Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment

Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment | 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 Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment Tsuneo Kawahara, Shuhei Iida, Kazuma Isoda, Sungdo Kim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4534999/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 Background Platelet-rich plasma (PRP) therapy is a promising treatment modality for knee osteoarthritis (OA). However, exercise therapy and activity of daily living (ADL) guidance are also recommended as core treatments in the Osteoarthritis Research Society International (OARSI) guidelines. However, there is limited research on the efficacy of combined PRP and exercise therapy. This study aimed to verify the effectiveness of this combined treatment. Methods The participants were patients diagnosed with knee OA and treated between January 2021 and December 2022. They were divided into three groups: 1) PRP + exercise therapy (PE group), 2) PRP therapy only (P group), and 3) exercise therapy only (E group). Outcomes were measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and conducted before, 1 month, 3 months, and 1 year after treatment. Statistical analysis was performed using a one-way analysis of variance for within-group comparisons according to the time of each score. For those that showed a difference, the Bonferroni multiple comparison method was used to validate the results (p < 0.05). The treatment response rate was determined using the Outcome Measures in Rheumatology (OMERACT)-OARSI Responder criteria. Results There were no differences in pre-treatment KOOS between the three groups. In the PE group, pain, symptoms, and ADL improved after 1 month and continued to improve until 1 year. The P group showed improvement in pain after 1 month, but no significant changes were observed in the other items. In contrast, the E group showed improvement in each item from 3 months onwards, with all items remaining unchanged at 1 year. The PE group had a higher response rate than the other groups, with 50.0% at 1 month, 56.3% at 3 months, and 68.8% at 1 year, according to the responder criteria. Conclusions The combined treatment of PRP and exercise therapy demonstrated the synergistic advantages of both and proved to be most effective up to 1 year after treatment. Platelet-rich plasma exercise therapy knee osteoarthritis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background While platelet-rich plasma (PRP) has been shown to possess anti-inflammatory properties by modulating the canonical nuclear factor κB signaling pathway in multiple cell types, including synoviocytes, macrophages, and chondrocytes; however, the cellular and molecular mechanisms underlying this potential therapeutic effect remain poorly understood [ 1 ]. PRP was initially used for bone graft regeneration in oral surgery and has subsequently been used in many fields, including cosmetics and sports orthopedics [ 2 , 3 , 4 ]. Many reports have been published on its efficacy in promoting healing during the repair of various soft tissues such as the rotator cuff, Achilles tendon, ligaments, and bones [ 5 , 6 , 7 ]. Several systematic reviews on the use of PRP for knee osteoarthritis (OA) have shown short-term therapeutic effects [1,8,9.10]. Its effectiveness was also demonstrated by a consensus at the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) in 2022 [ 11 ]. Exercise therapy for patients with knee OA was considered 'core treatment' in the 2014 Osteoarthritis Research Society International (OARSI) guidelines and remained so in the 2019 guidelines [ 12 , 13 ]. Patient education was also classified as a 'core treatment,' although it was noted that randomized controlled trial (RCT) data were lacking. This classification is consistent with the latest Japanese clinical practice guidelines [ 14 ]. Several studies have reported the therapeutic efficacy of combined therapies for treating knee OA. In 62 patients with knee OA, Rayegani et al. showed that intra-articular PRP knee joint injections, combined with exercise therapy, were effective in reducing pain and improving stiffness and quality of life compared with exercise therapy alone [ 15 ]. Badr et al. also divided 60 patients with knee OA into three groups according to treatment modality (PRP plus exercise, PRP alone, and exercise alone) and found that the combination treatment group showed the most significant changes in the visual analog scale, Western Ontario and McMaster Universities (WOMAC) score, and joint tenderness after 6 months of treatment [ 16 ]. However, there are few to no reports on the effectiveness of PRP treatment combined with exercise therapy 1 year after treatment. Therefore, this study aimed to examine the efficacy of combined PRP and exercise therapy for up to 1 year post-treatment. Methods The participants were patients diagnosed with knee OA and treated between January 2021 and December 2022. Exclusion criteria included inflammatory arthritis, acute trauma, previous lower limb fracture or surgery, and inability to continue treatment. The participants were divided into three groups: (1) PRP and exercise therapy (PE group), (2) PRP therapy only (P group), and (3) exercise therapy only (E group). As a rule, the doctor presented these treatment methods to the patient during the regular medical treatment consultation, and the patient made the choice. Great care was taken to ensure no intentional influence from the doctor. The allocation of participants to each group was based on the report by Badr et al. [ 16 ], and the data collection flowchart is shown in Fig. 1 . For PRP therapy, PRP was prepared with a dedicated kit (MyCells®) after blood collection from the patient. Centrifugation was performed at 3,500 rpm for 7 min. The platelet type was leukocyte-poor PRP. For exercise therapy, the patients were interviewed more specifically about the movements they needed to perform daily and at work. They were given specific advice on how to use each body part and how to be aware of the position of the center of gravity when performing these movements from a kinematic perspective. Additionally, orthodox physiotherapy was provided to improve physical functions such as joint range of motion, muscle strength, and balance ability. The therapy was conducted 1–2 times per week. The Knee Injury and Osteoarthritis Outcome Score (KOOS) has been used in periodic surveys and consists of five subscales—pain, symptom, activity of daily living (ADL), sports, and quality of life—and demonstrates good test-retest reproducibility. Furthermore, the validated WOMAC assesses the knee OA index in its complete and original form and correlates with the SF-36 (Medical Outcomes Study [MOS] short form 36 health survey) and the Lysholm knee scoring scale, making it appropriate for the study [ 17 , 18 ]. The survey was conducted at four timepoints: pre-treatment, 1 month post-treatment, 3 months post-treatment, and 1 year post-treatment. The Outcome Measures in Rheumatology (OMERACT) responder criteria from the OARSI were used to determine the treatment response outcome in this study. Pham et al. (2004) used the KOOS score to assess responder status, indicating the presence of a treatment effect [ 19 ]. The effectiveness assessment flowchart is shown in Fig. 2 . Statistical analyses were performed using FreeJSTAT Ver. 13.0. The changes over time in each group and differences between groups in terms of the amount of change over time were tested using a one-way analysis of variance. Significant differences were further analyzed using the Bonferroni multiple comparison method (p < 0.05). Results Data were collected for up to one year for 16 patients in the PE group, 15 patients in the P group, and 18 patients in the E group. Table 1 presents the baseline data and KOOS values for each group. At baseline, the KOOS values did not differ significantly between groups. Table 1. Basic data and KOOS at baseline data PE group P group E group n 16 15 18 Age 69.9 ± 8.7 70.3 ± 11.1 74.8 ± 6.0 KL Ⅱ:9, Ⅲ:5, Ⅳ;2 Ⅰ:1, Ⅱ:8, Ⅲ:6 Ⅱ:7, Ⅲ:7, Ⅳ;4 Flexion ROM 124.1 ± 11.9 121.9 ± 10.9 126.1 ± 11.3 Extension ROM -5.6 ± 5.1 -6.3 ± 5.0 -5.6 ± 5.4 KOOS baseline Pain 53.0 ± 20.7 61.7 ± 12.5 56.3 ± 12.7 Symptom 57.4 ± 18.7 66.9 ± 16.8 61.9 ± 17.0 ADL 71.7 ± 17.5 80.3 ± 12.2 70.9 ± 14.3 Sports 42.2 ± 26.7 54.7 ± 19.8 38.3 ± 18.3 QOL 38.7 ± 20.3 47.9 ± 14.9 42.7 ± 17.4 Total 58.6 ± 16.9 67.9 ± 10.9 59.7 ± 12.4 Basic data and KOOS scores at baseline for participants in each group are shown. Values are presented as mean ± standard deviation. KL, Kellgren Lawrence; ROM, range of motion; KOOS, Knee Injury and Osteoarthritis Outcome Score; ADL, activity of daily living; QOL, quality of life The changes in scores over the course of treatment are shown in Table 2 and Fig. 3 . In the PE group, pain, symptoms, and ADL improved after 1 month and continued to improve until 1 year. The P group showed improvement in the pain item after 1 month; however, there was no significant change in the other items. The E group showed improvement in each item after 3 months, with all items remaining the same after 1 year. Table 2. KOOS in each period PE group P group E group KOOS 1M Pain 70.5 ± 16.4 78.7 ± 14.0 62.7 ± 12.4 Symptom 68.3 ± 16.1 79.0 ± 9.7 63.7 ± 13.7 ADL 81.1 ± 11.9 86.3 ± 13.1 75.9 ± 14.7 Sports 53.1 ± 26.9 67.0 ± 17.5 43.6 ± 20.8 QOL 50.8 ± 17.5 55.8 ± 13.5 45.1 ± 17.5 Total 70.5 ± 14.2 78.3 ± 11.0 64.3 ± 13.2 KOOS 3M Pain 76.4 ± 13.2 83.1 ± 13.0 67.7 ± 13.4 Symptom 75.9 ± 14.0 80.7 ± 11.2 67.5 ± 14.8 ADL 86.5 ± 7.0 89.2 ± 10.3 79.2 ± 14.2 Sports 59.7 ± 22.3 73.3 ± 17.4 47.5 ± 22.5 QOL 60.5 ± 18.2 65.4 ± 16.2 50.7 ± 18.0 Total 76.9 ± 10.2 82.3 ± 10.9 68.3 ± 13.7 KOOS 1Y Pain 77.1 ± 17.5 85.3 ± 12.2 76.5 ± 14.4 Symptom 76.3 ± 15.0 82.1 ± 16.0 77.0 ± 12.6 ADL 83.1 ± 12.6 92.6 ± 9.5 84.1 ± 10.1 Sports 54.7 ± 25.5 80.0 ± 24.0 58.6 ± 20.5 QOL 57.8 ± 26.0 74.1 ± 22.1 56.6 ± 22.6 Total 74.9 ± 14.6 86.1 ± 12.7 75.6 ± 12.1 The KOOS for each period in each group is presented. Values are presented as mean ± standard deviation. KOOS, Knee Injury and Osteoarthritis Outcome Score; ADL, activity of daily living; QOL, quality of life The treatment response according to the responder criteria is shown in Fig. 4 . At 1 month, 50.0% of the PE group, 53.3% of the P group, and 22.2% of the E group, with the E group showing clearly lower values. At 3 months, 56.3% in the PE group, 53.3% in the P group, and 44.4% in the E group showed improvement in each group. After 1 year, 68.8% of the PE group and 61.1% of the E group showed improvement, with a slight decline in PRP alone (46.6% of the P group), while the E group showed a much higher value than in the previous timepoints, indicating late improvement. Discussion This study is the first to examine the efficacy of PRP combined with exercise therapy for up to 1 year after treatment. Many guidelines have shown the effectiveness of exercise therapy for knee OA. The latest OARSI guidelines, reported in 2019, offer comprehensive and patient-centered treatment profiles for individuals with knee, hip, and polyarticular OA [ 13 ]. This treatment modality facilitates individualized treatment decisions for OA management [ 13 ]. The panel considered structured land-based exercise programs, dietary weight management in combination with exercise, and mind-body exercises (such as Tai Chi and Yoga) to be effective and safe for all patients with knee OA, regardless of comorbidities [ 13 ]. Conversely, aquatic exercise, which is supported by a modest evidence base and demonstrates robust benefits on pain and objective measures of function, was previously recommended alongside land-based exercise in previous guidelines. However, it received a conditional recommendation because of accessibility issues, financial burden, and uptake concerns [ 13 ]. However, the number of sets of specific exercises to be performed during exercise therapy was not specified. This omission may stem from the need to tailor exercise regimens to the patient’s individual physical characteristics and social circumstances. The author of this paper believes that patient education is important in this respect. In clinical practice, patients receive monthly written instructions outlining knee OA, detailing changes in their symptoms and the prescribed physiotherapy regimen (including a self-training menu), and proceed only after signing a consent form. Patient education is also considered a standard treatment according to the OARSI guidelines, despite the lack of RCT data [ 13 ]. Considering the individuality of patients influenced by variations in their living environments, reference can also be made to the Japanese practice guidelines. The latest edition of these guidelines was revised in 2023 [ 14 ]. These guidelines also affirm the effectiveness of exercise therapy and patient education in managing knee OA. Patient education encompasses instructions for real-life and work-related activities. Often, movements and weight distribution in daily routines are performed in a familiar manner, which may inadvertently exacerbate symptoms. According to Sahrmann’s kinesiopathological model of the movement system [ 20 ], detecting abnormal movement is important. In terms of teaching movement in real-life scenarios, the effectiveness of motor skill training (MST) was demonstrated by van Dillen et al. [ 21 ]. Although their study focused on patients with low back pain (LBP), individuals with chronic LBP who underwent MST had greater short-term and long-term improvements in function compared to those who received strength and flexibility exercises (SFE) [ 21 ]. van Dillen et al. suggested that person-specific MST tailored to functional activities limited by LBP should be considered in the treatment of patients with chronic LBP [ 21 ]. The results of our study indicated a delayed onset of the benefits of exercise therapy. This can be attributed to the fact that exercise therapy at the clinic was provided 1–2 times a week for 40 min per session. Therefore, it took longer than 1 month for motor learning to improve body perception and movement, with the effectiveness becoming evident after 3 months and continuing for 1 year. In this study, we demonstrated the anti-inflammatory and pain-relieving effects of PRP therapy for knee OA, which showed a high therapeutic effect 1 month after treatment. These results were comparable to those of previous reports. According to the latest consensus by ESSKA, PRP is effective in patients with mild to moderate OA (KL grade 3 or less), as indicated by Grade A evidence. It provides greater and longer-lasting symptomatic improvement compared to hyaluronic acid injections (Grade B), and it also offers longer-lasting symptomatic improvement than steroid injections. Moreover, PRP therapy is not chondrotoxic (Grade A) and has demonstrated cartilage regeneration. While one animal study has shown other disease-modifying effects, evidence in humans is still lacking (Grade C) [ 11 ]. Currently, PRP therapy is primarily positioned as a treatment for symptomatic improvement in knee OA. The high pain-relieving effect reported in previous studies is consistent with the results of this study; however, the long-term durability of the treatment effect differs from our findings, which showed a slight decrease in efficacy after 1 year of treatment. This is a limitation of PRP therapy, and future research is needed to determine the effective platelet concentration and optimal frequency of treatment. In our study, some patients received multiple PRP treatments, in which case the timing of the first PRP treatment was used as the baseline, and the data were analyzed as a single group. The KOOS values for the P group also showed a slightly higher score at baseline. However, the difference was not statistically significant, suggesting that the treatment effect was less apparent than in the other groups. Furthermore, the combination of PRP and exercise therapy in this study showed the highest therapeutic efficacy, aligning with previous reports. The strong anti-inflammatory and pain-relieving properties of PRP are thought to promote the ease of engaging in active exercise therapy at the early stages of treatment. Badr et al. also observed similar trends, noting that combined PRP and exercise therapy outperformed PRP or exercise therapy alone, indicating an additive effect. However, their data were limited to 6 months post-treatment [ 16 ]. They further emphasized the need for additional research to optimize the prescription and utilization of PRP and exercise therapy. This study has some limitations. First, the outcomes were limited to a simple physical function assessment and patient-oriented assessment (KOOS), which did not provide more detailed insights into treatment effects, such as the assessment of cartilage quality using MRI. Second, the sample size was small, and there were several drop-off cases in each group, the details of which could not be fully ascertained. Lastly, the follow-up period was limited to 1 year. Knee OA is a chronic condition, and 1 year after treatment falls within the short- to medium-term category. Longer-term follow-up results are necessary for a better perspective. Conclusion The combined treatment of PRP and exercise therapy leveraged the advantages of both and demonstrated its highest effectiveness within the 1-year timeframe. Abbreviations PRP platelet-rich plasma OA osteoarthritis OARSI Osteoarthritis Research Society International KOOS Knee Injury and Osteoarthritis Outcome Score OMERACT Outcome Measures in Rheumatology ADL Activity of Daily Living QOL Quality of Life ESSKA European Society of Sports Traumatology, Knee Surgery & Arthroscopy RCT Randomized Controlled Trial WOMAC Western Ontario and McMaster University osteoarthritis MST motor skill training SFE strength and flexibility exercise LBP Low Back Pain KL Kellgren Lawrence MRI magnetic resonance imaging Declarations Ethics approval and consent to participate We informed the participants both orally and in writing about the main purpose of this study and the Declaration of Helsinki, emphasizing the priority of protection and rights, their freedom to participate or discontinue, and the potential physical effects. We then obtained their written consent. The study was approved by the Teikyo Heisei University Ethics Review Committee (2024-022). Consent for publication Not applicable. Availability of data and materials The data were available from corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding None. Acknowledgments We would like to thank Editage ( www.editage.jp ) for English language editing. Authors’ contributions All authors made significant contributions to the research concept, design, data collection, data analysis and interpretation, critical correction of important intellectual content, and final approval of the submitted version. Specific contributions include: (1) Conception and design of research: TK and SK (2) Data acquisition: TK (3) Data analysis and interpretation: TK, SI and SK. (4) Draft article: TK and SK (5) Critically revised important intellectual content: TK, SI, KI, and SK. (6) Final approval of the submitted version: TK, SI, KI, and SK References Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013;9:721–30. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:638–46. Roukis TS, Zgonis T, Tiernan B. Autologous platelet-rich plasma for wound and osseous healing: a review of the literature and commercially available products. Adv Ther. 2006;23:218–37. Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009;17:602–8. von Wehren L, Blanke F, Todorov A, Heisterbach P, Sailer J, Majewski M. The effect of subacromial injections of autologous conditioned plasma versus cortisone for the treatment of symptomatic partial rotator cuff tears. Knee Surg Sports Traumatol Arthrosc. 2016;24:3787–92. Sánchez M, Anitua E, Azofra J, Andía I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 2007;35:245–51. Zhu T, Zhou J, Hwang J, Xu X, et al. Effects of Platelet-Rich Plasma on Clinical Outcomes After Anterior Cruciate Ligament Reconstruction: a Systematic Review and Meta-analysis. Orthop J Sports Med. 2022;10:23259671211061535. Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP injections for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Cartilage. 2021;13:S364–75. Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21:224. Rodríguez-Merchán EC. Intra-articular platelet-rich plasma injection in knee osteoarthritis: a review of their current molecular mechanisms of action and their degree of efficacy. Int J Mol Sci. 2022;23:1301. ESSKA ORBIT Consensus Complete Report. 2022. https://www.esska.org/page/projects . Accessed January 8, 2024. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363–88. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019;27:1578–89. Japanese Orthopaedic Association (JOA). Clinical Practice Guidelines on the Management of Osteoarthritis of the Knee. The Japanese Orthopaedic Association; 2023. Rayegani SM, Raeissadat SA, Taheri MS, Babaee M, Bahrami MH, Eliaspour D, et al. Does intra articular platelet rich plasma injection improve function, pain and quality of life in patients with osteoarthritis of the knee? A randomized clinical trial. Orthop Rev (Pavia). 2014;6:5405. Badr MEM, Hafez EAR, El-Ghaweet AI, El-Sayed HM. Intra-articular injection of platelet – rich plasma and therapeutic exercise in knee osteoarthritis. Egypt Rheumatol Rehabil. 2019;46:1–10. KOOS User’s Guide 1.1. 2012. https://www.yumpu.com/en/document/view/8808692/koos-users-guide-knee-injury-and-osteoarthritis-outcome-score- . Accessed January 8, 2024. Roos EM, Lohmander LS. Knee injury and osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64. Pham T, van der Hejime D, Altman RD, et al. OMERACT-OARSI Initiative: osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil. 2004;12:389–99. Sahrmann S, Azevedo DC, Dillen LV. Diagnosis and treatment of movement system impairment syndromes. Braz J Phys Ther. 2017;21:391–9. van Dillen LR, Lanier VM, Steger-May K, Wallendorf M, Norton BJ, Civello JM, et al. Effect of motor skill training in functional activities vs strength and flexibility exercise on function in people with chronic low back pain: A randomized clinical trial. JAMA Neurol. 2021;78:385–95. 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. We do this by developing innovative software and high quality services for the global research community. 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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-4534999","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317988651,"identity":"05c56132-e8c1-4203-935f-f42a0234824b","order_by":0,"name":"Tsuneo Kawahara","email":"data:image/png;base64,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","orcid":"","institution":"Mizue Orthopedic Clinic","correspondingAuthor":true,"prefix":"","firstName":"Tsuneo","middleName":"","lastName":"Kawahara","suffix":""},{"id":317988652,"identity":"25d148e7-7a04-4ec5-bff7-2ec2a8f49532","order_by":1,"name":"Shuhei Iida","email":"","orcid":"","institution":"Faculty of Health and Medical Sciences Department of Physical Therapy, Teikyo Heisei University","correspondingAuthor":false,"prefix":"","firstName":"Shuhei","middleName":"","lastName":"Iida","suffix":""},{"id":317988653,"identity":"05f8baf2-8d57-4ec5-a675-c4ca9a861ca7","order_by":2,"name":"Kazuma Isoda","email":"","orcid":"","institution":"Mizue Orthopedic Clinic","correspondingAuthor":false,"prefix":"","firstName":"Kazuma","middleName":"","lastName":"Isoda","suffix":""},{"id":317988654,"identity":"4141f99a-b90b-4775-b61f-fdbc47df03da","order_by":3,"name":"Sungdo Kim","email":"","orcid":"","institution":"Mizue Orthopedic Clinic","correspondingAuthor":false,"prefix":"","firstName":"Sungdo","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2024-06-05 15:03:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4534999/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4534999/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60185442,"identity":"7656e410-3b93-441d-b6d8-2e9b3136b2cc","added_by":"auto","created_at":"2024-07-12 18:42:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":319240,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of patients assigned to each group and data collection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were divided into three treatment groups, and data were collected at baseline, 1 month, 3 months, and 1 year after treatment.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4534999/v1/f4470e97448c86d0606592df.png"},{"id":60185441,"identity":"c161c105-a028-405a-9571-fb6260ccdd96","added_by":"auto","created_at":"2024-07-12 18:42:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":397275,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOMERACT-OARSI set of responder criteria.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFlowchart of indicators defining patients who respond to treatment and improve. Modified and adapted from reference [19].\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4534999/v1/a923919e29c4f077939f1376.png"},{"id":60185443,"identity":"6ba340f4-9e2d-4d59-9412-e080f2c8b1d4","added_by":"auto","created_at":"2024-07-12 18:42:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":537277,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in KOOS scores for each group.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn each graph, the vertical axis shows the KOOS value and the horizontal axis shows the time of each check. The black bars show the scores of the PE group, the dotted bars show the scores of the P group, and the grey bars show the scores of the E group. (a)–(e) Scores for each of the KOOS items: pain, symptoms, ADL, sports, and QOL, respectively; (f) shows the total score. The horizontal lines at the top of the graph connect statistically significant differences, with * indicating a p-value of less than 0.05 and ** indicating a p-value of less than 0.01.\u003c/p\u003e\n\u003cp\u003eKOOS: Knee Injury and Osteoarthritis Outcome Score; ADL: Activity of Daily Living; QOL: Quality of Life\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4534999/v1/1aa05c6a6396177293acb76d.png"},{"id":60185444,"identity":"63926d14-d78c-47c1-9ff7-014769731420","added_by":"auto","created_at":"2024-07-12 18:42:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":259851,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults of OMERACT-OARSI Responder Criteria.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePercentage of responders based on OMERACT-OARSI responder criteria in each group\u003c/p\u003e\n\u003cp\u003eOMERACT: Outcome Measures in Rheumatology; Osteoarthritis Research Society International\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4534999/v1/378a48a6bcd788403e1128fe.png"},{"id":60186648,"identity":"9a4beaee-a1e2-47f3-b488-1c6b2c96b48a","added_by":"auto","created_at":"2024-07-12 18:58:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2128782,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4534999/v1/b6c53d66-cddf-4261-9835-97633c830d85.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment","fulltext":[{"header":"Background","content":"\u003cp\u003eWhile platelet-rich plasma (PRP) has been shown to possess anti-inflammatory properties by modulating the canonical nuclear factor κB signaling pathway in multiple cell types, including synoviocytes, macrophages, and chondrocytes; however, the cellular and molecular mechanisms underlying this potential therapeutic effect remain poorly understood [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePRP was initially used for bone graft regeneration in oral surgery and has subsequently been used in many fields, including cosmetics and sports orthopedics [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany reports have been published on its efficacy in promoting healing during the repair of various soft tissues such as the rotator cuff, Achilles tendon, ligaments, and bones [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Several systematic reviews on the use of PRP for knee osteoarthritis (OA) have shown short-term therapeutic effects [1,8,9.10]. Its effectiveness was also demonstrated by a consensus at the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) in 2022 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExercise therapy for patients with knee OA was considered 'core treatment' in the 2014 Osteoarthritis Research Society International (OARSI) guidelines and remained so in the 2019 guidelines [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patient education was also classified as a 'core treatment,' although it was noted that randomized controlled trial (RCT) data were lacking. This classification is consistent with the latest Japanese clinical practice guidelines [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral studies have reported the therapeutic efficacy of combined therapies for treating knee OA. In 62 patients with knee OA, Rayegani et al. showed that intra-articular PRP knee joint injections, combined with exercise therapy, were effective in reducing pain and improving stiffness and quality of life compared with exercise therapy alone [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Badr et al. also divided 60 patients with knee OA into three groups according to treatment modality (PRP plus exercise, PRP alone, and exercise alone) and found that the combination treatment group showed the most significant changes in the visual analog scale, Western Ontario and McMaster Universities (WOMAC) score, and joint tenderness after 6 months of treatment [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, there are few to no reports on the effectiveness of PRP treatment combined with exercise therapy 1 year after treatment.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to examine the efficacy of combined PRP and exercise therapy for up to 1 year post-treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe participants were patients diagnosed with knee OA and treated between January 2021 and December 2022. Exclusion criteria included inflammatory arthritis, acute trauma, previous lower limb fracture or surgery, and inability to continue treatment. The participants were divided into three groups: (1) PRP and exercise therapy (PE group), (2) PRP therapy only (P group), and (3) exercise therapy only (E group). As a rule, the doctor presented these treatment methods to the patient during the regular medical treatment consultation, and the patient made the choice.\u003c/p\u003e \u003cp\u003eGreat care was taken to ensure no intentional influence from the doctor. The allocation of participants to each group was based on the report by Badr et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and the data collection flowchart is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor PRP therapy, PRP was prepared with a dedicated kit (MyCells\u0026reg;) after blood collection from the patient. Centrifugation was performed at 3,500 rpm for 7 min. The platelet type was leukocyte-poor PRP.\u003c/p\u003e \u003cp\u003eFor exercise therapy, the patients were interviewed more specifically about the movements they needed to perform daily and at work. They were given specific advice on how to use each body part and how to be aware of the position of the center of gravity when performing these movements from a kinematic perspective. Additionally, orthodox physiotherapy was provided to improve physical functions such as joint range of motion, muscle strength, and balance ability. The therapy was conducted 1\u0026ndash;2 times per week.\u003c/p\u003e \u003cp\u003eThe Knee Injury and Osteoarthritis Outcome Score (KOOS) has been used in periodic surveys and consists of five subscales\u0026mdash;pain, symptom, activity of daily living (ADL), sports, and quality of life\u0026mdash;and demonstrates good test-retest reproducibility. Furthermore, the validated WOMAC assesses the knee OA index in its complete and original form and correlates with the SF-36 (Medical Outcomes Study [MOS] short form 36 health survey) and the Lysholm knee scoring scale, making it appropriate for the study [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe survey was conducted at four timepoints: pre-treatment, 1 month post-treatment, 3 months post-treatment, and 1 year post-treatment.\u003c/p\u003e \u003cp\u003eThe Outcome Measures in Rheumatology (OMERACT) responder criteria from the OARSI were used to determine the treatment response outcome in this study. Pham et al. (2004) used the KOOS score to assess responder status, indicating the presence of a treatment effect [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The effectiveness assessment flowchart is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eStatistical analyses were performed using FreeJSTAT Ver. 13.0. The changes over time in each group and differences between groups in terms of the amount of change over time were tested using a one-way analysis of variance. Significant differences were further analyzed using the Bonferroni multiple comparison method (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eData were collected for up to one year for 16 patients in the PE group, 15 patients in the P group, and 18 patients in the E group. Table\u0026nbsp;1 presents the baseline data and KOOS values for each group. At baseline, the KOOS values did not differ significantly between groups.\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table\u0026nbsp;1. Basic data and KOOS at baseline data\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eE group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅡ:9, Ⅲ:5, Ⅳ;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅠ:1, Ⅱ:8, Ⅲ:6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅡ:7, Ⅲ:7, Ⅳ;4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFlexion ROM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e121.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e126.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtension ROM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKOOS baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.0\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSports\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.7\u0026thinsp;\u0026plusmn;\u0026thinsp;19.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.7\u0026thinsp;\u0026plusmn;\u0026thinsp;20.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\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\u003eBasic data and KOOS scores at baseline for participants in each group are shown. Values are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. KL, Kellgren Lawrence; ROM, range of motion; KOOS, Knee Injury and Osteoarthritis Outcome Score; ADL, activity of daily living; QOL, quality of life\u003c/p\u003e\n\u003cp\u003eThe changes in scores over the course of treatment are shown in Table\u0026nbsp;2 and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. In the PE group, pain, symptoms, and ADL improved after 1 month and continued to improve until 1 year. The P group showed improvement in the pain item after 1 month; however, there was no significant change in the other items. The E group showed improvement in each item after 3 months, with all items remaining the same after 1 year.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table\u0026nbsp;2. KOOS in each period\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eE group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKOOS 1M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSports\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.1\u0026thinsp;\u0026plusmn;\u0026thinsp;26.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKOOS 3M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSports\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKOOS 1Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSports\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.7\u0026thinsp;\u0026plusmn;\u0026thinsp;25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.0\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;26.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.1\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.6\u0026thinsp;\u0026plusmn;\u0026thinsp;22.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\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\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe KOOS for each period in each group is presented. Values are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. KOOS, Knee Injury and Osteoarthritis Outcome Score; ADL, activity of daily living; QOL, quality of life\u003c/p\u003e\n\u003cp\u003eThe treatment response according to the responder criteria is shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 1 month, 50.0% of the PE group, 53.3% of the P group, and 22.2% of the E group, with the E group showing clearly lower values.\u003c/p\u003e\n\u003cp\u003eAt 3 months, 56.3% in the PE group, 53.3% in the P group, and 44.4% in the E group showed improvement in each group.\u003c/p\u003e\n\u003cp\u003eAfter 1 year, 68.8% of the PE group and 61.1% of the E group showed improvement, with a slight decline in PRP alone (46.6% of the P group), while the E group showed a much higher value than in the previous timepoints, indicating late improvement.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first to examine the efficacy of PRP combined with exercise therapy for up to 1 year after treatment.\u003c/p\u003e \u003cp\u003e Many guidelines have shown the effectiveness of exercise therapy for knee OA.\u003c/p\u003e \u003cp\u003eThe latest OARSI guidelines, reported in 2019, offer comprehensive and patient-centered treatment profiles for individuals with knee, hip, and polyarticular OA [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This treatment modality facilitates individualized treatment decisions for OA management [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe panel considered structured land-based exercise programs, dietary weight management in combination with exercise, and mind-body exercises (such as Tai Chi and Yoga) to be effective and safe for all patients with knee OA, regardless of comorbidities [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Conversely, aquatic exercise, which is supported by a modest evidence base and demonstrates robust benefits on pain and objective measures of function, was previously recommended alongside land-based exercise in previous guidelines. However, it received a conditional recommendation because of accessibility issues, financial burden, and uptake concerns [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the number of sets of specific exercises to be performed during exercise therapy was not specified.\u003c/p\u003e \u003cp\u003eThis omission may stem from the need to tailor exercise regimens to the patient\u0026rsquo;s individual physical characteristics and social circumstances. The author of this paper believes that patient education is important in this respect. In clinical practice, patients receive monthly written instructions outlining knee OA, detailing changes in their symptoms and the prescribed physiotherapy regimen (including a self-training menu), and proceed only after signing a consent form.\u003c/p\u003e \u003cp\u003ePatient education is also considered a standard treatment according to the OARSI guidelines, despite the lack of RCT data [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Considering the individuality of patients influenced by variations in their living environments, reference can also be made to the Japanese practice guidelines.\u003c/p\u003e \u003cp\u003eThe latest edition of these guidelines was revised in 2023 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These guidelines also affirm the effectiveness of exercise therapy and patient education in managing knee OA. Patient education encompasses instructions for real-life and work-related activities. Often, movements and weight distribution in daily routines are performed in a familiar manner, which may inadvertently exacerbate symptoms. According to Sahrmann\u0026rsquo;s kinesiopathological model of the movement system [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], detecting abnormal movement is important. In terms of teaching movement in real-life scenarios, the effectiveness of motor skill training (MST) was demonstrated by van Dillen et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Although their study focused on patients with low back pain (LBP), individuals with chronic LBP who underwent MST had greater short-term and long-term improvements in function compared to those who received strength and flexibility exercises (SFE) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. van Dillen et al. suggested that person-specific MST tailored to functional activities limited by LBP should be considered in the treatment of patients with chronic LBP [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results of our study indicated a delayed onset of the benefits of exercise therapy. This can be attributed to the fact that exercise therapy at the clinic was provided 1\u0026ndash;2 times a week for 40 min per session. Therefore, it took longer than 1 month for motor learning to improve body perception and movement, with the effectiveness becoming evident after 3 months and continuing for 1 year.\u003c/p\u003e \u003cp\u003eIn this study, we demonstrated the anti-inflammatory and pain-relieving effects of PRP therapy for knee OA, which showed a high therapeutic effect 1 month after treatment. These results were comparable to those of previous reports. According to the latest consensus by ESSKA, PRP is effective in patients with mild to moderate OA (KL grade 3 or less), as indicated by Grade A evidence. It provides greater and longer-lasting symptomatic improvement compared to hyaluronic acid injections (Grade B), and it also offers longer-lasting symptomatic improvement than steroid injections. Moreover, PRP therapy is not chondrotoxic (Grade A) and has demonstrated cartilage regeneration. While one animal study has shown other disease-modifying effects, evidence in humans is still lacking (Grade C) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Currently, PRP therapy is primarily positioned as a treatment for symptomatic improvement in knee OA.\u003c/p\u003e \u003cp\u003eThe high pain-relieving effect reported in previous studies is consistent with the results of this study; however, the long-term durability of the treatment effect differs from our findings, which showed a slight decrease in efficacy after 1 year of treatment. This is a limitation of PRP therapy, and future research is needed to determine the effective platelet concentration and optimal frequency of treatment. In our study, some patients received multiple PRP treatments, in which case the timing of the first PRP treatment was used as the baseline, and the data were analyzed as a single group. The KOOS values for the P group also showed a slightly higher score at baseline. However, the difference was not statistically significant, suggesting that the treatment effect was less apparent than in the other groups.\u003c/p\u003e \u003cp\u003eFurthermore, the combination of PRP and exercise therapy in this study showed the highest therapeutic efficacy, aligning with previous reports. The strong anti-inflammatory and pain-relieving properties of PRP are thought to promote the ease of engaging in active exercise therapy at the early stages of treatment. Badr et al. also observed similar trends, noting that combined PRP and exercise therapy outperformed PRP or exercise therapy alone, indicating an additive effect. However, their data were limited to 6 months post-treatment [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. They further emphasized the need for additional research to optimize the prescription and utilization of PRP and exercise therapy.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, the outcomes were limited to a simple physical function assessment and patient-oriented assessment (KOOS), which did not provide more detailed insights into treatment effects, such as the assessment of cartilage quality using MRI. Second, the sample size was small, and there were several drop-off cases in each group, the details of which could not be fully ascertained. Lastly, the follow-up period was limited to 1 year. Knee OA is a chronic condition, and 1 year after treatment falls within the short- to medium-term category. Longer-term follow-up results are necessary for a better perspective.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe combined treatment of PRP and exercise therapy leveraged the advantages of both and demonstrated its highest effectiveness within the 1-year timeframe.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eplatelet-rich plasma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eosteoarthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOARSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOsteoarthritis Research Society International\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKOOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKnee Injury and Osteoarthritis Outcome Score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOMERACT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOutcome Measures in Rheumatology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eActivity of Daily Living\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQOL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eQuality of Life\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESSKA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society of Sports Traumatology, Knee Surgery \u0026amp; Arthroscopy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRandomized Controlled Trial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWOMAC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWestern Ontario and McMaster University osteoarthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emotor skill training\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSFE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estrength and flexibility exercise\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow Back Pain\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKellgren Lawrence\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe informed the participants both orally and in writing about the main purpose of this study and the Declaration of Helsinki, emphasizing the priority of protection and rights, their freedom to participate or discontinue, and the potential physical effects. We then obtained their written consent.\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Teikyo Heisei University Ethics Review Committee\u0026nbsp;(2024-022).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were available from corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (\u003ca href=\"https://ind01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.editage.jp%2F\u0026data=05|01|[email protected]|d19236e0dfe043ead77308db5a614048|762d8873d7774e7fbb6be4d2cccca312|0|0|638203145963925545|Unknown|TWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D|3000|||\u0026sdata=3Ft%2BFi9diYBeORMgJke%2Bb2yLcVUtqgNyMTRE2M073GY%3D\u0026reserved=0\"\u003ewww.editage.jp\u003c/a\u003e) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e All authors made significant contributions to the research concept, design, data collection, data analysis and interpretation, critical correction of important intellectual content, and final approval of the submitted version.\u003c/p\u003e\n\u003cp\u003eSpecific contributions include:\u003c/p\u003e\n\u003cp\u003e(1) Conception and design of research: TK and SK\u003c/p\u003e\n\u003cp\u003e(2) Data acquisition: TK\u003c/p\u003e\n\u003cp\u003e(3) Data analysis and interpretation: TK, SI\u0026nbsp;and SK.\u003c/p\u003e\n\u003cp\u003e(4) Draft article: TK and SK\u003c/p\u003e\n\u003cp\u003e(5) Critically revised important intellectual content: TK,\u0026nbsp;SI,\u0026nbsp;KI, and SK.\u003c/p\u003e\n\u003cp\u003e(6) Final approval of the submitted version: TK, SI, KI, and SK\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAndia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013;9:721\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:638\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoukis TS, Zgonis T, Tiernan B. Autologous platelet-rich plasma for wound and osseous healing: a review of the literature and commercially available products. Adv Ther. 2006;23:218\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009;17:602\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Wehren L, Blanke F, Todorov A, Heisterbach P, Sailer J, Majewski M. The effect of subacromial injections of autologous conditioned plasma versus cortisone for the treatment of symptomatic partial rotator cuff tears. Knee Surg Sports Traumatol Arthrosc. 2016;24:3787\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026aacute;nchez M, Anitua E, Azofra J, And\u0026iacute;a I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 2007;35:245\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu T, Zhou J, Hwang J, Xu X, et al. Effects of Platelet-Rich Plasma on Clinical Outcomes After Anterior Cruciate Ligament Reconstruction: a Systematic Review and Meta-analysis. Orthop J Sports Med. 2022;10:23259671211061535.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFilardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP injections for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Cartilage. 2021;13:S364\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21:224.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodr\u0026iacute;guez-Merch\u0026aacute;n EC. Intra-articular platelet-rich plasma injection in knee osteoarthritis: a review of their current molecular mechanisms of action and their degree of efficacy. Int J Mol Sci. 2022;23:1301.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eESSKA ORBIT Consensus Complete Report. 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.esska.org/page/projects\u003c/span\u003e\u003cspan address=\"https://www.esska.org/page/projects\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed January 8, 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019;27:1578\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJapanese Orthopaedic Association (JOA). Clinical Practice Guidelines on the Management of Osteoarthritis of the Knee. The Japanese Orthopaedic Association; 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRayegani SM, Raeissadat SA, Taheri MS, Babaee M, Bahrami MH, Eliaspour D, et al. Does intra articular platelet rich plasma injection improve function, pain and quality of life in patients with osteoarthritis of the knee? A randomized clinical trial. Orthop Rev (Pavia). 2014;6:5405.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBadr MEM, Hafez EAR, El-Ghaweet AI, El-Sayed HM. Intra-articular injection of platelet \u0026ndash; rich plasma and therapeutic exercise in knee osteoarthritis. Egypt Rheumatol Rehabil. 2019;46:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKOOS User\u0026rsquo;s Guide 1.1. 2012. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.yumpu.com/en/document/view/8808692/koos-users-guide-knee-injury-and-osteoarthritis-outcome-score-\u003c/span\u003e\u003cspan address=\"https://www.yumpu.com/en/document/view/8808692/koos-users-guide-knee-injury-and-osteoarthritis-outcome-score-\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed January 8, 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoos EM, Lohmander LS. Knee injury and osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePham T, van der Hejime D, Altman RD, et al. OMERACT-OARSI Initiative: osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil. 2004;12:389\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahrmann S, Azevedo DC, Dillen LV. Diagnosis and treatment of movement system impairment syndromes. Braz J Phys Ther. 2017;21:391\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Dillen LR, Lanier VM, Steger-May K, Wallendorf M, Norton BJ, Civello JM, et al. Effect of motor skill training in functional activities vs strength and flexibility exercise on function in people with chronic low back pain: A randomized clinical trial. JAMA Neurol. 2021;78:385\u0026ndash;95.\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":"Platelet-rich plasma, exercise therapy, knee osteoarthritis","lastPublishedDoi":"10.21203/rs.3.rs-4534999/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4534999/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePlatelet-rich plasma (PRP) therapy is a promising treatment modality for knee osteoarthritis (OA). However, exercise therapy and activity of daily living (ADL) guidance are also recommended as core treatments in the Osteoarthritis Research Society International (OARSI) guidelines. However, there is limited research on the efficacy of combined PRP and exercise therapy. This study aimed to verify the effectiveness of this combined treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe participants were patients diagnosed with knee OA and treated between January 2021 and December 2022. They were divided into three groups: 1) PRP\u0026thinsp;+\u0026thinsp;exercise therapy (PE group), 2) PRP therapy only (P group), and 3) exercise therapy only (E group). Outcomes were measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and conducted before, 1 month, 3 months, and 1 year after treatment. Statistical analysis was performed using a one-way analysis of variance for within-group comparisons according to the time of each score. For those that showed a difference, the Bonferroni multiple comparison method was used to validate the results (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The treatment response rate was determined using the Outcome Measures in Rheumatology (OMERACT)-OARSI Responder criteria.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were no differences in pre-treatment KOOS between the three groups. In the PE group, pain, symptoms, and ADL improved after 1 month and continued to improve until 1 year. The P group showed improvement in pain after 1 month, but no significant changes were observed in the other items. In contrast, the E group showed improvement in each item from 3 months onwards, with all items remaining unchanged at 1 year. The PE group had a higher response rate than the other groups, with 50.0% at 1 month, 56.3% at 3 months, and 68.8% at 1 year, according to the responder criteria.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe combined treatment of PRP and exercise therapy demonstrated the synergistic advantages of both and proved to be most effective up to 1 year after treatment.\u003c/p\u003e","manuscriptTitle":"Verification of the effectiveness of combined platelet-rich plasma therapy and exercise therapy for patients with knee osteoarthritis up to one year post-treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-12 18:42:10","doi":"10.21203/rs.3.rs-4534999/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":"9fdb1669-ae9f-4d2c-9277-a78b131d043b","owner":[],"postedDate":"July 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-12T18:42:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-12 18:42:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4534999","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4534999","identity":"rs-4534999","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}