Efficacy of extracorporeal shock wave therapy in the treatment of bone marrow edema in different parts of the knee joints

Efficacy of extracorporeal shock wave therapy in the treatment of bone marrow edema in different parts of the knee joints | 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 Efficacy of extracorporeal shock wave therapy in the treatment of bone marrow edema in different parts of the knee joints Hao Hu, Hanwen Liu, Kun Yu, Yinshen Liu, Maoru LI, Haili Mao, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3845537/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 The purpose of this prospective study was to evaluate the effectiveness of extracorporeal shock wave therapy (ESWT) in reducing symptoms and normalizing imaging features in periprosthetic bone marrow edema syndrome (BMES) of the knee. Methods The clinical data of 42 patients with knee bone marrow edema syndrome who attended the Department of Joint Surgery of the Affiliated Hospital of Southwest Medical University from January 2021 to December 2023 were collected, and they were divided into three groups according to the different parts of the knee edema: the femur group (26 cases), the tibia group (9 cases), and the patella group (7 cases). The visual analog scale (VAS) of pain, the knee score (HSS) of the Hospital for Special Surgery of the United States , and the area of BME on magnetic resonance imaging (cm 2 ) were observed before and after three months of shock wave treatment in each group. Results Overall VAS score decreased from 5.40 ± 1.624 to 1.57 ± 1.328 before treatment (P < 0.05), and HSS score increased from 83.05 ± 9.063 to 93.00 ± 4.129 before treatment (P < 0.05); the area of BMES decreased from 3.876 ± 3.277 cm 2 before treatment to 1.294 ± 0.352 cm 2 (P 0.05) Conclusion Overall ESWT is effective in the treatment of periprosthetic BMES, leading to a decrease in VAS scores, an increase in HSS scores, and a significant decrease in the area of bone marrow edema on T2WI of MRI (except for the patellofemoral group where the decrease in the area of bone marrow edema was not statistically significant, but the overall trend was downward). extracorporeal shock wave knee bone marrow edema Figures Figure 1 Figure 2 INTRODUCTION Bone marrow edema (BME) syndrome refers to increased interstitial fluid in the interstitial spaces between the bone marrow and is a reversible, self-limiting disorder that manifests as ill-defined, homogeneous areas of intermediate signal intensity on T1-weighted (T1W) images and high signal intensity on fat-suppressed T2-weighted (T2W) images [1]. Some scholars have suggested that bone marrow edema syndrome is an early, reversible ischemic necrosis with mostly painful clinical manifestations, and imaging is usually difficult to detect on X-rays, with high sensitivity and specificity of MRI examination [2]. BME usually affects the epiphyses of the load-bearing joints, most commonly the hip, but also the knee, ankle, and foot, but it may also present as "wandering" BME with multiple episodes at different sites [3]. In the knee, it is seen in the knee, the ankle, and the foot. In the knee, it is seen for a variety of reasons, including: ischemic (exfoliative osteochondritis, osteonecrosis, or complex localized pain syndrome), mechanical (bone bruise or contusion, microfracture, or stress fracture), and other reasons (osteoarthritis, surgery, or cancer) [4]. Although multiple factors are known to cause bone marrow edema in BME, this reversible, nonspecific disease usually spreads from the medullary space to the subchondral regions of the joints [5]. BME in the subchondral bone BME in the subchondral bone significantly increases the risk of structural progression in knee osteoarthritis, and increased mechanical loading in cases of knee osteoarthritis can lead to microfractures in the subchondral metaphyseal region, resulting in the collapse of the involved compartment of bone, which may be associated with biomechanical changes in knee osteoarthritis [5–7]. The current clinical management of bone marrow edema syndrome includes weight reduction, nonsteroidal anti-inflammatory drugs, intravenous prostacyclin and bisphosphonates, and surgical treatment with core decompression, but there is no gold standard yet [8] .Extracorporeal shockwave (ESWT) is now proven to have significant efficacy in the treatment of musculoskeletal disorders, including the reduction of bone marrow edema due to early osteonecrosis of the femoral head [9]. ESWT has been shown to reduce pain, improve hip function, and normalize the MRI signal of bone marrow edema in early osteonecrosis of the femoral head, avoiding the risks of surgical infection, postoperative fracture, and deep vein thrombosis compared to invasive surgery [10]. Extracorporeal shock wave (ESWT) can activate many neovascularizations and tissue regeneration due to its angiogenic and trophic effects on tissues [11] .ESWT has been shown to be an effective method of tissue regeneration. ESWT has been shown to be an effective, reliable, and noninvasive treatment for reducing pain in patients with osteoarthritis BME of the knee, normalizing MRI signals, and potentially shortening the natural course of this disease [12] .Galina Eremina presented a numerical model of the knee joint to study the regenerative effects of shockwave therapy with computer assistance. The results showed that the chondrogenic process is initiated only when the compressive stress is greater than a threshold of 0.15 MPa; the tissue starts to differentiate considerably when the torsional strain is higher than a threshold of 0.05%; the optimal level corresponding to the fluid pressure is 68 kpa, and the energy flux density of the therapeutic shockwave loading should be more than 0.3 mJ/mm 2, However, the clinical efficacy of the treatment has not yet been demonstrated [13] . We therefore designed a prospective pilot study to validate the efficacy of ESWT in the treatment of bone marrow edema in different parts of the knee. METHODS Participants and design Participants and design Clinical data were collected from 42 patients with knee bone marrow edema syndrome who attended the Department of Joint Surgery of the Affiliated Hospital of Southwest Medical University from January 2021 to December 2023, and they were divided into three groups according to the site of knee edema: femoral group (26 patients), tibial group (9 patients), and patellofemoral group (7 patients). There were a total of 42 patients (15 males and 27 females) aged 16–73 years (mean age, 49.02 ± 12.73 years). Inclusion criteria: 1. Patients > 16 years of age with acute and chronic knee pain and MRI suggestive of areas of bone high-intensity signal on T2W sequences. Exclusion criteria: 1. BME with any MRI finding of ischemic necrosis, defined as subchondral crescentic areas (low-intensity signal subchondral areas on T1W sequences); 2. advanced osteoarthritis of the knee (grade 3 or 4); 3. third-degree damage to the medial and lateral meniscus of the knee; 4. previous surgical treatment of the affected knee; 5. systemic diseases such as SLE, alcoholism, rheumatoid arthritis, autoimmune diseases, and other diseases. rheumatoid arthritis, autoimmune diseases or tumors. Written informed consent was obtained from each patient, which was approved by the Ethics Committee of Southwest Medical University Hospital. Experimental procedure Experimental design Personalized ESWT Each patient received a shockwave treatment consisting of 1 shockwave treatment every 1 week for 5 weeks (5 sessions in total), using a shockwave electromagnetic source (SWISS DOLORCLAST smart Switzerland). During each session, 2000 injections were administered at high energy with an energy flux density ranging from 0.22 to 0.43 mJ / mm 2 at 10 Hz. The site was localized according to imaging and local compression of the most painful point, and each patient received shockwave therapy with the knees bent at 100°(Fig. 1 ),no strenuous activities were allowed during the treatment period, and the affected limb was normally weight-bearing. Observation indicators Patients' gender, age, duration of symptoms in months, any comorbidity with other diseases, and history of trauma were recorded. All patients were clinically assessed by the same examiner according to the knee HSS rating scale, which includes pain, function, mobility, muscle strength, flexion deformity, and stability. Patients were also asked to assess their pain level on a 10-point visual analog scale (VAS), where 0 indicates no pain and 10 indicates maximum possible or intolerable pain. Scoring was based on the Hospital for Specialty Surgery Knee Score (HSS) 100-point scale. These scores were assessed before treatment as well as 3 months after treatment. All patients underwent knee MRI before and 3 months after treatment. The presence of focal subchondral low-intensity signal areas (a possible expression of early osteonecrosis) was assessed and excluded on T1W sequences. Areas of bone marrow lesions were assessed on fat-suppressed fast spin-echo T2W sequences. Areas of edema were obtained by measuring the area on the same sagittal and coronal slices of the MRI scans before and after treatment. statistical analysis We used SPSS 25.0 statistical software for analysis, and all patients were followed up to. Measurements were expressed as x ± s. Paired t-tests were used to compare VAS scores, HSS scores and BMES areas before and after ESWT, and chi-square tests were used to test whether there were any significant differences between the groups, with P < 0.05 being considered statistically significant. RESULTS The demographic and clinical characteristics of the subjects at baseline are shown in Table 1. The raw data for all patients including the mean and standard deviation of all dependent variables before and after the test are shown in Table 2. Statistical significance for all analyses was set at P < 0.05. Overall VAS scores decreased from 5.40 ± 1.624 to 1.57 ± 1.328 before treatment (P < 0.05), with VAS scores in the femoral group decreasing from 5.24 ± 1.76 to 1.57 ± 1.21 before treatment (P < 0.05); in the tibial group, VAS scores decreased from 5.67 ± 1.12 before treatment to 1.56 ± 1.13 points (P < 0.05); VAS score in the patella group decreased from 5.86 ± 2.12 points before treatment to 1.43 ± 1.51 (P < 0.05). The difference before and after treatment was statistically significant. As Table 1 is shown ( Chart 2 ). Overall HSS score increased from 83.05 ± 9.063 before treatment to 93.00 ± 4.129 (P < 0.05); HSS score in the femoral group increased from 82.12 ± 9.11 before treatment to 92.73 ± 4.71 (P < 0.05); HSS score in the tibial group increased from 87.22 ± 5.47 before treatment to 94.44 ± 3.17 points (P < 0.05); HSS score in the patella group increased from 81.14 ± 11.89 points before treatment to 92.14 ± 1.14 points (P < 0.05). The difference before and after treatment was statistically significant. As Table 2 is shown ( Chart 3 ). Overall BMES area decreased from 3.876 ± 3.277 cm 2 before treatment to 1.294 ± 0.352 cm 2 (P < 0.05), with a statistically significant difference before and after treatment. The BMES area in the femur group decreased from 3.438 ± 3.742 cm 2 to 1.346 ± 1.532 cm 2 (P < 0.05) before treatment, and the difference between before and after treatment was statistically significant; the BMES area in the tibia group decreased from 4.467 ± 0.789 cm 2 to 1.940 ± 0.988 cm 2 (P 0.05) before treatment, and the difference before and after treatment was not statistically significant. As Table 3 is shown( Chart 4 ). Comparison between groups before and after shockwave treatment was performed using the chi-square test, as shown in Fig. 3. p-values were greater than 0.05, and the differences between groups were not statistically significant. Typical cases of extracorporeal shockwave treatment of bone marrow edema of the knee (femoral, tibial, and patellar groups) at T2WI, as shown in Fig. 2 . DISCUSSION Periprosthetic bone marrow lesions (BMLs) are a common finding on MRI.BML is defined as an alteration in bone marrow signal intensity with high signal on T2WI with or without low T1WI signal.BMLs often originate in subchondral or non-subchondral bone, and are pathologically diverse.These include traumatic bone contusions and fractures, post-surgical imaging changes in cartilage, osteoarthritis (OA), transient BML syndrome, spontaneous incomplete fractures (SIFK), and true osteonecrosis (ON)., transient BML syndrome, spontaneous incomplete fractures (SIFK) and true osteonecrosis (ON). [14] BMES is considered a self-limiting disease, with clinical resolution in 3–24 months and complete disappearance of the edema signal on MRI [15]. BMES is considered to be a self-limiting disease. It has been suggested that once BMES is present in ischemic necrosis of the femoral head, it means that it has entered ARCO III. stage [16], and there is no evidence whether BMES will further develop into osteonecrosis. It is crucial to rule out other causes of bone marrow edema on MRI such as post-traumatic injury, stress fracture, osteoarthritis, osteomyelitis, septic arthritis, neuropathic joint disease, myeloproliferative disorders, hemoglobinopathies, and malignant neoplasms through clinical, radiological, and serological evaluation [17]. The cause of bone marrow edema in the knee can be followed up at a later date during long-term follow-up. The treatment of BMES remains controversial, and in general, BMES can be effectively improved without treatment [18]. However, there is a consensus on the importance of early treatment to reduce pain and shorten the course of the disease and to avoid possible subchondral bone collapse [9]. BMES treatment can be surgical or non-surgical. Invasive surgical treatments, such as core decompression or subchondroplasty, are considered to be effective treatments for BMES in the presence of recurrent or persistent pain [8, 15]. Surgical treatment is an expensive modality and carries the risk of complications, which include wound infection, hematoma formation, deep vein thrombosis, reflex sensorineural dystrophy, and fractures associated with bone canal drilling [2, 8] .The most common non-surgical treatments for BMES are bisphosphonates, prostacyclin, pulsed electromagnetic fields, extracorporeal shock waves, and hyperbaric oxygen therapy [19]. ESWT is becoming more and more accepted and has the advantages of good analgesia, high safety, good tolerance, high compliance, and good results in the treatment of BMES [20]. In our follow-up all patients did not experience any adverse effects, and the patients were easy to accept the treatment plan with high degree of cooperation.The aim of BMES treatment is to shorten the clinical course and reduce the pain of the patients, and ESWT is effective in relieving the pain and improving the function of the affected knee joints. In this study, ESWT significantly reduced symptoms and pain in three groups (femoral, tibial, and patellar) of BMES patients in a short period of time, resulting in an increase in knee HSS scores and a decrease in the area of bone marrow edema on MRI. This study provides medical evidence for the efficacy of ESWT in treating periprosthetic BMES in the knee in a short period of time. The exact mechanism by which ESWT operates is still unclear, but literature suggests that regeneration is more effective when the compressive stress is greater than 0.15 MPa, the curvature strain is higher than 0.05%, the fluid pressure is 68 kpa, and the energy flux density should exceed 0.3 mJ/mm 2 [13]. The regeneration results are better when the energy flux density should be more than 3 mJ/mm Moreover, the amount of new bone formation is directly dependent on the applied EFD, so when treating bone-related diseases with shockwaves, either too low or too high an energy dose is detrimental to the formation of new bone. Therefore, it is very important to choose the appropriate EFD according to the different musculoskeletal conditions and sites in order to not only improve the efficacy of shockwave therapy but also minimize the side effects of localized shockwaves. [21]. This can not only improve the efficacy of the shock wave, but also minimize the side effects of the local shock wave. Therefore, the range of energy flux density selected in this experiment is 0.22 to 0.43 mJ / mm 2 , the frequency is 10 Hz, which is adjusted according to the tolerance degree of the patients, and the effective threshold of the specific shockwave needs to be verified by further experiments. The etiology and pathogenesis of BMES are unclear; histologic findings suggest that abnormal vascular proliferation and increased focal bone conversion are accepted hypotheses for BMES [22] .ESWT is now widely used in musculoskeletal disorders, and the effectiveness of ESWT has been recognized, with literature demonstrating the efficacy of ESWT in the treatment of BMES caused by osteonecrosis of the femoral head (ONFH) by relieving pain and achieving functional recovery [23] . ESWT has also been shown to be effective in osteonecrosis, where it can better induce inward tissue growth and neovascularization; this is associated with an increase in the expression of angiogenic growth factors, including BMP-2, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and proliferating cell nuclear antigen (PCNA), and promotes cell proliferation and osteogenesis [24]. Shockwave therapy improves tissue healing, including stimulation of osteoblasts and periosteal cells as well as stem cell differentiation, and increased secretion of nitric oxide synthase and vascular endothelial growth factor, which leads to increased neovascularization [19, 25]. In a review by Furia et al. it was described that shockwave therapy promotes bone healing by stimulating vascularization in stress fractures, while shockwave therapy has a beneficial effect on bone healing in stress fractures [26] .ESWT not only stimulates the growth of osteoblasts and periosteal cells, but also induces osteogenic differentiation of mesenchymal stem cells, and significantly increases the production of osteocalcin, c-terminal type I procollagen (a marker of bone matrix deposition), and several growth factors [27–29] .Vascular endothelial growth factor (VEGF), transforming growth factor (TGF-Beta1), bone morphogenetic protein (BMP-2), vascular vasculature factor (vWF), and alkaline phosphatase (ALP) are significantly elevated in the peripheral blood of ESWT patients [27–29]. Unfocused shock waves positively affect bone microarchitecture by enhancing tissue mass and strength in healthy bones, and reduce bone loss in osteoporotic bones [30]. The positive effects of ESWT on bone metabolism can be explained by the close anatomical and functional links between vascular elements, bone marrow matrix and activated bone cells [9] . ESWT has been reported in the literature for the treatment of bone marrow edema in the knee and for normalizing bone marrow edema in arthritis [12]. This study provides reference for the treatment of periprosthetic BMES in the knee joint. The patients were divided into three groups (femur group, tibia group, and patella group) according to the different parts of the knee joint, and were provided with shockwave treatment plans individually according to the lesion sites suggested on the MRI images of the patients, and the patients' cooperation was relatively high, and the comparisons of before and after treatment of ESWT as well as the comparisons between the groups were performed after a three-month follow-up period. The overall VAS score decreased from 5.40 ± 1.624 to 1.57 ± 1.328 before treatment (P < 0.05); the overall HSS score increased from 83.05 ± 9.063 to 93.00 ± 4.129 before treatment (P < 0.05); the overall BMES area decreased from 3.876 ± 3.277 cm 2 before treatment to 1.294 ± 0.352 cm 2 (P < 0.05). Although no significant difference was seen between the three groups, in general the efficacy of shockwave treatment for BMES in the femur, tibia, and patella around the knee joint was better. This study has the advantages of simple operation as well as reproducibility, high patient acceptability, to some extent provides reference for the current study on shock wave treatment of bone marrow edema of the knee joint, and this study groups different parts of the knee joint for comparison and provides direction for future research. The limitations of this study are that there was no control group, the number of patients was relatively small, and the follow-up time was short. So in future studies we would like to conduct standardized multicenter randomized controlled trials with large sample sizes as well as studies with long follow-up. In the next step, we expect to design the efficacy of extracorporeal shock wave therapy combined with bisphosphonates comparing the efficacy of both extracorporeal shock wave therapy alone. CONCLUSION Overall ESWT is effective in the treatment of periprosthetic BMES, resulting in lower VAS scores, higher HSS scores, and a significant reduction in the area of bone marrow edema on T2WI of MRI (except for the patella group where the reduction in the area of bone marrow edema was not statistically significant, but the overall trend was downward). The results of this study showed no significant difference in efficacy for ESWT for treating different parts of the knee (femur, tibia, patella), but more randomized controlled trials are needed to verify this in the future. Declarations INSTITUTIONAL REVIEW COMMITTEE DECLARATION: The study protocol was approved by the Clinical Trial Ethics Committee of Southwest Medical University Hospital (KY2024007). Funding Statement: This study was not supported by any funding. Conflict of interest statement: The authors declare that they have no conflict of interest. Data and Material Sharing Statement: The datasets used and/or analyzed in this study are available from the corresponding authors upon reasonable request. Author information: Hao Hu: Orthopedic Department, Affiliated Hospital of Southwest Medical University, 646099, Sichuan Province, China. corresponding author：Xing Guo, Burns and Plastic Surgery Department and Ambulatory Surgery Center, Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou 646099, Sichuan Province, China. 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Supplementary Files Table1.xlsx Demographic and clinical characteristics ESWT extracorporeal shockwave therapy Table2.xlsx Change in knee function evaluation score after extracorporeal shockwave therapy ESWT extracorporeal shockwave therapy, VAS Visual analogue scale. HSS Hospital for special surgery knee score Table3.xlsx Comparison of VAS, HSS, and edema area (cm 2 ) in the three groups before and after shock wave treatment is shown in Table 3. Charts.docx 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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University","correspondingAuthor":false,"prefix":"","firstName":"Hanwen","middleName":"","lastName":"Liu","suffix":""},{"id":266018499,"identity":"1f4ebf35-2cd7-4cfa-8d38-8d3d95906287","order_by":2,"name":"Kun Yu","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Yu","suffix":""},{"id":266018500,"identity":"0e022c89-ff41-4644-98c2-23395560ee87","order_by":3,"name":"Yinshen Liu","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yinshen","middleName":"","lastName":"Liu","suffix":""},{"id":266018501,"identity":"77d7dacf-3e09-4eea-b666-ec651cd02a5e","order_by":4,"name":"Maoru LI","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Maoru","middleName":"","lastName":"LI","suffix":""},{"id":266018502,"identity":"cac5ac53-ccfc-47a8-b386-6b239f769492","order_by":5,"name":"Haili Mao","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Haili","middleName":"","lastName":"Mao","suffix":""},{"id":266018503,"identity":"a9aab909-0607-4ac4-a288-5994c756b82d","order_by":6,"name":"Xing Guo","email":"","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xing","middleName":"","lastName":"Guo","suffix":""},{"id":266018504,"identity":"7f9a7741-f065-4e2b-a83f-274a1a3282a8","order_by":7,"name":"Meiyun Tan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDCCAyDCwEaOH8pnbCCshRlIFKQZSzaQpuXDocQNB4jVwnf7/NHNPAYHEjefP2O6mYfBRnbDAeZnD/BpkTyXzHabx+CO8bYbOWa3eRjSjDccYDM3wKfF4AwzSMsz2W03eLcBtRwGupCHTYIILYcZN/efBWn5T7wWxQ0MuSAtBwhrkTzDbHZzjkGascSN/G9ARrLxzMNsZni18J1hfHbjzR9gVPYfS7vxpsJOtu948zO8WkCAiQfhTiBmJqQeCBh/EKFoFIyCUTAKRjAAAN4CT+TLFTMhAAAAAElFTkSuQmCC","orcid":"","institution":"Affiliated Hospital of Southwest Medical University","correspondingAuthor":true,"prefix":"","firstName":"Meiyun","middleName":"","lastName":"Tan","suffix":""}],"badges":[],"createdAt":"2024-01-08 13:44:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3845537/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3845537/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49435416,"identity":"50f0f5c0-61a9-4de2-85af-a14674a57152","added_by":"auto","created_at":"2024-01-10 20:03:00","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76509,"visible":true,"origin":"","legend":"\u003cp\u003eSubjects receiving extracorporeal shock wave therapy\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/a3fccf434e982e21bc33bf64.jpg"},{"id":49435422,"identity":"fc84c8df-f1a6-4379-8e4a-d742997cd45f","added_by":"auto","created_at":"2024-01-10 20:03:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":24878061,"visible":true,"origin":"","legend":"\u003cp\u003eT2WI sagittal images of patients receiving extracorporeal shockwave therapy, before versus after 3 months of treatment in the femoral group (a, b), before versus after 3 months of treatment in the tibial group (c, d), and before versus after 3 months of treatment in the patella (e, f).\u003c/p\u003e","description":"","filename":"Onlinefigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/fc6d3848a7d955458a2800d4.png"},{"id":49655955,"identity":"6afe33e2-22ca-4a5b-b5b8-3115ca6ce423","added_by":"auto","created_at":"2024-01-16 03:40:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3762387,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/70a23026-f8ce-4b40-b679-b41a1b62074f.pdf"},{"id":49435417,"identity":"bc50be71-2b3f-4d15-ba3d-0eb7c079c456","added_by":"auto","created_at":"2024-01-10 20:03:00","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":9225,"visible":true,"origin":"","legend":"\u003cp\u003eDemographic and clinical characteristics\u003c/p\u003e\n\u003cp\u003eESWT extracorporeal shockwave therapy\u003c/p\u003e","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/3622fa1d67c9100d9248bb84.xlsx"},{"id":49435418,"identity":"63fb47f8-3d15-481b-b5df-877e12dc0c18","added_by":"auto","created_at":"2024-01-10 20:03:00","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10085,"visible":true,"origin":"","legend":"\u003cp\u003eChange in knee function evaluation score after extracorporeal shockwave therapy\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eESWT \u003c/em\u003eextracorporeal shockwave therapy, VAS Visual analogue scale.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHSS \u003c/em\u003eHospital for special surgery knee score\u003c/p\u003e","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/a4090a42b46f0f668a466303.xlsx"},{"id":49435420,"identity":"5e484b6e-e327-4f70-b2e4-1e5f183fd238","added_by":"auto","created_at":"2024-01-10 20:03:01","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10928,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of VAS, HSS, and edema area (cm\u003csup\u003e2\u003c/sup\u003e ) in the three groups before and after shock wave treatment is shown in Table 3.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/ca712227b0108c19e7207618.xlsx"},{"id":49435419,"identity":"2337fd9a-27ec-4d04-82ee-6b1d6fdae3a8","added_by":"auto","created_at":"2024-01-10 20:03:00","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":294381,"visible":true,"origin":"","legend":"","description":"","filename":"Charts.docx","url":"https://assets-eu.researchsquare.com/files/rs-3845537/v1/394faadb64f274d0127e1f2d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of extracorporeal shock wave therapy in the treatment of bone marrow edema in different parts of the knee joints","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBone marrow edema (BME) syndrome refers to increased interstitial fluid in the interstitial spaces between the bone marrow and is a reversible, self-limiting disorder that manifests as ill-defined, homogeneous areas of intermediate signal intensity on T1-weighted (T1W) images and high signal intensity on fat-suppressed T2-weighted (T2W) images [1]. Some scholars have suggested that bone marrow edema syndrome is an early, reversible ischemic necrosis with mostly painful clinical manifestations, and imaging is usually difficult to detect on X-rays, with high sensitivity and specificity of MRI examination [2]. BME usually affects the epiphyses of the load-bearing joints, most commonly the hip, but also the knee, ankle, and foot, but it may also present as \"wandering\" BME with multiple episodes at different sites [3]. In the knee, it is seen in the knee, the ankle, and the foot. In the knee, it is seen for a variety of reasons, including: ischemic (exfoliative osteochondritis, osteonecrosis, or complex localized pain syndrome), mechanical (bone bruise or contusion, microfracture, or stress fracture), and other reasons (osteoarthritis, surgery, or cancer) [4]. Although multiple factors are known to cause bone marrow edema in BME, this reversible, nonspecific disease usually spreads from the medullary space to the subchondral regions of the joints [5]. BME in the subchondral bone BME in the subchondral bone significantly increases the risk of structural progression in knee osteoarthritis, and increased mechanical loading in cases of knee osteoarthritis can lead to microfractures in the subchondral metaphyseal region, resulting in the collapse of the involved compartment of bone, which may be associated with biomechanical changes in knee osteoarthritis [5\u0026ndash;7]. The current clinical management of bone marrow edema syndrome includes weight reduction, nonsteroidal anti-inflammatory drugs, intravenous prostacyclin and bisphosphonates, and surgical treatment with core decompression, but there is no gold standard yet [8] .Extracorporeal shockwave (ESWT) is now proven to have significant efficacy in the treatment of musculoskeletal disorders, including the reduction of bone marrow edema due to early osteonecrosis of the femoral head [9]. ESWT has been shown to reduce pain, improve hip function, and normalize the MRI signal of bone marrow edema in early osteonecrosis of the femoral head, avoiding the risks of surgical infection, postoperative fracture, and deep vein thrombosis compared to invasive surgery [10]. Extracorporeal shock wave (ESWT) can activate many neovascularizations and tissue regeneration due to its angiogenic and trophic effects on tissues [11] .ESWT has been shown to be an effective method of tissue regeneration. ESWT has been shown to be an effective, reliable, and noninvasive treatment for reducing pain in patients with osteoarthritis BME of the knee, normalizing MRI signals, and potentially shortening the natural course of this disease [12] .Galina Eremina presented a numerical model of the knee joint to study the regenerative effects of shockwave therapy with computer assistance. The results showed that the chondrogenic process is initiated only when the compressive stress is greater than a threshold of 0.15 MPa; the tissue starts to differentiate considerably when the torsional strain is higher than a threshold of 0.05%; the optimal level corresponding to the fluid pressure is 68 kpa, and the energy flux density of the therapeutic shockwave loading should be more than 0.3 mJ/mm\u003csup\u003e2,\u003c/sup\u003e However, the clinical efficacy of the treatment has not yet been demonstrated [13] .\u003c/p\u003e \u003cp\u003eWe therefore designed a prospective pilot study to validate the efficacy of ESWT in the treatment of bone marrow edema in different parts of the knee.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eParticipants and design Participants and design\u003c/p\u003e \u003cp\u003eClinical data were collected from 42 patients with knee bone marrow edema syndrome who attended the Department of Joint Surgery of the Affiliated Hospital of Southwest Medical University from January 2021 to December 2023, and they were divided into three groups according to the site of knee edema: femoral group (26 patients), tibial group (9 patients), and patellofemoral group (7 patients). There were a total of 42 patients (15 males and 27 females) aged 16\u0026ndash;73 years (mean age, 49.02\u0026thinsp;\u0026plusmn;\u0026thinsp;12.73 years). Inclusion criteria: 1. Patients\u0026thinsp;\u0026gt;\u0026thinsp;16 years of age with acute and chronic knee pain and MRI suggestive of areas of bone high-intensity signal on T2W sequences. Exclusion criteria: 1. BME with any MRI finding of ischemic necrosis, defined as subchondral crescentic areas (low-intensity signal subchondral areas on T1W sequences); 2. advanced osteoarthritis of the knee (grade 3 or 4); 3. third-degree damage to the medial and lateral meniscus of the knee; 4. previous surgical treatment of the affected knee; 5. systemic diseases such as SLE, alcoholism, rheumatoid arthritis, autoimmune diseases, and other diseases. rheumatoid arthritis, autoimmune diseases or tumors. Written informed consent was obtained from each patient, which was approved by the Ethics Committee of Southwest Medical University Hospital.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eExperimental procedure\u003c/h2\u003e \u003cp\u003eExperimental design\u003c/p\u003e \u003cp\u003ePersonalized ESWT\u003c/p\u003e \u003cp\u003eEach patient received a shockwave treatment consisting of 1 shockwave treatment every 1 week for 5 weeks (5 sessions in total), using a shockwave electromagnetic source (SWISS DOLORCLAST smart Switzerland). During each session, 2000 injections were administered at high energy with an energy flux density ranging from 0.22 to 0.43 mJ / mm\u003csup\u003e2\u003c/sup\u003e at 10 Hz. The site was localized according to imaging and local compression of the most painful point, and each patient received shockwave therapy with the knees bent at 100\u0026deg;(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e),no strenuous activities were allowed during the treatment period, and the affected limb was normally weight-bearing.\u003c/p\u003e \u003cp\u003eObservation indicators\u003c/p\u003e \u003cp\u003ePatients' gender, age, duration of symptoms in months, any comorbidity with other diseases, and history of trauma were recorded. All patients were clinically assessed by the same examiner according to the knee HSS rating scale, which includes pain, function, mobility, muscle strength, flexion deformity, and stability. Patients were also asked to assess their pain level on a 10-point visual analog scale (VAS), where 0 indicates no pain and 10 indicates maximum possible or intolerable pain. Scoring was based on the \u003cem\u003eHospital for Specialty Surgery Knee Score\u003c/em\u003e (HSS) 100-point scale. These scores were assessed before treatment as well as 3 months after treatment. All patients underwent knee MRI before and 3 months after treatment. The presence of focal subchondral low-intensity signal areas (a possible expression of early osteonecrosis) was assessed and excluded on T1W sequences. Areas of bone marrow lesions were assessed on fat-suppressed fast spin-echo T2W sequences. Areas of edema were obtained by measuring the area on the same sagittal and coronal slices of the MRI scans before and after treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003estatistical analysis\u003c/h2\u003e \u003cp\u003e We used SPSS 25.0 statistical software for analysis, and all patients were followed up to. Measurements were expressed as x\u0026thinsp;\u0026plusmn;\u0026thinsp;s. Paired t-tests were used to compare VAS scores, HSS scores and BMES areas before and after ESWT, and chi-square tests were used to test whether there were any significant differences between the groups, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 being considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe demographic and clinical characteristics of the subjects at baseline are shown in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eThe raw data for all patients including the mean and standard deviation of all dependent variables before and after the test are shown in Table\u0026nbsp;2. Statistical significance for all analyses was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eOverall VAS scores decreased from 5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.624 to 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.328 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with VAS scores in the femoral group decreasing from 5.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76 to 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); in the tibial group, VAS scores decreased from 5.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 before treatment to 1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13 points (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); VAS score in the patella group decreased from 5.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12 points before treatment to 1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The difference before and after treatment was statistically significant. As Table\u0026nbsp;1 is shown ( Chart \u003cspan refid=\"Str1\" class=\"InternalRef\"\u003e2\u003c/span\u003e ).\u003c/p\u003e \u003cp\u003eOverall HSS score increased from 83.05\u0026thinsp;\u0026plusmn;\u0026thinsp;9.063 before treatment to 93.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.129 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); HSS score in the femoral group increased from 82.12\u0026thinsp;\u0026plusmn;\u0026thinsp;9.11 before treatment to 92.73\u0026thinsp;\u0026plusmn;\u0026thinsp;4.71 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); HSS score in the tibial group increased from 87.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.47 before treatment to 94.44\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17 points (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); HSS score in the patella group increased from 81.14\u0026thinsp;\u0026plusmn;\u0026thinsp;11.89 points before treatment to 92.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14 points (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The difference before and after treatment was statistically significant. As Table\u0026nbsp;2 is shown ( Chart \u003cspan refid=\"Str2\" class=\"InternalRef\"\u003e3\u003c/span\u003e ).\u003c/p\u003e \u003cp\u003eOverall BMES area decreased from 3.876\u0026thinsp;\u0026plusmn;\u0026thinsp;3.277 cm\u003csup\u003e2\u003c/sup\u003e before treatment to 1.294\u0026thinsp;\u0026plusmn;\u0026thinsp;0.352 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with a statistically significant difference before and after treatment. The BMES area in the femur group decreased from 3.438\u0026thinsp;\u0026plusmn;\u0026thinsp;3.742 cm\u003csup\u003e2\u003c/sup\u003e to 1.346\u0026thinsp;\u0026plusmn;\u0026thinsp;1.532 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) before treatment, and the difference between before and after treatment was statistically significant; the BMES area in the tibia group decreased from 4.467\u0026thinsp;\u0026plusmn;\u0026thinsp;0.789 cm\u003csup\u003e2\u003c/sup\u003e to 1.940\u0026thinsp;\u0026plusmn;\u0026thinsp;0.988 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) before treatment, and the difference between before and after treatment was statistically significant; BMES area in the patella group decreased from 1.814\u0026thinsp;\u0026plusmn;\u0026thinsp;1.705 cm\u003csup\u003e2\u003c/sup\u003e to 0.772\u0026thinsp;\u0026plusmn;\u0026thinsp;0.612 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) before treatment, and the difference before and after treatment was not statistically significant. As Table\u0026nbsp;3 is shown( Chart \u003cspan refid=\"Str3\" class=\"InternalRef\"\u003e4\u003c/span\u003e ).\u003c/p\u003e \u003cp\u003eComparison between groups before and after shockwave treatment was performed using the chi-square test, as shown in Fig.\u0026nbsp;3. p-values were greater than 0.05, and the differences between groups were not statistically significant.\u003c/p\u003e \u003cp\u003eTypical cases of extracorporeal shockwave treatment of bone marrow edema of the knee (femoral, tibial, and patellar groups) at T2WI, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e .\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePeriprosthetic bone marrow lesions (BMLs) are a common finding on MRI.BML is defined as an alteration in bone marrow signal intensity with high signal on T2WI with or without low T1WI signal.BMLs often originate in subchondral or non-subchondral bone, and are pathologically diverse.These include traumatic bone contusions and fractures, post-surgical imaging changes in cartilage, osteoarthritis (OA), transient BML syndrome, spontaneous incomplete fractures (SIFK), and true osteonecrosis (ON)., transient BML syndrome, spontaneous incomplete fractures (SIFK) and true osteonecrosis (ON). [14] BMES is considered a self-limiting disease, with clinical resolution in 3\u0026ndash;24 months and complete disappearance of the edema signal on MRI [15]. BMES is considered to be a self-limiting disease. It has been suggested that once BMES is present in ischemic necrosis of the femoral head, it means that it has entered ARCO III. stage [16], and there is no evidence whether BMES will further develop into osteonecrosis. It is crucial to rule out other causes of bone marrow edema on MRI such as post-traumatic injury, stress fracture, osteoarthritis, osteomyelitis, septic arthritis, neuropathic joint disease, myeloproliferative disorders, hemoglobinopathies, and malignant neoplasms through clinical, radiological, and serological evaluation [17]. The cause of bone marrow edema in the knee can be followed up at a later date during long-term follow-up.\u003c/p\u003e \u003cp\u003eThe treatment of BMES remains controversial, and in general, BMES can be effectively improved without treatment [18]. However, there is a consensus on the importance of early treatment to reduce pain and shorten the course of the disease and to avoid possible subchondral bone collapse [9]. BMES treatment can be surgical or non-surgical. Invasive surgical treatments, such as core decompression or subchondroplasty, are considered to be effective treatments for BMES in the presence of recurrent or persistent pain [8, 15]. Surgical treatment is an expensive modality and carries the risk of complications, which include wound infection, hematoma formation, deep vein thrombosis, reflex sensorineural dystrophy, and fractures associated with bone canal drilling [2, 8] .The most common non-surgical treatments for BMES are bisphosphonates, prostacyclin, pulsed electromagnetic fields, extracorporeal shock waves, and hyperbaric oxygen therapy [19]. ESWT is becoming more and more accepted and has the advantages of good analgesia, high safety, good tolerance, high compliance, and good results in the treatment of BMES [20]. In our follow-up all patients did not experience any adverse effects, and the patients were easy to accept the treatment plan with high degree of cooperation.The aim of BMES treatment is to shorten the clinical course and reduce the pain of the patients, and ESWT is effective in relieving the pain and improving the function of the affected knee joints. In this study, ESWT significantly reduced symptoms and pain in three groups (femoral, tibial, and patellar) of BMES patients in a short period of time, resulting in an increase in knee HSS scores and a decrease in the area of bone marrow edema on MRI. This study provides medical evidence for the efficacy of ESWT in treating periprosthetic BMES in the knee in a short period of time.\u003c/p\u003e \u003cp\u003eThe exact mechanism by which ESWT operates is still unclear, but literature suggests that regeneration is more effective when the compressive stress is greater than 0.15 MPa, the curvature strain is higher than 0.05%, the fluid pressure is 68 kpa, and the energy flux density should exceed 0.3 mJ/mm \u003csup\u003e2\u003c/sup\u003e [13]. The regeneration results are better when the energy flux density should be more than 3 mJ/mm Moreover, the amount of new bone formation is directly dependent on the applied EFD, so when treating bone-related diseases with shockwaves, either too low or too high an energy dose is detrimental to the formation of new bone. Therefore, it is very important to choose the appropriate EFD according to the different musculoskeletal conditions and sites in order to not only improve the efficacy of shockwave therapy but also minimize the side effects of localized shockwaves. [21]. This can not only improve the efficacy of the shock wave, but also minimize the side effects of the local shock wave. Therefore, the range of energy flux density selected in this experiment is 0.22 to 0.43 mJ / mm\u003csup\u003e2\u003c/sup\u003e, the frequency is 10 Hz, which is adjusted according to the tolerance degree of the patients, and the effective threshold of the specific shockwave needs to be verified by further experiments.\u003c/p\u003e \u003cp\u003eThe etiology and pathogenesis of BMES are unclear; histologic findings suggest that abnormal vascular proliferation and increased focal bone conversion are accepted hypotheses for BMES [22] .ESWT is now widely used in musculoskeletal disorders, and the effectiveness of ESWT has been recognized, with literature demonstrating the efficacy of ESWT in the treatment of BMES caused by osteonecrosis of the femoral head (ONFH) by relieving pain and achieving functional recovery [23] .\u003c/p\u003e \u003cp\u003eESWT has also been shown to be effective in osteonecrosis, where it can better induce inward tissue growth and neovascularization; this is associated with an increase in the expression of angiogenic growth factors, including BMP-2, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and proliferating cell nuclear antigen (PCNA), and promotes cell proliferation and osteogenesis [24]. Shockwave therapy improves tissue healing, including stimulation of osteoblasts and periosteal cells as well as stem cell differentiation, and increased secretion of nitric oxide synthase and vascular endothelial growth factor, which leads to increased neovascularization [19, 25]. In a review by Furia et al. it was described that shockwave therapy promotes bone healing by stimulating vascularization in stress fractures, while shockwave therapy has a beneficial effect on bone healing in stress fractures [26] .ESWT not only stimulates the growth of osteoblasts and periosteal cells, but also induces osteogenic differentiation of mesenchymal stem cells, and significantly increases the production of osteocalcin, c-terminal type I procollagen (a marker of bone matrix deposition), and several growth factors [27\u0026ndash;29] .Vascular endothelial growth factor (VEGF), transforming growth factor (TGF-Beta1), bone morphogenetic protein (BMP-2), vascular vasculature factor (vWF), and alkaline phosphatase (ALP) are significantly elevated in the peripheral blood of ESWT patients [27\u0026ndash;29]. Unfocused shock waves positively affect bone microarchitecture by enhancing tissue mass and strength in healthy bones, and reduce bone loss in osteoporotic bones [30]. The positive effects of ESWT on bone metabolism can be explained by the close anatomical and functional links between vascular elements, bone marrow matrix and activated bone cells [9] .\u003c/p\u003e \u003cp\u003eESWT has been reported in the literature for the treatment of bone marrow edema in the knee and for normalizing bone marrow edema in arthritis [12]. This study provides reference for the treatment of periprosthetic BMES in the knee joint. The patients were divided into three groups (femur group, tibia group, and patella group) according to the different parts of the knee joint, and were provided with shockwave treatment plans individually according to the lesion sites suggested on the MRI images of the patients, and the patients' cooperation was relatively high, and the comparisons of before and after treatment of ESWT as well as the comparisons between the groups were performed after a three-month follow-up period. The overall VAS score decreased from 5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.624 to 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.328 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); the overall HSS score increased from 83.05\u0026thinsp;\u0026plusmn;\u0026thinsp;9.063 to 93.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.129 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); the overall BMES area decreased from 3.876\u0026thinsp;\u0026plusmn;\u0026thinsp;3.277 cm\u003csup\u003e2\u003c/sup\u003e before treatment to 1.294\u0026thinsp;\u0026plusmn;\u0026thinsp;0.352 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Although no significant difference was seen between the three groups, in general the efficacy of shockwave treatment for BMES in the femur, tibia, and patella around the knee joint was better.\u003c/p\u003e \u003cp\u003eThis study has the advantages of simple operation as well as reproducibility, high patient acceptability, to some extent provides reference for the current study on shock wave treatment of bone marrow edema of the knee joint, and this study groups different parts of the knee joint for comparison and provides direction for future research. The limitations of this study are that there was no control group, the number of patients was relatively small, and the follow-up time was short. So in future studies we would like to conduct standardized multicenter randomized controlled trials with large sample sizes as well as studies with long follow-up. In the next step, we expect to design the efficacy of extracorporeal shock wave therapy combined with bisphosphonates comparing the efficacy of both extracorporeal shock wave therapy alone.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOverall ESWT is effective in the treatment of periprosthetic BMES, resulting in lower VAS scores, higher HSS scores, and a significant reduction in the area of bone marrow edema on T2WI of MRI (except for the patella group where the reduction in the area of bone marrow edema was not statistically significant, but the overall trend was downward). The results of this study showed no significant difference in efficacy for ESWT for treating different parts of the knee (femur, tibia, patella), but more randomized controlled trials are needed to verify this in the future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eINSTITUTIONAL REVIEW COMMITTEE DECLARATION: The study protocol was approved by the Clinical Trial Ethics Committee of Southwest Medical University Hospital (KY2024007).\u003c/p\u003e\n\u003cp\u003eFunding Statement: This study was not supported by any funding.\u003c/p\u003e\n\u003cp\u003eConflict of interest statement: The authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eData and Material Sharing Statement: The datasets used and/or analyzed in this study are available from the corresponding authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003eAuthor information:\u003c/p\u003e\n\u003cp\u003eHao Hu: Orthopedic Department,\u0026nbsp;Affiliated Hospital of Southwest Medical University, 646099, Sichuan Province, China.\u003c/p\u003e\n\u003cp\u003ecorresponding author：Xing Guo, Burns and Plastic Surgery Department and Ambulatory Surgery Center,\u0026nbsp;Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou 646099, Sichuan Province, China.\u003c/p\u003e\n\u003cp\u003eMei-yun Tan：Professor, Orthopedic Department, Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou 646099, Sichuan Province, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eC.E. 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Notarnicola, L. Moretti, S. Patella, V. Patella, A. Zallone, B. Moretti, EXTRACORPOREAL SHOCK WAVES STIMULATE OSTEOBLAST ACTIVITIES, Ultrasound Med. Biol. 35(12) (2009) 2093-2100.\u003c/li\u003e\n \u003cli\u003eO.P. van der Jagt, J.C. van der Linden, W. Schaden, H.T. van Schie, T.M. Piscaer, J.A.N. Verhaar, H. Weinans, J.H. Waarsing, Unfocused Extracorporeal Shock Wave Therapy as Potential Treatment for Osteoporosis, J. Orthop. Res. 27(11) (2009) 1528-1533.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Chart","content":"\u003cp\u003eChart 2, 3 and 4 are available in the Supplementary Files section.\u003c/p\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":"extracorporeal shock wave, knee, bone marrow edema","lastPublishedDoi":"10.21203/rs.3.rs-3845537/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3845537/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe purpose of this prospective study was to evaluate the effectiveness of extracorporeal shock wave therapy (ESWT) in reducing symptoms and normalizing imaging features in periprosthetic bone marrow edema syndrome (BMES) of the knee.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe clinical data of 42 patients with knee bone marrow edema syndrome who attended the Department of Joint Surgery of the Affiliated Hospital of Southwest Medical University from January 2021 to December 2023 were collected, and they were divided into three groups according to the different parts of the knee edema: the femur group (26 cases), the tibia group (9 cases), and the patella group (7 cases). The visual analog scale (VAS) of pain, the \u003cem\u003eknee score\u003c/em\u003e (HSS) \u003cem\u003eof the Hospital for Special Surgery of the United States\u003c/em\u003e, and the area of BME on magnetic resonance imaging (cm\u003csup\u003e2\u003c/sup\u003e ) were observed before and after three months of shock wave treatment in each group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOverall VAS score decreased from 5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.624 to 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.328 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and HSS score increased from 83.05\u0026thinsp;\u0026plusmn;\u0026thinsp;9.063 to 93.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.129 before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); the area of BMES decreased from 3.876\u0026thinsp;\u0026plusmn;\u0026thinsp;3.277 cm\u003csup\u003e2\u003c/sup\u003e before treatment to 1.294\u0026thinsp;\u0026plusmn;\u0026thinsp;0.352 cm\u003csup\u003e2\u003c/sup\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) before and after treatment. There was no significant difference between the three groups before and after treatment. (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05)\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOverall ESWT is effective in the treatment of periprosthetic BMES, leading to a decrease in VAS scores, an increase in HSS scores, and a significant decrease in the area of bone marrow edema on T2WI of MRI (except for the patellofemoral group where the decrease in the area of bone marrow edema was not statistically significant, but the overall trend was downward).\u003c/p\u003e","manuscriptTitle":"Efficacy of extracorporeal shock wave therapy in the treatment of bone marrow edema in different parts of the knee joints","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-10 20:02:56","doi":"10.21203/rs.3.rs-3845537/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":"6532c01d-6529-428c-9954-4826eaa99ca4","owner":[],"postedDate":"January 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-16T03:31:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-10 20:02:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3845537","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3845537","identity":"rs-3845537","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}