Long-Term Efficacy of Intra-Articular PRP Injections Versus Conventional Therapy in Early-Stage Knee Osteoarthritis: A 5-Year Retrospective Study

Long-Term Efficacy of Intra-Articular PRP Injections Versus Conventional Therapy in Early-Stage Knee Osteoarthritis: A 5-Year Retrospective Study | 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 Long-Term Efficacy of Intra-Articular PRP Injections Versus Conventional Therapy in Early-Stage Knee Osteoarthritis: A 5-Year Retrospective Study Chenghong Wen, Qiang Hua, Wenduo Qian, Jide Su, Mingming Lei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6436349/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This study aimed to evaluate the long-term clinical efficacy of intra-articular platelet-rich plasma (PRP) injections compared to conventional therapy in patients with early-stage knee osteoarthritis (KOA). We focused on assessing improvements in pain, joint function, and quality of life over a 5-year period. Methods A retrospective cohort study was conducted involving 116 patients with bilateral early-stage KOA (Kellgren–Lawrence Grade I–II) treated between January 2019 and December 2019. Patients were divided into two groups: Group A received a standardized management protocol for osteoarthritis (SMPO) combined with three PRP injections administered at weeks 0, 2, and 4, while Group B received SMPO alone. Outcome measures, including the Visual Analog Scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for joint function, and the SF-36 Health Survey for quality of life, were assessed at baseline and at the 5-year follow-up. Results Both groups demonstrated a progressive decline in outcome scores over the 5-year follow-up, indicating worsening pain, function, and quality of life. However, statistical comparisons revealed no significant differences between the PRP-treated group and the control group across all evaluated parameters (P > 0.05). Conclusion The long-term results indicate that intra-articular PRP injections do not provide significant advantages over conventional management in early-stage knee osteoarthritis. These findings highlight the need for further research to optimize PRP treatment protocols and explore potential patient subgroups that might benefit from this regenerative therapy approach. Trial registration Not applicable Knee Osteoarthritis PRP Long-Term Efficacy Introduction Knee osteoarthritis (KOA) is a prevalent degenerative joint disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and synovial inflammation, culminating in chronic pain, functional disability, and diminished quality of life[ 1 ]. Globally, KOA impacts over 250 million individuals, with rising prevalence attributed to aging populations and increasing obesity rates[ 2 ]. Current non-surgical therapeutic strategies—including oral analgesics, intra-articular corticosteroids, and hyaluronic acid (HA) injections—focus predominantly on symptomatic relief but fail to halt disease progression or stimulate cartilage regeneration[ 3 ]. Consequently, regenerative therapies such as platelet-rich plasma (PRP) have gained attention for their potential to modulate inflammatory pathways, enhance tissue repair, and delay the need for surgical intervention[ 4 ]. PRP, an autologous blood product enriched with platelets and bioactive factors (e.g., PDGF, TGF-β, VEGF), exerts dual therapeutic mechanisms in KOA management: (1) suppression of pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and matrix metalloproteinases (MMPs) to attenuate cartilage breakdown, and (2) promotion of chondrocyte proliferation, extracellular matrix synthesis, and mesenchymal stem cell (MSC) differentiation to facilitate cartilage regeneration[ 2 , 5 ]. Clinical evidence suggests that PRP outperforms HA and corticosteroids in short-term pain reduction and functional improvement, particularly in early-stage KOA (Kellgren-Lawrence grades I–III)[ 6 , 7 ]. Nevertheless, findings remain contradictory. While certain randomized controlled trials (RCTs) report sustained efficacy of PRP at 12–24 months, others, such as the RESTORE trial, demonstrate no significant advantage over placebo at 12 months[ 8 , 9 ]. Critically, long-term outcomes (> 5 years) remain underexplored, hindering definitive clinical consensus. This retrospective cohort study evaluates 58 early-stage KOA patients treated with intra-articular PRP injections at our institution, compared to 58 matched controls receiving conventional therapy (NSAIDs or HA). Our primary objective is to investigate the long-term clinical efficacy of intra-articular PRP in early-stage KOA, with emphasis on sustained symptom relief, functional outcomes, and protocol optimization. Method Ethical Approval This retrospective study was conducted with approval from the Institutional Review Board of Chengdu Sport University Affiliated Hospital (Ethics Committee reference number: [20240115]). Prior to data collection, written informed consent was obtained from all participants through comprehensive face-to-face consultations followed by formal documentation procedures. The investigation strictly adhered to the ethical principles outlined in the Declaration of Helsinki (2013 revision). All collected patient information was anonymized and processed in compliance with international data protection standards (GDPR) and China's Personal Information Protection Law (PIPL) to ensure confidentiality and privacy safeguards. Participants and Design This retrospective cohort study initially identified 136 consecutive patients with bilateral early-stage knee osteoarthritis (Kellgren-Lawrence Grade 1–2) who received either a standardized management protocol for osteoarthritis (SMPO) combined with platelet-rich plasma (PRP) injections (at week 0, 2 and 4) (Group A) or SMPO alone (Group B) in both knee joints at our institution between January 2019 and December 2019. Standardized Management Protocol for Osteoarthritis (SMPO): Core Non-Pharmacological Interventions Patient Education: Implementation of disease-modifying lifestyle modification programs. Weight Management Structured plan targeting a ≥5% reduction in body weight (as per ESCEO guidelines). Exercise Therapy Daily neuromuscular training (30 minutes per day). Pharmacological Protocol (Acute Phase) For cases of refractory pain (VAS ≥4), initiate a 2-month therapeutic course using oral NSAIDs (e.g., celecoxib 200 mg once daily), topical NSAIDs (diclofenac gel three times daily), glucosamine sulfate (1500 mg daily), and diacerein (50 mg twice daily). Post-Treatment Maintenance Following the 2-month pharmacotherapy phase, continue the foundational triad of education, weight control, and exercise. PRP Preparation: We collected 40 cc of blood from each patient. Ten milliliters of blood was sent to a certified tissue laboratory for control and quality testing, while the remaining 30 mL was manually processed in a sterile syringe to yield a total of 6 mL of leukocyte-depleted PRP (3 mL per knee). The 30 mL of blood was centrifuged in sodium citrate tubes at 400 g for 10 minutes; the plasma was collected and erythrocytes were discarded. The plasma was then centrifuged again at 800 g for 15 minutes, the supernatant was discarded, and the pellet was resuspended to the desired volume. Inclusion Criteria: Radiologically confirmed bilateral knee osteoarthritis (KL Grade 1–2) (defined according to the MRI and/ or radiography). Failure of at least 3 months of continuous foundational triad therapy (education, weight control, exercise). Acute phase bilateral knee pain (VAS ≥4). Exclusion Criteria: Systemic inflammatory or autoimmune arthritis. History of major knee trauma or surgery. Severe meniscal pathology causing mechanical symptoms. Intra-articular interventions within the previous 3 months. Hematologic, oncologic, or metabolic comorbidities. Anticoagulant or antiplatelet therapy. Inability to complete a 5-year follow-up. Exclusion Rationale: Two cases were excluded due to uncontrolled diabetes mellitus. Four subjects who had undergone total knee arthroplasty by the five-year follow-up were excluded. Five subjects with recent intra-articular hyaluronic acid injections were excluded. Six screening candidates declined to provide informed consent. Three participants were lost to follow-up within 60 months. After applying stringent eligibility criteria, 116 subjects were enrolled for final analysis (Table 1). Observation indicators At 5 years following the initial treatment, both patient groups underwent comprehensive evaluation using multiple standardized outcome measures. These included the acute phase Visual Analog Scale (VAS) for pain intensity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [10] for assessing pain, stiffness, and physical function and the SF-36 Health Survey for overall quality of life [11]. The VAS provides a simple and validated method for quantifying pain on a scale of 0 to 10 [12]. The WOMAC index, widely recognized in osteoarthritis research, has been established as a reliable tool to capture the multidimensional impact of joint degeneration on daily activities [13]. While the SF-36 questionnaire enables a holistic appraisal of health-related quality of life across various domains [14]. Together, these measures offer a comprehensive, multidimensional evaluation of the long-term clinical efficacy of the treatment protocols. Statistical Analysis Continuous variables are presented as mean ± standard deviation, while categorical data are reported as frequencies with percentages. Between-group comparisons of continuous variables were analyzed using independent samples Student's t-tests. Categorical variables were compared using Pearson's chi-square test. All analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA), with statistical significance defined as a two-tailed P-value <0.05. Sample Size and Post Hoc Power Analysis A post hoc power analysis was performed to evaluate whether the sample size was sufficient to detect a clinically meaningful difference in Visual Analog Scale (VAS) scores between the two groups at the 5-year follow-up. Assuming a two-tailed α = 0.05, a standard deviation of 1.2, and a minimal clinically important difference (MCID) of 1.0 in VAS scores, the calculated power for the current sample size (n = 58 per group) was 84.3%. Therefore, the study was adequately powered to detect clinically relevant differences between groups for the primary outcome. Results General Information From January 2019 to December 2019, a total of 116 patients (58 per group) with bilateral early-stage knee osteoarthritis (Kellgren-Lawrence Grade I-II) enrolled in this retrospective cohort study. Patients were divided into Group A, receiving a standardized management protocol for osteoarthritis (SMPO) combined with platelet-rich plasma (PRP) injections at weeks 0, 2, and 4, and Group B, receiving SMPO alone. No statistically significant differences were observed between the groups in gender distribution (Female: 72.4% vs. 69.0%; Male: 27.6% vs. 31.0%; P = 0.166), mean age (50.48±2.74 vs. 51.05±2.74 years; P = 0.575), K-L classification (Grade I: 32 vs. 34; Grade II: 26 vs. 24; P = 0.141), or BMI (25.40 ± 0.62 vs. 25.25 ± 0.44 kg/m²; P = 0.152). Statistical analyses using chi-square (χ²) and t-tests confirmed homogeneity in baseline parameters ( P > 0.05 for all), ensuring comparability between groups. This balanced baseline profile supports the validity of subsequent outcome comparisons between SMPO+PRP and SMPO-only interventions. Table 1 . Patient Demographics Group A (n=58) Group B (n=58) Statistical Value P Value Gender Female (%) 42（72.4） 40（69.0） χ 2 =0.683 0.166 Male (%) 16（27.6） 18（31.0） Age (years) 50.48±2.74 51.05±2.74 t =-1.117 0.575 K-L Classification Grade I 32 34 χ 2 =0.708 0.141 Grade II 26 24 Body Mass Index (kg/m²) 25.40±0.62 25. 25±0.44 t= 1.442 0.152 Visual Analog Scale The study compared baseline and 5-year postoperative Visual Analog Scale (VAS) pain scores between Group A (n=58) and Group B (n=58). At baseline, Group A had a mean VAS score of 4.64±0.52, while Group B scored 4.80±0.59, with no statistically significant difference between groups ( t = -1.510, P =0.406). By the 5th year, VAS scores increased in both groups: Group A to 5.41±1.17 and Group B to 5.44±1.16, but the intergroup difference remained non-significant ( t =-0.160, P =0.849). The table demonstrates no long-term divergence in pain outcomes between the two groups over the 5-year follow-up period (Table 2). Table 2 . Visual Analog Scale, WOMAC and IKDC score Group A (n=58) Group B (n=58) Statistical Value P Value VAS score Baseline 4.64±0.52 4.80±0.59 t =-1.510 0.406 5 th year 5.41±1.17 5.44±1.16 t =-0.160 0.849 WOMAC score This study compared WOMAC scores (pain, stiffness, physical function) between Group A (n=58) and Group B (n=58) at baseline and 5-year follow-up. Baseline scores showed no significant intergroup differences (e.g., pain: 8.41±2.12 vs. 8.64±2.35, t = -0.620, P = 0.537). By the 5th year, scores worsened comparably in both groups, such as pain increasing to 9.76±3.52 (Group A) and 9.43±3.41 (Group B) (t = 0.520, P = 0.606). Similar trends were observed for stiffness and physical function. No statistically significant differences were detected between groups at either time point (P > 0.05 for all comparisons, Table 3), indicating parallel declines in WOMAC outcomes over 5 years with no meaningful intergroup disparities. Table 3 . WOMAC score Group A (n=58) Group B (n=58) Statistical Value P Value Pain Baseline 8.41±2.12 8.64±2.35 t =-0.620 0.537 5 th year 9.76±3.52 9.43±3.41 t =0.520 0.606 Stiffness Baseline 3.02±0.82 2.98±0.85 t =-0.240 0.812 5 th year 4.02±1.48 3.95±1.52 t =0.250 0.801 Physical Function Baseline 19.83±3.21 20.12±3.07 t =-0.480 0.634 5 th year 26.53±7.89 25.78±8.12 t =0.480 0.632 SF-36 Health Survey This study compared SF-36 Health Survey scores between Group A (n=58) and Group B (n=58) at baseline and 5-year follow-up. For all eight domains (e.g., Physical Functioning, Role Physical, Bodily Pain), baseline scores showed no significant intergroup differences (P > 0.05). At the 5th year, scores declined comparably in both groups across most domains. For example, Physical Functioning decreased from 57.34±10.89 (Group A) and 57.12±11.25 (Group B) at baseline to 49.78±6.89 and 49.64±6.52, respectively (t = 0.110–1.210, P = 0.230–0.920). Similarly, Role Emotional scores declined from 74.16±5.62 (Group A) and 75.05±5.94 (Group B) to 68.24±6.37 and 69.16±6.72 (t = 0.820, P = 0.410). Notably, no statistically significant differences were observed between groups at either time point for any domain (P > 0.05 for all comparisons, Table 4). These results indicate parallel declines in health-related quality of life over 5 years in both groups, with no meaningful intergroup disparities (Table 4). Table 4 . SF-36 Health Survey Group A (n=58) Group B (n=58) Statistical Value P Value Physical Functioning Baseline 57.34±10.89 57.12±11.25 t = 0.110 0.910 5 th year 49.78±6.89 49.64±6.52 t = 0.130 0.900 Role Physical Baseline 53.62±7.85 53.48±8.12 t = 0.100 0.920 5 th year 47.12±4.87 48.05±5.12 t = 1.210 0.230 Bodily Pain Baseline 54.08±4.95 54.97±5.21 t = 1.020 0.310 5 th year 47.26±5.32 48.14±5.67 t = 0.940 0.350 General Health Baseline 61.34±5.72 62.95±6.08 t = 1.520 0.130 5 th year 55.24±6.52 56.12±6.81 t = 0.760 0.450 Vitality Baseline 65.34±5.67 67.12±5.82 t = 1.640 0.100 5 th year 62.14±6.37 63.26±6.72 t = 0.980 0.330 Social Functioning Baseline 70.53±6.21 71.63±6.58 t = 1.120 0.260 5 th year 64.52±5.47 65.43±5.82 t = 0.910 0.360 Role Emotional Baseline 74.16±5.62 75.05±5.94 t =0.890 0.380 5 th year 68.24±6.37 69.16±6.72 t = 0.820 0.410 Mental Health Baseline 76.84±4.65 78.24±5.12 t =1.350 0.180 5 th year 67.84±6.82 69.05±7.15 t = 1.280 0.200 Health Change Baseline 3.02±0.29 3.10±0.31 t =0.810 0.420 5 th year 3.37±0.32 3.48±0.35 t = 0.890 0.380 Discussion The long-term follow-up data presented in this study indicate that, at the 5-year mark, intra-articular platelet-rich plasma (PRP) injections do not offer statistically significant benefits compared with conventional management protocols in terms of pain, functional status, and quality of life among patients with early-stage KOA. These findings are in line with several recent randomized controlled trials and systematic reviews that have questioned the sustained clinical efficacy of PRP beyond the short-term improvements reported in previous studies [1, 4, 8, 9, 15]. Lack of Long-Term Superiority Despite initial expectations and promising short-term data—where PRP has been shown to modulate inflammatory mediators, promote chondrocyte proliferation, and enhance extracellular matrix synthesis [2, 5] —our study’s 5-year follow-up reveals comparable deterioration in pain scores (as measured by VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and SF-36 scores between PRP-treated patients and the control group. Similar observations have been reported in studies such as Bennell et al. [9] and Yurtbay et al. [8], while additional longitudinal analyses have reported transient benefits that do not persist [16, 17]. It is noteworthy that while some short- and mid-term trials indicate transient benefits [6, 7], these improvements tend to attenuate over time. This phenomenon may be related to the progressive nature of osteoarthritis and the multifactorial etiology of joint degeneration [2, 3, 18]. Our findings underscore the possibility that the initially observed improvement may be due to placebo effects or short-term biological modulation that is insufficient to alter the natural history of the disease in the long run. Biological Mechanisms and PRP Variability PRP preparations, although rich in growth factors such as PDGF, TGF-β, and VEGF, present considerable variability in platelet concentration and bioactive factor content [4, 5]. This heterogeneity could contribute to inconsistent clinical outcomes across studies. In fact, recent evidence suggests that variations in the cytokine profile and growth factor composition of PRP may lead to different therapeutic responses [17]. Variability in preparation protocols, injection intervals, and even patient-specific factors (such as baseline inflammation and activity level) may lead to different therapeutic responses [18]. Novel imaging studies have demonstrated that the biochemical composition of cartilage may change over time following PRP injections, potentially affecting long-term outcomes [18]. In our study, the standardized preparation of leukocyte-depleted PRP did not translate into long-term clinical benefit, which is consistent with meta-analytic data suggesting that the magnitude of benefit diminishes with time [19]. Comparison with Conventional Management The control group in our study was managed with a standardized protocol including patient education, weight management, exercise therapy, and pharmacological interventions (primarily NSAIDs). Remarkably, both groups experienced parallel declines in functional scores and quality of life measures over 5 years. This suggests that for early-stage KOA, the conventional management approach is as effective as adding PRP injections in terms of long-term outcomes. This is supported by evidence from large-scale studies and recent systematic reviews comparing PRP with hyaluronic acid and corticosteroid injections, where no significant long-term differences were detected [7, 20]. Clinical Implications For practicing clinicians, the present findings emphasize the importance of managing patient expectations regarding PRP therapy for KOA. While the short-term benefits may offer temporary relief, our evidence does not support a significant long-term advantage regarding pain reduction, joint function, or overall quality of life. This highlights the need for a balanced treatment approach that integrates non-pharmacological interventions and considers PRP as an adjunct rather than a definitive long-term solution [1, 2, 7]. Clinicians should also be aware of the potential economic implications and patient burden associated with repeated injections, especially when long-term superiority is not established [21]. Methodological Considerations and Limitations It is critical to acknowledge some limitations in our study. First, the retrospective design may entail inherent biases, including selection bias and loss to follow-up. Although baseline characteristics were balanced between the groups, unaccounted confounders may still exist. Second, the sample size—although adequate for the current analysis—may not be sufficiently powered to detect smaller but clinically relevant differences between treatments. Future studies should incorporate larger, multicenter designs and robust randomization procedures to validate these findings. Lastly, variations in PRP formulation and injection technique remain an important source of heterogeneity in the literature. Standardization of protocols across studies might offer clearer insights into the true efficacy of PRP [22-24]. Implications for Future Research Future research is warranted to address several unanswered questions. First, there is a need for well-designed randomized controlled trials (RCTs) with longer follow-up periods that compare different PRP formulations (e.g., leukocyte-rich vs. leukocyte-poor) as well as different dosing schedules. Second, mechanistic studies exploring the molecular interactions between PRP constituents and joint tissues could elucidate why short-term benefits are not sustained over longer periods [25, 26]. Finally, biomarker studies may help identify patient subgroups more likely to respond to PRP treatment, thereby paving the way for personalized medicine approaches in osteoarthritis treatment [27]. Future PRP research should focus on more constructive directions such as individual variability in treatment response and biomarkers. Integration with Current Literature An extensive body of literature now suggests that while PRP injections are a promising intervention for early-stage knee osteoarthritis, the current evidence calls for cautious interpretation of its long-term benefits. In addition to our findings, recent authoritative studies such as Tang et al. [1] and the Global Burden of Disease Study on osteoarthritis [2] have highlighted the complex interplay between degenerative changes and inflammation that may not be fully mitigated by PRP alone. Furthermore, systematic reviews and meta-analyses have demonstrated that the long-term functional and symptomatic outcomes of PRP are at best comparable to conventional treatments, which reinforces the notion that additional research is required to optimize treatment protocols [28, 29]. Study Limitations This study has several limitations. First, the retrospective nature of the design may introduce selection bias and limits causal inference. Second, the study was conducted at a single center, which may reduce generalizability. Third, although the PRP preparation was standardized, variability in biological composition and potential batch-to-batch differences were not analyzed. Additionally, imaging follow-up and biomarker evaluations were not included, which limits mechanistic interpretation. Future multicenter, randomized controlled trials with standardized PRP protocols and longer follow-up are warranted. In summary, while PRP injections may offer transient symptomatic relief in KOA, our 5-year data indicate that they do not provide a distinct long-term advantage over conventional therapy. This underscores the importance of adopting a multimodal treatment strategy that emphasizes patient education, lifestyle modifications, and targeted pharmacotherapy, while continuing to refine regenerative approaches through rigorous clinical trials and mechanistic research. Declarations Author contributions Conceptualization, C.W. and Q.H.; methodology, C.W. and Q.H.; data analysis, C.W. and W.Q.; writing—original draft preparation, C.W. and W.Q.; writing—review and editing, C.W. , J.S and M.L.. All authors have read and agreed to the published version of the manuscript. Funding This research did not receive any specific grant from funding agencies in thepublic, commercial, or not-for-profit sectors. Availability of Data and Materials The datasets used in this study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The study was approved by the Ethics Committee of Affiliated Sport Hospital of Chengdu Sport University in accordance with the ethical guidelines of the Helsinkideclaration. Informed consent to participate was obtained from all subjects involved in the study. 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Osteoarthritis year in review 2019: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2020;28(3):296–315. Dai WL, Zhou AG, Zhang H, et al. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy. 2017;33(3):659–e670651. Nie LY, Zhao K, Ruan J, et al. Effectiveness of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Clinical Trials. Orthop J Sports Med. 2021;9(3):2325967120973284. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6436349","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453515144,"identity":"1356ede5-dcda-4783-bea5-1c8a9e9c1521","order_by":0,"name":"Chenghong Wen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYJACZhBhAOUkMLA3Nj78QIIWgwQGnsPNxhKkaZFIbxPgwaPc4Hjvwc8FFXfstrP3Hn7xcc+fPH7Jh20MEgx2croNOLScOZcsPePMs+SdPefSLGc8MyiWnJ3Y9qCAIdnY7AB2LWY3csyYedsOJxsAGcY8BwwSN9xObDeQYDiQuA2XlvtvgFr+IWu5ebBNggeflhs8QC0Nh+2AWowfg7XcYMSvxf5MjrE0z7HDCQZnzpgxzjhgnDizJxEYyAa4/SLZfsbwM0/NYXuD4z3GHz4ckEvsZz/+8OGHCjs5XFpgILGBgYENKQINcKpEOBCImQklk1EwCkbBKBihAAAMXmWAlqcYLwAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Sport Hospital of Chengdu Sport University","correspondingAuthor":true,"prefix":"","firstName":"Chenghong","middleName":"","lastName":"Wen","suffix":""},{"id":453515145,"identity":"86270d1c-df11-434d-bbb4-d02b9e288a6d","order_by":1,"name":"Qiang Hua","email":"","orcid":"","institution":"Affiliated Sport Hospital of Chengdu Sport University","correspondingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Hua","suffix":""},{"id":453515146,"identity":"a603f874-a4a1-424b-b379-dd4cab5ac341","order_by":2,"name":"Wenduo Qian","email":"","orcid":"","institution":"Affiliated Sport Hospital of Chengdu Sport University","correspondingAuthor":false,"prefix":"","firstName":"Wenduo","middleName":"","lastName":"Qian","suffix":""},{"id":453515147,"identity":"cfb296a8-7fb0-4d78-a47c-590ab9e072e6","order_by":3,"name":"Jide Su","email":"","orcid":"","institution":"Affiliated Sport Hospital of Chengdu Sport University","correspondingAuthor":false,"prefix":"","firstName":"Jide","middleName":"","lastName":"Su","suffix":""},{"id":453515148,"identity":"8fc3171d-0de5-44da-be2a-35405ff97fa4","order_by":4,"name":"Mingming Lei","email":"","orcid":"","institution":"Affiliated Sport Hospital of Chengdu Sport University","correspondingAuthor":false,"prefix":"","firstName":"Mingming","middleName":"","lastName":"Lei","suffix":""}],"badges":[],"createdAt":"2025-04-12 20:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6436349/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6436349/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89819985,"identity":"0d29a91b-64c2-4ee8-8ee7-5994cab81ac8","added_by":"auto","created_at":"2025-08-25 11:17:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":773766,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6436349/v1/a889ad99-8ac3-4b6c-a38b-a6ddf0b1c74b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-Term Efficacy of Intra-Articular PRP Injections Versus Conventional Therapy in Early-Stage Knee Osteoarthritis: A 5-Year Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKnee osteoarthritis (KOA) is a prevalent degenerative joint disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and synovial inflammation, culminating in chronic pain, functional disability, and diminished quality of life[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Globally, KOA impacts over 250\u0026nbsp;million individuals, with rising prevalence attributed to aging populations and increasing obesity rates[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Current non-surgical therapeutic strategies\u0026mdash;including oral analgesics, intra-articular corticosteroids, and hyaluronic acid (HA) injections\u0026mdash;focus predominantly on symptomatic relief but fail to halt disease progression or stimulate cartilage regeneration[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, regenerative therapies such as platelet-rich plasma (PRP) have gained attention for their potential to modulate inflammatory pathways, enhance tissue repair, and delay the need for surgical intervention[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePRP, an autologous blood product enriched with platelets and bioactive factors (e.g., PDGF, TGF-β, VEGF), exerts dual therapeutic mechanisms in KOA management: (1) suppression of pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and matrix metalloproteinases (MMPs) to attenuate cartilage breakdown, and (2) promotion of chondrocyte proliferation, extracellular matrix synthesis, and mesenchymal stem cell (MSC) differentiation to facilitate cartilage regeneration[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Clinical evidence suggests that PRP outperforms HA and corticosteroids in short-term pain reduction and functional improvement, particularly in early-stage KOA (Kellgren-Lawrence grades I\u0026ndash;III)[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nevertheless, findings remain contradictory. While certain randomized controlled trials (RCTs) report sustained efficacy of PRP at 12\u0026ndash;24 months, others, such as the RESTORE trial, demonstrate no significant advantage over placebo at 12 months[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Critically, long-term outcomes (\u0026gt;\u0026thinsp;5 years) remain underexplored, hindering definitive clinical consensus.\u003c/p\u003e \u003cp\u003eThis retrospective cohort study evaluates 58 early-stage KOA patients treated with intra-articular PRP injections at our institution, compared to 58 matched controls receiving conventional therapy (NSAIDs or HA). Our primary objective is to investigate the long-term clinical efficacy of intra-articular PRP in early-stage KOA, with emphasis on sustained symptom relief, functional outcomes, and protocol optimization.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was conducted with approval from the Institutional Review Board of Chengdu Sport University Affiliated Hospital (Ethics Committee reference number: [20240115]). Prior to data collection, written informed consent was obtained from all participants through comprehensive face-to-face consultations followed by formal documentation procedures. The investigation strictly adhered to the ethical principles outlined in the Declaration of Helsinki (2013 revision). All collected patient information was anonymized and processed in compliance with international data protection standards (GDPR) and China\u0026apos;s Personal Information Protection Law (PIPL) to ensure confidentiality and privacy safeguards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants and Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort study initially identified 136 consecutive patients with bilateral early-stage knee osteoarthritis (Kellgren-Lawrence Grade 1\u0026ndash;2) who received either a standardized management protocol for osteoarthritis (SMPO) combined with platelet-rich plasma (PRP) injections (at week 0, 2 and 4) (Group A) or SMPO alone (Group B) in both knee joints at our institution between January 2019 and December 2019.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStandardized Management Protocol for Osteoarthritis (SMPO):\u003c/em\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eCore Non-Pharmacological Interventions\u003cul\u003e\n \u003cli\u003ePatient Education: Implementation of disease-modifying lifestyle modification programs.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eWeight Management\u003cul\u003e\n \u003cli\u003eStructured plan targeting a\u0026nbsp;\u0026ge;5% reduction in body weight (as per ESCEO guidelines).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eExercise Therapy\u003cul\u003e\n \u003cli\u003eDaily neuromuscular training (30 minutes per day).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003ePharmacological Protocol (Acute Phase)\u003cul\u003e\n \u003cli\u003eFor cases of refractory pain (VAS\u0026nbsp;\u0026ge;4), initiate a 2-month therapeutic course using oral NSAIDs (e.g., celecoxib 200 mg once daily), topical NSAIDs (diclofenac gel three times daily), glucosamine sulfate (1500 mg daily), and diacerein (50 mg twice daily).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003ePost-Treatment Maintenance\u003cul\u003e\n \u003cli\u003eFollowing the 2-month pharmacotherapy phase, continue the foundational triad of education, weight control, and exercise.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cem\u003ePRP Preparation:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe collected 40 cc of blood from each patient. Ten milliliters of blood was sent to a certified tissue laboratory for control and quality testing, while the remaining 30 mL was manually processed in a sterile syringe to yield a total of 6 mL of leukocyte-depleted PRP (3 mL per knee). The 30 mL of blood was centrifuged in sodium citrate tubes at 400 g for 10 minutes; the plasma was collected and erythrocytes were discarded. The plasma was then centrifuged again at 800 g for 15 minutes, the supernatant was discarded, and the pellet was resuspended to the desired volume.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInclusion Criteria:\u003c/em\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eRadiologically confirmed bilateral knee osteoarthritis (KL Grade 1\u0026ndash;2) (defined according to the MRI and/ or radiography).\u003c/li\u003e\n \u003cli\u003eFailure of at least 3 months of continuous foundational triad therapy (education, weight control, exercise).\u003c/li\u003e\n \u003cli\u003eAcute phase bilateral knee pain (VAS\u0026nbsp;\u0026ge;4).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cem\u003eExclusion Criteria:\u003c/em\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eSystemic inflammatory or autoimmune arthritis.\u003c/li\u003e\n \u003cli\u003eHistory of major knee trauma or surgery.\u003c/li\u003e\n \u003cli\u003eSevere meniscal pathology causing mechanical symptoms.\u003c/li\u003e\n \u003cli\u003eIntra-articular interventions within the previous 3 months.\u003c/li\u003e\n \u003cli\u003eHematologic, oncologic, or metabolic comorbidities.\u003c/li\u003e\n \u003cli\u003eAnticoagulant or antiplatelet therapy.\u003c/li\u003e\n \u003cli\u003eInability to complete a 5-year follow-up.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cem\u003eExclusion Rationale:\u003c/em\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eTwo cases were excluded due to uncontrolled diabetes mellitus.\u003c/li\u003e\n \u003cli\u003eFour subjects who had undergone total knee arthroplasty by the five-year follow-up were excluded.\u003c/li\u003e\n \u003cli\u003eFive subjects with recent intra-articular hyaluronic acid injections were excluded.\u003c/li\u003e\n \u003cli\u003eSix screening candidates declined to provide informed consent.\u003c/li\u003e\n \u003cli\u003eThree participants were lost to follow-up within 60 months.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAfter applying stringent eligibility criteria, 116 subjects were enrolled for final analysis (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObservation indicators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt 5 years following the initial treatment, both patient groups underwent comprehensive evaluation using multiple standardized outcome measures. These included the acute phase Visual Analog Scale (VAS) for pain intensity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [10] for assessing pain, stiffness, and physical function and the SF-36 Health Survey for overall quality of life [11]. The VAS provides a simple and validated method for quantifying pain on a scale of 0 to 10 [12]. The WOMAC index, widely recognized in osteoarthritis research, has been established as a reliable tool to capture the multidimensional impact of joint degeneration on daily activities [13]. While the SF-36 questionnaire enables a holistic appraisal of health-related quality of life across various domains [14]. Together, these measures offer a comprehensive, multidimensional evaluation of the long-term clinical efficacy of the treatment protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables are presented as mean \u0026plusmn; standard deviation, while categorical data are reported as frequencies with percentages. Between-group comparisons of continuous variables were analyzed using independent samples Student\u0026apos;s t-tests. Categorical variables were compared using Pearson\u0026apos;s chi-square test. All analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA), with statistical significance defined as a two-tailed P-value \u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size and Post Hoc Power Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA post hoc power analysis was performed to evaluate whether the sample size was sufficient to detect a clinically meaningful difference in Visual Analog Scale (VAS) scores between the two groups at the 5-year follow-up. Assuming a two-tailed \u0026alpha; = 0.05, a standard deviation of 1.2, and a minimal clinically important difference (MCID) of 1.0 in VAS scores, the calculated power for the current sample size (n = 58 per group) was 84.3%. Therefore, the study was adequately powered to detect clinically relevant differences between groups for the primary outcome.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eGeneral Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom January 2019 to December 2019,\u0026nbsp;a total of 116 patients (58 per group) with bilateral early-stage knee osteoarthritis (Kellgren-Lawrence Grade I-II) enrolled in this retrospective cohort study. Patients were divided into Group A, receiving a standardized management protocol for osteoarthritis (SMPO) combined with platelet-rich plasma (PRP) injections at weeks 0, 2, and 4, and Group B, receiving SMPO alone. No statistically significant differences were observed between the groups in gender distribution (Female: 72.4% vs. 69.0%; Male: 27.6% vs. 31.0%; \u003cem\u003eP\u003c/em\u003e = 0.166), mean age (50.48\u0026plusmn;2.74 vs. 51.05\u0026plusmn;2.74 years; \u003cem\u003eP\u003c/em\u003e = 0.575), K-L classification (Grade I: 32 vs. 34; Grade II: 26 vs. 24; \u003cem\u003eP\u003c/em\u003e = 0.141), or BMI (25.40 \u0026plusmn; 0.62 vs. 25.25 \u0026plusmn; 0.44 kg/m\u0026sup2;; P = 0.152). Statistical analyses using chi-square (\u0026chi;\u0026sup2;) and t-tests confirmed homogeneity in baseline parameters (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05 for all), ensuring comparability between groups. This balanced baseline profile supports the validity of subsequent outcome comparisons between SMPO+PRP and SMPO-only interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Patient Demographics\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"630\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003eGroup A (n=58)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003eGroup B (n=58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eStatistical Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cem\u003eP Value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eFemale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e42（72.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e40（69.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e=0.683\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eMale (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e16（27.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e18（31.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e50.48\u0026plusmn;2.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e51.05\u0026plusmn;2.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-1.117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eK-L Classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eGrade I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e=0.708\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eGrade II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBody Mass Index (kg/m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e25.40\u0026plusmn;0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e25. 25\u0026plusmn;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et=\u003c/em\u003e1.442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eVisual Analog Scale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study compared baseline and 5-year postoperative Visual Analog Scale (VAS) pain scores between Group A (n=58) and Group B (n=58). At baseline, Group A had a mean VAS score of 4.64\u0026plusmn;0.52, while Group B scored 4.80\u0026plusmn;0.59, with no statistically significant difference between groups (\u003cem\u003et\u003c/em\u003e = -1.510, \u003cem\u003eP\u003c/em\u003e=0.406). By the 5th year, VAS scores increased in both groups: Group A to 5.41\u0026plusmn;1.17 and Group B to 5.44\u0026plusmn;1.16, but the intergroup difference remained non-significant (\u003cem\u003et\u003c/em\u003e=-0.160, \u003cem\u003eP\u003c/em\u003e=0.849). The table demonstrates no long-term divergence in pain outcomes between the two groups over the 5-year follow-up period (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Visual Analog Scale, WOMAC and IKDC score\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"630\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003eGroup A (n=58)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003eGroup B (n=58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eStatistical Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cem\u003eP Value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eVAS score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e4.64\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e4.80\u0026plusmn;0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-1.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.406\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e5.41\u0026plusmn;1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e5.44\u0026plusmn;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eWOMAC score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study compared WOMAC scores (pain, stiffness, physical function) between Group A (n=58) and Group B (n=58) at baseline and 5-year follow-up. Baseline scores showed no significant intergroup differences (e.g., pain: 8.41\u0026plusmn;2.12 vs. 8.64\u0026plusmn;2.35, t = -0.620, P = 0.537). By the 5th year, scores worsened comparably in both groups, such as pain increasing to 9.76\u0026plusmn;3.52 (Group A) and 9.43\u0026plusmn;3.41 (Group B) (t = 0.520, P = 0.606). Similar trends were observed for stiffness and physical function. No statistically significant differences were detected between groups at either time point (P \u0026gt; 0.05 for all comparisons, Table 3), indicating parallel declines in WOMAC outcomes over 5 years with no meaningful intergroup disparities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. WOMAC score\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"630\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003eGroup A (n=58)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003eGroup B (n=58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eStatistical Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cem\u003eP Value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e8.41\u0026plusmn;2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e8.64\u0026plusmn;2.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e9.76\u0026plusmn;3.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e9.43\u0026plusmn;3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.606\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eStiffness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e3.02\u0026plusmn;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e2.98\u0026plusmn;0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.812\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e4.02\u0026plusmn;1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e3.95\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003ePhysical Function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e19.83\u0026plusmn;3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e20.12\u0026plusmn;3.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e26.53\u0026plusmn;7.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e25.78\u0026plusmn;8.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.632\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eSF-36 Health Survey\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study compared SF-36 Health Survey scores between Group A (n=58) and Group B (n=58) at baseline and 5-year follow-up. For all eight domains (e.g., Physical Functioning, Role Physical, Bodily Pain), baseline scores showed no significant intergroup differences (P \u0026gt; 0.05). At the 5th year, scores declined comparably in both groups across most domains. For example, Physical Functioning decreased from 57.34\u0026plusmn;10.89 (Group A) and 57.12\u0026plusmn;11.25 (Group B) at baseline to 49.78\u0026plusmn;6.89 and 49.64\u0026plusmn;6.52, respectively (t = 0.110\u0026ndash;1.210, P = 0.230\u0026ndash;0.920). Similarly, Role Emotional scores declined from 74.16\u0026plusmn;5.62 (Group A) and 75.05\u0026plusmn;5.94 (Group B) to 68.24\u0026plusmn;6.37 and 69.16\u0026plusmn;6.72 (t = 0.820, P = 0.410). Notably, no statistically significant differences were observed between groups at either time point for any domain (P \u0026gt; 0.05 for all comparisons, Table 4). These results indicate parallel declines in health-related quality of life over 5 years in both groups, with no meaningful intergroup disparities (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e. SF-36 Health Survey\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"630\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003eGroup A (n=58)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003eGroup B (n=58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eStatistical Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cem\u003eP Value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003ePhysical Functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e57.34\u0026plusmn;10.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e57.12\u0026plusmn;11.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e49.78\u0026plusmn;6.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e49.64\u0026plusmn;6.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.900\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eRole Physical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e53.62\u0026plusmn;7.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e53.48\u0026plusmn;8.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.920\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e47.12\u0026plusmn;4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e48.05\u0026plusmn;5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBodily Pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e54.08\u0026plusmn;4.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e54.97\u0026plusmn;5.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e47.26\u0026plusmn;5.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e48.14\u0026plusmn;5.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=\u0026nbsp;0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eGeneral Health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e61.34\u0026plusmn;5.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e62.95\u0026plusmn;6.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e55.24\u0026plusmn;6.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e56.12\u0026plusmn;6.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.450\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eVitality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e65.34\u0026plusmn;5.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e67.12\u0026plusmn;5.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e62.14\u0026plusmn;6.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e63.26\u0026plusmn;6.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eSocial Functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e70.53\u0026plusmn;6.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e71.63\u0026plusmn;6.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e64.52\u0026plusmn;5.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e65.43\u0026plusmn;5.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eRole Emotional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e74.16\u0026plusmn;5.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e75.05\u0026plusmn;5.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e68.24\u0026plusmn;6.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e69.16\u0026plusmn;6.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.410\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eMental Health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e76.84\u0026plusmn;4.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e78.24\u0026plusmn;5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=1.350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e67.84\u0026plusmn;6.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e69.05\u0026plusmn;7.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 1.280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eHealth Change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e3.02\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e3.10\u0026plusmn;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=0.810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e5\u003csup\u003eth\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e3.37\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e3.48\u0026plusmn;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e= 0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe long-term follow-up data presented in this study indicate that, at the 5-year mark, intra-articular platelet-rich plasma (PRP) injections do not offer statistically significant benefits compared with conventional management protocols in terms of pain, functional status, and quality of life among patients with early-stage KOA. These findings are in line with several recent randomized controlled trials and systematic reviews that have questioned the sustained clinical efficacy of PRP beyond the short-term improvements reported in previous studies [1, 4, 8, 9, 15].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLack of Long-Term Superiority\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite initial expectations and promising short-term data\u0026mdash;where PRP has been shown to modulate inflammatory mediators, promote chondrocyte proliferation, and enhance extracellular matrix synthesis [2, 5] \u0026mdash;our study\u0026rsquo;s 5-year follow-up reveals comparable deterioration in pain scores (as measured by VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and SF-36 scores between PRP-treated patients and the control group. Similar observations have been reported in studies such as Bennell et al. [9] and Yurtbay et al. [8], while additional longitudinal analyses have reported transient benefits that do not persist [16, 17]. It is noteworthy that while some short- and mid-term trials indicate transient benefits [6, 7], these improvements tend to attenuate over time. This phenomenon may be related to the progressive nature of osteoarthritis and the multifactorial etiology of joint degeneration [2, 3, 18]. Our findings underscore the possibility that the initially observed improvement may be due to placebo effects or short-term biological modulation that is insufficient to alter the natural history of the disease in the long run.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiological Mechanisms and PRP Variability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePRP preparations, although rich in growth factors such as PDGF, TGF-\u0026beta;, and VEGF, present considerable variability in platelet concentration and bioactive factor content [4, 5]. This heterogeneity could contribute to inconsistent clinical outcomes across studies. In fact, recent evidence suggests that variations in the cytokine profile and growth factor composition of PRP may lead to different therapeutic responses [17]. Variability in preparation protocols, injection intervals, and even patient-specific factors (such as baseline inflammation and activity level) may lead to different therapeutic responses [18]. Novel imaging studies have demonstrated that the biochemical composition of cartilage may change over time following PRP injections, potentially affecting long-term outcomes [18]. In our study, the standardized preparation of leukocyte-depleted PRP did not translate into long-term clinical benefit, which is consistent with meta-analytic data suggesting that the magnitude of benefit diminishes with time [19].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparison with Conventional Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe control group in our study was managed with a standardized protocol including patient education, weight management, exercise therapy, and pharmacological interventions (primarily NSAIDs). Remarkably, both groups experienced parallel declines in functional scores and quality of life measures over 5 years. This suggests that for early-stage KOA, the conventional management approach is as effective as adding PRP injections in terms of long-term outcomes. This is supported by evidence from large-scale studies and recent systematic reviews comparing PRP with hyaluronic acid and corticosteroid injections, where no significant long-term differences were detected [7, 20].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor practicing clinicians, the present findings emphasize the importance of managing patient expectations regarding PRP therapy for KOA. While the short-term benefits may offer temporary relief, our evidence does not support a significant long-term advantage regarding pain reduction, joint function, or overall quality of life. This highlights the need for a balanced treatment approach that integrates non-pharmacological interventions and considers PRP as an adjunct rather than a definitive long-term solution [1, 2, 7]. Clinicians should also be aware of the potential economic implications and patient burden associated with repeated injections, especially when long-term superiority is not established [21].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodological Considerations and Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is critical to acknowledge some limitations in our study. First, the retrospective design may entail inherent biases, including selection bias and loss to follow-up. Although baseline characteristics were balanced between the groups, unaccounted confounders may still exist. Second, the sample size\u0026mdash;although adequate for the current analysis\u0026mdash;may not be sufficiently powered to detect smaller but clinically relevant differences between treatments. Future studies should incorporate larger, multicenter designs and robust randomization procedures to validate these findings. Lastly, variations in PRP formulation and injection technique remain an important source of heterogeneity in the literature. Standardization of protocols across studies might offer clearer insights into the true efficacy of PRP [22-24].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications for Future Research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFuture research is warranted to address several unanswered questions. First, there is a need for well-designed randomized controlled trials (RCTs) with longer follow-up periods that compare different PRP formulations (e.g., leukocyte-rich vs. leukocyte-poor) as well as different dosing schedules. Second, mechanistic studies exploring the molecular interactions between PRP constituents and joint tissues could elucidate why short-term benefits are not sustained over longer periods [25, 26]. Finally, biomarker studies may help identify patient subgroups more likely to respond to PRP treatment, thereby paving the way for personalized medicine approaches in osteoarthritis treatment [27]. Future PRP research should focus on more constructive directions such as individual variability in treatment response and biomarkers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntegration with Current Literature\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn extensive body of literature now suggests that while PRP injections are a promising intervention for early-stage knee osteoarthritis, the current evidence calls for cautious interpretation of its long-term benefits. In addition to our findings, recent authoritative studies such as Tang et al. [1] and the Global Burden of Disease Study on osteoarthritis [2] have highlighted the complex interplay between degenerative changes and inflammation that may not be fully mitigated by PRP alone. Furthermore, systematic reviews and meta-analyses have demonstrated that the long-term functional and symptomatic outcomes of PRP are at best comparable to conventional treatments, which reinforces the notion that additional research is required to optimize treatment protocols [28, 29].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the retrospective nature of the design may introduce selection bias and limits causal inference. Second, the study was conducted at a single center, which may reduce generalizability. Third, although the PRP preparation was standardized, variability in biological composition and potential batch-to-batch differences were not analyzed. Additionally, imaging follow-up and biomarker evaluations were not included, which limits mechanistic interpretation. Future multicenter, randomized controlled trials with standardized PRP protocols and longer follow-up are warranted.\u003c/p\u003e\n\u003cp\u003eIn summary, while PRP injections may offer transient symptomatic relief in KOA, our 5-year data indicate that they do not provide a distinct long-term advantage over conventional therapy. This underscores the importance of adopting a multimodal treatment strategy that emphasizes patient education, lifestyle modifications, and targeted pharmacotherapy, while continuing to refine regenerative approaches through rigorous clinical trials and mechanistic research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, C.W. and Q.H.; methodology, C.W. and Q.H.; data analysis, C.W. and W.Q.; writing\u0026mdash;original draft preparation, C.W. and W.Q.; writing\u0026mdash;review and editing, C.W. , J.S and M.L.. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in thepublic, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used in this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Affiliated Sport Hospital of Chengdu Sport University in accordance with the ethical guidelines of the Helsinkideclaration. Informed consent to participate was obtained from all subjects involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior to the study, all participants signed an informed consent form agreeing to the publication of the information/images in this research. The subject of the images signed the consent form agreeing to publication in an online open-access journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTang S, Yao L, Ruan J, et al. Single-cell atlas of human infrapatellar fat pad and synovium implicates APOE signaling in osteoarthritis pathology. Sci Transl Med. 2024;16(731):eadf4590.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaborators GBDO. Global, regional, and national burden of osteoarthritis, 1990\u0026ndash;2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(9):e508\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMintarjo JA, Poerwanto E, Tedyanto EH. Current Non-surgical Management of Knee Osteoarthritis. Cureus. 2023;15(6):e40966.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePelluri R, Sridevi B, Guntupalli C, et al. Effect of platelet-rich plasma versus placebo or corticosteroid for knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials. J Clin Orthop Trauma. 2025;62:102870.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePartan RU, Putra KM, Hafizzanovian H et al. Clinical Outcome of Multiple Platelet-Rich Plasma Injection and Correlation with PDGF-BB in the Treatment of Knee Osteoarthritis. J Pers Med 2024, 14(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou S, Guan A, Guan Z, et al. Clinical efficacy analysis of autologous PRP combined with arthroscopy in the treatment of stage II-III KOA. Minerva Surg.; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Q, Ye H, Yang Y, et al. The efficacy and safety of intra-articular platelet-rich plasma versus sodium hyaluronate for the treatment of osteoarthritis: Meta-analysis. PLoS ONE. 2025;20(3):e0314878.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYurtbay A, Say F, Cinka H, et al. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2022;142(10):2755\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBennell KL, Paterson KL, Metcalf BR, 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;326(20):2021\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBellamy N, Buchanan WW, Goldsmith CH, et al. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15(12):1833\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWare JE Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBjelkaroy MT, Benth JS, Simonsen TB, et al. Measuring pain intensity in older adults. 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Knee Surg Sports Traumatol Arthrosc. 2016;24(5):1665\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCole BJ, Karas V, Hussey K, et al. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017;45(2):339\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoeser RF, Goldring SR, Scanzello CR, et al. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697\u0026ndash;707.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen L, Yuan T, Chen S, et al. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017;12(1):16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen P, Huang L, Ma Y, et al. Intra-articular platelet-rich plasma injection for knee osteoarthritis: a summary of meta-analyses. J Orthop Surg Res. 2019;14(1):385.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamuelson EM, Ebel JA, Reynolds SB, et al. The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis. Arthroscopy. 2020;36(12):3072\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChahla J, Cinque ME, Piuzzi NS, et al. A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting: A Systematic Review of the Clinical Orthopaedic Literature. J Bone Joint Surg Am. 2017;99(20):1769\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTey RV, Haldankar P, Joshi VR et al. Variability in Platelet-Rich Plasma Preparations Used in Regenerative Medicine: A Comparative Analysis. Stem Cells Int. 2022, 2022:3852898.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMazzocca AD, McCarthy MB, Chowaniec DM, et al. Platelet-rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am. 2012;94(4):308\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFortier LA, Cole BJ. The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in Osteoarthritis: Response to Patel and Dhillon. Am J Sports Med. 2014;42(6):NP31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Z, Zhu P, Liao B, et al. Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis. J Orthop Surg Res. 2023;18(1):713.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Spil WE, Szilagyi IA. Osteoarthritis year in review 2019: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2020;28(3):296\u0026ndash;315.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDai WL, Zhou AG, Zhang H, et al. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy. 2017;33(3):659\u0026ndash;e670651.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNie LY, Zhao K, Ruan J, et al. Effectiveness of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Clinical Trials. Orthop J Sports Med. 2021;9(3):2325967120973284.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Knee, Osteoarthritis, PRP, Long-Term Efficacy","lastPublishedDoi":"10.21203/rs.3.rs-6436349/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6436349/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the long-term clinical efficacy of intra-articular platelet-rich plasma (PRP) injections compared to conventional therapy in patients with early-stage knee osteoarthritis (KOA). We focused on assessing improvements in pain, joint function, and quality of life over a 5-year period.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted involving 116 patients with bilateral early-stage KOA (Kellgren\u0026ndash;Lawrence Grade I\u0026ndash;II) treated between January 2019 and December 2019. Patients were divided into two groups: Group A received a standardized management protocol for osteoarthritis (SMPO) combined with three PRP injections administered at weeks 0, 2, and 4, while Group B received SMPO alone. Outcome measures, including the Visual Analog Scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for joint function, and the SF-36 Health Survey for quality of life, were assessed at baseline and at the 5-year follow-up.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBoth groups demonstrated a progressive decline in outcome scores over the 5-year follow-up, indicating worsening pain, function, and quality of life. However, statistical comparisons revealed no significant differences between the PRP-treated group and the control group across all evaluated parameters (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe long-term results indicate that intra-articular PRP injections do not provide significant advantages over conventional management in early-stage knee osteoarthritis. These findings highlight the need for further research to optimize PRP treatment protocols and explore potential patient subgroups that might benefit from this regenerative therapy approach.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e","manuscriptTitle":"Long-Term Efficacy of Intra-Articular PRP Injections Versus Conventional Therapy in Early-Stage Knee Osteoarthritis: A 5-Year Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 16:25:36","doi":"10.21203/rs.3.rs-6436349/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d483939e-8307-4fd4-8ba1-b39aa3be4bf4","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T11:08:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 16:25:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6436349","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6436349","identity":"rs-6436349","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}