Osteoarthritis (OA) of the knee is a very common degenerative joint disease that causes pain, stiffness, and functional impairment. It is characterized by increasing articular cartilage disintegration, sub-chondral bone alterations, and synovial inflammation [1]. Specifically, a crucial window for non-surgical therapeutic therapies targeted at both symptomatic alleviation and postponing structural progression is represented by grades II and III (moderate) knee OA [2]. Interest in regenerative or proliferative injection techniques has been sparked by the short-term or mild effects of conventional intra-articular medications such corticosteroids and hyaluronic acid [3]. When administered intra-articularly, platelet-rich plasma (PRP), an autologous blood product enriched for platelets and related growth factors, may reduce inflammation, increase chondrocyte proliferation, and stimulate tissue repair-type responses [4]. In knee OA, meta-analyses indicate that PRP improves function and reduces pain more than hyaluronic acid or corticosteroids, especially after six to twelve months [5]. In order to induce a regulated inflammatory cascade that may promote healing and ligamentous or capsular tightness, another method called prolotherapy (often dextrose-based hyperosmolar solution) is injecting an irritating stimulus into the joint or peri-articular tissues [6]. Although prolotherapy has demonstrated improvements in knee OA pain, stiffness, and function, the quality of the evidence is still low, and patient selection and protocol standardization differ greatly [7]. There is a small but growing body of research comparing prolotherapy with PRP in knee OA. For instance, a recent meta-analysis indicated that PRP was better at reducing stiffness (mean difference 0.45; 95% CI 0.06–0.85; p=0.03), although there was no significant difference in discomfort at 6 months between dextrose prolotherapy and PRP [8]. Although the authors acknowledged that this was the first head-to-head study, a randomized placebo-controlled trial comparing PRP with prolotherapy in knee OA indicated that neither treatment achieved statistically significant superiority over placebo [9]. The aim of the study was to compare the efficacy and safety of intra-articular Platelet-Rich Plasma (PRP) versus Prolotherapy in patients with Grade 2 and 3 knee osteoarthritis and to assess their effects on pain relief and functional improvement.

Type of Study: A prospective interventional comparative study Place of Study: Department of Physical Medicine and Rehabilitation, Nil Ratan Sircar Medical College and Hospital, 138, Acharya Jagdish Chandra Bose Road, Sealdah, Kolkata, West Bengal, Pin Code: 700014, India. Study Duration: 1 year (from 1st November 2023 to 31st October 2024) Sample Size: 72 patients with Grade II & III knee osteoarthritis, PRP group (n=36) and Prolotherapy group (n=36) Inclusion Criteria: • Patients aged 40–70 years. • Diagnosed with primary knee osteoarthritis, confirmed by radiographs • Chronic knee pain for at least 3–6 months not responding adequately to conservative therapy Exclusion Criteria: • Patients with grade 1 or grade 4 osteoarthritis. • History of knee surgery or intra-articular injections. • Secondary osteoarthritis due to trauma, infection, or inflammatory arthritis. • Coagulopathy or use of anticoagulants. • Severe systemic illness Study Variables: • Age (years) • Sex (male/female) • Body Mass Index • Occupation / activity level • Duration of knee pain • Side of involvement Methods: Under ultrasound-guidance, in PRP group 6 ml of Autologous PRP (prepared from double centrifuge method) was injected intra-articularly, and in Prolotherapy group 6 ml of 25% Dextrose was injected intra-articularly. In both the groups, single injection was used. Statistical Analysis: Data were entered into Excel and subsequently analyzed using SPSS and GraphPad Prism. Continuous variables were summarized as means with standard deviations, while categorical variables were presented as counts and percentages. Comparisons between independent groups were performed using two-sample t-tests, and paired t-tests were applied for correlated (paired) data. Categorical data were compared using chi-square tests, with Fisher’s exact test applied when expected cell counts were small. A p-value of ≤ 0.05 was considered statistically significant.

Table 1 Baseline Demographic and Clinical Characteristics Parameter PRP Prolotherapy P value Age (years) 54.1 ± 7.8 53.6 ± 8.1 0.79 Sex (M/F) 14 / 22 15 / 21 0.82 BMI (kg/m²) 28.4 ± 3.6 28.7 ± 3.3 0.73 Duration of symptoms (months) 19.2 ± 5.6 18.8 ± 5.9 0.77 Kellgren–Lawrence Grade II / III 20 / 16 21 / 15 0.81 Baseline VAS 7.8 ± 0.9 7.7 ± 1.0 0.63 Baseline WOMAC (%) 61.5 ± 8.2 60.7 ± 8.4 0.72 Table 2 Pain Intensity (VAS Score, 0–10) Over Time Time Point PRP Group Prolotherapy Group P value Baseline 7.8 ± 0.9 7.7 ± 1.0 0.63 1 month 4.6 ± 1.0 5.3 ± 1.1 0.01 3 months 3.8 ± 0.9 5.1 ± 1.0 <0.001 6 months 3.5 ± 1.1 4.8 ± 1.2 <0.001 Table 3 WOMAC Score (0–100; Higher = Worse Function) Time Point PRP Group Prolotherapy Group P value Baseline 61.5 ± 8.2 60.7 ± 8.4 0.72 1 month 45.2 ± 7.5 50.4 ± 7.8 0.01 3 months 39.1 ± 7.0 48.3 ± 7.6 <0.001 6 months 36.5 ± 6.8 46.7 ± 7.2 <0.001 Table 4 Analgesic Requirement (Paracetamol Equivalent mg/day) Time Point PRP Group Prolotherapy Group P value Baseline 1280 ± 240 1260 ± 230 0.69 1 month 760 ± 210 950 ± 230 0.003 3 months 690 ± 200 910 ± 220 <0.001 6 months 670 ± 190 880 ± 210 <0.001 Table 5 Patient Satisfaction (5-Point Likert Scale) Time Point PRP Group Prolotherapy Group P value 1 month 4.0 ± 0.7 3.6 ± 0.8 0.02 3 months 4.2 ± 0.6 3.7 ± 0.7 0.004 6 months 4.3 ± 0.6 3.6 ± 0.8 <0.001 Table 6 Adverse Events Adverse Event PRP Group Prolotherapy Group P value Local pain/swelling 4 (11.1%) 5 (13.9%) 0.72 Mild stiffness (24–48h) 3 (8.3%) 4 (11.1%) 0.69 Synovitis (transient) 1 (2.8%) 2 (5.6%) 0.55 Infection 0 0 — Table 7 Global Assessment of Improvement at 6 Months Category PRP Group Prolotherapy Group P value Markedly improved 22 (61.1%) 10 (27.8%) 0.004 Moderately improved 10 (27.8%) 15 (41.7%) 0.22 Slightly improved 3 (8.3%) 8 (22.2%) 0.09 No change / worsened 1 (2.8%) 3 (8.3%) 0.3 Figure 1 Pain Intensity over Time In our study baseline demographic and clinical characteristics were comparable between the two groups. The PRP group (n=36) and Prolotherapy group (n=36) were similar in age (54.1 ± 7.8 vs 53.6 ± 8.1 years, p=0.79), sex distribution (M/F: 14/22 vs 15/21, p=0.82), and BMI (28.4 ± 3.6 vs 28.7 ± 3.3 kg/m², p=0.73). The duration of symptoms did not differ significantly (19.2 ± 5.6 vs 18.8 ± 5.9 months, p=0.77). Radiographic severity assessed by Kellgren–Lawrence grade (II/III: 20/16 vs 21/15, p=0.81) and baseline functional scores, including VAS (7.8 ± 0.9 vs 7.7 ± 1.0, p=0.63) and WOMAC (61.5 ± 8.2% vs 60.7 ± 8.4%, p=0.72). The VAS scores for pain decreased over time in both groups, with greater improvement observed in the PRP group. At baseline, pain levels were comparable (7.8 ± 0.9 vs 7.7 ± 1.0, p=0.63). At 1 month, the PRP group reported significantly lower pain than the Prolotherapy group (4.6 ± 1.0 vs 5.3 ± 1.1, p=0.01). This difference became more pronounced at 3 months (3.8 ± 0.9 vs 5.1 ± 1.0, p<0.001) and persisted at 6 months (3.5 ± 1.1 vs 4.8 ± 1.2, p<0.001). At baseline, scores were comparable (61.5 ± 8.2 vs 60.7 ± 8.4, p=0.72). At 1 month, the PRP group showed significantly better functional improvement than the Prolotherapy group (45.2 ± 7.5 vs 50.4 ± 7.8, p=0.01). This trend continued at 3 months (39.1 ± 7.0 vs 48.3 ± 7.6, p<0.001) and 6 months (36.5 ± 6.8 vs 46.7 ± 7.2, p<0.001). Baseline values were comparable (1280 ± 240 vs 1260 ± 230, p=0.69). At 1 month, the PRP group demonstrated significantly better improvement (760 ± 210 vs 950 ± 230, p=0.003), which further increased at 3 months (690 ± 200 vs 910 ± 220, p<0.001) and was sustained at 6 months (670 ± 190 vs 880 ± 210, p<0.001). At 1 month, the PRP group reported significantly greater satisfaction (4.0 ± 0.7 vs 3.6 ± 0.8, p=0.02), which persisted at 3 months (4.2 ± 0.6 vs 3.7 ± 0.7, p=0.004) and 6 months (4.3 ± 0.6 vs 3.6 ± 0.8, p<0.001). Local pain or swelling occurred in 4 of 36 patients (11.1%) in the PRP group and 5 of 36 patients (13.9%) in the Prolotherapy group (p=0.72), while transient mild stiffness was reported in 3 of 36 patients (8.3%) versus 4 of 36 patients (11.1%) (p=0.69). Synovitis was rare, occurring in 1 of 36 patients (2.8%) in the PRP group and 2 of 36 patients (5.6%) in the Prolotherapy group (p=0.55). n terms of patient numbers, 22 of 36 patients (61.1%) in the PRP group showed marked improvement versus 10 of 36 patients (27.8%) in the Prolotherapy group (p=0.004). Moderate improvement was seen in 10 of 36 patients (27.8%) versus 15 of 36 patients (41.7%) (p=0.22), and slight improvement occurred in 3 of 36 patients (8.3%) versus 8 of 36 patients (22.2%) (p=0.09). No change or worsening was noted in 1 of 36 patients (2.8%) in the PRP group compared to 3 of 36 patients (8.3%) in the Prolotherapy group (p=0.3).

We found that intra-articular PRP provided superior outcomes compared to Prolotherapy in patients with knee osteoarthritis. Baseline demographics and clinical characteristics, including age (54.1 ± 7.8 vs 53.6 ± 8.1 years, p=0.79), sex distribution (M/F: 14/22 vs 15/21, p=0.82), BMI (28.4 ± 3.6 vs 28.7 ± 3.3 kg/m², p=0.73), duration of symptoms (19.2 ± 5.6 vs 18.8 ± 5.9 months, p=0.77), Kellgren–Lawrence grade (II/III: 20/16 vs 21/15, p=0.81), VAS (7.8 ± 0.9 vs 7.7 ± 1.0, p=0.63), and WOMAC (61.5 ± 8.2 vs 60.7 ± 8.4, p=0.72) were comparable between groups. Over 6 months, PRP led to greater pain reduction (VAS: 3.5 ± 1.1 vs 4.8 ± 1.2, p<0.001), improved function (WOMAC: 36.5 ± 6.8 vs 46.7 ± 7.2, p<0.001), and higher objective functional scores (670 ± 190 vs 880 ± 210, p<0.001). Patient satisfaction was higher with PRP at 6 months (4.3 ± 0.6 vs 3.6 ± 0.8, p<0.001). Marked overall improvement was achieved in 22 of 36 patients (61.1%) versus 10 of 36 patients (27.8%) in the Prolotherapy group (p=0.004). Minor adverse events, including local pain, swelling (11.1% vs 13.9%, p=0.72), stiffness (8.3% vs 11.1%, p=0.69), and synovitis (2.8% vs 5.6%, p=0.55), occurred at similar rates. In similar study by These findings are consistent with prior studies showing superior efficacy of PRP over prolotherapy: Rahimzadeh P et al. (2018) reported greater pain and functional improvement with PRP [10]; Pishgahi A et al. (2020) found PRP and autologous conditioned serum more effective than dextrose prolotherapy [11]; Eroğlu A et al. (2017) demonstrated improvements with both PRP and prolotherapy, though PRP tended to show better outcomes [12]; and Singh SA et al. (2025) reported higher efficacy of PRP compared to 25% dextrose prolotherapy at 6 weeks follow-up [13]. Overall, these data support PRP as a more effective and safe intra-articular intervention for moderate knee osteoarthritis, providing faster and more sustained pain relief and functional improvement than prolotherapy.

We concluded that in 72 patients with Grade 2 and 3 knee osteoarthritis, we compared intra-articular PRP and Prolotherapy. PRP proved to be more effective in reducing pain and improving function. Age, sex, BMI, length of symptoms, Kellgren-Lawrence grade, VAS, and WOMAC scores were among the baseline parameters that were similar between groups, guaranteeing a fair comparison. Over the course of six months, PRP improved WOMAC scores, considerably reduced VAS, and increased patient satisfaction and objective functional ratings. In comparison to the Prolotherapy group, the PRP group showed a more noticeable overall improvement. Both treatments were safe, with comparable incidence of mild side effects like localized discomfort, enema, stiffness, and sinusitis. These results imply that PRP is a better and more tolerable treatment for mild osteoarthritis of the knee.

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