Clinical Outcome of Intra-Articular Injection of Platelet Rich Plasma in Osteoarthritis Knee

Clinical Outcome of Intra-Articular Injection of Platelet Rich Plasma in Osteoarthritis Knee | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Outcome of Intra-Articular Injection of Platelet Rich Plasma in Osteoarthritis Knee Dr. Gaurav Bir Bajracharya, Prof. Dr. Shriraj Shrestha, Dr. Saurav Dahal, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6864842/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Introduction: Osteoarthritis (OA) of the knee is a prevalent condition that significantly impacts the quality of life for millions of individuals worldwide. As a leading cause of disability, its effective management is crucial. Intra-articular injections of platelet-rich plasma (PRP) have gained attention as a potential treatment, offering a biologic approach to enhance cartilage repair and reduce inflammation. This study evaluates the clinical efficacy of PRP injections in knee OA management, focusing on pain relief and functional improvement. Methods: The study involved 59 patients (61 knees) diagnosed with KL grade II and III knee OA who received PRP injections. Patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) scores. Evaluations were conducted at baseline and two, four, and six months post-injection to assess pain relief and functional improvement. Results: Significant reductions in VAS pain scores and WOMAC functional disability scores were observed following PRP therapy. Pain and stiffness improved notably within the first few months post-treatment, with KL grade II patients experiencing better outcomes than KL grade III patients. The study confirmed PRP’s effectiveness as a non-surgical intervention, with no severe adverse effects reported. Conclusion: PRP injections appear to be a viable regenerative treatment for knee OA, offering meaningful pain reduction and mobility enhancement. Although the initial benefits are significant, long-term efficacy remains uncertain, warranting further research. Establishing optimal patient selection criteria and repeated dosing protocols may enhance future outcomes. Osteoarthritis (OA) Knee pain Platelet-rich plasma (PRP) Joint function Cartilage repair Regenerative therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Osteoarthritis (OA) is a prevalent degenerative joint disorder, most commonly affecting the knee joint. Knee pain, the principle symptom of knee OA, leads to functional disability and is a leading cause of disability, particularly among the elderly, resulting in a decreased quality of life. 1 With increased lifespan and obesity, the prevalence of osteoarthritis is rising in the global population. It is estimated that 16% of individuals worldwide suffer from symptomatic knee OA. 2 Hip and knee OA rank among the top contributors to global disability, holding the 38th position in Disability-Adjusted Life Years (DALYs). The global age-standardized prevalence of knee OA is 3.8% with a higher prevalence in females than in males. 3 Similarly in Nepal, the prevalence of chronic knee pain was found to be 12.1%. 4 Osteoarthritis is a chronic disorder of synovial lined joints where there is progressive softening and disintegration of articular cartilage accompanied by the new growth of cartilage and bone at the joint margins, cyst formation, and sclerosis at subchondral regions of bone, mild synovitis, and capsular fibrosis. 5 Osteoarthritis differs from simple wear and tear in that it is asymmetrically distributed, often associated with abnormal loading rather than frictional wear. 6 It is not an inflammatory condition, although sometimes it can show signs of inflammation. In its most common form, osteoarthritis is unaccompanied by any systemic illness. Among many self-reported outcome measures, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) is one of the commonly used indexes for osteoarthritis patients. Higher scores represent greater limitations in function and more severe pain. 7 Despite technological advancements, radiography continues to be the most accessible method for evaluating knee osteoarthritis (OA). 8 The Kellgren and Lawrence (KL) classification is commonly employed to diagnose radiographic knee OA and assess its severity by examining osteophyte formation, joint space narrowing, and subchondral osteosclerosis. 9 This classification system is widely utilized in epidemiological studies on knee OA and was endorsed by the World Health Organization in 1961. 10 Current treatment approaches focus on symptom relief, improved function, and slowing disease progression. However, many modalities provide only short-term benefits and may carry side effects. As the search continues for effective alternatives, Platelet-Rich Plasma (PRP) therapy has emerged as a promising biologic intervention, harnessing autologous growth factors to stimulate cartilage repair and modulate inflammation. Among various growth factors present in PRP, some play crucial roles in OA management: Platelet-derived growth factor (PDGF) enhances collagen synthesis and cellular proliferation. Transforming growth factor-beta (TGF-β) promotes angiogenesis and reduces bone resorption. Vascular endothelial growth factor (VEGF) supports endothelial cell migration and vascular permeability. Epidermal growth factor (EGF) stimulates epithelial cell differentiation and mesenchymal cytokine secretion. Insulin-like growth factor (IGF) promotes cell growth, differentiation, and recruitment in bone, blood vessels, skin, and other tissues, stimulates collagen synthesis together with PDGF Fibroblast growth factor (FGF) promotes the proliferation of mesenchymal cells, chondrocytes, and osteoblasts, and stimulates the growth and differentiation of chondrocytes and osteoblasts. 11,12 Injecting PRP into the knee for osteoarthritis might prove to be the most effective, safe, and primary modality of treatment in the near future. Numerous studies highlight the effectiveness of PRP in treating knee osteoarthritis (OA). 13 However, some research presents conflicting results regarding its efficacy. There is significant controversy about the effectiveness of PRP in knee OA, and there are no definite guidelines about the amount, frequency, and timing of PRP injections for knee OA. Therefore, it is important to determine the effectiveness of PRP in osteoarthritis of the knee. The short-term effectiveness of PRP injections in managing knee osteoarthritis (OA) is well-documented in multiple reviews and studies. However, uncertainties remain regarding its long-term benefits. A direct comparative analysis between PRP and established treatments such as corticosteroids and hyaluronic acid could provide deeper insights into its sustained efficacy. Methods This prospective interventional study was conducted at the KIST Medical College and Teaching Hospital (KISTMCTH) from November 2022 to November 2023 after receiving ethical approval from the IRC-KISTMCTH dated November 17th, 2022, reference number 079/80/38. Clinical trial number: not applicable. Participants were selected based on the American College of Rheumatology (ACR) criteria for knee osteoarthritis (OA) diagnosis, with radiographic classification using Kellgren and Lawrence (KL) grading. Human Ethics and Consent to Participate : informed written consent was obtained from all human participants for the study. Patient Selection: The study recruited patients aged 50 years and older diagnosed with KL grade II and III knee OA through convenience sampling. Exclusion criteria included the use of pain medication, prior knee trauma, and loss to follow-up. A total of 59 patients (61 knees) were enrolled; bilateral cases were treated separately with at least a one-month interval between injections. Intervention Patients who met the inclusion criteria were selected for the study after signing the informed written consent to participate. 59 patients with 61 knees agreed to the study and were on regular follow-up. Before the PRP injection, thorough history, physical examination, pain assessment with the help of VAS score and WOMAC score, and X-ray of the affected knee were done along with platelet and RBS. Autologous PRP injection was prepared in the outpatient department by harvesting 16 ml of the patient’s venous blood from the cubital vein in 2 separate sodium citrate and gel-containing vacutainers as shown in figure 1 A. These vacutainers, are readily accessible in our hospital and filled up to their designated marking. Then the PRP machine (REMI PRP ULTRA, model ZICU-10151) was precooled without the whole blood. Speed, time, and temperature were pre-programmed: speed = 2500 rpm, time = 6 min, and temperature = +18 degrees Celsius. After the device was pre-cooled, the whole blood collected in two vacutainers placed across was centrifuged in two steps, first at a lower rate of 2700 rpm for male and 2600 for female for 12 min. After the first spin step, gel separates the whole blood into RBC and plasma. Then the second centrifugation was done for this vacutainer at 3200 rpm for 7 mins to get a higher concentration of platelets at the bottom as shown in figure 1C. 14 From this centrifuged test tube, the lower part of platelet-rich plasma (5 ml, i.e., controlled 2.5 ml from each tube) was isolated and collected using a 10 ml sterile syringe. Injection protocol : The injection procedure took place in the procedure room of OPD. The patient was positioned supine on the bed with knee flexed to 70 deg and the relevant areas were cleaned and covered with sterile drapes. 5 ml of this PRP was injected using an 18 G needle via an inferolateral approach into the involved knee joint. The position of the needle tip in the knee joint is confirmed by aspiration and the smooth passage of PRP into the knee joint without resistance. The whole process of separating and injecting platelet-rich plasma was done under strict aseptic precautions. The patient’s baseline platelet count was determined. The concentration of platelets in the final product was corroborated by the blood bank periodically. Post-injection, all the patients were prescribed ice fomentation locally along with a range of motion exercises (physiotherapy). The patients were advised to avoid NSAIDs for 2 days before and after injection. Paracetamol in a dose of 500 mg was allowed in case of febrile illness or discomfort due to pain. All the procedures were performed by a trained orthopedic surgeon. Pain was assessed using the VAS (0-10 cm scale) and functional limitations using the WOMAC index. Weight-bearing plain X-rays were obtained for KL grading. Assessments were performed at baseline and at 2-, 4-, and 6-months post-injection. Data were analyzed using SPSS version 16. Descriptive statistics were calculated. Repeated measures ANOVA was used for multiple comparisons, and paired t-tests for pairwise comparisons. A p-value < 0.05 was considered statistically significant. Results A total of 59 patients (61 knees) were included in the study. The mean age was 59.54 ± 8.318 years (range 50-82 years). There were 42 females (68.9%) and 19 males (31.1%). The right knee was involved in 32 (52.5%) patients and left in 29 (47.5%) patients as shown by figure 2. The mean duration of pain was 27.36 months (range 1-120 months) with mean duration of pain in male was 29.26 month and in female was 26.45 month as shown by figure 3. The distribution of KL grades was: KL grade II (n=40, 65.6%) and KL grade III (n=21, 34.4%) with age specific KL grade as shown in table 1. Table 1: Relation of Age category (in years) and KL grade Distribution AGE CATEGORY Total 50 - 59 60 - 69 70 - 79 80+ KL GRADE II 27 11 2 0 40 III 7 8 4 2 21 Total 34 19 6 2 61 The mean VAS score at pre-injection was 7.21 ± 0.951. Significant reductions in VAS scores were observed at 2 months (5.97 ± 0.894, p<0.01), 4 months (4.82 ± 0.940, p<0.01), and 6 months (3.82 ± 1.057, p<0.01) post-injection. (Table 2, Figure 4)' Table 2: Pairwise comparisons between VAS score at pre-injection, 2 months, 4 months, and 6 months. Mean SD P value Pair 1 VAS SCORE (PRE-INJECTION) 7.21 .951 <0.01 VAS SCORE (2MONTH) 5.96 .894 Pair 2 VAS SCORE (2MONTH) 5.96 .894 <0.01 VAS SCORE (4MONTH) 4.82 .940 Pair 3 VAS SCORE (4MONTH) 4.82 .940 <0.01 VASCORE (6MONTH) 3.82 1.057 Pair 4 VAS SCORE (PRE-INJECTION) 7.21 .951 <0.01 VASCORE (6MONTH) 3.82 1.057 The mean WOMAC score at baseline was 72.89 ± 5.007. Significant improvements were also observed at 2 months (62.84 ± 7.921, p<0.01), 4 months (50.97 ± 9.699, p<0.01), and 6 months (39.49 ± 11.346, p<0.01) post-injection (Table 3, Figure 5). Table 3: Pairwise comparisons between WOMAC score at pre injection, 4MONTH, 4 month and 6 months. Mean SD P value Pair 1 WOMAC SCORE (PREINJECTION) 72.89 5.007 <0.01 WOMAC SCORE (2MONTH) 62.84 7.921 Pair 2 WOMAC SCORE (2MONTH) 62.84 7.921 <0.01 WOMAC SCORE (4MONTH) 50.97 9.699 Pair 3 WOMAC SCORE (4MONTH) 50.97 9.699 <0.01 WOMAC SCORE (6MONTH) 39.49 11.346 Pair 4 WOMAC SCORE (PREINJECTION) 72.89 5.007 <0.01 WOMAC SCORE (6MONTH) 39.49 11.346 Patients aged 50-59 years showed the greatest improvement in both VAS and WOMAC scores. Older patients (80+ years) showed the least improvement. Patients didn’t report any serious adverse effects. However, 9 patients (9 knees) experienced pain at the injection site as a side effect requiring oral analgesic (Paracetamol) for pain relief. The incidence of injection site pain varied across different age groups: 11.7% in the 50-59 age group, 15.7% in the 60-69 age group, and 33.33% in the 70-79 age group, with no reports of pain in the 80+ age group. (Table 4) Table 4: Side effect according to age category. AGE CATEGORY Total 50 - 59 60 - 69 70 - 79 80+ SIDE EFFECTS NO 30 16 4 2 52 PAIN 4 (11.7%) 3 (15.7 %) 2 (33.33%) 0 (0 %) 9 Total 34 19 6 2 61 Discussion Osteoarthritis (OA) is one of the most common degenerative joint disorders, primarily affecting synovial joints. It is characterized by a progressive loss of hyaline cartilage, the formation of new bone structures known as osteophytes, and significant alterations in joint morphology. The etiology of OA involves a complex interplay between mechanical, biological, and biochemical factors, leading to an imbalance between cartilage degradation and repair mechanisms. This imbalance can be exacerbated by joint injuries, obesity, aging, and genetic predisposition. The pathophysiology of OA is driven by both inflammatory and non-inflammatory pathways, which together contribute to the breakdown of articular cartilage and the development of synovitis. Inflammatory cytokines, including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), play crucial roles in initiating and perpetuating the catabolic processes that lead to cartilage destruction, synovial inflammation, and chronic pain. Oxidative stress and metabolic alterations have also been implicated in OA progression, highlighting the multifactorial nature of this disease. These findings underscore the need for a multifaceted therapeutic approach that targets both the biochemical and biomechanical aspects of OA. 13 , 15 In our study, we evaluated the effectiveness of intra-articular Platelet-Rich Plasma (PRP) injections in patients diagnosed with Kellgren-Lawrence (KL) grade II and III knee osteoarthritis. The clinical outcomes were measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Visual Analog Scale (VAS) scores, which are well-established tools for assessing pain and functional limitations in OA patients. PRP has gained attention for its potential to promote cartilage repair and modulate inflammation due to its high concentration of growth factors. Our findings demonstrated significant improvements in both pain and functional outcomes over a three-month follow-up period, as evidenced by reductions in VAS and WOMAC scores. While these results are in line with several existing studies, we also observed some unique variations worth discussing. Patient Demographics Our study included 59 patients (61 knees) aged 50 years and older, all of whom had knee pain attributed to OA and were treated with PRP therapy. The mean age of participants was 59.54 ± 8.318 years, with the majority (55.7%) falling within the 50–59 age range. This age distribution aligns with previous findings that suggest PRP therapy tends to be more effective in younger patients with less severe OA, likely due to their greater regenerative potential. This observation is consistent with the conclusions of Filardo et al. (2010), who reported that younger individuals and those with early-stage degenerative changes showed better therapeutic responses to PRP. 16 Furthermore, a study by Chu et al. (2021) demonstrated that younger patients had more favorable outcomes, which might be attributed to their relatively intact cartilage and enhanced capacity for tissue repair. 17 A notable observation in our study was the predominance of female participants, who made up 68.9% of the cohort. This female predominance is consistent with the general epidemiology of OA, which tends to affect women more frequently, especially post-menopause. Hormonal changes, particularly estrogen deficiency, have been linked to accelerated cartilage degradation and increased susceptibility to OA in women. Previous studies, including those by Patel et al. (2013) and Kon et al. (2011), have also highlighted that women are disproportionately affected by OA due to a combination of hormonal, anatomical, and biomechanical factors. 18 , 19 Specifically, estrogen plays a protective role in cartilage health, and its decline during menopause may contribute significantly to the progression of OA in females. Laterality and Pain Duration In terms of laterality, our study revealed that 52.5% of patients experienced pain in the right knee, while 47.5% reported pain in the left knee. Interestingly, when examining gender-specific differences, we found that more males experienced right knee pain (14 vs. 5), while females had a higher prevalence of left knee pain (24 vs. 18). These findings may reflect underlying biomechanical and anatomical differences between genders, as suggested by previous literature. Zhang et al. (2010) reported that symptomatic knee OA affects approximately 10% of men and 13% of women aged 60 years or older in the United States, highlighting a higher prevalence of OA in women, which is consistent with our observation of a female predominance in knee pain cases. The authors attribute the gender differences in OA prevalence to factors like age, obesity, and joint injuries, which may also influence laterality and pain severity. The pain duration among participants in our study ranged from 1 to 120 months, with a mean duration of 27.33 months. Males reported a slightly longer average pain duration (29.26 months) compared to females (26.45 months), which may be indicative of differences in pain tolerance and healthcare-seeking behavior between genders. This observation aligns with Zhang et al.'s emphasis on the role of age and gender in OA progression, where men often delay seeking medical attention, leading to longer pain durations and potentially more severe symptoms by the time of diagnosis. The literature also highlights the growing prevalence of OA due to aging populations and the obesity epidemic, both of which are crucial factors influencing pain duration and severity in affected individuals. 20 Kellgren-Lawrence Grading The majority of our study's participants were classified as KL grade II (65.6%), with the remainder (34.4%) falling under KL grade III. This distribution highlights a focus on patients in the moderate stages of OA, where PRP therapy has been reported to be most beneficial. Patients with KL grade II OA had a mean age of 57.33 years, whereas those with KL grade III were older, with a mean age of 63.76 years. This trend aligns with the natural history of OA, where the severity of joint degeneration increases with age. Jati et al. (2021) also observed a similar age distribution in their study and concluded that PRP is particularly effective in the early to moderate stages of OA. 21 This aligns with our findings, where KL grade II patients generally showed better outcomes than those with grade III, though both groups demonstrated significant improvements over time. Pain and Function Improvement Our study's analysis of VAS scores revealed a marked reduction in pain over time. The baseline VAS score of 7.21 decreased to 5.97 at one month, 4.82 at two months, and 3.82 at three months. These results indicate substantial pain relief in a relatively short period, suggesting that PRP injections can effectively manage OA pain. When comparing KL grade II and III patients, we found that KL grade II individuals experienced slightly greater improvements in VAS scores (from 7.25 to 3.72) compared to those with KL grade III (from 7.14 to 4). These findings are consistent with the work of Campbell et al. (2015), who demonstrated that PRP significantly improves pain and functional outcomes, particularly in early-stage OA. 13 Further supporting our results, Upadhyay et al. (2024) reported a decrease in the mean VAS score from 6.80 pre-injection to 3.00 at six months post-injection. While our follow-up period was shorter (three months), the observed pattern of pain reduction aligns well with their findings, highlighting the potential of PRP as a short-term therapeutic option for knee OA. 22 Our study's early and significant pain relief further emphasizes that even a single PRP injection can provide notable benefits, reducing the need for multiple interventions. In terms of functional improvement, the WOMAC score also showed significant progress, decreasing from a baseline mean of 72.89 ± 5.007 to 39.49 ± 11.346 at three months. Patients with KL grade II had a greater reduction in WOMAC scores (from 72.53 to 38.65) compared to those with KL grade III (from 73.57 to 41.1). This reinforces the notion that PRP is more effective in treating the early stages of OA, potentially due to better cartilage integrity and a more robust healing response. Repeated ANOVA results demonstrated a statistically significant change in WOMAC scores over time, with a p-value < 0.01, supporting the observed improvements. Our findings correlate well with previous studies. For instance, Upadhyay et al. (2024) observed a similar decline in WOMAC scores from 72.7 pre-injection to 34.7 over six months. 22 Similarly, Patel et al. (2013) reported significant improvements in both pain and physical function with PRP treatment, as measured by the WOMAC index. These findings are mirrored in our study’s outcomes. 18 Additionally, Jati et al. (2021) found that PRP was more effective in early stages (KL II) than in advanced OA (KL III). In their study, the mean WOMAC score in KL II patients improved from 57.11 to 22.11 over six months, whereas KL III patients showed improvement from 59.21 to 32.12. 21 Although our follow-up period was shorter (three months), the trend of greater improvement in early-stage OA is consistent with these results. These consistent results across different studies highlight PRP’s efficacy in improving OA-related symptoms and enhancing patients’ quality of life. Age-based analysis showed that patients aged 50–59 had the greatest reduction in both VAS and WOMAC scores, while older patients, particularly those aged 80+, showed the least improvement. For instance, the VAS score for patients aged 50–59 dropped from 7.18 to 3.68, while for patients aged 80+, it only decreased from 8 to 5. This suggests that younger patients respond better to PRP treatment, likely due to better regenerative potential, as noted by Chu et al. (2021). 17 Similarly, the WOMAC score in the 50–59 age group decreased from 73.35 to 38.12, showing greater improvement compared to the 80 + age group (WOMAC: 75 to 49.5). Comparison with Other Studies The results of our study align well with the broader literature on PRP efficacy for knee OA. In particular: Patel et al. (2013): Their research demonstrated significant improvements in both WOMAC and pain scores following a single PRP injection, suggesting that even one injection can yield substantial clinical benefits. 18 This observation is consistent with our study's findings, where a single PRP injection led to sustained pain and function improvements over three months. Giuseppe Filardo (2010): Filardo's study indicated that PRP provides short-term pain relief and functional improvement, particularly in younger patients with milder OA, aligning with our study's age-related outcomes. Both studies highlight the transient nature of PRP's effects, noting that its benefits often decrease over time. While our study's follow-up was limited to three months, making it difficult to assess long-term effects, Filardo observed that the improvements in pain and function began to plateau after the three-month. 16 . Khoshbin et al. (2013): In their review, Khoshbin et al. found that PRP was superior to hyaluronic acid (HA) in improving functional scores such as WOMAC. This aligns with the significant improvements we observed in WOMAC scores in our study over the three-month period. However, while Khoshbin et al. noted significant enhancements in WOMAC scores, they did not observe major differences in VAS scores. In contrast, our study suggests that PRP may also provide notable short-term pain reduction, as reflected by the significant decrease in VAS scores during the same period. 23 Bennell et al. (2021): This randomized trial highlighted a lack of significant long-term differences between PRP and placebo in terms of pain relief, pointing towards PRP's short-term benefits rather than long-term efficacy. 24 Our study's focus on a three-month follow-up period is in agreement with these short-term positive outcomes. Adverse Effects and Safety Our study found that PRP injections were generally well-tolerated, with minimal side effects reported among participants. Nine patients / nine knees (14.8%) required oral analgesics (Paracetamol) for pain relief following the procedure, but no severe adverse reactions were noted. Interestingly, the incidence of injection site pain varied across different age groups: 11.7% in the 50–59 age group, 15.7% in the 60–69 age group, and 33.33% in the 70–79 age group, with no reports of pain in the 80 + age group. This trend suggests that younger patients might have a higher pain tolerance or a different inflammatory response to PRP injections. These findings are consistent with the existing literature, including the study by Filardo et al. (2010), which also reported minimal adverse effects associated with PRP therapy, reinforcing its safety profile. 16 However, studies like Campbell et al. (2015) have cautioned about increased local reactions with multiple PRP injections, which our study avoided by focusing solely on single-injection therapy. 13 This approach supports the notion that limited PRP use can minimize adverse effects while still providing therapeutic benefits. Future Directions While our study's short-term results with PRP injections are promising, the long-term efficacy of this treatment remains uncertain. Research by Kon et al. (2011) and Tucker et al. (2021) suggests that although PRP is effective in the short to medium term, its benefits may diminish over time, particularly in patients with more advanced stages of OA. 19 , 25 Future studies should focus on exploring the long-term outcomes of repeated PRP injections and investigate whether different formulations, such as leukocyte-rich or leukocyte-poor PRP, yield varying results. Additionally, personalized treatment protocols based on factors like age, Kellgren-Lawrence (KL) grade, and comorbidities should be developed to optimize therapeutic outcomes. Since our study specifically focused on patients with KL grade II and III OA, future research should aim to identify the patient subgroups that derive the most benefit from PRP therapy and determine its efficacy in more advanced stages, such as KL grade IV OA, where treatment success is less certain according to studies by Khoshbin et al. (2013) and Jati et al. (2021) 21 , 23 Limitations Intra-observer and inter-observer variability in evaluating the grades of KL grading The study was conducted at a single center with a small sample size and over a limited period, which may not be sufficient to generalize the results to the broader population. Therefore, further research with larger sample sizes and long-term follow-up is necessary to confirm the findings. The study did not compare PRP with other treatment modalities such as hyaluronic acid or corticosteroid injections. So better evaluation of the efficacy of PRP was not possible. Additionally, long-term follow-up using MRI is needed to assess cartilage regeneration. Conclusion Intra-articular PRP injections have shown to be an effective short-term treatment for reducing pain and improving function in patients with knee osteoarthritis, as evidenced by significant improvements in WOMAC and VAS scores. Our study, which involved injecting a highly concentrated mix of platelets into the joint cavity, consistently demonstrated reductions in pain and stiffness, along with clear improvements in patients’ quality of life. These findings align with broader literature supporting PRP use, particularly in early-stage osteoarthritis. However, further extended follow-up, additional randomized trials comparing PRP with corticosteroids and hyaluronic acid are necessary to establish its long-term efficacy and optimal usage guidelines. Abbreviations OA – Osteoarthritis PRP – Platelet-Rich Plasma KL – Kellgren and Lawrence (grading system for knee osteoarthritis) VAS – Visual Analogue Scale WOMAC – Western Ontario and McMaster Universities Arthritis Index DALYs – Disability-Adjusted Life Years ACR – American College of Rheumatology PDGF – Platelet-Derived Growth Factor TGF-β – Transforming Growth Factor-Beta VEGF – Vascular Endothelial Growth Factor EGF – Epidermal Growth Factor IGF – Insulin-like Growth Factor FGF – Fibroblast Growth Factor NSAIDs – Non-Steroidal Anti-Inflammatory Drugs MRI – Magnetic Resonance Imaging Declarations Ethics approval and consent to participate Ethics approval and consent to participate This study was conducted at KIST Medical College and Teaching Hospital (KISTMCTH) from November 2022 to November 2023, after receiving ethical approval from IRC-KISTMCTH on November 17, 2022 (Reference number: 079/80/38). All procedures performed in this study adhered to the Declaration of Helsinki guidelines to ensure ethical compliance. Informed written consent was obtained from all participants prior to their inclusion in the study. Patients were thoroughly briefed on the study objectives, potential risks, and benefits before signing the consent form. Consent for publication Not applicable. This study does not involve identifiable personal data, image Availability of data and materials The dataset supporting the findings of this study is provided as an additional file accompanying this manuscript. Further inquiries regarding the data can be directed to the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors' contributions Dr. Gaurav Bir Bajracharya (A): Conceptualization, Methodology, Data and information collection, Writing original draft, Review and editing Prof. Dr Shriraj Shrestha: Writing – Review and editing Dr Saurav Dahal: Writing – Review and editing Dr Suman Maharjan: Writing – Review and editing Acknowledgements I wish to extend my deep appreciation to Professor Dr. Shriraj Shrestha, from the Department of Orthopaedics at Kist Medical College and Teaching Hospital, for his unwavering guidance, encouragement, and continuous support throughout the entire duration of this endeavor. Without his invaluable assistance, this undertaking would not have come to fruition. I am equally grateful to Dr. Saurav Dahal a respected teacher and co-guide, who serves as a Lecturer in the Department of Orthopaedics. His consistent support, guidance, and motivation have been instrumental in shaping the course of this research. Furthermore, I extend my heartfelt thanks to all the esteemed faculty members of the Department of Orthopaedics at Kist Medical College and Teaching Hospital. Their consistent encouragement and support have been pivotal in the progression of my research. I am also indebted to my colleagues, Dr. Kushal Shah and Dr. Suraj Shakya, and juniors for their unwavering assistance in data collection for the thesis. My sincere gratitude extends to the patients who willingly participated in this study, as their cooperation and consent were essential for completing this work. I would also like to express my sincere gratitude to my parents Prof. Dr. Gautam Bir Bajracharya and Mrs. Tara Devi Bajracharya, and brother Dr. Bikram Bir Bajracharya, who have always supported me and provided continuous encouragement throughout my years of study. References Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet (London, England). 2019 Apr 27;393(10182):1745–59. Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. 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Int J Rheum Dis. 2019 Oct 1;22(10):1877–83. Braun HJ, Gold GE. Diagnosis of Osteoarthritis: Imaging. Bone. 2012 Aug;51(2):278. Kellgren JH, Lawrence JS. RADIOLOGICAL ASSESSMENT OF OSTEO-ARTHROSIS. Ann rheum Dis. 1957;494. Schiphof D, Boers M, Bierma-Zeinstra SMA. Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis. 2008 Jul 1;67(7):1034–6. Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet Rich Plasma: A short overview of certain bioactive components. Open Med. 2016 Aug 1;11(1):242–7. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020 Oct 2;21(20):1–36. Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR, et al. Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared with Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses. Arthrosc - J Arthrosc Relat Surg. 2015 Nov 1;31(11):2213–21. Gupta V, Parihar AS, Pathak M, Sharma VK. Comparison of Platelet-Rich Plasma Prepared Using Two Methods: Manual Double Spin Method versus a Commercially Available Automated Device. Indian Dermatol Online J. 2020 Jul 1;11(4):575–9. Lin X, Zhi F, Lan Q, Deng W, Hou X, Wan Q. Comparing the efficacy of different intra-articular injections for knee osteoarthritis: A network analysis. Med (United States). 2022 Aug 5;101(31):E29655. Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):528–35. Chu J, Duan W, Yu Z, Tao T, Xu J, Ma Q, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. 2022 Dec 1;30(12):4063–71. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013 Feb;41(2):356–64. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis. Arthrosc - J Arthrosc Relat Surg. 2011;27(11):1490–501. Zhang Y, Jordan JM. Epidemiology of Osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355. Jati S, Bansal H, Garg A J. To Evaluate the Functional Outcome of Platelet Rich Plasma Therapy in Osteoarthritis of Knee | Orthopaedic Journal of M. P. Chapter. 2021. Upadhyay V, Ambhure K, Mittal S. EFFICACY OF AUTOLOGOUS PLATELET-RICH PLASMA INJECTION IN KNEE OSTEOARTHRITIS. 2024;753–9. Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D, et al. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: A systematic review with quantitative synthesis. Arthrosc - J Arthrosc Relat Surg. 2013 Dec 1;29(12):2037–48. Bennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021 Nov;326(20). Tucker JD, Goetz LL, Duncan MB, Gilman JB, Elmore LW, Sell SA, et al. Randomized, Placebo-Controlled Analysis of the Knee Synovial Environment Following Platelet-Rich Plasma Treatment for Knee Osteoarthritis. PM&R. 2021 Jul 1;13(7):707–19. Additional Declarations No competing interests reported. Supplementary Files StudyDataset.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Mar, 2026 Reviews received at journal 21 Mar, 2026 Reviewers agreed at journal 11 Mar, 2026 Reviewers agreed at journal 06 Mar, 2026 Reviews received at journal 05 Dec, 2025 Reviewers agreed at journal 05 Dec, 2025 Reviews received at journal 31 Aug, 2025 Reviewers agreed at journal 26 Aug, 2025 Reviewers agreed at journal 21 Aug, 2025 Reviewers invited by journal 21 Jul, 2025 Editor invited by journal 18 Jul, 2025 Editor assigned by journal 20 Jun, 2025 Submission checks completed at journal 19 Jun, 2025 First submitted to journal 19 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Bajracharya","email":"data:image/png;base64,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","orcid":"","institution":"KIST Medical College","correspondingAuthor":true,"prefix":"Dr.","firstName":"Gaurav","middleName":"Bir","lastName":"Bajracharya","suffix":""},{"id":488663355,"identity":"69185fad-9d72-4b1b-93ec-a28eba11440b","order_by":1,"name":"Prof. Dr. Shriraj Shrestha","email":"","orcid":"","institution":"KIST Medical 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15:53:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6864842/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6864842/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87664939,"identity":"4d3a608d-a665-40b1-9c9f-898950a1cb04","added_by":"auto","created_at":"2025-07-27 11:01:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60475,"visible":true,"origin":"","legend":"\u003cp\u003ePRP preparation\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/0321f447dd765d50e7baa23d.jpg"},{"id":87664940,"identity":"e3ace594-df14-45c0-8a44-7b825a769168","added_by":"auto","created_at":"2025-07-27 11:01:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38684,"visible":true,"origin":"","legend":"\u003cp\u003eBar diagram showing number of patients with knee pain on either the right or left side, categorized by gender.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/a529a92574d195b0719ae3c8.jpg"},{"id":87664942,"identity":"058a970e-83c6-463c-a60e-5911158502d7","added_by":"auto","created_at":"2025-07-27 11:01:12","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44100,"visible":true,"origin":"","legend":"\u003cp\u003eBar diagram showing mean duration of pain on the basis of gender\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/b76397f62d03a894ab08305f.jpg"},{"id":87664946,"identity":"1207bda9-86ba-491c-95e0-f0fb6317f5e4","added_by":"auto","created_at":"2025-07-27 11:01:12","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":63578,"visible":true,"origin":"","legend":"\u003cp\u003eVAS score according to KL grade\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/f6ac1b5ad3635d20394b40fe.jpg"},{"id":87664948,"identity":"d589273d-dac9-46f3-ba7e-9dc571770d90","added_by":"auto","created_at":"2025-07-27 11:01:12","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":55660,"visible":true,"origin":"","legend":"\u003cp\u003eWOMAC score according to KL grade\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/8b6ec933340412fb9d6a0be6.jpg"},{"id":87666277,"identity":"cf8f3446-17b0-4cdd-9d99-16ada9fbc46f","added_by":"auto","created_at":"2025-07-27 11:17:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":972627,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/37e7ea0a-d95c-4968-99a1-bdf0c43651cf.pdf"},{"id":87666276,"identity":"1003b70e-8a9d-4088-9360-dd77325232e0","added_by":"auto","created_at":"2025-07-27 11:17:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":46289,"visible":true,"origin":"","legend":"","description":"","filename":"StudyDataset.docx","url":"https://assets-eu.researchsquare.com/files/rs-6864842/v1/4fa12a0deacd9a1fa3cd3bb9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical Outcome of Intra-Articular Injection of Platelet Rich Plasma in Osteoarthritis Knee\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoarthritis (OA) is a prevalent degenerative joint disorder, most commonly affecting the knee joint. Knee pain, the principle symptom of knee OA, leads to functional disability and is a leading cause of disability, particularly among the elderly, resulting in a decreased quality of life.\u003csup\u003e1\u003c/sup\u003e With increased lifespan and obesity, the prevalence of osteoarthritis is rising in the global population. It is estimated that 16% of individuals worldwide suffer from symptomatic knee OA.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHip and knee OA rank among the top contributors to global disability, holding the 38th position in Disability-Adjusted Life Years (DALYs).\u0026nbsp;The global age-standardized prevalence of knee OA is 3.8% with a higher prevalence in females than in males.\u003csup\u003e3\u003c/sup\u003e Similarly\u0026nbsp;in Nepal, the prevalence of chronic knee pain was found to be 12.1%.\u0026nbsp;\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eOsteoarthritis is a chronic disorder of synovial lined joints where there is progressive softening and disintegration of articular cartilage accompanied by the new growth of cartilage and bone at the joint margins, cyst formation, and sclerosis at subchondral regions of bone, mild synovitis, and capsular fibrosis.\u003csup\u003e5\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOsteoarthritis differs from simple wear and tear in that it is asymmetrically distributed, often associated with abnormal loading rather than frictional wear.\u003csup\u003e6\u003c/sup\u003e It is not an inflammatory condition, although sometimes it can show signs of inflammation. In its most common form, osteoarthritis is unaccompanied by any systemic illness.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong many self-reported outcome measures, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) is one of the commonly used indexes for osteoarthritis patients. Higher scores represent greater limitations in function and more severe pain. \u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eDespite technological advancements, radiography continues to be the most accessible method for evaluating knee osteoarthritis (OA).\u003csup\u003e8\u003c/sup\u003e The Kellgren and Lawrence (KL) classification is commonly employed to diagnose radiographic knee OA and assess its severity by examining osteophyte formation, joint space narrowing, and subchondral osteosclerosis.\u003csup\u003e9\u003c/sup\u003e This classification system is widely utilized in epidemiological studies on knee OA and was endorsed by the World Health Organization in 1961.\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eCurrent treatment approaches focus on symptom relief, improved function, and slowing disease progression. However, many modalities provide only short-term benefits and may carry side effects. As the search continues for effective alternatives, Platelet-Rich Plasma (PRP) therapy has emerged as a promising biologic intervention, harnessing autologous growth factors to stimulate cartilage repair and modulate inflammation.\u003c/p\u003e\n\u003cp\u003eAmong various growth factors present in PRP, some play crucial roles in OA management:\u003c/p\u003e\n\u003col style=\"list-style-type: lower-roman;\"\u003e\n \u003cli\u003ePlatelet-derived growth factor (PDGF) enhances collagen synthesis and cellular proliferation.\u003c/li\u003e\n \u003cli\u003eTransforming growth factor-beta (TGF-\u0026beta;) promotes angiogenesis and reduces bone resorption.\u003c/li\u003e\n \u003cli\u003eVascular endothelial growth factor (VEGF) supports endothelial cell migration and vascular permeability.\u003c/li\u003e\n \u003cli\u003eEpidermal growth factor (EGF) stimulates epithelial cell differentiation and mesenchymal cytokine secretion.\u003c/li\u003e\n \u003cli\u003eInsulin-like growth factor (IGF) promotes cell growth, differentiation, and recruitment in bone, blood vessels, skin, and other tissues, stimulates collagen synthesis together with PDGF\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFibroblast growth factor (FGF) promotes the proliferation of mesenchymal cells, chondrocytes, and osteoblasts, and stimulates the growth and differentiation of chondrocytes and osteoblasts. \u003csup\u003e11,12\u003c/sup\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eInjecting PRP into the knee for osteoarthritis might prove to be the most effective, safe, and primary modality of treatment in the near future. Numerous studies highlight the effectiveness of PRP in treating knee osteoarthritis (OA).\u003csup\u003e13\u003c/sup\u003e However, some research presents conflicting results regarding its efficacy. There is significant controversy about the effectiveness of PRP in knee OA, and there are no definite guidelines about the amount, frequency, and timing of PRP injections for knee OA. Therefore, it is important to determine the effectiveness of PRP in osteoarthritis of the knee.\u003c/p\u003e\n\u003cp\u003eThe short-term effectiveness of PRP injections in managing knee osteoarthritis (OA) is well-documented in multiple reviews and studies. However, uncertainties remain regarding its long-term benefits. A direct comparative analysis between PRP and established treatments such as corticosteroids and hyaluronic acid could provide deeper insights into its sustained efficacy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective interventional study was conducted at the KIST Medical College and Teaching Hospital (KISTMCTH) from November 2022 to November 2023 after receiving ethical approval\u0026nbsp;from the IRC-KISTMCTH dated November 17th, 2022, reference number 079/80/38. Clinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003eParticipants were selected based on the American College of Rheumatology (ACR) criteria for knee osteoarthritis (OA) diagnosis, with radiographic classification using Kellgren and Lawrence (KL) grading.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e: informed written consent was obtained from all human participants for the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Selection:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study recruited patients aged 50 years and older diagnosed with KL grade II and III knee OA through convenience sampling. Exclusion criteria included the use of pain medication, prior knee trauma, and loss to follow-up. A total of 59 patients (61 knees) were enrolled; bilateral cases were treated separately with at least a one-month interval between injections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients who met the inclusion criteria were selected for the study after signing the informed written consent to participate. 59 patients with 61 knees agreed to the study and were on regular follow-up. Before the PRP injection, thorough history, physical examination, pain assessment with the help of VAS score and WOMAC score, and X-ray of the affected knee were done along with platelet and RBS.\u003c/p\u003e\n\u003cp\u003eAutologous PRP injection was prepared in the outpatient department by harvesting 16 ml of the patient’s venous blood from the cubital vein in 2 separate sodium citrate and gel-containing vacutainers as shown in figure 1 A. These vacutainers, are readily accessible in our hospital and filled up to their designated marking.\u003c/p\u003e\n\u003cp\u003eThen the PRP machine (REMI PRP ULTRA, model ZICU-10151) was precooled without the whole blood. Speed, time, and temperature were pre-programmed: speed = 2500 rpm, time = 6 min, and temperature = +18 degrees Celsius.\u003c/p\u003e\n\u003cp\u003eAfter the device was pre-cooled, the whole blood collected in two vacutainers placed across was centrifuged in two steps, first at a lower rate of 2700 rpm for male and 2600 for female for 12 min. After the first spin step, gel separates the whole blood into RBC and plasma.\u003c/p\u003e\n\u003cp\u003eThen the second centrifugation was done for this vacutainer at 3200 rpm for 7 mins to get a higher concentration of platelets at the bottom as shown in figure 1C.\u003csup\u003e14\u003c/sup\u003e From this centrifuged test tube, the lower part of platelet-rich plasma (5 ml, i.e., controlled 2.5 ml from each tube) was isolated and collected using a 10 ml sterile syringe.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInjection protocol\u003c/strong\u003e: The injection procedure took place in the procedure room of OPD. The patient was positioned supine on the bed with knee flexed to 70 deg and the relevant areas were cleaned and covered with sterile drapes. 5 ml of this PRP was injected using an 18 G needle via an inferolateral approach into the involved knee joint. The position of the needle tip in the knee joint is confirmed by aspiration and the smooth passage of PRP into the knee joint without resistance. The whole process of separating and injecting platelet-rich plasma was done under strict aseptic precautions.\u003c/p\u003e\n\u003cp\u003eThe patient’s baseline platelet count was determined. The concentration of platelets in the final product was corroborated by the blood bank periodically.\u003c/p\u003e\n\u003cp\u003ePost-injection, all the patients were prescribed ice fomentation locally along with a range of motion exercises (physiotherapy). The patients were advised to avoid NSAIDs for 2 days before and after injection. Paracetamol in a dose of 500 mg was allowed in case of febrile illness or discomfort due to pain.\u003c/p\u003e\n\u003cp\u003eAll the procedures were performed by a trained orthopedic surgeon.\u003c/p\u003e\n\u003cp\u003ePain was assessed using the VAS (0-10 cm scale) and functional limitations using the WOMAC index. Weight-bearing plain X-rays were obtained for KL grading. Assessments were performed at baseline and at 2-, 4-, and 6-months post-injection.\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS version 16. Descriptive statistics were calculated. Repeated measures ANOVA was used for multiple comparisons, and paired t-tests for pairwise comparisons. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 59 patients (61 knees) were included in the study. The mean age was 59.54 \u0026plusmn; 8.318 years (range 50-82 years). There were 42 females (68.9%) and 19 males (31.1%). The right knee was involved in 32 (52.5%) patients and left in 29 (47.5%) patients as shown by figure 2.\u003c/p\u003e\n\u003cp\u003eThe mean duration of pain was 27.36 months (range 1-120 months) with mean duration of pain in male was 29.26 month and in female was 26.45 month as shown by figure 3.\u003c/p\u003e\n\u003cp\u003eThe distribution of KL grades was: KL grade II (n=40, 65.6%) and KL grade III (n=21, 34.4%) with age specific KL grade as shown in table 1.\u003c/p\u003e\n\u003cp\u003eTable 1: Relation of Age category (in years) and KL grade Distribution\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eAGE CATEGORY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e50 - 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e60 - 69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e70 - 79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e80+\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eKL GRADE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe mean VAS score at pre-injection was 7.21 \u0026plusmn; 0.951. Significant reductions in VAS scores were observed at 2 months (5.97 \u0026plusmn; 0.894, p\u0026lt;0.01), 4 months (4.82 \u0026plusmn; 0.940, p\u0026lt;0.01), and 6 months (3.82 \u0026plusmn; 1.057, p\u0026lt;0.01) post-injection. (Table 2, Figure 4)\u0026apos;\u003c/p\u003e\n\u003cp\u003eTable 2: Pairwise comparisons between VAS score at pre-injection, 2 months, 4 months, and 6 months.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (PRE-INJECTION)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (2MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e5.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.894\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (2MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e5.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (4MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (4MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVASCORE (6MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVAS SCORE (PRE-INJECTION)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e.951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVASCORE (6MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe mean WOMAC score at baseline was 72.89 \u0026plusmn; 5.007. Significant improvements were also observed at 2 months (62.84 \u0026plusmn; 7.921, p\u0026lt;0.01), 4 months (50.97 \u0026plusmn; 9.699, p\u0026lt;0.01), and 6 months (39.49 \u0026plusmn; 11.346, p\u0026lt;0.01) post-injection (Table 3, Figure 5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 3: Pairwise comparisons between WOMAC score at pre injection, 4MONTH, 4 month and 6 months.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (PREINJECTION)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e72.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (2MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e62.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e7.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (2MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e62.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e7.921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (4MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e50.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e9.699\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (4MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e50.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e9.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (6MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e39.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e11.346\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003ePair 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (PREINJECTION)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e72.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003eWOMAC SCORE (6MONTH)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e39.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e11.346\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePatients aged 50-59 years showed the greatest improvement in both VAS and WOMAC scores. Older patients (80+ years) showed the least improvement.\u003c/p\u003e\n\u003cp\u003ePatients didn\u0026rsquo;t report any serious adverse effects. However, 9 patients (9 knees) experienced pain at the injection site as a side effect requiring oral analgesic (Paracetamol) for pain relief.\u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe incidence of injection site pain varied across different age groups: 11.7% in the 50-59 age group, 15.7% in the 60-69 age group, and 33.33% in the 70-79 age group, with no reports of pain in the 80+ age group. (Table 4)\u003c/p\u003e\n\u003cp\u003eTable 4: Side effect according to age category.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 354px;\"\u003e\n \u003cp\u003eAGE CATEGORY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e50 - 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e60 - 69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e70 - 79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e80+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eSIDE EFFECTS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003ePAIN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4 (11.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e3 (15.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e2 (33.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e0 (0 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eOsteoarthritis (OA) is one of the most common degenerative joint disorders, primarily affecting synovial joints. It is characterized by a progressive loss of hyaline cartilage, the formation of new bone structures known as osteophytes, and significant alterations in joint morphology. The etiology of OA involves a complex interplay between mechanical, biological, and biochemical factors, leading to an imbalance between cartilage degradation and repair mechanisms. This imbalance can be exacerbated by joint injuries, obesity, aging, and genetic predisposition.\u003c/p\u003e\u003cp\u003eThe pathophysiology of OA is driven by both inflammatory and non-inflammatory pathways, which together contribute to the breakdown of articular cartilage and the development of synovitis. Inflammatory cytokines, including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), play crucial roles in initiating and perpetuating the catabolic processes that lead to cartilage destruction, synovial inflammation, and chronic pain. Oxidative stress and metabolic alterations have also been implicated in OA progression, highlighting the multifactorial nature of this disease. These findings underscore the need for a multifaceted therapeutic approach that targets both the biochemical and biomechanical aspects of OA.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn our study, we evaluated the effectiveness of intra-articular Platelet-Rich Plasma (PRP) injections in patients diagnosed with Kellgren-Lawrence (KL) grade II and III knee osteoarthritis. The clinical outcomes were measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Visual Analog Scale (VAS) scores, which are well-established tools for assessing pain and functional limitations in OA patients. PRP has gained attention for its potential to promote cartilage repair and modulate inflammation due to its high concentration of growth factors. Our findings demonstrated significant improvements in both pain and functional outcomes over a three-month follow-up period, as evidenced by reductions in VAS and WOMAC scores. While these results are in line with several existing studies, we also observed some unique variations worth discussing.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003ePatient Demographics\u003c/h2\u003e\u003cp\u003eOur study included 59 patients (61 knees) aged 50 years and older, all of whom had knee pain attributed to OA and were treated with PRP therapy. The mean age of participants was 59.54\u0026thinsp;\u0026plusmn;\u0026thinsp;8.318 years, with the majority (55.7%) falling within the 50\u0026ndash;59 age range. This age distribution aligns with previous findings that suggest PRP therapy tends to be more effective in younger patients with less severe OA, likely due to their greater regenerative potential. This observation is consistent with the conclusions of Filardo et al. (2010), who reported that younger individuals and those with early-stage degenerative changes showed better therapeutic responses to PRP.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Furthermore, a study by Chu et al. (2021) demonstrated that younger patients had more favorable outcomes, which might be attributed to their relatively intact cartilage and enhanced capacity for tissue repair.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA notable observation in our study was the predominance of female participants, who made up 68.9% of the cohort. This female predominance is consistent with the general epidemiology of OA, which tends to affect women more frequently, especially post-menopause. Hormonal changes, particularly estrogen deficiency, have been linked to accelerated cartilage degradation and increased susceptibility to OA in women. Previous studies, including those by Patel et al. (2013) and Kon et al. (2011), have also highlighted that women are disproportionately affected by OA due to a combination of hormonal, anatomical, and biomechanical factors.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Specifically, estrogen plays a protective role in cartilage health, and its decline during menopause may contribute significantly to the progression of OA in females.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaterality and Pain Duration\u003c/h3\u003e\n\u003cp\u003eIn terms of laterality, our study revealed that 52.5% of patients experienced pain in the right knee, while 47.5% reported pain in the left knee. Interestingly, when examining gender-specific differences, we found that more males experienced right knee pain (14 vs. 5), while females had a higher prevalence of left knee pain (24 vs. 18). These findings may reflect underlying biomechanical and anatomical differences between genders, as suggested by previous literature.\u003c/p\u003e\u003cp\u003eZhang et al. (2010) reported that symptomatic knee OA affects approximately 10% of men and 13% of women aged 60 years or older in the United States, highlighting a higher prevalence of OA in women, which is consistent with our observation of a female predominance in knee pain cases. The authors attribute the gender differences in OA prevalence to factors like age, obesity, and joint injuries, which may also influence laterality and pain severity.\u003c/p\u003e\u003cp\u003eThe pain duration among participants in our study ranged from 1 to 120 months, with a mean duration of 27.33 months. Males reported a slightly longer average pain duration (29.26 months) compared to females (26.45 months), which may be indicative of differences in pain tolerance and healthcare-seeking behavior between genders. This observation aligns with Zhang et al.'s emphasis on the role of age and gender in OA progression, where men often delay seeking medical attention, leading to longer pain durations and potentially more severe symptoms by the time of diagnosis. The literature also highlights the growing prevalence of OA due to aging populations and the obesity epidemic, both of which are crucial factors influencing pain duration and severity in affected individuals.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003eKellgren-Lawrence Grading\u003c/h3\u003e\n\u003cp\u003eThe majority of our study's participants were classified as KL grade II (65.6%), with the remainder (34.4%) falling under KL grade III. This distribution highlights a focus on patients in the moderate stages of OA, where PRP therapy has been reported to be most beneficial. Patients with KL grade II OA had a mean age of 57.33 years, whereas those with KL grade III were older, with a mean age of 63.76 years. This trend aligns with the natural history of OA, where the severity of joint degeneration increases with age. Jati et al. (2021) also observed a similar age distribution in their study and concluded that PRP is particularly effective in the early to moderate stages of OA.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e This aligns with our findings, where KL grade II patients generally showed better outcomes than those with grade III, though both groups demonstrated significant improvements over time.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePain and Function Improvement\u003c/h2\u003e\u003cp\u003eOur study's analysis of VAS scores revealed a marked reduction in pain over time. The baseline VAS score of 7.21 decreased to 5.97 at one month, 4.82 at two months, and 3.82 at three months. These results indicate substantial pain relief in a relatively short period, suggesting that PRP injections can effectively manage OA pain. When comparing KL grade II and III patients, we found that KL grade II individuals experienced slightly greater improvements in VAS scores (from 7.25 to 3.72) compared to those with KL grade III (from 7.14 to 4). These findings are consistent with the work of Campbell et al. (2015), who demonstrated that PRP significantly improves pain and functional outcomes, particularly in early-stage OA.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eFurther supporting our results, Upadhyay et al. (2024) reported a decrease in the mean VAS score from 6.80 pre-injection to 3.00 at six months post-injection. While our follow-up period was shorter (three months), the observed pattern of pain reduction aligns well with their findings, highlighting the potential of PRP as a short-term therapeutic option for knee OA.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Our study's early and significant pain relief further emphasizes that even a single PRP injection can provide notable benefits, reducing the need for multiple interventions.\u003c/p\u003e\u003cp\u003eIn terms of functional improvement, the WOMAC score also showed significant progress, decreasing from a baseline mean of 72.89\u0026thinsp;\u0026plusmn;\u0026thinsp;5.007 to 39.49\u0026thinsp;\u0026plusmn;\u0026thinsp;11.346 at three months. Patients with KL grade II had a greater reduction in WOMAC scores (from 72.53 to 38.65) compared to those with KL grade III (from 73.57 to 41.1). This reinforces the notion that PRP is more effective in treating the early stages of OA, potentially due to better cartilage integrity and a more robust healing response. Repeated ANOVA results demonstrated a statistically significant change in WOMAC scores over time, with a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.01, supporting the observed improvements.\u003c/p\u003e\u003cp\u003eOur findings correlate well with previous studies. For instance, Upadhyay et al. (2024) observed a similar decline in WOMAC scores from 72.7 pre-injection to 34.7 over six months.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Similarly, Patel et al. (2013) reported significant improvements in both pain and physical function with PRP treatment, as measured by the WOMAC index. These findings are mirrored in our study\u0026rsquo;s outcomes.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Additionally, Jati et al. (2021) found that PRP was more effective in early stages (KL II) than in advanced OA (KL III). In their study, the mean WOMAC score in KL II patients improved from 57.11 to 22.11 over six months, whereas KL III patients showed improvement from 59.21 to 32.12.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Although our follow-up period was shorter (three months), the trend of greater improvement in early-stage OA is consistent with these results. These consistent results across different studies highlight PRP\u0026rsquo;s efficacy in improving OA-related symptoms and enhancing patients\u0026rsquo; quality of life.\u003c/p\u003e\u003cp\u003eAge-based analysis showed that patients aged 50\u0026ndash;59 had the greatest reduction in both VAS and WOMAC scores, while older patients, particularly those aged 80+, showed the least improvement. For instance, the VAS score for patients aged 50\u0026ndash;59 dropped from 7.18 to 3.68, while for patients aged 80+, it only decreased from 8 to 5. This suggests that younger patients respond better to PRP treatment, likely due to better regenerative potential, as noted by Chu et al. (2021).\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Similarly, the WOMAC score in the 50\u0026ndash;59 age group decreased from 73.35 to 38.12, showing greater improvement compared to the 80\u0026thinsp;+\u0026thinsp;age group (WOMAC: 75 to 49.5).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eComparison with Other Studies\u003c/h2\u003e\u003cp\u003eThe results of our study align well with the broader literature on PRP efficacy for knee OA. In particular:\u003c/p\u003e\u003cp\u003ePatel et al. (2013): Their research demonstrated significant improvements in both WOMAC and pain scores following a single PRP injection, suggesting that even one injection can yield substantial clinical benefits.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e This observation is consistent with our study's findings, where a single PRP injection led to sustained pain and function improvements over three months.\u003c/p\u003e\u003cp\u003eGiuseppe Filardo (2010): Filardo's study indicated that PRP provides short-term pain relief and functional improvement, particularly in younger patients with milder OA, aligning with our study's age-related outcomes. Both studies highlight the transient nature of PRP's effects, noting that its benefits often decrease over time. While our study's follow-up was limited to three months, making it difficult to assess long-term effects, Filardo observed that the improvements in pain and function began to plateau after the three-month.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e\u003cp\u003eKhoshbin et al. (2013): In their review, Khoshbin et al. found that PRP was superior to hyaluronic acid (HA) in improving functional scores such as WOMAC. This aligns with the significant improvements we observed in WOMAC scores in our study over the three-month period. However, while Khoshbin et al. noted significant enhancements in WOMAC scores, they did not observe major differences in VAS scores. In contrast, our study suggests that PRP may also provide notable short-term pain reduction, as reflected by the significant decrease in VAS scores during the same period.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eBennell et al. (2021): This randomized trial highlighted a lack of significant long-term differences between PRP and placebo in terms of pain relief, pointing towards PRP's short-term benefits rather than long-term efficacy.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Our study's focus on a three-month follow-up period is in agreement with these short-term positive outcomes.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eAdverse Effects and Safety\u003c/h2\u003e\u003cp\u003eOur study found that PRP injections were generally well-tolerated, with minimal side effects reported among participants. Nine patients / nine knees (14.8%) required oral analgesics (Paracetamol) for pain relief following the procedure, but no severe adverse reactions were noted. Interestingly, the incidence of injection site pain varied across different age groups: 11.7% in the 50\u0026ndash;59 age group, 15.7% in the 60\u0026ndash;69 age group, and 33.33% in the 70\u0026ndash;79 age group, with no reports of pain in the 80\u0026thinsp;+\u0026thinsp;age group. This trend suggests that younger patients might have a higher pain tolerance or a different inflammatory response to PRP injections.\u003c/p\u003e\u003cp\u003eThese findings are consistent with the existing literature, including the study by Filardo et al. (2010), which also reported minimal adverse effects associated with PRP therapy, reinforcing its safety profile. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e However, studies like Campbell et al. (2015) have cautioned about increased local reactions with multiple PRP injections, which our study avoided by focusing solely on single-injection therapy.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e This approach supports the notion that limited PRP use can minimize adverse effects while still providing therapeutic benefits.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eFuture Directions\u003c/h2\u003e\u003cp\u003eWhile our study's short-term results with PRP injections are promising, the long-term efficacy of this treatment remains uncertain. Research by Kon et al. (2011) and Tucker et al. (2021) suggests that although PRP is effective in the short to medium term, its benefits may diminish over time, particularly in patients with more advanced stages of OA.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Future studies should focus on exploring the long-term outcomes of repeated PRP injections and investigate whether different formulations, such as leukocyte-rich or leukocyte-poor PRP, yield varying results.\u003c/p\u003e\u003cp\u003eAdditionally, personalized treatment protocols based on factors like age, Kellgren-Lawrence (KL) grade, and comorbidities should be developed to optimize therapeutic outcomes. Since our study specifically focused on patients with KL grade II and III OA, future research should aim to identify the patient subgroups that derive the most benefit from PRP therapy and determine its efficacy in more advanced stages, such as KL grade IV OA, where treatment success is less certain according to studies by Khoshbin et al. (2013) and Jati et al. (2021)\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eIntra-observer and inter-observer variability in evaluating the grades of KL grading The study was conducted at a single center with a small sample size and over a limited period, which may not be sufficient to generalize the results to the broader population. Therefore, further research with larger sample sizes and long-term follow-up is necessary to confirm the findings. The study did not compare PRP with other treatment modalities such as hyaluronic acid or corticosteroid injections. So better evaluation of the efficacy of PRP was not possible. Additionally, long-term follow-up using MRI is needed to assess cartilage regeneration.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIntra-articular PRP injections have shown to be an effective short-term treatment for reducing pain and improving function in patients with knee osteoarthritis, as evidenced by significant improvements in WOMAC and VAS scores. Our study, which involved injecting a highly concentrated mix of platelets into the joint cavity, consistently demonstrated reductions in pain and stiffness, along with clear improvements in patients\u0026rsquo; quality of life. These findings align with broader literature supporting PRP use, particularly in early-stage osteoarthritis. However, further extended follow-up, additional randomized trials comparing PRP with corticosteroids and hyaluronic acid are necessary to establish its long-term efficacy and optimal usage guidelines.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eOA\u003c/strong\u003e – Osteoarthritis\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePRP\u003c/strong\u003e – Platelet-Rich Plasma\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eKL\u003c/strong\u003e – Kellgren and Lawrence (grading system for knee osteoarthritis)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eVAS\u003c/strong\u003e – Visual Analogue Scale\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWOMAC\u003c/strong\u003e – Western Ontario and McMaster Universities Arthritis Index\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDALYs\u003c/strong\u003e – Disability-Adjusted Life Years\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eACR\u003c/strong\u003e – American College of Rheumatology\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePDGF\u003c/strong\u003e – Platelet-Derived Growth Factor\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTGF-β\u003c/strong\u003e – Transforming Growth Factor-Beta\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eVEGF\u003c/strong\u003e – Vascular Endothelial Growth Factor\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eEGF\u003c/strong\u003e – Epidermal Growth Factor\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIGF\u003c/strong\u003e – Insulin-like Growth Factor\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFGF\u003c/strong\u003e – Fibroblast Growth Factor\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNSAIDs\u003c/strong\u003e – Non-Steroidal Anti-Inflammatory Drugs\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMRI\u003c/strong\u003e – Magnetic Resonance Imaging\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eEthics approval and consent to participate This study was conducted at KIST Medical College and Teaching Hospital (KISTMCTH) from November 2022 to November 2023, after receiving ethical approval from IRC-KISTMCTH on November 17, 2022 (Reference number: 079/80/38). All procedures performed in this study adhered to the Declaration of Helsinki guidelines to ensure ethical compliance. Informed written consent was obtained from all participants prior to their inclusion in the study. Patients were thoroughly briefed on the study objectives, potential risks, and benefits before signing the consent form.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable. This study does not involve identifiable personal data, image\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe dataset supporting the findings of this study is provided as an additional file accompanying this manuscript. Further inquiries regarding the data can be directed to the corresponding author upon reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding \u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eAuthors' contributions\u003c/h2\u003e\n\u003cp\u003eDr. Gaurav Bir Bajracharya (A): Conceptualization, Methodology, Data and information collection, Writing original draft, Review and editing\u003c/p\u003e\n\u003cp\u003eProf. Dr Shriraj Shrestha: Writing – Review and editing\u003c/p\u003e\n\u003cp\u003eDr Saurav Dahal: Writing – Review and editing\u003c/p\u003e\n\u003cp\u003eDr Suman Maharjan: Writing – Review and editing\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eI wish to extend my deep appreciation to Professor Dr. Shriraj Shrestha, from the Department of Orthopaedics at Kist Medical College and Teaching Hospital, for his unwavering guidance, encouragement, and continuous support throughout the entire duration of this endeavor. Without his invaluable assistance, this undertaking would not have come to fruition. \u003c/p\u003e\n\u003cp\u003eI am equally grateful to Dr. Saurav Dahal a respected teacher and co-guide, who serves as a Lecturer in the Department of Orthopaedics. His consistent support, guidance, and motivation have been instrumental in shaping the course of this research. \u003c/p\u003e\n\u003cp\u003eFurthermore, I extend my heartfelt thanks to all the esteemed faculty members of the Department of Orthopaedics at Kist Medical College and Teaching Hospital. Their consistent encouragement and support have been pivotal in the progression of my research. \u003c/p\u003e\n\u003cp\u003eI am also indebted to my colleagues, Dr. Kushal Shah and Dr. Suraj Shakya, and juniors for their unwavering assistance in data collection for the thesis. My sincere gratitude extends to the patients who willingly participated in this study, as their cooperation and consent were essential for completing this work. \u003c/p\u003e\n\u003cp\u003eI would also like to express my sincere gratitude to my parents Prof. Dr. Gautam Bir Bajracharya and Mrs. Tara Devi Bajracharya, and brother Dr. Bikram Bir Bajracharya, who have always supported me and provided continuous encouragement throughout my years of study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet (London, England). 2019 Apr 27;393(10182):1745\u0026ndash;59. \u003c/li\u003e\n\u003cli\u003eCui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Dec 1;29\u0026ndash;30:100587. \u003c/li\u003e\n\u003cli\u003eCross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eBahadur D, Kshetri B. Knee pain and knee pain related disability in adults of the Western Development Region of Nepal Student Declaration. 2017; \u003c/li\u003e\n\u003cli\u003eBardoloi B, Bhutia C, Bhatia D, Paul S. Knee Osteoarthritis: An Overview of Recent Interventions. Avestia Publ J Biomed Eng Biosci. 2017;4:2564\u0026ndash;4998. \u003c/li\u003e\n\u003cli\u003eRemst DFG, Blaney Davidson EN, van der Kraan PM. Unravelling osteoarthritis-related synovial fibrosis: a step closer to solving joint stiffness. Rheumatology. 2015 Nov 1;54(11):1954\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eNakarmi S, Haq SA, Vaidya B. Translation, validation and cross-cultural adaptation of the Nepali version of WOMAC \u0026reg; LK 3.1. Int J Rheum Dis. 2019 Oct 1;22(10):1877\u0026ndash;83. \u003c/li\u003e\n\u003cli\u003eBraun HJ, Gold GE. Diagnosis of Osteoarthritis: Imaging. Bone. 2012 Aug;51(2):278. \u003c/li\u003e\n\u003cli\u003eKellgren JH, Lawrence JS. RADIOLOGICAL ASSESSMENT OF OSTEO-ARTHROSIS. Ann rheum Dis. 1957;494. \u003c/li\u003e\n\u003cli\u003eSchiphof D, Boers M, Bierma-Zeinstra SMA. Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis. 2008 Jul 1;67(7):1034\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003ePavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet Rich Plasma: A short overview of certain bioactive components. Open Med. 2016 Aug 1;11(1):242\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eEverts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020 Oct 2;21(20):1\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eCampbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR, et al. Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared with Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses. Arthrosc - J Arthrosc Relat Surg. 2015 Nov 1;31(11):2213\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eGupta V, Parihar AS, Pathak M, Sharma VK. Comparison of Platelet-Rich Plasma Prepared Using Two Methods: Manual Double Spin Method versus a Commercially Available Automated Device. Indian Dermatol Online J. 2020 Jul 1;11(4):575\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eLin X, Zhi F, Lan Q, Deng W, Hou X, Wan Q. Comparing the efficacy of different intra-articular injections for knee osteoarthritis: A network analysis. Med (United States). 2022 Aug 5;101(31):E29655. \u003c/li\u003e\n\u003cli\u003eFilardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):528\u0026ndash;35. \u003c/li\u003e\n\u003cli\u003eChu J, Duan W, Yu Z, Tao T, Xu J, Ma Q, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. 2022 Dec 1;30(12):4063\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003ePatel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013 Feb;41(2):356\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eKon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis. Arthrosc - J Arthrosc Relat Surg. 2011;27(11):1490\u0026ndash;501. \u003c/li\u003e\n\u003cli\u003eZhang Y, Jordan JM. Epidemiology of Osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355. \u003c/li\u003e\n\u003cli\u003eJati S, Bansal H, Garg A J. To Evaluate the Functional Outcome of Platelet Rich Plasma Therapy in Osteoarthritis of Knee | Orthopaedic Journal of M. P. Chapter. 2021. \u003c/li\u003e\n\u003cli\u003eUpadhyay V, Ambhure K, Mittal S. EFFICACY OF AUTOLOGOUS PLATELET-RICH PLASMA INJECTION IN KNEE OSTEOARTHRITIS. 2024;753\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKhoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D, et al. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: A systematic review with quantitative synthesis. Arthrosc - J Arthrosc Relat Surg. 2013 Dec 1;29(12):2037\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eBennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021 Nov;326(20). \u003c/li\u003e\n\u003cli\u003eTucker JD, Goetz LL, Duncan MB, Gilman JB, Elmore LW, Sell SA, et al. Randomized, Placebo-Controlled Analysis of the Knee Synovial Environment Following Platelet-Rich Plasma Treatment for Knee Osteoarthritis. PM\u0026amp;R. 2021 Jul 1;13(7):707\u0026ndash;19.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Osteoarthritis (OA), Knee pain, Platelet-rich plasma (PRP), Joint function, Cartilage repair, Regenerative therapy","lastPublishedDoi":"10.21203/rs.3.rs-6864842/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6864842/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e\u003cbr\u003e\nOsteoarthritis (OA) of the knee is a prevalent condition that significantly impacts the quality of life for millions of individuals worldwide. As a leading cause of disability, its effective management is crucial. Intra-articular injections of platelet-rich plasma (PRP) have gained attention as a potential treatment, offering a biologic approach to enhance cartilage repair and reduce inflammation. This study evaluates the clinical efficacy of PRP injections in knee OA management, focusing on pain relief and functional improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nThe study involved 59 patients (61 knees) diagnosed with KL grade II and III knee OA who received PRP injections. Patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) scores. Evaluations were conducted at baseline and two, four, and six months post-injection to assess pain relief and functional improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nSignificant reductions in VAS pain scores and WOMAC functional disability scores were observed following PRP therapy. Pain and stiffness improved notably within the first few months post-treatment, with KL grade II patients experiencing better outcomes than KL grade III patients. The study confirmed PRP’s effectiveness as a non-surgical intervention, with no severe adverse effects reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nPRP injections appear to be a viable regenerative treatment for knee OA, offering meaningful pain reduction and mobility enhancement. Although the initial benefits are significant, long-term efficacy remains uncertain, warranting further research. Establishing optimal patient selection criteria and repeated dosing protocols may enhance future outcomes.\u003c/p\u003e","manuscriptTitle":"Clinical Outcome of Intra-Articular Injection of Platelet Rich Plasma in Osteoarthritis Knee","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-27 11:01:08","doi":"10.21203/rs.3.rs-6864842/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-26T06:15:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-21T21:24:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"278129789846495525383774128646776966904","date":"2026-03-11T22:31:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39100371988224404079733828208725591055","date":"2026-03-06T17:48:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-06T03:51:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"337128543211815073364803171224782762281","date":"2025-12-05T23:29:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-31T16:35:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"322433464460270664839161063545321924728","date":"2025-08-26T14:08:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9447579603077968052838561599987103145","date":"2025-08-21T16:19:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-21T13:45:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-18T10:07:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-20T07:28:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-19T15:14:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2025-06-19T15:10:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3401bdfc-ddd4-431b-966f-ffd317c8937e","owner":[],"postedDate":"July 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-09T14:53:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-27 11:01:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6864842","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6864842","identity":"rs-6864842","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}