Long-term clinical efficacy and imaging evaluation of submandibular joint injection of hyaluronic acid for irreversible anterior displacement of the articular disc

Long-term clinical efficacy and imaging evaluation of submandibular joint injection of hyaluronic acid for irreversible anterior displacement of the articular disc | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Long-term clinical efficacy and imaging evaluation of submandibular joint injection of hyaluronic acid for irreversible anterior displacement of the articular disc Chuanbao Wang, Kai Xu, Yajing Liu, Haoyu Shi, Xianbin Liu, Guohao Wu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8008867/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Anterior disc displacement without reduction (ADDwoR) represents a common and debilitating subtype of temporomandibular disorder, manifesting as restricted mouth opening and joint pain that profoundly affects patients’ quality of life. This study aims to evaluate the long-term clinical efficacy and associated structural changes of patients with ADDwoR treated with intra-articular injections of sodium hyaluronate into the superior compartment of the temporomandibular joint (TMJ). In total, 209 patients diagnosed with ADDwoR who presented to the clinic between January 2016 and June 2023 were included. Of these, 27 patients underwent complete magnetic resonance imaging evaluations both before and after treatment (follow-up duration: 1–6 years. The therapeutic protocol consisted of joint lavage followed by sodium hyaluronate injection administered every 2 weeks; three consecutive sessions comprised one full treatment course. Magnetic resonance imaging was used to measure the length of the joint disc and its displacement distance. Clinical efficacy was assessed using the Craniomandibular Index (CMI), Jaw Functional Limitation Scale, and psychological assessment tools, including the Generalized Anxiety Disorder Questionnaire-7, Patient Health Questionnaire-9 (PHQ-9), and Patient Health Questionnaire-15. Post-treatment results revealed no statistically significant differences in joint disc length (8.95 ± 1.26 mm vs. 8.46 ± 1.10 mm) or disc displacement distance (3.79 ± 1.36 mm vs. 4.36 ± 1.96 mm) (P > 0.05). However, both the Dysfunction Index and Craniomandibular Index demonstrated significant reductions following treatment (P < 0.001). Functional improvement was further supported by a marked decrease in the Jaw Functional Limitation Scale score, from 81.59 ± 40.55 to 30.59 ± 25.57 (P < 0.001). Additionally, psychological assessments indicated significant improvements in anxiety (Generalized Anxiety Disorder Questionnaire-7) and depression (Patient Health Questionnaire-9) scores (P < 0.05). While hyaluronic acid injections do not restore the anatomical configuration of the articular disc, existing evidence and findings from this study suggest they effectively reduce inflammation and enhance joint lubrication. These therapeutic effects contribute to functional recovery and alleviate the psychological distress associated with chronic TMJ dysfunction. To further substantiate the long-term protective benefits of this intervention on TMJ structure and function, future research should incorporate larger sample sizes and adopt a prospective, controlled study design. Temporomandibular joint hyaluronic acid disc displacement intra-articular injection long-term outcomes Figures Figure 1 Introduction Anterior disc displacement without reduction (ADDwoR) is the most common subtype of temporomandibular disorders (TMDs) [ 1 ] , which, as a group, represent the second most prevalent chronic musculoskeletal pain condition after low back pain, affecting approximately 6%–9% of adults globally [ 2 ] . ADDwoR is primarily characterized by limited mouth opening and joint pain, symptoms that significantly impair patients’ quality of life [ 3 , 4 ] . Historically, treatment options for TMD have included invasive procedures such as arthrocentesis [ 5 ] , arthroscopy, and open surgical approaches for disc reduction or resection [ 6 ] . Although these techniques require strict aseptic protocols, they also carry the risk of postoperative infection. Non-invasive therapies, including occlusal splint therapy [ 7 ] , arthrolysis, and muscle relaxation techniques, offer a more conservative approach but typically produce slower therapeutic outcomes and necessitate long-term adherence. These methods often have limited efficacy in cases involving severe joint adhesions or structural deformities, and their success is highly dependent on patient compliance. Moreover, persistent pain may hinder some patients’ ability to cooperate with these conservative treatments. Pharmacologic interventions such as intra-articular injections of hyaluronic acid (HA) have emerged as rapid-acting alternatives for pain relief and inflammation control. HA enhances joint lubrication and reduces intra-articular friction, thereby improving joint function [ 8 ] . HA is an acidic mucopolysaccharide first isolated in 1934 from the vitreous humor of a bull’s eye by Meyer et al., a professor of ophthalmology at Columbia University [ 9 ] . Owing to its unique molecular structure and physicochemical characteristics [ 10 ] , HA performs several crucial physiological functions in the human body. These include joint lubrication, regulation of vascular wall permeability, facilitation of protein, water, and electrolyte transport, and promotion of wound healing [ 11 ] . In recent years, HA injections into the temporomandibular joint (TMJ) cavity have demonstrated promising short-term efficacy in the treatment of TMD [ 4 , 12 , 13 ] . However, long-term imaging-based evidence remains limited. This study addresses that gap by using magnetic resonance imaging (MRI) to evaluate pre- and post-treatment structural changes and assess the clinical effectiveness of HA injections administered into the upper compartment of the TMJ for the management of ADDwoR. Materials and Methods 2.1.Study design This study is a single-center retrospective cohort study. All enrolled patients received the same standardized treatment protocol—intra-articular injection of sodium hyaluronate following joint lavage—without a control group. No randomization or prospective group assignment was performed; all eligible patients who met the inclusion criteria during the study period were included in the treatment cohort. 2.2.Selection criteria Clinical trial number: not applicable. This study enrolled 209 patients with ADDwoR who received treatment at the Temporomandibular Joint Disease Clinic of the Department of Oral and Maxillofacial Surgery, Liao Cheng Peoples Hospital, from January 2016 to June 2023. Telephonic follow-ups were conducted, and MRI rechecks were scheduled for January–March 2024. Ultimately, MRI images before and after treatment were collected from 27 patients. Of the 209 patients who received HA injections, only 27 completed the follow-up MRI examinations, while the remaining 182 patients did not participate for significant symptom resolution, waiving off re-examination (n = 130), travel constraints (n = 32), and loss to follow-up (n = 20). The ages of the patients ranged from 14 to 60 years. All patients fully understood the research content and voluntarily provided their signed informed consent forms. The study protocol was approved by the Ethics Committee of Liao Cheng People’s Hospital, with the ethical review report number (2023250). The patient inclusion criteria included the following: ① clinical manifestations of ADDwoR (such as limited mouth opening, pain, and mandibular deviation toward the affected side during mouth opening); ② involvement of the temporomandibular joint; ③ confirmation of ADDwoR through MRI without disc perforation; ④ at least 1 year between the last treatment and the recheck. The exclusion criteria included ① temporomandibular joint tumors, fractures, history of temporomandibular joint surgery, or systemic arthritis; ② cardiovascular diseases, organic lesions, poor quality MRI images, mental disorders, and cognitive impairments; ③ anterior ear infection. 2.3.Reagent materials Sterile gloves, a disposable oral instrument tray, a 5-mL syringe, an iodine swab, lidocaine hydrochloride injection, and HA injection were used. 2.4.Treatment The patient was positioned semi-recumbently on a dental chair, with the head turned toward the unaffected side to fully expose the puncture site. This site was identified in the depression between the tragus and the mandibular condyle. After routine disinfection, the patient was instructed to open their mouth widely, thereby increasing joint space and negative intra-articular pressure, which facilitated successful needle insertion. The needle was advanced in an anterosuperomedial direction into the superior joint compartment to a depth of approximately 2–2.5 cm. Once the bone surface was contacted, the needle was slightly withdrawn. Subsequently, 3 mL of 2% lidocaine was injected for local anesthesia. Without repositioning the needle, 1 mL of HA was then administered. After the injection, the needle was slowly removed, and sterile cotton balls were applied to the surgical area for 5 min to achieve compression and hemostasis. The patient was instructed to gently open and close the mouth several times, promoting joint mobility and ensuring optimal contact between the injected medication and intra-articular tissues. This procedure—comprising joint lavage followed by HA injection—was repeated once every 2 weeks, with three consecutive sessions constituting one full course of treatment [ 14 ] . 2.5.Evaluation criteria MRI Evaluation: All patients underwent MRI of the TMJ pretreatment and again during a follow-up in 2024. The same radiologist conducted all image analyses to maintain consistency. Measurements included the length and displacement of the articular disc on both the affected and unaffected sides, taken before and after treatment. For image evaluation, the largest sagittal section of the condyle—usually the central slice—was selected for analysis. Reference points and lines were delineated using Adobe Photoshop CS5 software (Fig. 1 ). The condylar long axis was determined using the two-step method proposed by Nebbe et al. and Xie et al. [ 15 , 16 ] . First, the largest circle (O1) was fitted to the anterior, posterior, and superior contours of the condylar head, effectively isolating it from the neck. Second, a smaller incircle (O2) was drawn in the most curved region between the condylar head and neck. The line connecting the centers of O1 and O2 defined the long axis of the condylar head (line y). Points A and C were identified as the anterior and posterior margins of the disc along this axis, while point B was the midpoint of the middle zone of the disc. Point D represents the intersection of the condylar axis (y) with the condylar surface. The linear distances from A to B and from B to C were measured, and their sum defined the total length of the articular disc (Fig. 1 ). In cases where the disc was severely deformed and the middle zone could not be identified, the distance from A to C was measured directly. The distance from point C to point D was recorded as the disc displacement relative to the condyle [ 17 , 18 ] . All measurements were performed using MB-Ruler software, with a precision of up to 0.01 mm, to ensure accurate quantification of disc length and displacement. Sagittal MRI image illustrating the methodology for determining the condylar long axis (line y) and disc landmarks (points A, B, C, D). The sum of distances A-B and B-C defines the disc length, while the distance from C to D indicates the disc displacement. Scale evaluation: 1. Subjective symptom assessment: Treatment efficacy was assessed using multiple validated scales, including the Jaw Functional Limitation Scale (JFLS), the Generalized Anxiety Disorder Questionnaire-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9) for depression screening, and the Patient Health Questionnaire-15 (PHQ-15) for somatic symptom evaluation. Before the assessment, each item was explained to the patients in detail, and they were asked to self-evaluate their condition based on their symptoms. 2. TMJ function assessment: The functional status of TMJ was evaluated using the Craniomandibular Index (CMI) [ 19 ] , which comprises several components: mandibular movement (MM, 16 items), joint noise (JN, 8 items), joint palpation (JP, 3 items), and palpation of the masseter and associated muscle groups (MP, 15 items). The following indices were calculated: Dysfunction Index (DI) = (MM + JN + JP)/26, Palpation Index (PI) = MP/28, CMI = (DI + PI)/2. Quality Control: All patients diagnosed with irreversible anterior disc displacement of TMJ were evaluated and treated by the same expert specializing in TMDs, based on both clinical presentation and imaging findings. Research indicators were selected by a single trained investigator based on previously published protocols. All data measurements and analyses were performed by the same experienced researcher to ensure consistency and minimize interobserver variability. Statistical Analysis: Data analysis was performed using SPSS (version 25.0; IBM Corp., Chicago, IL, USA). A 95% confidence interval was adopted, and a p-value of < 0.05 was considered statistically significant. Quantitative data were expressed as mean ± standard deviation (mean ± SD). Paired sample comparisons were conducted using both the paired t-test and the Wilcoxon signed-rank test to account for data distribution characteristics. Conclusion and Results Table 1 Index number Pre-treatment (Mean ± SD) Pre-treatment (Mean ± SD) P value Length of articular disc (mm) Mean ± SD 8.95 ± 1.26 8.46 ± 1.10 0.08 a Displacement length of the articular disc (mm) Mean ± SD 3.79 ± 1.36 4.36 ± 1.96 0.08 b a paired t-test b Wilcoxon symbol-rank test MRI assessment: The average pre-treatment disc length was 8 mm. Following treatment, the mean disc length increased from 3.79 mm to 4.36 mm; however, this change was not statistically significant (P > 0.05). Similarly, the average displacement distance decreased from 9.8 mm to 8.46 mm, but this reduction also did not reach statistical significance (P > 0.05). These findings indicate that there were no statistically significant changes in either the length or displacement of the articular disc before and after treatment. Table 2 DI and CMI showed significant reductions following treatment (P < 0.001). Patients experienced marked relief from adverse symptoms, indicating that the intervention was clinically effective. Comparison of Fricton temporomandibular joint disorder index before and after treatment of irreversible TMD pre-displacement (n = 27) Index number Pretherapy Mean ± SD Post-treatment Mean ± SD t price Effect size (Cohen's d) Functional disorder index DI 0.467 ± 0.125 0.172 ± 0.112 13.279 * 2.41 (Large) Muscle tenderness index PI 0.149 ± 0.162 0.044 ± 0.093 Temporomandibular joint index CMI 0.308 ± 0.119 0.108 ± 0.086 8.633 * 1.67 (Large) Note: *P < 0.001 Table 3 Comparison of the JFLS score and the incidence of anxiety, depression, and somatic symptoms before and after treatment Index number Pretherapy Post-treatment P value JFLS score Mean ± SD 81.59 ± 40.55 30.59 ± 25.57 0 GAD7 anxiety scale score Mean ± SD 6.48 ± 6.08 3.74 ± 3.29 0.021 PHQ9 depression screening score Mean ± SD 6.78 ± 6.22 3.3 ± 3.45 0.002 PHQ15 somatic symptom cluster scale Mean ± SD 5.3 ± 4.79 4.96 ± 3.94 0.603 The pretreatment GAD-7 and PHQ-9 scores were significantly higher than the post-treatment scores, with the differences reaching statistical significance according to the paired t-test (P 0.05), also shown in Table 3 . Discussion Based on MRI findings, the present study assessed changes in disc condition—specifically disc length, position, and morphology—before and after treatment. The average length of the TMJ disc decreased from 8.98 mm to 8.46 mm (P > 0.05), while the average displacement distance increased from 3.79 mm to 4.36 mm (P > 0.05), as shown in Table 1 . These changes in disc length and displacement distance were not statistically significant. Although MRI did not show significant disc repositioning (P > 0.05), the absence of further degenerative changes (vs. untreated cohorts [ 21 ] ) implied that HA possibly protected joint integrity. Functional gains (CMI, JFLS) likely stem from HA’s anti-inflammatory and lubricating properties rather than from anatomical correction [ 20 ] . These results suggest that sodium hyaluronate primarily alleviates inflammation and pain rather than repositioning the joint disc. This observation aligns with findings from Ying Kai Hu [ 21 ] , where untreated patients with ADDwoR showed a significant reduction in disc length (from 8.29 mm to 7.21 mm) and an increase in displacement distance (from 5.29 mm to 6.40 mm). Therefore, although statistical significance was not achieved in the present study, the treatment may have contributed to the prevention of further disc deterioration. The lack of significance may be due to the limited sample size, suggesting that larger-scale studies are warranted for validation. Comparison of the CMI before and after treatment for ADDwoR (Table 2 ) showed a statistically significant reduction (P < 0.01), providing clinical evidence that HA injections can improve mandibular functional movement in patients with ADDwoR. TMDs comprise a group of musculoskeletal and neuromuscular conditions affecting the TMJ, associated musculature, and related osseous structures. The etiology of TMDs is multifactorial, involving biological, environmental, emotional, social, and cognitive components. Psychological factors such as anxiety and depression are significant contributors to the onset and persistence of TMDs [ 22 ] . In the present study, patients’ psychological states improved following treatment, with significant reductions in anxiety and depression scores (Table 3 ). Additionally, JFLS scores were markedly reduced, indicating enhanced jaw function and a favorable therapeutic outcome. ADDwoR, one of the most common subtypes of TMD, is characterized by limited mouth opening and TMJ pain [ 23 , 24 ] , both of which can substantially impair quality of life. While some studies suggest that the symptoms of untreated ADDwoR may resolve spontaneously in certain cases, others indicate that symptoms may persist or worsen, potentially leading to irreversible structural damage [ 25 , 26 ] . Progressive pathological changes include condylar bone resorption and destruction, disc deformation, and alterations in facial morphology and masticatory function, all of which negatively impact patients’ physical and psychological health [ 27 ] . As the only articulating joint in the maxillofacial region, the TMJ must withstand significant functional stress due to its role in daily mastication, making treatment of joint-related disorders particularly challenging. Clinically, the management of ADDwoR typically involves a multidisciplinary approach [ 8 ] , ranging from conservative therapies to surgical interventions, following a stepwise treatment protocol [ 28 , 29 ] . The dissociation between significant functional improvement and the lack of structural changes on MRI clarifies HA’s primary action mechanism, which is symptomatic and functional modulation rather than anatomical disc repositioning. [ 30 ] . The pathophysiology of ADDwoR involves inflammatory mediators (e.g., IL-1, TNF-α) and mechanical compression, underpinning TMJ pain [ 31 – 33 ] . In this context, we concurred that HA injections exert their therapeutic effect by restoring the pathological joint environment [ 34 , 35 ] . This multifaceted action counteracts the synovial fluid deficiency and compositional abnormalities detected in TMD [ 36 ] , [ 37 ] , thereby breaking the cycle of pain, inflammation, and limited mandibular movement [ 38 ] . [ 39 ] . [ 40 ] . HA, a natural component secreted by synovial B cells, exists as sodium salts within the synovial fluid and cartilage matrix and exerts multiple biological effects [ 41 , 42 ] , such as providing lubrication to reduce friction [ 30 , 34 , 35 ] , forming a barrier against inflammatory mediators [ 43 ] , facilitating regulation of synovial fluid rheology [ 44 ] , and potentially supporting synovial cell and cartilage homeostasis [ 41 ] . .Our long-term outcomes position HA injection as a core minimally invasive therapy within the TMD treatment hierarchy, serving as an effective intermediary between conservative modalities and surgery, as supported by a recent network meta-analysis by Al-Moraissi et al. [ 43 ] , which confirms the efficacy of HA for arthrogenous TMDs. For patients with contraindications to surgery or in those seeking a potent conservative option, HA injections represent a viable first-line strategy to halt functional deterioration. Notably, while HA excels in symptom control and may protect joint integrity, its capacity to regenerate articular cartilage or reverse established disc deformation is likely limited, as also concurred by our findings. Future research should thus analyze HA with orthobiologics like platelet-rich plasma (PRP), which are theorized to have greater regenerative potential, to help establish their distinct roles. HA injection provides effective short-term relief [ 29 , 45 , 46 ] . Its long-term efficacy over 12 months is also supported by patient-reported outcomes and imaging studies, underscoring its clinical value. Specifically, in the management of ADDwoR, intra-articular HA injection has demonstrated significant symptomatic relief and psychological improvement. Although structural changes in the joint did not reach statistical significance, the observed functional improvements hold substantial clinical importance. Future research should focus on further validating the long-term structural protective effects and elucidating the underlying mechanisms of HA through large-scale, prospective, controlled trials. This study has several limitations that should be considered. First, its retrospective design introduces the potential for recall and selection bias. Second, the absence of a control group (e.g., untreated patients or those receiving saline injections) precludes definitive conclusions regarding placebo effects or natural disease progression. Third, the non-randomized, single-arm design limits causal inferences. Furthermore, the small subset of patients who completed MRI follow-up may limit the statistical power and introduce selection bias. To address these limitations, future research should be designed as a prospective cohort study, incorporating a control group, increasing sample size, and implementing more rigorous follow-up procedures to minimize bias. Ultimately, prospective, randomized controlled trials are warranted to validate the long-term efficacy and structural protective effects of hyaluronic acid injections in ADDwoR. To address these limitations, future research will be designed as a prospective cohort study, incorporating a control group, increasing sample size, and implementing more rigorous follow-up procedures to minimize bias. Declarations Author Contributions Chuanbao Wang: writing – original draft, writing – review and editing. KaiXu: writing – original draft, writing – review and editing. Yajing Liu: writing – review and editing. Haoyu Shi: writing – review and editing. Xianbin Liu: data curation, writing – review and editing. Guohao Wu: data curation, writing, review, and editing. Xueping Huang: data curation, writing – review and editing. Yingying Wang: data curation, writing, review, and editing. Keyi Li: writing, review, and editing. Huaqiang Zhao: writing, review, and editing. Acknowledgments The authors would like to acknowledge the patient and the multidisciplinary care team who have contributed to his care. Human Ethics and Consent to Participate declarations This study involving human participants was reviewed and approved by the Ethics Committee of Liaocheng People's Hospital (Approval No. 2023250). Informed consent was obtained from all participants. Consent for publication: not applicable.All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Conflicts of Interest The authors declare no conflicts of interest. Funding Declaration This work was supported by the [Technology Research and Development Program of Shandong Province] (Grant Numbers 2022YDSF003) and the [ Natural Science Foundation of Shandong Province] (Grant Number 2023FYM113). 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Intra-Articular Injections into the Inferior versus Superior Compartment of the Temporomandibular Joint: A Systematic Review and Meta-Analysis [J]. J Clin Med, 2023, 12(4). CHRISTIDIS N, AL-MORAISSI E A, BARJANDI G, et al. Pharmacological Treatments of Temporomandibular Disorders: A Systematic Review Including a Network Meta-Analysis [J]. Drugs, 2024, 84(1): 59-81. SHIMOJO A A M, PIRES A M B, LICHY R, et al. The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles [J]. Journal of Biomedical Materials Research Part A, 2014, 103(2): 730-7. KELEMEN K, KöNIG J, VáNCSA S, et al. Efficacy of different intraarticular injection materials in the arthrocentesis of arthrogenic temporomandibular disorders: A systematic review and network meta-analysis of randomized controlled trials [J]. Journal of Prosthodontic Research, 2025, 69(2): 203-14. TUROSZ N, CHECINSKA K, CHECINSKI M, et al. Temporomandibular Joint Injections and Lavage: An Overview of Reviews [J]. J Clin Med, 2024, 13(10). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Dec, 2025 Reviews received at journal 21 Dec, 2025 Reviews received at journal 19 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviews received at journal 18 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviewers invited by journal 18 Dec, 2025 Editor assigned by journal 08 Dec, 2025 Submission checks completed at journal 07 Dec, 2025 First submitted to journal 07 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-8008867","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":563651577,"identity":"a27dc75a-0ce5-42b8-ba31-0d0d8e25e753","order_by":0,"name":"Chuanbao Wang","email":"","orcid":"","institution":"Shandong Second Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chuanbao","middleName":"","lastName":"Wang","suffix":""},{"id":563651578,"identity":"3d0444e8-14d7-4a34-9ece-8c2d7f25faed","order_by":1,"name":"Kai Xu","email":"","orcid":"","institution":"Liaocheng People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Xu","suffix":""},{"id":563651579,"identity":"5914ef40-7c56-4071-9893-ee597c1d51fc","order_by":2,"name":"Yajing Liu","email":"","orcid":"","institution":"Liaocheng People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yajing","middleName":"","lastName":"Liu","suffix":""},{"id":563651580,"identity":"6187cf8e-ff42-451b-bdc2-7957aa7a6bdc","order_by":3,"name":"Haoyu Shi","email":"","orcid":"","institution":"Shandong First Medical University \u0026 Shandong Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Haoyu","middleName":"","lastName":"Shi","suffix":""},{"id":563651581,"identity":"3aa7a814-28ce-4cb4-bcf2-4de1dc6bf1a3","order_by":4,"name":"Xianbin Liu","email":"","orcid":"","institution":"Liaocheng People's 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Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Huaqiang","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2025-11-02 04:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8008867/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8008867/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98845631,"identity":"654a7832-604a-40a7-b3d3-8edeb8a3513f","added_by":"auto","created_at":"2025-12-23 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04:28:39","extension":"html","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101029,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8008867/v1/39b201dea6860ca7b42db867.html"},{"id":99308395,"identity":"2da5da4a-1e19-4843-8ab3-a2c9986a272a","added_by":"auto","created_at":"2025-12-31 16:08:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":298525,"visible":true,"origin":"","legend":"\u003cp\u003eMagnetic resonance imaging (MRI) measurement of temporomandibular joint disc length and displacement.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8008867/v1/06044c76476038ba5d2f025d.png"},{"id":100406121,"identity":"e39394fd-bbc6-4d12-83d7-b3abd914c16c","added_by":"auto","created_at":"2026-01-16 12:42:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1133850,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8008867/v1/541c7c22-e49f-4c1c-98a8-10b55b1d1fea.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term clinical efficacy and imaging evaluation of submandibular joint injection of hyaluronic acid for irreversible anterior displacement of the articular disc","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnterior disc displacement without reduction (ADDwoR) is the most common subtype of temporomandibular disorders (TMDs)\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, which, as a group, represent the second most prevalent chronic musculoskeletal pain condition after low back pain, affecting approximately 6%\u0026ndash;9% of adults globally\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. ADDwoR is primarily characterized by limited mouth opening and joint pain, symptoms that significantly impair patients\u0026rsquo; quality of life\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Historically, treatment options for TMD have included invasive procedures such as arthrocentesis\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, arthroscopy, and open surgical approaches for disc reduction or resection\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Although these techniques require strict aseptic protocols, they also carry the risk of postoperative infection. Non-invasive therapies, including occlusal splint therapy\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, arthrolysis, and muscle relaxation techniques, offer a more conservative approach but typically produce slower therapeutic outcomes and necessitate long-term adherence. These methods often have limited efficacy in cases involving severe joint adhesions or structural deformities, and their success is highly dependent on patient compliance. Moreover, persistent pain may hinder some patients\u0026rsquo; ability to cooperate with these conservative treatments. Pharmacologic interventions such as intra-articular injections of hyaluronic acid (HA) have emerged as rapid-acting alternatives for pain relief and inflammation control. HA enhances joint lubrication and reduces intra-articular friction, thereby improving joint function\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHA is an acidic mucopolysaccharide first isolated in 1934 from the vitreous humor of a bull\u0026rsquo;s eye by Meyer et al., a professor of ophthalmology at Columbia University\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Owing to its unique molecular structure and physicochemical characteristics\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, HA performs several crucial physiological functions in the human body. These include joint lubrication, regulation of vascular wall permeability, facilitation of protein, water, and electrolyte transport, and promotion of wound healing\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. In recent years, HA injections into the temporomandibular joint (TMJ) cavity have demonstrated promising short-term efficacy in the treatment of TMD\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. However, long-term imaging-based evidence remains limited. This study addresses that gap by using magnetic resonance imaging (MRI) to evaluate pre- and post-treatment structural changes and assess the clinical effectiveness of HA injections administered into the upper compartment of the TMJ for the management of ADDwoR.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1.Study design\u003c/h2\u003e \u003cp\u003eThis study is a single-center retrospective cohort study. All enrolled patients received the same standardized treatment protocol\u0026mdash;intra-articular injection of sodium hyaluronate following joint lavage\u0026mdash;without a control group. No randomization or prospective group assignment was performed; all eligible patients who met the inclusion criteria during the study period were included in the treatment cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2.Selection criteria\u003c/h2\u003e \u003cp\u003e \u003cb\u003eClinical trial number: not applicable.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e This study enrolled 209 patients with ADDwoR who received treatment at the Temporomandibular Joint Disease Clinic of the Department of Oral and Maxillofacial Surgery, Liao Cheng Peoples Hospital, from January 2016 to June 2023. Telephonic follow-ups were conducted, and MRI rechecks were scheduled for January\u0026ndash;March 2024. Ultimately, MRI images before and after treatment were collected from 27 patients. Of the 209 patients who received HA injections, only 27 completed the follow-up MRI examinations, while the remaining 182 patients did not participate for significant symptom resolution, waiving off re-examination (n\u0026thinsp;=\u0026thinsp;130), travel constraints (n\u0026thinsp;=\u0026thinsp;32), and loss to follow-up (n\u0026thinsp;=\u0026thinsp;20). The ages of the patients ranged from 14 to 60 years. All patients fully understood the research content and voluntarily provided their signed informed consent forms. The study protocol was approved by the Ethics Committee of Liao Cheng People\u0026rsquo;s Hospital, with the ethical review report number (2023250). The patient inclusion criteria included the following: ① clinical manifestations of ADDwoR (such as limited mouth opening, pain, and mandibular deviation toward the affected side during mouth opening); ② involvement of the temporomandibular joint; ③ confirmation of ADDwoR through MRI without disc perforation; ④ at least 1 year between the last treatment and the recheck. The exclusion criteria included ① temporomandibular joint tumors, fractures, history of temporomandibular joint surgery, or systemic arthritis; ② cardiovascular diseases, organic lesions, poor quality MRI images, mental disorders, and cognitive impairments; ③ anterior ear infection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3.Reagent materials\u003c/h2\u003e \u003cp\u003eSterile gloves, a disposable oral instrument tray, a 5-mL syringe, an iodine swab, lidocaine hydrochloride injection, and HA injection were used.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4.Treatment\u003c/h2\u003e \u003cp\u003eThe patient was positioned semi-recumbently on a dental chair, with the head turned toward the unaffected side to fully expose the puncture site. This site was identified in the depression between the tragus and the mandibular condyle. After routine disinfection, the patient was instructed to open their mouth widely, thereby increasing joint space and negative intra-articular pressure, which facilitated successful needle insertion. The needle was advanced in an anterosuperomedial direction into the superior joint compartment to a depth of approximately 2\u0026ndash;2.5 cm. Once the bone surface was contacted, the needle was slightly withdrawn. Subsequently, 3 mL of 2% lidocaine was injected for local anesthesia. Without repositioning the needle, 1 mL of HA was then administered. After the injection, the needle was slowly removed, and sterile cotton balls were applied to the surgical area for 5 min to achieve compression and hemostasis. The patient was instructed to gently open and close the mouth several times, promoting joint mobility and ensuring optimal contact between the injected medication and intra-articular tissues. This procedure\u0026mdash;comprising joint lavage followed by HA injection\u0026mdash;was repeated once every 2 weeks, with three consecutive sessions constituting one full course of treatment\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5.Evaluation criteria\u003c/h2\u003e \u003cp\u003eMRI Evaluation: All patients underwent MRI of the TMJ pretreatment and again during a follow-up in 2024. The same radiologist conducted all image analyses to maintain consistency. Measurements included the length and displacement of the articular disc on both the affected and unaffected sides, taken before and after treatment. For image evaluation, the largest sagittal section of the condyle\u0026mdash;usually the central slice\u0026mdash;was selected for analysis. Reference points and lines were delineated using Adobe Photoshop CS5 software (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The condylar long axis was determined using the two-step method proposed by Nebbe et al. and Xie et al.\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. First, the largest circle (O1) was fitted to the anterior, posterior, and superior contours of the condylar head, effectively isolating it from the neck. Second, a smaller incircle (O2) was drawn in the most curved region between the condylar head and neck. The line connecting the centers of O1 and O2 defined the long axis of the condylar head (line y). Points A and C were identified as the anterior and posterior margins of the disc along this axis, while point B was the midpoint of the middle zone of the disc. Point D represents the intersection of the condylar axis (y) with the condylar surface. The linear distances from A to B and from B to C were measured, and their sum defined the total length of the articular disc (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In cases where the disc was severely deformed and the middle zone could not be identified, the distance from A to C was measured directly. The distance from point C to point D was recorded as the disc displacement relative to the condyle\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. All measurements were performed using MB-Ruler software, with a precision of up to 0.01 mm, to ensure accurate quantification of disc length and displacement.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSagittal MRI image illustrating the methodology for determining the condylar long axis (line y) and disc landmarks (points A, B, C, D). The sum of distances A-B and B-C defines the disc length, while the distance from C to D indicates the disc displacement.\u003c/p\u003e \u003cp\u003eScale evaluation: 1. Subjective symptom assessment: Treatment efficacy was assessed using multiple validated scales, including the Jaw Functional Limitation Scale (JFLS), the Generalized Anxiety Disorder Questionnaire-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9) for depression screening, and the Patient Health Questionnaire-15 (PHQ-15) for somatic symptom evaluation. Before the assessment, each item was explained to the patients in detail, and they were asked to self-evaluate their condition based on their symptoms. 2. TMJ function assessment: The functional status of TMJ was evaluated using the Craniomandibular Index (CMI)\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, which comprises several components: mandibular movement (MM, 16 items), joint noise (JN, 8 items), joint palpation (JP, 3 items), and palpation of the masseter and associated muscle groups (MP, 15 items). The following indices were calculated: Dysfunction Index (DI) = (MM\u0026thinsp;+\u0026thinsp;JN\u0026thinsp;+\u0026thinsp;JP)/26, Palpation Index (PI)\u0026thinsp;=\u0026thinsp;MP/28, CMI = (DI\u0026thinsp;+\u0026thinsp;PI)/2.\u003c/p\u003e \u003cp\u003eQuality Control: All patients diagnosed with irreversible anterior disc displacement of TMJ were evaluated and treated by the same expert specializing in TMDs, based on both clinical presentation and imaging findings. Research indicators were selected by a single trained investigator based on previously published protocols. All data measurements and analyses were performed by the same experienced researcher to ensure consistency and minimize interobserver variability.\u003c/p\u003e \u003cp\u003eStatistical Analysis: Data analysis was performed using SPSS (version 25.0; IBM Corp., Chicago, IL, USA). A 95% confidence interval was adopted, and a p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Quantitative data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD). Paired sample comparisons were conducted using both the paired t-test and the Wilcoxon signed-rank test to account for data distribution characteristics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion and Results","content":"\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-treatment (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePre-treatment (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of articular disc (mm) Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisplacement length of the articular disc (mm) Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ea paired t-test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eb Wilcoxon symbol-rank test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMRI assessment: The average pre-treatment disc length was 8 mm. Following treatment, the mean disc length increased from 3.79 mm to 4.36 mm; however, this change was not statistically significant (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Similarly, the average displacement distance decreased from 9.8 mm to 8.46 mm, but this reduction also did not reach statistical significance (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These findings indicate that there were no statistically significant changes in either the length or displacement of the articular disc before and after treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDI and CMI showed significant reductions following treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients experienced marked relief from adverse symptoms, indicating that the intervention was clinically effective.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eComparison of Fricton temporomandibular joint disorder index before and after treatment of irreversible TMD pre-displacement (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePretherapy\u003c/p\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et price\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffect size (Cohen's d)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFunctional disorder index DI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.467\u0026thinsp;\u0026plusmn;\u0026thinsp;0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.172\u0026thinsp;\u0026plusmn;\u0026thinsp;0.112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.279\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.41 (Large)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle tenderness index PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.149\u0026thinsp;\u0026plusmn;\u0026thinsp;0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.044\u0026thinsp;\u0026plusmn;\u0026thinsp;0.093\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporomandibular joint index CMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.308\u0026thinsp;\u0026plusmn;\u0026thinsp;0.119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.108\u0026thinsp;\u0026plusmn;\u0026thinsp;0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.633\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.67 (Large)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNote: *P\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eComparison of the JFLS score and the incidence of anxiety, depression, and somatic symptoms before and after treatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePretherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJFLS score Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.59\u0026thinsp;\u0026plusmn;\u0026thinsp;40.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.59\u0026thinsp;\u0026plusmn;\u0026thinsp;25.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGAD7 anxiety scale score Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;6.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePHQ9 depression screening score Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePHQ15 somatic symptom cluster scale Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe pretreatment GAD-7 and PHQ-9 scores were significantly higher than the post-treatment scores, with the differences reaching statistical significance according to the paired t-test (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In contrast, no significant difference was observed in PHQ-15 scores before and after treatment, with the paired t-test indicating no statistical significance (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), also shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBased on MRI findings, the present study assessed changes in disc condition\u0026mdash;specifically disc length, position, and morphology\u0026mdash;before and after treatment. The average length of the TMJ disc decreased from 8.98 mm to 8.46 mm (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), while the average displacement distance increased from 3.79 mm to 4.36 mm (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. These changes in disc length and displacement distance were not statistically significant. Although MRI did not show significant disc repositioning (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), the absence of further degenerative changes (vs. untreated cohorts \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e) implied that HA possibly protected joint integrity. Functional gains (CMI, JFLS) likely stem from HA\u0026rsquo;s anti-inflammatory and lubricating properties rather than from anatomical correction\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. These results suggest that sodium hyaluronate primarily alleviates inflammation and pain rather than repositioning the joint disc. This observation aligns with findings from Ying Kai Hu\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e, where untreated patients with ADDwoR showed a significant reduction in disc length (from 8.29 mm to 7.21 mm) and an increase in displacement distance (from 5.29 mm to 6.40 mm). Therefore, although statistical significance was not achieved in the present study, the treatment may have contributed to the prevention of further disc deterioration. The lack of significance may be due to the limited sample size, suggesting that larger-scale studies are warranted for validation. Comparison of the CMI before and after treatment for ADDwoR (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) showed a statistically significant reduction (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), providing clinical evidence that HA injections can improve mandibular functional movement in patients with ADDwoR. TMDs comprise a group of musculoskeletal and neuromuscular conditions affecting the TMJ, associated musculature, and related osseous structures. The etiology of TMDs is multifactorial, involving biological, environmental, emotional, social, and cognitive components. Psychological factors such as anxiety and depression are significant contributors to the onset and persistence of TMDs\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. In the present study, patients\u0026rsquo; psychological states improved following treatment, with significant reductions in anxiety and depression scores (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Additionally, JFLS scores were markedly reduced, indicating enhanced jaw function and a favorable therapeutic outcome.\u003c/p\u003e \u003cp\u003eADDwoR, one of the most common subtypes of TMD, is characterized by limited mouth opening and TMJ pain\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, both of which can substantially impair quality of life. While some studies suggest that the symptoms of untreated ADDwoR may resolve spontaneously in certain cases, others indicate that symptoms may persist or worsen, potentially leading to irreversible structural damage\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Progressive pathological changes include condylar bone resorption and destruction, disc deformation, and alterations in facial morphology and masticatory function, all of which negatively impact patients\u0026rsquo; physical and psychological health\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. As the only articulating joint in the maxillofacial region, the TMJ must withstand significant functional stress due to its role in daily mastication, making treatment of joint-related disorders particularly challenging. Clinically, the management of ADDwoR typically involves a multidisciplinary approach\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, ranging from conservative therapies to surgical interventions, following a stepwise treatment protocol\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. The dissociation between significant functional improvement and the lack of structural changes on MRI clarifies HA\u0026rsquo;s primary action mechanism, which is symptomatic and functional modulation rather than anatomical disc repositioning.\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. The pathophysiology of ADDwoR involves inflammatory mediators (e.g., IL-1, TNF-α) and mechanical compression, underpinning TMJ pain\u003csup\u003e[\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this context, we concurred that HA injections exert their therapeutic effect by restoring the pathological joint environment\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. This multifaceted action counteracts the synovial fluid deficiency and compositional abnormalities detected in TMD \u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e, \u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e, thereby breaking the cycle of pain, inflammation, and limited mandibular movement\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e. \u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. \u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e. HA, a natural component secreted by synovial B cells, exists as sodium salts within the synovial fluid and cartilage matrix and exerts multiple biological effects\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e, such as providing lubrication to reduce friction\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e, forming a barrier against inflammatory mediators\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e, facilitating regulation of synovial fluid rheology\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e, and potentially supporting synovial cell and cartilage homeostasis\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e. .Our long-term outcomes position HA injection as a core minimally invasive therapy within the TMD treatment hierarchy, serving as an effective intermediary between conservative modalities and surgery, as supported by a recent network meta-analysis by Al-Moraissi et al.\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e, which confirms the efficacy of HA for arthrogenous TMDs. For patients with contraindications to surgery or in those seeking a potent conservative option, HA injections represent a viable first-line strategy to halt functional deterioration.\u003c/p\u003e \u003cp\u003eNotably, while HA excels in symptom control and may protect joint integrity, its capacity to regenerate articular cartilage or reverse established disc deformation is likely limited, as also concurred by our findings. Future research should thus analyze HA with orthobiologics like platelet-rich plasma (PRP), which are theorized to have greater regenerative potential, to help establish their distinct roles.\u003c/p\u003e \u003cp\u003eHA injection provides effective short-term relief\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e. Its long-term efficacy over 12 months is also supported by patient-reported outcomes and imaging studies, underscoring its clinical value. Specifically, in the management of ADDwoR, intra-articular HA injection has demonstrated significant symptomatic relief and psychological improvement. Although structural changes in the joint did not reach statistical significance, the observed functional improvements hold substantial clinical importance. Future research should focus on further validating the long-term structural protective effects and elucidating the underlying mechanisms of HA through large-scale, prospective, controlled trials.\u003c/p\u003e \u003cp\u003eThis study has several limitations that should be considered. First, its retrospective design introduces the potential for recall and selection bias. Second, the absence of a control group (e.g., untreated patients or those receiving saline injections) precludes definitive conclusions regarding placebo effects or natural disease progression. Third, the non-randomized, single-arm design limits causal inferences. Furthermore, the small subset of patients who completed MRI follow-up may limit the statistical power and introduce selection bias. To address these limitations, future research should be designed as a prospective cohort study, incorporating a control group, increasing sample size, and implementing more rigorous follow-up procedures to minimize bias. Ultimately, prospective, randomized controlled trials are warranted to validate the long-term efficacy and structural protective effects of hyaluronic acid injections in ADDwoR. To address these limitations, future research will be designed as a prospective cohort study, incorporating a control group, increasing sample size, and implementing more rigorous follow-up procedures to minimize bias.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contributions\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003eChuanbao Wang:\u003c/strong\u003e writing \u0026ndash; original draft, writing \u0026ndash; review and editing.\u003cstrong\u003e\u0026nbsp;KaiXu:\u003c/strong\u003e writing \u0026ndash; original draft, writing \u0026ndash; review and editing.\u003cstrong\u003e\u0026nbsp;Yajing Liu:\u003c/strong\u003e writing \u0026ndash; review and editing.\u003cstrong\u003e\u0026nbsp;Haoyu Shi:\u003c/strong\u003e writing \u0026ndash; review and editing. \u003cstrong\u003eXianbin Liu:\u003c/strong\u003e data curation, writing \u0026ndash; review and editing. \u003cstrong\u003eGuohao Wu:\u003c/strong\u003e data curation, writing, review, and editing.\u003cstrong\u003e\u0026nbsp;Xueping Huang:\u003c/strong\u003e data curation, writing \u0026ndash; review and editing. \u003cstrong\u003eYingying Wang:\u003c/strong\u003e data curation, writing, review, and editing. \u003cstrong\u003eKeyi Li:\u003c/strong\u003e writing, review, and editing. \u003cstrong\u003eHuaqiang Zhao:\u003c/strong\u003e writing, review, and editing.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAcknowledgments\u003c/h2\u003e\n\u003cp\u003eThe authors would like to acknowledge the patient and the multidisciplinary care team who have contributed to his care.\u003c/p\u003e\n\u003ch2\u003eHuman Ethics and Consent to Participate declarations\u003c/h2\u003e\n\u003cp\u003eThis study involving human participants was reviewed and approved by the Ethics Committee of Liaocheng People\u0026apos;s Hospital (Approval No. 2023250). \u0026nbsp;Informed consent was obtained from all participants. Consent for publication: not applicable.All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003ch2\u003eFunding Declaration\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the [Technology Research and Development Program of Shandong Province] (Grant Numbers 2022YDSF003) and the [\u0026nbsp;Natural Science Foundation of Shandong Province] (Grant Number 2023FYM113).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The datasets generated and analysed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAL-MORAISSI E A, AL-OTAIBI K, ALMAWERI A A, et al. 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Functional disorders of the temporomandibular joints: Internal derangement of the temporomandibular joint [J]. The Kaohsiung Journal of Medical Sciences, 2018, 34(4): 223-30.\u003c/li\u003e\n\u003cli\u003eKONTTINEN Y T, SAARI H, SANTAVIRTA S, et al. Synovial Fibroblasts [J]. Scandinavian Journal of Rheumatology, 2009, 17(sup76): 95-103.\u003c/li\u003e\n\u003cli\u003eGUARDA-NARDINI L, ROSSI A, RAMONDA R, et al. Effectiveness of treatment with viscosupplementation in temporomandibular joints with or without effusion [J]. International Journal of Oral and Maxillofacial Surgery, 2014, 43(10): 1218-23.\u003c/li\u003e\n\u003cli\u003eMARINHO A, NUNES C, REIS S. Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation [J]. Biomolecules, 2021, 11(10).\u003c/li\u003e\n\u003cli\u003eCHECINSKI M, CHECINSKA K, TUROSZ N, et al. Intra-Articular Injections into the Inferior versus Superior Compartment of the Temporomandibular Joint: A Systematic Review and Meta-Analysis [J]. J Clin Med, 2023, 12(4).\u003c/li\u003e\n\u003cli\u003eCHRISTIDIS N, AL-MORAISSI E A, BARJANDI G, et al. Pharmacological Treatments of Temporomandibular Disorders: A Systematic Review Including a Network Meta-Analysis [J]. Drugs, 2024, 84(1): 59-81.\u003c/li\u003e\n\u003cli\u003eSHIMOJO A A M, PIRES A M B, LICHY R, et al. The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles [J]. Journal of Biomedical Materials Research Part A, 2014, 103(2): 730-7.\u003c/li\u003e\n\u003cli\u003eKELEMEN K, K\u0026ouml;NIG J, V\u0026aacute;NCSA S, et al. Efficacy of different intraarticular injection materials in the arthrocentesis of arthrogenic temporomandibular disorders: A systematic review and network meta-analysis of randomized controlled trials [J]. Journal of Prosthodontic Research, 2025, 69(2): 203-14.\u003c/li\u003e\n\u003cli\u003eTUROSZ N, CHECINSKA K, CHECINSKI M, et al. Temporomandibular Joint Injections and Lavage: An Overview of Reviews [J]. J Clin Med, 2024, 13(10).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Temporomandibular joint, hyaluronic acid, disc displacement, intra-articular injection, long-term outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8008867/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8008867/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnterior disc displacement without reduction (ADDwoR) represents a common and debilitating subtype of temporomandibular disorder, manifesting as restricted mouth opening and joint pain that profoundly affects patients\u0026rsquo; quality of life. This study aims to evaluate the long-term clinical efficacy and associated structural changes of patients with ADDwoR treated with intra-articular injections of sodium hyaluronate into the superior compartment of the temporomandibular joint (TMJ). In total, 209 patients diagnosed with ADDwoR who presented to the clinic between January 2016 and June 2023 were included. Of these, 27 patients underwent complete magnetic resonance imaging evaluations both before and after treatment (follow-up duration: 1\u0026ndash;6 years. The therapeutic protocol consisted of joint lavage followed by sodium hyaluronate injection administered every 2 weeks; three consecutive sessions comprised one full treatment course. Magnetic resonance imaging was used to measure the length of the joint disc and its displacement distance. Clinical efficacy was assessed using the Craniomandibular Index (CMI), Jaw Functional Limitation Scale, and psychological assessment tools, including the Generalized Anxiety Disorder Questionnaire-7, Patient Health Questionnaire-9 (PHQ-9), and Patient Health Questionnaire-15. Post-treatment results revealed no statistically significant differences in joint disc length (8.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26 mm vs. 8.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10 mm) or disc displacement distance (3.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36 mm vs. 4.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96 mm) (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, both the Dysfunction Index and Craniomandibular Index demonstrated significant reductions following treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Functional improvement was further supported by a marked decrease in the Jaw Functional Limitation Scale score, from 81.59\u0026thinsp;\u0026plusmn;\u0026thinsp;40.55 to 30.59\u0026thinsp;\u0026plusmn;\u0026thinsp;25.57 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, psychological assessments indicated significant improvements in anxiety (Generalized Anxiety Disorder Questionnaire-7) and depression (Patient Health Questionnaire-9) scores (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). While hyaluronic acid injections do not restore the anatomical configuration of the articular disc, existing evidence and findings from this study suggest they effectively reduce inflammation and enhance joint lubrication. These therapeutic effects contribute to functional recovery and alleviate the psychological distress associated with chronic TMJ dysfunction. To further substantiate the long-term protective benefits of this intervention on TMJ structure and function, future research should incorporate larger sample sizes and adopt a prospective, controlled study design.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"Long-term clinical efficacy and imaging evaluation of submandibular joint injection of hyaluronic acid for irreversible anterior displacement of the articular disc","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-23 04:28:35","doi":"10.21203/rs.3.rs-8008867/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-26T05:52:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-21T14:00:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-19T07:14:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69793161554781973258311689708903204601","date":"2025-12-19T04:48:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-18T14:15:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244034685796523140596337052223772984971","date":"2025-12-18T13:56:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"337495589723965407275516083707459486618","date":"2025-12-18T13:34:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-18T12:34:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-08T14:22:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-07T16:53:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2025-12-07T16:48:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9e9b8288-c57f-4940-92dc-ebbc5c0e8fca","owner":[],"postedDate":"December 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T15:08:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-23 04:28:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8008867","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8008867","identity":"rs-8008867","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}