Unveiling the Landscape of MRONJ Awareness (2025) : A Comprehensive National Cross-Sectional Study of Tunisian Dentists' Knowledge, Attitudes, and Practices

Unveiling the Landscape of MRONJ Awareness (2025) : A Comprehensive National Cross-Sectional Study of Tunisian Dentists' Knowledge, Attitudes, and Practices | 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 Unveiling the Landscape of MRONJ Awareness (2025) : A Comprehensive National Cross-Sectional Study of Tunisian Dentists' Knowledge, Attitudes, and Practices Safa Jemli, aya Mtiri, Hiba Bettaieb, malek Dhifallah, Manel Boudokhane, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8823147/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract Background:Medication-related osteonecrosis of the jaw (MRONJ) represents a significant complication for patients receiving antiresorptive therapy. Dentists play a pivotal role in prevention, early detection, and management, yet global studies suggest variable practitioner preparedness.This study aimed to assess the current knowledge, attitudes, and clinical practices (KAP) of Tunisian dentists concerning MRONJ and identify factors influencing competency. Methods:A nationwide, cross-sectional online survey was distributed in September 2024. The validated 26-item questionnaire covered demographics, MRONJ knowledge, risk perception, and reported clinical behaviors. Data were analyzed descriptively and analytically. Results:Among 106 respondents (mean age: 30 years; 79.2% female; 83% general practitioners), key findings revealed a profound knowledge-practice gap. While 77.4% identified intravenous bisphosphonates and extractions as primary risks, only 11.3% felt confident managing affected patients. Clinical caution was pronounced: 87.7% were reluctant to perform surgery, 63.2% would routinely refer, and 39.6% had refused treatment. Analytical results identified younger age (<35 years), specialist status, and urban practice as significant positive correlates with accurate knowledge (p<0.05). A defensive cycle emerged, linking low patient exposure to higher anxiety and avoidance behaviors. Conclusion:This first national study in Tunisia highlights critical deficits in dentist preparedness for MRONJ, driven by knowledge gaps and risk overestimation. The findings underscore an urgent need for structured, continuous education programs, clear national guidelines, and interdisciplinary collaboration to transform defensive practice into evidence-based, proactive patient management. Medication-Related Osteonecrosis of the Jaw (MRONJ) bisphosphonates antiresorptive agents dental education knowledge-attitude-practice Tunisia survey Figures Figure 1 Introduction The landscape of dental care has evolved to require meticulous consideration of a patient's systemic health and pharmacological profile [ 1 ]. The widespread therapeutic use of bisphosphonates (BPs) and other antiresorptive agents for conditions like osteoporosis and bone metastases has introduced a complex iatrogenic risk: Medication-Related Osteonecrosis of the Jaw (MRONJ) [ 2 , 3 ]. First formally described in 2003, MRONJ is defined as exposed bone in the maxillofacial region that persists for more than eight weeks in a patient with a history of antiresorptive or antiangiogenic therapy, in the absence of prior radiation therapy to the jaws [ 4 ]. The reported incidence of MRONJ is highly variable, reflecting differences in drug potency, route of administration, and underlying disease. For patients receiving high-dose intravenous BPs for oncological indications, estimates range from 0.8% to 12%, whereas the risk for those on oral BPs for osteoporosis is substantially lower, generally cited at less than 0.1% per year [ 5 , 6 ]. This stark disparity in risk profile underscores the necessity for nuanced clinical judgment and risk stratification. Dental professionals are uniquely positioned at the frontline of MRONJ prevention and early intervention. Their responsibilities span pre-therapy dental clearance, ongoing oral health optimization during treatment, patient education, and the management of early-stage disease [ 7 , 8 ]. However, international literature consistently reveals a troubling variability in dentists' awareness, understanding, and application of established MRONJ guidelines. This inconsistency can lead to a spectrum of outcomes, from delayed diagnosis to overly defensive practices that may unjustly deny patients necessary dental care [ 9 , 10 ]. Despite the global recognition of this clinical challenge, there is a paucity of data from North African regions. To our knowledge, no prior study has evaluated the preparedness of the Tunisian dental community regarding MRONJ. This study, therefore, sought to comprehensively assess the knowledge, attitudes, and self-reported practices (KAP) of Tunisian dentists concerning MRONJ. By identifying specific knowledge gaps, sources of clinical anxiety, and factors associated with better preparedness, this research aims to inform the development of targeted educational initiatives and clinical guidelines to improve patient safety and care standards nationally. Methods Study Design This national cross-sectional study was conducted in September 2024 using an anonymous, web-based survey. The study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional research. Study setting and Sampling The target population comprised all licensed General practitioners and dental specialists actively practicing in Tunisia, including both the public and private healthcare sectors.. Dental students, dental assistants, hygienists, and non-practicing dentists were excluded. A non-probability convenience sampling strategy was employed due to the absence of a centralized national mailing registry. The survey link was disseminated through professional social media groups restricted to Tunisian dentists (Facebook and LinkedIn), as well as via institutional and professional networks to maximize national geographic coverage. Sample Size Estimation An a priori sample size was estimated based on the following assumptions: Expected proportion of dentists with adequate MRONJ knowledge: 50% (most conservative estimate to maximize sample size) Desired confidence level: 95% Margin of error: 10% Using the formula for a single proportion in cross-sectional studies: n=Z2⋅p⋅(1−p)d2n = \frac{{Z^2 \cdot p \cdot (1-p)}}{{d^2}}n=d2Z2⋅p⋅(1−p) Where: Z=1.96Z = 1.96Z=1.96 (for 95% confidence) p=0.5p = 0.5p=0.5 d=0.10d = 0.10d=0.10 n=(1.96)2⋅0.5⋅0.50.12≈96n = \frac{{(1.96)^2 \cdot 0.5 \cdot 0.5}}{{0.1^2}} \approx 96n=0.12(1.96)2⋅0.5⋅0.5≈96 Thus, a minimum of 96 participants was required. Our final sample included 106 respondents, meeting this threshold. Survey Instrument and Validation The data collection tool was a structured, self-administered questionnaire developed in French, the primary language of dental education in Tunisia. Its development followed a multi-stage process: Item Generation: A preliminary set of questions was developed based on a thorough review of international MRONJ guidelines (AAOMS, SFCO) and similar KAP studies [4,9,11]. Expert Validation: content validity was evaluated by an expert panel composed of three senior oral and maxillofacial surgeons and one consultant rheumatologist The panel assessed clarity, relevance, comprehensiveness, and alignment with current evidence-based guidelines. Minor wording modifications were implemented based on consensus feedback. Pilot Testing: A pilot version was administered to 15 dentists not included in the final sample to assess comprehensibility, flow, and time required for completion (approximately 7-10 minutes). Minor adjustments to wording were made based on feedback. Reliability Analysis:Internal consistency of the Attitudes section (5 items) was assessed using Cronbach’s alpha . The resulting alpha coefficient was 0.82 , indicating good reliability and internal consistency. The final questionnaire consisted of 26 items across four sections: Section A: Demographic and Professional Characteristics (6 items: age, gender, years of experience, specialty, practice sector, geographic location). Section B: Knowledge Assessment (10 items: BP indications, MRONJ definition, risk factors, incidence, preventive protocols, management stages). Section C: Attitudes and Perceptions (5 items: confidence level, anxiety, perception of risk severity). Section D: Reported Clinical Practices (5 items: frequency of encountering BP patients, treatment modifications, referral patterns, history of treatment refusal). Response formats included multiple-choice, Likert scales (e.g., "Not confident" to "Very confident"), and binary (Yes/No) options.The questionnaire was specifically developed for the purpose of this study and was not derived from a previously validated published instrument. The full English version of the questionnaire is provided as Additional file 1. Data Collection Procedure The questionnaire was built and distributed using Google Forms®. The survey link was actively disseminated over a four-week period through professionally focused social media groups (Facebook, LinkedIn) exclusive to Tunisian dentists, as well as through personal networks of the research team to ensure nationwide reach. Outcome Measures: Primary outcome are MRONJ-related knowledge (risk, preventive measures, procedural awareness) and s econdary outcomes are a ttitudes, confidence, anxiety and self-reported practices. Statistical Analysis All survey data were extracted from Google Forms into Microsoft Excel 365 and cleaned for completeness prior to analysis. Descriptive statistics were calculated for demographic, professional, and clinical variables. Categorical variables (e.g., gender, professional status, practice location, years of practice) were summarized as counts and percentages, while continuous variables (e.g., age) were presented as mean ± standard deviation (SD). Knowledge, attitudes, and practices (KAP) scores were analyzed separately. The internal consistency of the attitudes section was assessed using Cronbach’s alpha , with a value of 0.82 indicating good reliability. Univariate analyses were conducted to explore associations between independent variables (age group 15, professional status [general practitioner vs specialist], practice sector [public vs private], and practice location [urban vs rural]) and key dependent outcomes: Correct knowledge of MRONJ risk associated with oral bisphosphonates Self-reported confidence in managing BP patients Defensive clinical behaviors (treatment refusal, routine referral, reluctance to perform surgery) For categorical comparisons, Chi-square tests were used, with Fisher’s exact test applied when expected cell counts were <5. Mean differences for continuous variables were assessed using independent t-tests or ANOVA where appropriate. Multivariable logistic regression models were performed to identify independent predictors of accurate MRONJ knowledge and defensive clinical behavior. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. Statistical significance was set at p < 0.05 . All analyses were conducted using Microsoft Excel 365 for descriptive statistics and SPSS version 28 (IBM Corp., Armonk, NY, USA) for inferential analyses. Results are presented both narratively and in tables, with clear cross-tabulations linking demographic/professional variables to KAP outcomes. Bias Control and Study Limitations Several measures were implemented to reduce potential bias:anonymous data collection to reduce social desirability bias,nationwide dissemination to improve geographic representation and clear inclusion criteria to ensure professional homogeneity.However, the study remains subject to:Selection bias due to convenience sampling,self-report bias and inability to infer causality due to cross-sectional design.These limitations were acknowledged and considered in the interpretation of findings. Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki. The study protocol was submitted to the Ethics Committee of the Faculty of Dental Medicine of Monastir, Tunisia. The Committee reviewed the protocol and confirmed that formal ethical approval was not required due to the anonymous, voluntary, and non-interventional nature of the survey involving healthcare professionals only, in accordance with national regulations governing observational questionnaire-based studies (Reference number: FMDM/EC/2024/09-017). Electronic informed consent to participate was obtained from all participants prior to accessing the questionnaire. Participants were informed about the purpose of the study, the voluntary nature of their participation, and the anonymity of data collection. Submission of the completed questionnaire was considered as confirmation of consent. No personal or identifiable data were collected. Results Participant Characteristics A total of 106 dentists completed the survey. The mean age was 30.1 ± 5.8 years, and 79.2% were female . The majority were general practitioners (83%) , while 17% were specialists, including oral surgeons, periodontists, and prosthodontists. Years of clinical practice were distributed as follows: ≤5 years: 65.1% (n = 69), 6–15 years: 26.4% (n = 28), and >15 years: 8.5% (n = 9). Practice locations were predominantly urban (71.7%) , with near-equal representation in public (54.7%) and private (45.3%) sectors. Table 1 summarizes participant demographics. Table 1. Demographic and Professional Characteristics of Participants (N = 106) Characteristic n % Age 15 9 8.5 Urban 76 71.7 Public Sector 58 54.7 Clinical Exposure and Attitudes Most dentists reported low exposure to patients on bisphosphonates, with 86.8% managing fewer than five patients per month . When presented with a hypothetical BP patient requiring dental care: 55.7% reported moderate to high anxiety 87.7% were reluctant to perform surgical procedures 63.2% indicated they would routinely seek specialist consultation before intervention The Attitudes section demonstrated good internal consistency ( Cronbach’s alpha = 0.82 ). Knowledge Assessment Overall, dentists demonstrated awareness of key MRONJ risk factors, but substantial knowledge gaps were observed: 77.4% correctly identified intravenous bisphosphonates and tooth extraction as major triggers 41.5% correctly recognized the low annual risk (<0.1%) of MRONJ in patients on oral bisphosphonates for osteoporosis 45.3% incorrectly believed that a mandatory drug holiday is always required prior to extraction Only 11.3% of participants felt confident managing BP patients, while 53.8% reported moderate confidence These gaps translated into clinical decisions: 39.6% of dentists had refused to treat a BP patient at least once due to MRONJ concerns. Predictors of Knowledge and Clinical Behavior Univariate Associations Chi-square analyses showed that: Age <35 years was associated with correct knowledge of oral BP risk (p = 0.03) Specialist status was associated with higher knowledge (p = 0.04) Urban practice location correlated with better knowledge (p = 0.04) No significant association was observed for practice sector (public vs private) Multivariable Logistic Regression Binary logistic regression identified independent predictors of accurate MRONJ knowledge: Table 2 . Multivariable Logistic Regression Analysis of Factors Associated with Accurate Knowledge of MRONJ Risk (Oral Bisphosphonates) Predictor aOR 95% CI p-value Age <35 2.3 1.1–4.9 0.03 Specialist 2.7 1.1–6.6 0.04 Urban location 2.1 1.0–4.5 0.04 Defensive clinical behaviors were significantly associated with higher anxiety (OR = 3.2, 95% CI 1.5–6.8, p = 0.002). Analysis revealed a recursive "Cycle of Defensive Practice." The cycle (figure 1 )is initiated by limited clinical exposure, with 86.8% of participants managing fewer than five bleeding disorder patients monthly. This low exposure correlates with poorer retention of complex guidelines (p=0.02). Subsequently, deficient knowledge predicts heightened clinical anxiety (OR=3.2), which is a direct driver of avoidance behaviors, including treatment refusal (39.6%) and routine referral (63.2%) Conversely, specialists and recent graduates were more likely to break this cycle, demonstrating not only better knowledge but also a greater propensity to co-manage rather than outright refer complex cases. This first national assessment demonstrates that while Tunisian dentists are aware of MRONJ, knowledge deficits, low exposure, and anxiety contribute to defensive clinical behaviors . These findings underscore the need for targeted educational interventions, national guidelines, and interdisciplinary support networks to enhance both confidence and evidence-based patient management. Discussion This study provides the first comprehensive assessment of the Tunisian dental community's readiness to address MRONJ, revealing a landscape marked by awareness of the threat but hampered by significant knowledge deficits and consequent clinical apprehension. The very low confidence level (11.3%) is particularly telling and aligns with findings from other regions, such as Mexico and Spain, where only 15-20% of dentists felt comfortable managing these patients [9,11]. This pervasive discomfort suggests a global challenge in translating guideline knowledge into clinical confidence. The knowledge gaps identified are not trivial. The widespread belief in mandatory drug holidays (45.3%) is a major concern. Current international consensus strongly advises against routine cessation of oral BPs for dental procedures, as the drugs have a prolonged skeletal half-life, and discontinuation may negatively impact the patient's primary bone disease without reducing MRONJ risk [4,12]. This misconception likely stems from earlier, more cautious recommendations and highlights a critical failure in disseminating updated evidence to practicing clinicians. Our analytical findings offer valuable insights into the drivers of this gap. The significant advantage of younger dentists (<35 years) points to the successful integration of MRONJ into more recent dental curricula. The specialist-GP divide underscores the value of focused postgraduate training. Perhaps most importantly, the elucidated "Cycle of Defensive Practice" provides a conceptual model for why well-intentioned dentists default to avoidance. When faced with a high-stakes, low-frequency complication, limited personal experience breeds uncertainty, which in the absence of robust supporting knowledge and protocols, naturally leads to risk-averse behavior [13]. This defensive posture, while understandable, carries significant public health implications. The refusal of care (reported by 39.6%) can lead to untreated dental infection and pain, potentially forcing patients to choose between their oncological/bone health and their oral health. It may also inadvertently increase risk, as emergency interventions for acute infections in poor oral environments are more traumatic than planned, preventative care [14]. Limitations This study has limitations inherent to its design. The cross-sectional, self-reported nature captures stated, not observed, practices and cannot establish causality. The use of convenience sampling and online distribution may introduce selection bias, potentially over-representing tech-savvy and urban practitioners. The sample size, while adequate for an initial national survey, limits the power for more complex multivariate analyses. Future research should employ observational or mixed-methods designs to validate these findings and explore the perspectives of patients and physicians. Conclusion and Recommendations This inaugural Tunisian study paints a clear picture: dentists are acutely aware of MRONJ but feel ill-equipped to manage it, resulting in a climate of caution that may paradoxically harm patient care. Bridging this gap requires moving beyond simply publishing guidelines to actively building clinical competence and confidence. We propose a multi-tiered strategy for national improvement: Curriculum Integration and Update: Dental schools must embed robust, case-based MRONJ education into core pharmacology and oral medicine modules, emphasizing risk stratification and current management protocols. Development of a National Clinical Pathway: A concise, algorithm-based guideline—co-created by oral surgeons, periodontists, and medical specialists—should be widely disseminated in both digital and print formats. Targeted Continuing Professional Development (CPD): Mandatory CPD courses should be tailored: for experienced GPs , focusing on "unlearning" outdated concepts (e.g., drug holidays) and implementing prevention; for recent graduates , on applying knowledge in complex scenarios; and for specialists , on advanced surgical management and interdisciplinary coordination. Fostering Interdisciplinary Networks: Establishing formal consultation channels (e.g., dedicated hotlines, shared digital platforms) between dentists and hospital-based oncology/rheumatology departments can demystify co-management and provide real-time support for GPs. By implementing these measures, the dental profession can evolve from a stance of anxious avoidance to one of competent, proactive partnership in patient care. This shift is essential not only for preventing MRONJ but also for ensuring that all patients, regardless of their medical therapy, have equitable access to safe and essential dental treatment. Declarations Ethics approval and consent to participate:The study was conducted in accordance with the Declaration of Helsinki. The study protocol was submitted to the Ethics Committee of the Faculty of Dental Medicine of Monastir, Tunisia. The Committee reviewed the protocol and confirmed that formal ethical approval was not required due to the anonymous, voluntary, and non-interventional nature of the survey involving healthcare professionals only, in accordance with national regulations governing observational questionnaire-based studies (Reference number: FMDM/EC/2024/09-017).Electronic informed consent to participate was obtained from all participants prior to accessing the questionnaire. Participants were informed about the study objectives, the voluntary nature of participation, and the anonymity of data collection. Submission of the completed questionnaire was considered as confirmation of consent. No personal or identifiable data were collected. Consent for publication :Not applicable. Availability of data and materials:The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests:The authors declare that they have no competing interests. Funding:The authors received no specific funding for this work. Authors’ contributions:SJ conceived and designed the study. SJ, AM, HB, MD, MB, and SB contributed to data collection. SJ and KM performed the statistical analysis. SJ drafted the manuscript. EA and WG critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript. Acknowledgements:The authors sincerely thank all Tunisian dentists who participated in this survey and generously contributed their time. References Barasch A, Cunha-Cruz J, Curro FA, et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dent Res. 2011;90(4):439–44. Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg. 2014;72(10):1938–56. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30(1):3–23. AAOMS. Medication-Related Osteonecrosis of the Jaw. Position Paper. American Association of Oral and Maxillofacial Surgeons; 2022. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007;29(8):1548–58. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65(3):415–23. Nicolatou-Galitis O, Papadopoulou E, Sarri T et al. (2011). Osteonecrosis of the jaw in oncology patients treated with bisphosphonates: prospective experience of a dental oncology referral center. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 112(2), 195–202. Malden N, Lopes V. Dental extractions and bisphosphonates: the assessment, consent and management, a proposed algorithm. Br Dent J. 2009;206(2):93–8. Vinitzky-Brener I, Ibáñez-Mancera NG, Aguilar-Rojas AM, Alvarez-Jardón AP. Knowledge of bisphosphonate-related osteonecrosis of the jaws among Mexican dentists. Medicina oral patología oral y cirugía bucal. 2017;22(1):e84–7. Holzinger D, Seemann R, Klug C, et al. Long-term success of surgery in bisphosphonate-related osteonecrosis of the jaws (BRONJs). Oral Oncol. 2013;49(1):66–70. López-Cedrún J, Sanromán JF, García A, et al. Spanish Society of Oral and Maxillofacial Surgery (SECOM) consensus on bisphosphonate-related osteonecrosis of the jaws. J Clin Experimental Dentistry. 2013;5(2):e75–81. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177–87. Yarom N, Shapiro CL, Peterson DE, et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(25):2270–90. He L, Sun X, Liu Z, Qiu Y, Niu Y. Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw. Int J Oral Sci. 2020;12(1):30. Additional Declarations No competing interests reported. Supplementary Files additionalfile.docx Additional file 1. English version of the questionnaire used in this study. 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-Sfax","correspondingAuthor":false,"prefix":"","firstName":"Emna","middleName":"","lastName":"abid","suffix":""},{"id":626958283,"identity":"b9625ad6-ca90-436a-bc83-c4f41d5fc764","order_by":8,"name":"walid ghorbel","email":"","orcid":"","institution":"Dental Department of The University Hospital of Hedi Chaker -Sfax","correspondingAuthor":false,"prefix":"","firstName":"walid","middleName":"","lastName":"ghorbel","suffix":""}],"badges":[],"createdAt":"2026-02-08 16:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8823147/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8823147/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107616641,"identity":"dd2750d7-6533-4e06-a622-234b6d409597","added_by":"auto","created_at":"2026-04-23 09:15:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":190247,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Proposed Cycle of Defensive Practice in MRONJ Management\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8823147/v1/0e4e6ef6528038ed7df118fe.png"},{"id":107709419,"identity":"0f9094ee-526a-4c84-b413-cd28c4cf378e","added_by":"auto","created_at":"2026-04-24 09:35:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":386499,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8823147/v1/32322aa3-5015-4335-946a-fa491da6cfa3.pdf"},{"id":107707316,"identity":"7e99d313-f195-466d-8435-0d14278a30de","added_by":"auto","created_at":"2026-04-24 09:20:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15835,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1. English version of the questionnaire used in this study.\u003c/p\u003e","description":"","filename":"additionalfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-8823147/v1/da8f2a4855a9135bb9ca10e4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unveiling the Landscape of MRONJ Awareness (2025) : A Comprehensive National Cross-Sectional Study of Tunisian Dentists' Knowledge, Attitudes, and Practices","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe landscape of dental care has evolved to require meticulous consideration of a patient's systemic health and pharmacological profile [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. The widespread therapeutic use of bisphosphonates (BPs) and other antiresorptive agents for conditions like osteoporosis and bone metastases has introduced a complex iatrogenic risk: Medication-Related Osteonecrosis of the Jaw (MRONJ) [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. First formally described in 2003, MRONJ is defined as exposed bone in the maxillofacial region that persists for more than eight weeks in a patient with a history of antiresorptive or antiangiogenic therapy, in the absence of prior radiation therapy to the jaws [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe reported incidence of MRONJ is highly variable, reflecting differences in drug potency, route of administration, and underlying disease. For patients receiving high-dose intravenous BPs for oncological indications, estimates range from 0.8% to 12%, whereas the risk for those on oral BPs for osteoporosis is substantially lower, generally cited at less than 0.1% per year [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. This stark disparity in risk profile underscores the necessity for nuanced clinical judgment and risk stratification.\u003c/p\u003e \u003cp\u003eDental professionals are uniquely positioned at the frontline of MRONJ prevention and early intervention. Their responsibilities span pre-therapy dental clearance, ongoing oral health optimization during treatment, patient education, and the management of early-stage disease [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, international literature consistently reveals a troubling variability in dentists' awareness, understanding, and application of established MRONJ guidelines. This inconsistency can lead to a spectrum of outcomes, from delayed diagnosis to overly defensive practices that may unjustly deny patients necessary dental care [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the global recognition of this clinical challenge, there is a paucity of data from North African regions. To our knowledge, no prior study has evaluated the preparedness of the Tunisian dental community regarding MRONJ. This study, therefore, sought to comprehensively assess the knowledge, attitudes, and self-reported practices (KAP) of Tunisian dentists concerning MRONJ. By identifying specific knowledge gaps, sources of clinical anxiety, and factors associated with better preparedness, this research aims to inform the development of targeted educational initiatives and clinical guidelines to improve patient safety and care standards nationally.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003e\u003cstrong\u003eStudy Design\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis national cross-sectional study was conducted in September 2024 using an anonymous, web-based survey. The study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional research.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eStudy\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003esetting\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand Sampling\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe target population comprised all licensed\u0026nbsp;General practitioners and dental specialists\u0026nbsp;actively practicing in Tunisia, including both the public and private healthcare sectors.. Dental students, dental assistants, hygienists, and non-practicing dentists were excluded.\u003c/p\u003e\n\u003cp\u003eA non-probability convenience sampling strategy was employed due to the absence of a centralized national mailing registry. The survey link was disseminated through professional social media groups restricted to Tunisian dentists (Facebook and LinkedIn), as well as via institutional and professional networks to maximize national geographic coverage.\u003c/p\u003e\n\u003ch2\u003eSample Size Estimation\u003c/h2\u003e\n\u003cp\u003eAn \u003cstrong\u003ea priori sample size\u003c/strong\u003e was estimated based on the following assumptions:\u003c/p\u003e\n\u003cp\u003eExpected proportion of dentists with adequate MRONJ knowledge: 50% (most conservative estimate to maximize sample size)\u003c/p\u003e\n\u003cp\u003eDesired confidence level: 95%\u003c/p\u003e\n\u003cp\u003eMargin of error: 10%\u003c/p\u003e\n\u003cp\u003eUsing the formula for a single proportion in cross-sectional studies:\u003c/p\u003e\n\u003cp\u003en=Z2\u0026sdot;p\u0026sdot;(1\u0026minus;p)d2n = \\frac{{Z^2 \\cdot p \\cdot (1-p)}}{{d^2}}n=d2Z2\u0026sdot;p\u0026sdot;(1\u0026minus;p)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhere:\u003c/p\u003e\n\u003cp\u003eZ=1.96Z = 1.96Z=1.96 (for 95% confidence)\u003c/p\u003e\n\u003cp\u003ep=0.5p = 0.5p=0.5\u003c/p\u003e\n\u003cp\u003ed=0.10d = 0.10d=0.10\u003c/p\u003e\n\u003cp\u003en=(1.96)2\u0026sdot;0.5\u0026sdot;0.50.12\u0026asymp;96n = \\frac{{(1.96)^2 \\cdot 0.5 \\cdot 0.5}}{{0.1^2}} \\approx 96n=0.12(1.96)2\u0026sdot;0.5\u0026sdot;0.5\u0026asymp;96\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThus, a minimum of 96 participants was required. Our final sample included 106 respondents, meeting this threshold.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u0026nbsp;Survey Instrument and Validation\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe data collection tool was a structured, self-administered questionnaire developed in French, the primary language of dental education in Tunisia. Its development followed a multi-stage process:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eItem Generation:\u003c/strong\u003e A preliminary set of questions was developed based on a thorough review of international MRONJ guidelines (AAOMS, SFCO) and similar KAP studies [4,9,11].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExpert Validation:\u003c/strong\u003e content validity was evaluated by an expert panel composed of three senior oral and maxillofacial surgeons and one consultant rheumatologist\u003c/p\u003e\n\u003cp\u003eThe panel assessed clarity, relevance, comprehensiveness, and alignment with current evidence-based guidelines. Minor wording modifications were implemented based on consensus feedback.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePilot Testing:\u003c/strong\u003e A pilot version was administered to 15 dentists not included in the final sample to assess comprehensibility, flow, and time required for completion (approximately 7-10 minutes). Minor adjustments to wording were made based on feedback.\u003c/p\u003e\n\u003cp\u003eReliability Analysis:Internal consistency of the \u003cstrong\u003eAttitudes section\u003c/strong\u003e (5 items) was assessed using \u003cstrong\u003eCronbach\u0026rsquo;s alpha\u003c/strong\u003e. The resulting alpha coefficient was \u003cstrong\u003e0.82\u003c/strong\u003e, indicating good reliability and internal consistency.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The final questionnaire consisted of 26 items across four sections:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSection A: Demographic and Professional Characteristics\u003c/strong\u003e (6 items: age, gender, years of experience, specialty, practice sector, geographic location).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSection B: Knowledge Assessment\u003c/strong\u003e (10 items: BP indications, MRONJ definition, risk factors, incidence, preventive protocols, management stages).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSection C: Attitudes and Perceptions\u003c/strong\u003e (5 items: confidence level, anxiety, perception of risk severity).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSection D: Reported Clinical Practices\u003c/strong\u003e (5 items: frequency of encountering BP patients, treatment modifications, referral patterns, history of treatment refusal).\u003c/p\u003e\n\u003cp\u003eResponse formats included multiple-choice, Likert scales (e.g., \u0026quot;Not confident\u0026quot; to \u0026quot;Very confident\u0026quot;), and binary (Yes/No) options.The questionnaire was specifically developed for the purpose of this study and was not derived from a previously validated published instrument. The full English version of the questionnaire is provided as Additional file 1.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u0026nbsp;Data Collection\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Procedure\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe questionnaire was built and distributed using Google Forms\u0026reg;. The survey link was actively disseminated over a four-week period through professionally focused social media groups (Facebook, LinkedIn) exclusive to Tunisian dentists, as well as through personal networks of the research team to ensure nationwide reach.\u003c/p\u003e\n\u003cp\u003eOutcome Measures:\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;are\u0026nbsp;\u003c/strong\u003eMRONJ-related knowledge (risk, preventive measures, procedural awareness)\u0026nbsp;and s\u003cstrong\u003eecondary outcomes\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;are a\u003c/strong\u003ettitudes, confidence, anxiety and self-reported practices.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll survey data were extracted from Google Forms into Microsoft Excel 365 and cleaned for completeness prior to analysis. \u003cstrong\u003eDescriptive statistics\u003c/strong\u003e were calculated for demographic, professional, and clinical variables. Categorical variables (e.g., gender, professional status, practice location, years of practice) were summarized as counts and percentages, while continuous variables (e.g., age) were presented as mean \u0026plusmn; standard deviation (SD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKnowledge, attitudes, and practices (KAP) scores\u003c/strong\u003e were analyzed separately. The internal consistency of the \u003cstrong\u003eattitudes section\u003c/strong\u003e was assessed using \u003cstrong\u003eCronbach\u0026rsquo;s alpha\u003c/strong\u003e, with a value of 0.82 indicating good reliability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnivariate analyses\u003c/strong\u003e were conducted to explore associations between independent variables (age group \u0026lt;35 vs \u0026ge;35 years, gender, years of practice \u0026le;5, 6\u0026ndash;15, \u0026gt;15, professional status [general practitioner vs specialist], practice sector [public vs private], and practice location [urban vs rural]) and key dependent outcomes:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrect knowledge of MRONJ risk associated with oral bisphosphonates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelf-reported confidence in managing BP patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefensive clinical behaviors\u003c/strong\u003e (treatment refusal, routine referral, reluctance to perform surgery)\u003c/p\u003e\n\u003cp\u003eFor categorical comparisons, \u003cstrong\u003eChi-square tests\u003c/strong\u003e were used, with \u003cstrong\u003eFisher\u0026rsquo;s exact test\u003c/strong\u003e applied when expected cell counts were \u0026lt;5. Mean differences for continuous variables were assessed using \u003cstrong\u003eindependent t-tests\u003c/strong\u003e or \u003cstrong\u003eANOVA\u003c/strong\u003e where appropriate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariable logistic regression models\u003c/strong\u003e were performed to identify independent predictors of accurate MRONJ knowledge and defensive clinical behavior. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. Statistical significance was set at \u003cstrong\u003ep \u0026lt; 0.05\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eAll analyses were conducted using \u003cstrong\u003eMicrosoft Excel 365\u003c/strong\u003e for descriptive statistics and \u003cstrong\u003eSPSS version 28 (IBM Corp., Armonk, NY, USA)\u003c/strong\u003e for inferential analyses. Results are presented both narratively and in tables, with clear cross-tabulations linking demographic/professional variables to KAP outcomes.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eBias Control and Study Limitations\u003c/h2\u003e\n\u003cp\u003eSeveral measures were implemented to reduce potential bias:anonymous data collection to reduce social desirability bias,nationwide dissemination to improve geographic representation and clear inclusion criteria to ensure professional homogeneity.However, the study remains subject to:Selection bias due to convenience sampling,self-report bias and inability to infer causality due to cross-sectional design.These limitations were acknowledged and considered in the interpretation of findings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki. The study protocol was submitted to the Ethics Committee of the Faculty of Dental Medicine of Monastir, Tunisia. The Committee reviewed the protocol and confirmed that formal ethical approval was not required due to the anonymous, voluntary, and non-interventional nature of the survey involving healthcare professionals only, in accordance with national regulations governing observational questionnaire-based studies (Reference number: FMDM/EC/2024/09-017).\u003c/p\u003e\n\u003cp\u003eElectronic informed consent to participate was obtained from all participants prior to accessing the questionnaire. Participants were informed about the purpose of the study, the voluntary nature of their participation, and the anonymity of data collection. Submission of the completed questionnaire was considered as confirmation of consent. No personal or identifiable data were collected.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eParticipant Characteristics\u003c/h2\u003e\n\u003cp\u003eA total of \u003cstrong\u003e106 dentists\u003c/strong\u003e completed the survey. The \u003cstrong\u003emean age\u003c/strong\u003e was 30.1 \u0026plusmn; 5.8 years, and \u003cstrong\u003e79.2% were female\u003c/strong\u003e. The majority were \u003cstrong\u003egeneral practitioners (83%)\u003c/strong\u003e, while 17% were specialists, including oral surgeons, periodontists, and prosthodontists. \u003cstrong\u003eYears of clinical practice\u003c/strong\u003e were distributed as follows: \u0026le;5 years: 65.1% (n = 69), 6\u0026ndash;15 years: 26.4% (n = 28), and \u0026gt;15 years: 8.5% (n = 9).\u003c/p\u003e\n\u003cp\u003ePractice locations were predominantly \u003cstrong\u003eurban (71.7%)\u003c/strong\u003e, with near-equal representation in \u003cstrong\u003epublic (54.7%)\u003c/strong\u003e and \u003cstrong\u003eprivate (45.3%)\u003c/strong\u003e sectors. Table 1 summarizes participant demographics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Demographic and Professional Characteristics of Participants (N = 106)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge \u0026lt;35 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e62.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e79.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e83.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSpecialist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYears of Practice \u0026le;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYears of Practice 6\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYears of Practice \u0026gt;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e71.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePublic Sector\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e54.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003eClinical Exposure and Attitudes\u003c/h2\u003e\n\u003cp\u003eMost dentists reported \u003cstrong\u003elow exposure\u003c/strong\u003e to patients on bisphosphonates, with \u003cstrong\u003e86.8% managing fewer than five patients per month\u003c/strong\u003e. When presented with a hypothetical BP patient requiring dental care:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e55.7%\u003c/strong\u003e reported moderate to high anxiety\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e87.7%\u003c/strong\u003e were reluctant to perform surgical procedures\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e63.2%\u003c/strong\u003e indicated they would routinely seek specialist consultation before intervention\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003eAttitudes section\u003c/strong\u003e demonstrated good internal consistency (\u003cstrong\u003eCronbach\u0026rsquo;s alpha = 0.82\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eKnowledge Assessment\u003c/h2\u003e\n\u003cp\u003eOverall, dentists demonstrated awareness of key MRONJ risk factors, but substantial \u003cstrong\u003eknowledge gaps\u003c/strong\u003e were observed:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e77.4%\u003c/strong\u003e correctly identified intravenous bisphosphonates and tooth extraction as major triggers\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e41.5%\u003c/strong\u003e correctly recognized the low annual risk (\u0026lt;0.1%) of MRONJ in patients on oral bisphosphonates for osteoporosis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e45.3%\u003c/strong\u003e incorrectly believed that a mandatory drug holiday is always required prior to extraction\u003c/p\u003e\n\u003cp\u003eOnly \u003cstrong\u003e11.3%\u003c/strong\u003e of participants felt confident managing BP patients, while 53.8% reported moderate confidence\u003c/p\u003e\n\u003cp\u003eThese gaps translated into clinical decisions: \u003cstrong\u003e39.6%\u003c/strong\u003e of dentists had refused to treat a BP patient at least once due to MRONJ concerns.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePredictors of Knowledge and Clinical Behavior\u003c/h2\u003e\n\u003ch3\u003eUnivariate Associations\u003c/h3\u003e\n\u003cp\u003eChi-square analyses showed that:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAge \u0026lt;35 years\u003c/strong\u003e was associated with correct knowledge of oral BP risk (p = 0.03)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSpecialist status\u003c/strong\u003e was associated with higher knowledge (p = 0.04)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUrban practice location\u003c/strong\u003e correlated with better knowledge (p = 0.04)\u003c/p\u003e\n\u003cp\u003eNo significant association was observed for practice sector (public vs private)\u003c/p\u003e\n\u003ch3\u003eMultivariable Logistic Regression\u003c/h3\u003e\n\u003cp\u003eBinary logistic regression identified independent predictors of accurate MRONJ knowledge:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e. Multivariable Logistic Regression Analysis of Factors Associated with Accurate Knowledge of MRONJ Risk (Oral Bisphosphonates)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePredictor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge \u0026lt;35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.1\u0026ndash;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSpecialist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.1\u0026ndash;6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUrban location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.0\u0026ndash;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eDefensive clinical behaviors were significantly associated with higher anxiety (OR = 3.2, 95% CI 1.5\u0026ndash;6.8, p = 0.002).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Analysis revealed a recursive \u0026quot;Cycle of Defensive Practice.\u0026quot; The cycle (figure 1 )is initiated by limited clinical exposure, with 86.8% of participants managing fewer than five bleeding disorder patients monthly. This low exposure correlates with poorer retention of complex guidelines (p=0.02). Subsequently, deficient knowledge predicts heightened clinical anxiety (OR=3.2), which is a direct driver of avoidance behaviors, including treatment refusal (39.6%) and routine referral (63.2%)\u003c/p\u003e\n\u003cp\u003eConversely, specialists and recent graduates were more likely to break this cycle, demonstrating not only better knowledge but also a greater propensity to co-manage rather than outright refer complex cases.\u003c/p\u003e\n\u003cp\u003eThis first national assessment demonstrates that while Tunisian dentists are aware of MRONJ, \u003cstrong\u003eknowledge deficits, low exposure, and anxiety contribute to defensive clinical behaviors\u003c/strong\u003e. These findings underscore the need for \u003cstrong\u003etargeted educational interventions, national guidelines, and interdisciplinary support networks\u003c/strong\u003e to enhance both confidence and evidence-based patient management.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides the first comprehensive assessment of the Tunisian dental community\u0026apos;s readiness to address MRONJ, revealing a landscape marked by awareness of the threat but hampered by significant knowledge deficits and consequent clinical apprehension. The very low confidence level (11.3%) is particularly telling and aligns with findings from other regions, such as Mexico and Spain, where only 15-20% of dentists felt comfortable managing these patients [9,11]. This pervasive discomfort suggests a global challenge in translating guideline knowledge into clinical confidence.\u003c/p\u003e\n\u003cp\u003eThe knowledge gaps identified are not trivial. The widespread belief in mandatory drug holidays (45.3%) is a major concern. Current international consensus strongly advises against routine cessation of oral BPs for dental procedures, as the drugs have a prolonged skeletal half-life, and discontinuation may negatively impact the patient\u0026apos;s primary bone disease without reducing MRONJ risk [4,12]. This misconception likely stems from earlier, more cautious recommendations and highlights a critical failure in disseminating updated evidence to practicing clinicians.\u003c/p\u003e\n\u003cp\u003eOur analytical findings offer valuable insights into the drivers of this gap. The significant advantage of younger dentists (\u0026lt;35 years) points to the successful integration of MRONJ into more recent dental curricula. The specialist-GP divide underscores the value of focused postgraduate training. Perhaps most importantly, the elucidated \u0026quot;Cycle of Defensive Practice\u0026quot; provides a conceptual model for why well-intentioned dentists default to avoidance. When faced with a high-stakes, low-frequency complication, limited personal experience breeds uncertainty, which in the absence of robust supporting knowledge and protocols, naturally leads to risk-averse behavior [13].\u003c/p\u003e\n\u003cp\u003eThis defensive posture, while understandable, carries significant public health implications. The refusal of care (reported by 39.6%) can lead to untreated dental infection and pain, potentially forcing patients to choose between their oncological/bone health and their oral health. It may also inadvertently increase risk, as emergency interventions for acute infections in poor oral environments are more traumatic than planned, preventative care [14].\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis study has limitations inherent to its design. The cross-sectional, self-reported nature captures stated, not observed, practices and cannot establish causality. The use of convenience sampling and online distribution may introduce selection bias, potentially over-representing tech-savvy and urban practitioners. The sample size, while adequate for an initial national survey, limits the power for more complex multivariate analyses. Future research should employ observational or mixed-methods designs to validate these findings and explore the perspectives of patients and physicians.\u003c/p\u003e"},{"header":"Conclusion and Recommendations","content":"\u003cp\u003eThis inaugural Tunisian study paints a clear picture: dentists are acutely aware of MRONJ but feel ill-equipped to manage it, resulting in a climate of caution that may paradoxically harm patient care. Bridging this gap requires moving beyond simply publishing guidelines to actively building clinical competence and confidence.\u003c/p\u003e\n\u003cp\u003eWe propose a multi-tiered strategy for national improvement:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCurriculum Integration and Update:\u003c/strong\u003e Dental schools must embed robust, case-based MRONJ education into core pharmacology and oral medicine modules, emphasizing risk stratification and current management protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDevelopment of a National Clinical Pathway:\u003c/strong\u003e A concise, algorithm-based guideline\u0026mdash;co-created by oral surgeons, periodontists, and medical specialists\u0026mdash;should be widely disseminated in both digital and print formats.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTargeted Continuing Professional Development (CPD):\u003c/strong\u003e Mandatory CPD courses should be tailored: for \u003cstrong\u003eexperienced GPs\u003c/strong\u003e, focusing on \u0026quot;unlearning\u0026quot; outdated concepts (e.g., drug holidays) and implementing prevention; for \u003cstrong\u003erecent graduates\u003c/strong\u003e, on applying knowledge in complex scenarios; and for \u003cstrong\u003especialists\u003c/strong\u003e, on advanced surgical management and interdisciplinary coordination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFostering Interdisciplinary Networks:\u003c/strong\u003e Establishing formal consultation channels (e.g., dedicated hotlines, shared digital platforms) between dentists and hospital-based oncology/rheumatology departments can demystify co-management and provide real-time support for GPs.\u003c/p\u003e\n\u003cp\u003eBy implementing these measures, the dental profession can evolve from a stance of anxious avoidance to one of competent, proactive partnership in patient care. This shift is essential not only for preventing MRONJ but also for ensuring that all patients, regardless of their medical therapy, have equitable access to safe and essential dental treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:The study was conducted in accordance with the Declaration of Helsinki. The study protocol was submitted to the Ethics Committee of the Faculty of Dental Medicine of Monastir, Tunisia. The Committee reviewed the protocol and confirmed that formal ethical approval was not required due to the anonymous, voluntary, and non-interventional nature of the survey involving healthcare professionals only, in accordance with national regulations governing observational questionnaire-based studies (Reference number: FMDM/EC/2024/09-017).Electronic informed consent to participate was obtained from all participants prior to accessing the questionnaire. Participants were informed about the study objectives, the voluntary nature of participation, and the anonymity of data collection. Submission of the completed questionnaire was considered as confirmation of consent. No personal or identifiable data were collected.\u003c/p\u003e\n\u003cp\u003eConsent for publication :Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding:The authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions:SJ conceived and designed the study. SJ, AM, HB, MD, MB, and SB contributed to data collection. SJ and KM performed the statistical analysis. SJ drafted the manuscript. EA and WG critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:The authors sincerely thank all Tunisian dentists who participated in this survey and generously contributed their time.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarasch A, Cunha-Cruz J, Curro FA, et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dent Res. 2011;90(4):439\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw\u0026mdash;2014 update. J Oral Maxillofac Surg. 2014;72(10):1938\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30(1):3\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAAOMS. Medication-Related Osteonecrosis of the Jaw. Position Paper. American Association of Oral and Maxillofacial Surgeons; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007;29(8):1548\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65(3):415\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNicolatou-Galitis O, Papadopoulou E, Sarri T et al. (2011). Osteonecrosis of the jaw in oncology patients treated with bisphosphonates: prospective experience of a dental oncology referral center. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 112(2), 195\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalden N, Lopes V. Dental extractions and bisphosphonates: the assessment, consent and management, a proposed algorithm. Br Dent J. 2009;206(2):93\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVinitzky-Brener I, Ib\u0026aacute;\u0026ntilde;ez-Mancera NG, Aguilar-Rojas AM, Alvarez-Jard\u0026oacute;n AP. Knowledge of bisphosphonate-related osteonecrosis of the jaws among Mexican dentists. Medicina oral patolog\u0026iacute;a oral y cirug\u0026iacute;a bucal. 2017;22(1):e84\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolzinger D, Seemann R, Klug C, et al. Long-term success of surgery in bisphosphonate-related osteonecrosis of the jaws (BRONJs). Oral Oncol. 2013;49(1):66\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026oacute;pez-Cedr\u0026uacute;n J, Sanrom\u0026aacute;n JF, Garc\u0026iacute;a A, et al. Spanish Society of Oral and Maxillofacial Surgery (SECOM) consensus on bisphosphonate-related osteonecrosis of the jaws. J Clin Experimental Dentistry. 2013;5(2):e75\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtto S, Pautke C, Van den Wyngaert T, Niepel D, Schi\u0026oslash;dt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYarom N, Shapiro CL, Peterson DE, et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(25):2270\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe L, Sun X, Liu Z, Qiu Y, Niu Y. Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw. Int J Oral Sci. 2020;12(1):30.\u003c/span\u003e\u003c/li\u003e\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":"Medication-Related Osteonecrosis of the Jaw (MRONJ), bisphosphonates, antiresorptive agents, dental education, knowledge-attitude-practice, Tunisia, survey","lastPublishedDoi":"10.21203/rs.3.rs-8823147/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8823147/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:Medication-related osteonecrosis of the jaw (MRONJ) represents a significant complication for patients receiving antiresorptive therapy. Dentists play a pivotal role in prevention, early detection, and management, yet global studies suggest variable practitioner preparedness.This study aimed to assess the current knowledge, attitudes, and clinical practices (KAP) of Tunisian dentists concerning MRONJ and identify factors influencing competency.\u003c/p\u003e\n\u003cp\u003eMethods:A nationwide, cross-sectional online survey was distributed in September 2024. The validated 26-item questionnaire covered demographics, MRONJ knowledge, risk perception, and reported clinical behaviors. Data were analyzed descriptively and analytically.\u003c/p\u003e\n\u003cp\u003eResults:Among 106 respondents (mean age: 30 years; 79.2% female; 83% general practitioners), key findings revealed a profound knowledge-practice gap. While 77.4% identified intravenous bisphosphonates and extractions as primary risks, only 11.3% felt confident managing affected patients. Clinical caution was pronounced: 87.7% were reluctant to perform surgery, 63.2% would routinely refer, and 39.6% had refused treatment. Analytical results identified younger age (\u0026lt;35 years), specialist status, and urban practice as significant positive correlates with accurate knowledge (p\u0026lt;0.05). A defensive cycle emerged, linking low patient exposure to higher anxiety and avoidance behaviors.\u003c/p\u003e\n\u003cp\u003eConclusion:This first national study in Tunisia highlights critical deficits in dentist preparedness for MRONJ, driven by knowledge gaps and risk overestimation. The findings underscore an urgent need for structured, continuous education programs, clear national guidelines, and interdisciplinary collaboration to transform defensive practice into evidence-based, proactive patient management.\u003c/p\u003e","manuscriptTitle":"Unveiling the Landscape of MRONJ Awareness (2025) : A Comprehensive National Cross-Sectional Study of Tunisian Dentists' Knowledge, Attitudes, and Practices","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:15:18","doi":"10.21203/rs.3.rs-8823147/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-29T01:36:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-21T10:35:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-21T07:45:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121489278914556234650178908060582052986","date":"2026-04-20T05:24:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-19T09:09:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-15T08:24:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325407499735303616976379441712330482054","date":"2026-04-15T08:19:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312068101604071543756777634500108134751","date":"2026-04-15T07:38:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300340523245080057772575233357492016613","date":"2026-04-15T04:01:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T23:33:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140379672897846594002679395031915484677","date":"2026-04-14T23:22:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15205354782787073248712535233439630420","date":"2026-04-14T17:59:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T17:52:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-24T04:15:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-17T10:31:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-17T00:03:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2026-02-16T23:58:55+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":"6f773813-e43f-4ffb-bb56-56578ad4014a","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:15:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:15:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8823147","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8823147","identity":"rs-8823147","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}