%). The distribution of participants across the three OA grades was nearly equal: Grade 2 (33.1%), Grade 3 (33.8%), and Grade 4 (33.1%). Half of the patients received bilateral injections.

Table 1: Patients’ demographics and clinical data.

The Wilcoxon signed-rank test was used to identify statistically significant median differences in WOMAC subscales (pain, stiffness, function, and total score) and PHQ-9 scores pre- and post- IA-PRP injection; the results are presented in Table 2. Additionally, the Benjamini–Hochberg method was utilized to control for type-1 error (False Discovery Rate). The results showed that the median WOMAC pain score decreased from 7 (pre-injection) to 3 (post-injection), demonstrating a statistically significant difference and a large effect size. Similar improvements were observed in the median scores of WOMAC stiffness (pre-injection 1 to post-injection 0), WOMAC function (pre-injection 17 to post-injection 8), WOMAC total (pre-injection 24 to post-injection 11), and PHQ-9 (pre-injection 4 to post-injection 1)—all showing statistically significant differences and large effect size.

Table 2: Wilcoxon signed- rank for median differences between pre and post plasma infiltration treatment.

MANCOVA was used to verify the presence of statistically significant differences in post-injection WOMAC pain, stiffness, function, total score, and PHQ-9 after controlling for age, BMI, and baseline differences (see Table 3). Statistically significant differences were observed in all outcomes, as determined by the Bonferroni post hoc test. Patients in Grade 3 had lower WOMAC pain, stiffness, function, and total score compared to those in Grade 4, while patients in Grades 2 and 3 had lower PHQ-9 scores compared to those in Grade 4. Partial eta-values indicated small to moderate effect sizes for WOMAC pain, stiffness, function, and total score, and a large effect size for PHQ-9.

Table 3: Comparing of post-test pain, stiffness, function, total WOMAC and depression score between OA grades after controlling age, BMI and baseline differences as covariates using MANCOVA.