Surgical management of medication-related osteonecrosis of the jaw improves quality of life without deterioration in oral function

Surgical management of medication-related osteonecrosis of the jaw improves quality of life without deterioration in oral function | 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 Article Surgical management of medication-related osteonecrosis of the jaw improves quality of life without deterioration in oral function Sachiko YAMASAKI, Tomoaki SHINTANI, Kota MORISHITA, Fumitaka OBAYASHI, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9101394/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Although medication-related osteonecrosis of the jaw (MRONJ) is frequently treated surgically, bone resection and tooth loss may compromise oral function. This study longitudinally evaluated patient-reported quality of life (QOL) and objective oral functional parameters following surgical management of MRONJ and explored biological and mechanical factors associated with recurrence. Forty-eight patients with Stage 2–3 MRONJ underwent surgical management and were prospectively followed. QOL was assessed using a validated MRONJ-specific instrument preoperatively and at 6 months. Objective oral functional parameters were evaluated preoperatively and at 3 and 6 months. Longitudinal changes were analyzed using nonparametric repeated-measures models, and recurrence-related factors were explored using regression analyses. Total QOL significantly improved at 6 months. Despite invasive resection procedures, key oral functional parameters remained stable without significant deterioration. Recurrence occurred in 20.8% of patients and was strongly associated with systemic factors, particularly concomitant chemotherapy. Higher masticatory performance, occlusal force, and tongue pressure demonstrated trends toward shorter recurrence-free intervals, suggesting a potential role of mechanical loading. Reduced salivary flow volume was significantly associated with earlier recurrence. These findings suggest that surgical treatment may contribute to restoration of functional equilibrium while highlighting potential biological and mechanical determinants of recurrence. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Osteonecrosis Quality of Life Mastication Saliva Occlusion Risk Factors Figures Figure 1 Figure 2 Introduction Medication-related osteonecrosis of the jaw (MRONJ) represents a complex interface between systemic pharmacologic therapy and localized bone pathology [ 1 , 2 ]. Although contemporary management strategies emphasize mucosal closure and radiographic resolution, structural healing alone does not fully reflect therapeutic success. Quality of life (QOL) constitutes a critical clinical endpoint in MRONJ, as the substantial burden of pain, infection, halitosis, and functional impairment impact the daily activities and psychosocial well-being of patients [ 3 , 4 ]. Oral health–related QOL in MRONJ is frequently compromised because the disease disrupts essential functions such as mastication and swallowing [ 3 , 5 ]. Although surgical outcomes are commonly evaluated by structural resolution, these measures do not necessarily capture functional recovery or patient-centered benefit [ 4 ]. The 2022 American Association of Oral and Maxillofacial Surgeons (AAOMS) position paper highlights QOL improvement as a key therapeutic goal [ 6 ]. Similarly, the 2023 Japanese position paper has supported proactive surgical management in selected patients [ 7 ]. However, longitudinal studies integrating patient-reported outcomes with objective functional parameters remain limited. Therefore, whether surgical eradication of necrotic bone compromises or restores stomatognathic function remains unclear. Beyond its clinical manifestations, MRONJ represents a disruption of the delicate balance between bone remodeling, mucosal integrity, and mechanical loading within the stomatognathic system. While antiresorptive therapy suppresses osteoclastic activity and reduces skeletal turnover, the jaw is uniquely exposed to repetitive functional stress and microbial challenge. How these systemic and local forces interact to influence postoperative recovery and recurrence remains poorly understood. In particular, whether restoration of structural continuity translates into recovery of biomechanical and environmental homeostasis has not been systematically examined. Recurrence has traditionally been attributed to systemic risk factors and incomplete resection. Nevertheless, postoperative functional loading and oral environmental stability may also influence recurrence dynamics. Accordingly, this study longitudinally evaluated patient-reported QOL and objective oral functional parameters following surgical management of MRONJ and explored their association with recurrence. Methods Study population and study design This prospective cohort study was conducted and reported in accordance with the STROBE guidelines. The study was approved by the Ethics Committee of Hiroshima University (Approval number: E-2022-0176) and prospectively registered in the UMIN Clinical Trials Registry (UMIN000048986). Written informed consent was obtained from all participants. Eligible participants included patients diagnosed with MRONJ who underwent surgical treatment at the Department of Oral and Maxillofacial Surgery, Hiroshima University Hospital (Japan), between October 2022 and December 2025. MRONJ diagnosis was established based on the AAOMS position paper criteria [ 6 ]. A total of 48 consecutive patients who underwent surgical treatment for MRONJ at our institution were included in the study cohort. All patients were enrolled in a prospective clinical follow-up program and were scheduled for postoperative evaluation at regular intervals. Participants completed QOL questionnaires prior to surgical treatment and at approximately 6 months postoperatively. Detailed oral functional examinations were performed preoperatively and at 3 and 6 months after surgery. Postoperative QOL assessments were scheduled at 6 months after surgery in accordance with the institutional follow-up protocol. Among the 48 patients, 43 had available paired preoperative and postoperative QOL data at the 6-month time point and were therefore included in the longitudinal paired QOL analyses. The remaining five patients had not yet reached the 6-month postoperative time point or were unable to complete postoperative QOL assessment due to death or difficulty attending follow-up visits. These patients were included in the baseline and perioperative analyses but were excluded from paired QOL analyses due to unavailable follow-up data (Supplementary Fig. S1 ). QOL measurements and data collection QOL was assessed using a validated MRONJ-specific questionnaire derived from the University of Washington QOL questionnaire, the EORTC QLQ-H&N35, and the Functional Assessment of Cancer Therapy–Head and Neck, as previously reported in the literature [ 8 ] and approved by the Hiroshima University Ethics Committee. The questionnaire comprised 13 items assessing the following domains: pain, appearance, daily activity, recreation, swallowing, chewing, speech, taste, halitosis, salivary function, mood, and anxiety. Responses were recorded using 4- or 5-point Likert-type scales. For ease of interpretation, all domain scores were transformed to a standardized 0–100 scale, with higher scores indicating better QOL. The total QOL score, defined as the sum of the standardized domain scores, was prespecified as the primary outcome. Individual QOL subdomains were analyzed as secondary and exploratory outcomes. Analyses of the QOL changes were conducted using data from participants who completed QOL assessments at least 6 months postoperatively. This approach reflects real-world clinical practice in this population and enhances the generalizability of the findings. Clinical variables and oral functional assessment Baseline clinical and demographic data were collected for each patient, including age, sex, body mass index (BMI), smoking history, alcohol consumption, history of antiresorptive agent (ARA) use (type, duration, and indication), medical comorbidities (malignancy, diabetes mellitus, autoimmune disease), history of chemotherapy and steroid use, MRONJ stage, lesion site, and clinical manifestations (infection, bone exposure, extraoral fistula, sensory disturbance, and pathological fracture). Surgical procedures were categorized as sequestrectomy with peripheral ostectomy, partial maxillectomy, marginal mandibulectomy, segmental mandibulectomy, or hemimandibulectomy. The number of remaining teeth and presence or absence of MRONJ recurrence were also recorded. To minimize potential sources of bias, surgical indications and procedures were determined by departmental consensus prior to treatment. All operations were performed by board-certified oral and maxillofacial surgeons with more than 15 years of clinical experience, and outcome assessments were conducted using standardized criteria. Consecutive patient enrollment and predefined follow-up protocols were employed to reduce selection and information bias. Oral functional examinations included assessment of: (1) the degree of tongue coating, (2) oral bacterial count, (3) salivary flow volume, (4) oral mucosal moisture, (5) occlusal force, (6) lip motor function, (7) tongue pressure, (8) masticatory function, and (9) swallowing function. These parameters capture complementary dimensions of stomatognathic performance: biomechanical loading (occlusal force, masticatory performance, tongue pressure), neuromotor coordination (oral diadochokinesis), and oral environmental stability (salivary flow, mucosal moisture, bacterial count). This approach evaluates whether surgical intervention alters the functional ecosystem beyond structural healing alone. Moreover, periodontal parameters—including periodontal inflamed surface area (PISA), bleeding on probing, periodontal epithelial surface area, and probing pocket depth—were also evaluated. Objective oral function assessments were performed by calibrated examiners with more than 15 years of experience, ensuring inter-rater reliability. Measurements of occlusal force and tongue pressure were conducted using validated instruments (Dental Prescale II, JMS Co., Ltd., Tokyo, Japan), and reproducibility was confirmed with repeated measurements in a subset of patients (intraclass correlation coefficient > 0.90). This methodological rigor enhances confidence in longitudinal comparisons. Definition of healing Healing of MRONJ was defined as the absence of exposed bone and inflammatory signs, including drainage, gingival redness, or pain. Patients were followed for recurrence from the date of surgical treatment until January 30, 2026, providing a uniform observation period for the assessment of MRONJ recurrence. Handling of missing data Due to the inclusion of elderly and oncologic patients, some follow-up data were missing because of death or difficulty attending follow-up visits (e.g., fracture or deterioration of general condition). Therefore, complete-case analyses were primarily performed. As sensitivity analyses, nonparametric methods accommodating incomplete observations were also applied, and results were compared to assess the robustness of the findings. Statistical analysis This prospective cohort study followed 48 patients with Stage 2–3 MRONJ undergoing surgery from October 2022 to January 30, 2026. Continuous variables are presented as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables are expressed as frequencies and percentages. Paired comparisons of QOL scores were performed using the Wilcoxon signed-rank test. Longitudinal changes in oral functional parameters were analyzed using the Friedman test for repeated nonparametric measures with post-hoc Steel tests for multiple comparisons. Associations between clinical variables and recurrence were evaluated using chi-square or Fisher’s exact tests for categorical variables and nonparametric tests for continuous variables. For time-to-event analyses, Cox proportional hazards models were constructed to identify factors associated with recurrence. Variables considered clinically relevant based on prior literature were entered into multivariable models to address potential confounding. The proportional hazards assumption was verified by inspection of Schoenfeld residuals. Subgroup analyses were performed in dentate patients to examine the association between periodontal inflammatory burden and recurrence. Interaction terms were not formally tested due to the limited number of events. Missing follow-up data due to death or loss to follow-up were primarily handled using complete-case analyses. Sensitivity analyses using nonparametric methods including all available observations were performed to confirm the robustness of results. Continuous oral functional variables were dichotomized based on receiver-operating characteristic (ROC) curve–derived cut-off values when appropriate. The median follow-up period was estimated using the reverse Kaplan–Meier method. A two-sided p value < 0.05 was considered statistically significant. All analyses were performed using JMP Pro version 18.0 (SAS Institute Inc., Cary, NC, USA). Results Patient cohort and follow-up A total of 48 patients were included in the study, comprising 27 and 21 patients with underlying malignancies and osteoporosis, respectively. Based on the AAOMS staging, 31 patients (64.6%) presented with Stage 2 MRONJ and 17 (35.4%) with Stage 3. The mandible was the most frequent site of involvement (62.5%), and denosumab was the most commonly used antiresorptive agent (54.2%). Of the initial cohort, 43 patients (89.6%) completed the 6-month postoperative follow-up including QOL assessments. The median follow-up period for the entire cohort was 14 (1–38) months (Supplementary Table S1 ). Changes in the QOL scores (Primary and Secondary Outcomes) The primary outcome, the total QOL score, demonstrated a significant improvement following surgical treatment (Table 1 ). The mean total score increased from 956.7 ± 189.5 preoperatively to 1041.5 ± 127.3 at 6 months postoperatively, representing a mean paired difference of 84.8 (95% CI: 40.2–129.3; p = 0.0002, Wilcoxon signed-rank test) (Fig. 1-1a). Detailed analysis of the individual subdomains revealed that the most substantial gains occurred in psychological and symptom-related areas. Specifically, the anxiety score exhibited a dramatic increase, with a mean paired improvement of 34.0 (95% confidence interval [CI]: 21.7–46.2; p < 0.0001), representing the largest magnitude of change among all evaluated domains (Fig. 1-1b). Significant postoperative gains were also observed in pain, which improved by a mean of 16.3 (95% CI: 10.0–22.5; p < 0.0001) (Fig. 1-1c), and halitosis, which showed a mean increase of 12.0 (95% CI: 5.0–18.9; p = 0.0004) (Fig. 1-1d). Table 1 Changes in the quality of life (QOL) scores before and after surgical treatment for medication-related osteonecrosis of the jaw (MRONJ) (n = 43) Domain Preoperative score Median [IQR] Postoperative score (6 months) Median [IQR] p value (Wilcoxon) Total QOL score 1060 (925–1150) 1140 (1035–1230) 0.0069 Pain 75 (75–100) 100(75–100) < 0.0001 Appearance 75 (50–100) 100 (75–100) 0.0776 Daily activity 100 (50–100) 100 (75–100) 0.2502 Recreation 100 (50–100) 100 (75–100) 0.4345 Swallowing 100 (100–100) 100 (100–100) 0.5176 Chewing 50 (50–100) 50 (50–100) 0.1850 Speech 100 (100–100) 100 (70–100) 0.5020 Taste 100 (70–100) 100 (70–100) 0.9290 Saliva 100 (100–100) 100 (100–100) 0.4985 Mood 100 (75–100) 100 (75–100) 0.4175 Halitosis 100 (70–100) 100 (100–100) 0.0049 Worry/Anxiety 30 (30–70) 100 (70–100) < 0.0001 Data are presented as median [interquartile range]. Preoperative and postoperative (6-month) QOL scores were compared using the Wilcoxon signed-rank test. A p value < 0.05 was considered statistically significant. The total QOL score represents the sum of all domain scores, with higher scores indicating better QOL. IQR: interquartile range Contrary to these symptomatic improvements, domains related to physical oral functions remained stable without signs of surgical compromise. No significant deterioration was observed in chewing (mean difference: − 7.0; 95% CI: − 16.2 to 2.3; p = 0.1353) (Fig. 1-1e) or swallowing (mean difference: − 2.3; 95% CI: − 7.7 to 3.0; p = 0.5126) (Fig. 1-1f). Similarly, taste perception demonstrated no significant change following the intervention (mean difference: 1.7; 95% CI: − 7.3 to 10.7; p = 0.7675). Pain and psychological domains improved significantly, while functional domains remained stable (Table 1 ). Changes in Objective Oral Function Comprehensive examinations of objective oral function were conducted to evaluate the longitudinal impact of surgical intervention. Friedman test analyses in patients with complete paired data across three time points revealed that the majority of oral functional parameters remained stable throughout the evaluation period (Table 2 ). Table 2 Results of the Friedman test for oral functional parameters Parameter χ² (df = 2) p value Swallowing function 0.054 0.973 Degree of tongue coating 3.007 0.222 Oral bacterial count 3.813 0.149 Oral bacterial level 0.584 0.747 Salivary flow volume 1.226 0.542 Oral mucosal moisture 0.299 0.861 Occlusal force 2.848 0.289 Tongue pressure 1.211 0.546 Masticatory function 2.438 0.296 Swallowing function 0.054 0.973 Lip motor function /pa/ 4.483 0.106 Lip motor function /ta/ 9.156 0.010 Lip motor function /ka/ 0.455 0.796 Friedman test results for oral functional parameters measured at three time points (preoperative, 3 months, and 6 months after surgery). No significant temporal changes were observed in any parameters. Consistent findings were observed in the supplementary Steel test analyses comparing baseline values with each follow-up time point using all available data, which are presented in Supplementary Table S2 . Specifically, no significant longitudinal changes were observed in the occlusal force (χ 2 = 2.848, p = 0.289), masticatory function (χ 2 = 2.438, p = 0.296), or swallowing function (χ 2 = 0.054, p = 0.973). Similarly, indicators of the oral environment and minor motor functions, including oral bacterial count (χ 2 = 3.813, p = 0.149), salivary flow volume (χ 2 = 1.226, p = 0.542), oral mucosal moisture (χ 2 = 0.299, p = 0.861), and tongue pressure (χ 2 = 1.211, p = 0.546), exhibited no significant deterioration (Fig. 1– 2 ). Oral diadochokinesis was employed to assess specific motor functions: the syllable /pa/ for lip closure (related to food spillage), /ta/ for anterior tongue elevation (related to bolus transport), and /ka/ for posterior tongue movement (related to the initiation of swallowing). While /pa/ (χ 2 = 4.483, p = 0.106) and /ka/ (χ 2 = 0.455, p = 0.796) remained unchanged, tongue motor function /ta/ exhibited a statistically significant longitudinal change (χ 2 = 9.156, p = 0.010) (Table 2 ). Risk Factors Associated with MRONJ Recurrence During the observation period, MRONJ recurrence was documented in 10 of 48 patients (20.8%). Univariate analyses revealed that demographic and lifestyle factors were not significantly associated with recurrence (Table 3 ). Table 3 Comprehensive univariate analyses of factors associated with medication-related osteonecrosis of the jaw (MRONJ) recurrence Variable Recurrence (n = 10) Median (IQR) Non-recurrence (n = 37) Median (IQR) Statistical test p value Demographics Age (years) 72.5 (64.25–77.75) 76.0 (64.0–80.0) Wilcoxon rank-sum 0.4195 Sex (male), n (%) 6 (60.0) 13 (35.1) Fisher’s exact 0.2757 BMI (kg/m 2 ) 22.24 (20.75–28.15) 22.06 (19.91–24.18) Wilcoxon rank-sum 0.5242 Lifestyle factors Smoking history, n (%) 5 (50.0) 14 (37.8) Fisher’s exact 0.4964 Alcohol consumption, n (%) 4 (40.0) 13 (35.1) χ² test 0.7775 Disease-related factors MRONJ stage 2 (2–3) 2 (2–3) Wilcoxon rank-sum 0.7907 Jaw location (mandible), n (%) 6 (60.0) 25 (67.6) χ² test 0.8489 Lesion site (molar region), n (%) 8 (80.0) 30 (81.1) χ² test 0.4218 Medication-related factors Antiresorptive type (denosumab), n (%) 8 (80.0) 22 (59.5) Fisher’s exact 0.2894 High-dose therapy, n (%) 8 (80.0) 16 (43.2) χ² test 0.0391 Injectable administration, n (%) 10 (100.0) 27 (73.0) χ² test 0.0193 Corticosteroid use, n (%) 4 (40.0) 16 (43.2) χ² test 0.8537 Chemotherapy, n (%) 10 (100.0) 20 (54.1) χ² test 0.0012 Surgical factors Surgical procedure (segmental resection), n (%) 10 (100.0) 26 (70.3) χ² test 0.0134 Oral condition Remaining teeth (number) 24.5 (5.75–27.25) 23.0 (15.5–27.0) Wilcoxon rank-sum 0.7538 Degree of Tongue coating (%) 61.1 (47.2–68.1) 38.9 (11.1–58.4) Wilcoxon rank-sum 0.0600 Oral bacterial count (x 10 4 CFU/mL) 585.5 (221–1197.5) 581 (314–1885) Wilcoxon rank-sum 0.5242 Oral bacterial level score 4 (3–5) 4 (3.5–5) Wilcoxon rank-sum 0.5816 Salivary flow volume (g/2 min) 2.81 (1.19–3.50) 3.32 (1.77–4.60) Wilcoxon rank-sum 0.3427 Oral mucosal moisture 29.35 (27.13–31.28) 30.10 (27.55–31.20) Wilcoxon rank-sum 0.6304 Oral function Occlusal force (N) 437.4 (46.4–593.8) 281.4 (104.6–587.0) Wilcoxon rank-sum 0.9482 Tongue pressure (kPa) 28.65 (22.1–39.6) 26.4 (19.5–34.9) Wilcoxon rank-sum 0.4747 Masticatory performance function (mg/dL) 210.8 (72.9–264.6) 147.0 (107.8–195.3) Wilcoxon rank-sum 0.1643 Swallowing function 1 (0–2.75) 0 (0–1.5) Wilcoxon rank-sum 0.3425 Periodontal burden PISA (mm²)* 159.4 (119.4–297.4) 33.0 (22.1–126.5) Wilcoxon rank-sum 0.055† Values are presented as median (interquartile range) unless otherwise indicated. P values were calculated using Wilcoxon rank-sum tests or Fisher’s exact tests, as appropriate. Bold values indicate variables with statistical significance or borderline significance ( p < 0.10). * PISA values were available in a limited subset of patients and were analyzed in an exploratory manner. † Due to limited sample size, PISA results should be interpreted cautiously. IQR: interquartile range, BMI: body mass index, MRONJ: medication-related osteonecrosis of the jaw, CFU: colony forming unit, PISA: periodontal inflamed surface area. In contrast, treatment-related factors emerged as prominent determinants. Patients receiving high-dose antiresorptive therapy exhibited a significantly higher recurrence rate compared to those on low-dose therapy ( p = 0.039, Pearson chi-square and Cochran–Armitage trend tests), with an odds ratio (OR) of 5.25 (95% CI: 0.98–28.18). Regarding surgical intervention, marginal or partial resection was associated with higher recurrence rates compared with segmental procedures ( p = 0.013, likelihood ratio test). Despite the need for extensive resection in selected cases, postoperative total QOL scores improved significantly, and essential oral functions were preserved. This suggests that a carefully planned surgical strategy, supported by comprehensive preoperative imaging, can achieve an optimal balance between curative resection and the preservation of patient-centered outcomes. Among oral functional parameters, degree of tongue coating demonstrated a trend toward association with recurrence in univariate testing ( p = 0.060). Additionally, in the subset of 18 dentate patients, higher PISA values tended to be associated with recurrence (Supplementary Table S3). Consistent with previous reports, high-dose antiresorptive therapy, injectable administration, and concomitant chemotherapy were significantly associated with recurrence. In contrast, several oral functional and periodontal parameters did not reach statistical significance but demonstrated directional trends, suggesting potential additional influences beyond established systemic risk factors. Multivariable logistic regression analyses were performed using two complementary models to evaluate independent predictors (Supplementary Table S4). In both models, concomitant chemotherapy was consistently and independently associated with an increased risk of recurrence (Model 1: OR 5.30; Model 2: OR 10.4). In Model 1, which focused on oral function, reduced masticatory performance demonstrated a trend toward association with recurrence; however, it did not reach statistical significance. In Model 2, marginal/partial resection remained significantly associated with recurrence ( p = 0.013). In univariate analyses, treatment-related factors demonstrated stronger associations with recurrence than local oral functional parameters. Concomitant chemotherapy was significantly associated with earlier recurrence in univariate Cox proportional hazards analysis ( p = 0.003, log-rank test). Injectable administration of antiresorptive agents was also associated with a significantly increased risk of recurrence ( p = 0.031) (Supplementary Table S5). ROC curve analyses were performed to explore potential cut-off values for selected oral functional parameters (Supplementary Table S6). However, the discriminative ability of these parameters was modest, and dichotomized variables based on these cut-offs did not demonstrate statistically significant associations with recurrence. Several oral functional parameters demonstrated consistent trends toward a shorter time to recurrence in univariate Cox proportional hazards analyses; however, these associations did not reach conventional levels of statistical significance. In the present study, high masticatory function, high occlusal force, and high tongue pressure—each reflecting a vigorous stomatognathic function—were associated with an increased risk of recurrence (all p < 0.10). These findings suggest that higher mechanical loading on the surgical site during mastication may adversely affect bone stability in patients with MRONJ. This is consistent with the frequent clinical observation of tori (torus mandibularis or palatinus) in this patient population, signifying a history of excessive occlusal stress. Additionally, a decreased salivary flow volume rate was identified as a potential risk factor, while degree of tongue coating and oral mucosal moisture demonstrated no significant association (Fig. 2 , Supplementary Table S7). Due to the limited number of recurrences, multivariable Cox proportional hazards modeling including selected clinical and treatment-related variables did not identify any independent predictors of recurrence. Therefore, recurrence-related factors were primarily evaluated using univariate Cox analyses. Discussion The present study demonstrated that surgical management of MRONJ is associated with restoration of symptomatic and functional balance rather than functional deterioration. Although previous reports have suggested that surgical resection of jaw pathology may result in long-term improvements in the QOL following resolution of inflammation and pathological burden [ 9 – 11 ], longitudinal objective evaluation following MRONJ surgery remains limited. In the present cohort, despite bone resection and tooth loss, objective measures remained stable over time, while patient-reported QOL improved significantly. These functional parameters reflect different components of stomatognathic performance and are widely used as objective indicators of oral functional status in clinical and epidemiological research. Functional impairment in MRONJ is presumably driven more by inflammatory burden than structural loss. The pathophysiology of MRONJ involves chronic inflammatory processes and compromised bone remodeling associated with antiresorptive agents, which are believed to interfere with mucosal integrity and neuromuscular coordination [ 6 , 12 ]. These findings indicate that functional impairment in MRONJ may be driven more strongly by persistent inflammatory burden rather than structural deficit alone. Chronic infection, nociceptive input, and mucosal instability likely interfere with neuromuscular coordination and adaptive oral function. Surgical necrotic bone removal may therefore attenuate inhibitory inflammatory signaling, permitting functional recalibration within the stomatognathic system. Within this framework, surgery can be interpreted not solely as tissue removal, but as an intervention that facilitates re-establishment of biological and functional equilibrium. Recurrence analyses revealed a layered pattern of risk. Systemic factors—particularly concomitant chemotherapy—were the strongest determinants of recurrence occurrence. The reproducibility of these established systemic risk factors strengthens the internal validity of the cohort. Against this background, the directional associations observed for oral functional and periodontal parameters suggest that local mechanical and environmental conditions may further modulate recurrence dynamics beyond systemic susceptibility alone. In contrast, functional parameters were not independent predictors but demonstrated directional trends in time-to-event analyses. Higher occlusal force, greater masticatory performance, and increased tongue pressure were associated with shorter recurrence-free intervals; however, statistical significance was limited by event number. These observations suggest the potential role of mechanical loading in modulating bone stability under pharmacologically suppressed remodeling conditions; however, causal relationships cannot be established in this observational study [ 13 , 14 ]. The coexistence of antiresorptive-induced suppression of bone turnover and localized mechanical strain may create a vulnerability window in which adaptive remodeling capacity is exceeded. This mechanobiological interaction warrants further investigation [ 6 , 13 , 15 , 16 ]. Reduced salivary flow was significantly associated with earlier recurrence, underscoring the importance of oral environmental stability. Saliva contributes to mucosal defense, microbial homeostasis, and wound healing, and its impairment has been linked to delayed healing and persistent inflammation in head and neck conditions [ 17 ]. To our knowledge, the relationship between reduced salivary flow and MRONJ recurrence has not been specifically examined in previous studies. Collectively, these findings suggest that recurrence dynamics may reflect the interaction among systemic vulnerability, mechanical stress, and environmental homeostasis rather than any single determinant. Certain limitations should be acknowledged, including the modest sample size and single-center design, which constrained multivariable time-to-event modeling and render mechanistic interpretations hypothesis-generating. Nevertheless, the prospective longitudinal integration of patient-reported and objective functional outcomes provides a clinically relevant framework that may extend beyond this specific cohort. Validation in multicenter settings is warranted. Although the observed associations suggest a potential influence of mechanical loading on postoperative bone stability, the present study was not designed to determine causal mechanisms, and further experimental and biomechanical studies are required. Surgical MRONJ management restores functional and symptomatic balance. These findings highlight the importance of integrating functional assessment into surgical decision-making and postoperative management strategies for patients with MRONJ. Recurrence dynamics are influenced by systemic vulnerability, mechanical loading, and oral environmental stability. Multidimensional assessment integrating patient-reported outcomes and objective function is recommended. Mechanobiological frameworks can inform individualized postoperative strategies to optimize long-term outcomes. Declarations Competing Interests Statement The authors declare no competing financial interests. Funding information This research was partially supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (No. 23K093981A). Author Contribution Author contributions Sachiko YAMASAKI: Contributed to conception, design, data acquisition, analysis, and interpretation, drafted and critically revised manuscript. Tomoaki SHINTANI: Contributed to design, acquisition, and analysis, critically revised manuscript. Kota MORISHITA: Contributed to conception and interpretation, drafted and critically revised manuscript. Fumitaka OBAYASHI: Contributed to conception and acquisition, drafted and critically revised manuscript. Nami OBAYASHI: Contributed to conception and interpretation, drafted and critically revised manuscript. Tamamo MATSUYAMA: Contributed to conception and interpretation, drafted and critically revised manuscript. Natsuki EBOSHIDA: Contributed to conception and analysis, drafted and critically revised manuscript. Kensaku MATSUI: Contributed to conception and analysis, drafted and critically revised manuscript. Mirai HIGAKI: Contributed to conception and interpretation, drafted and critically revised manuscript. Atsuko HAMADA: Contributed to conception and interpretation, drafted and critically revised manuscript. Nanako ITO: Contributed to conception and analysis, drafted and critically revised manuscript. Koichi KOIZUMI: Contributed to conception and acquisition, drafted and critically revised manuscript. Mikihito KAJIYA: Contributed to conception and interpretation, drafted and critically revised manuscript. Souichi YANAMOTO: Contributed to conception and interpretation, drafted and critically revised manuscript. All authors gave their final approval and agree to be accountable for all aspects of the work. Acknowledgement We would like to thank Dr. Hiromi Nishi for patient referrals and treatment support. Data Availability The datasets generated and analyzed during the current study are not publicly available due to ethical and privacy restrictions but are available from the corresponding author on reasonable request and with approval of the institutional ethics committee. References Otto, S., Pautke, C., Opelz, C., Niepel, D. & Schiødt, M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat. Rev. 69 , 177–187. 10.1016/j.ctrv.2018.06.005 (2018). Yarom, N. et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline. J. Clin. Oncol. 37 , 2270–2290. 10.1200/JCO.19.01186 (2019). Tenore, G. et al. Does medication-related osteonecrosis of the jaw influence the quality of life of cancer patients? Biomedicines 8 , 95. 10.3390/biomedicines8040095 (2020). Bensi, C. et al. Quality of life in patients affected by medication-related osteonecrosis of the jaws: a systematic review. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 132 , 182–189. 10.1016/j.oooo.2021.03.006 (2021). Sato, T. et al. Which symptoms negatively affect the oral health-related quality of life in patients with osteonecrosis of the jaw? Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 130 , 175–180. 10.1016/j.oooo.2020.03.051 (2020). Ruggiero, S. L. et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2022 update. J. Oral Maxillofac. Surg. 80 , 920–943. 10.1016/j.joms.2022.02.008 (2022). Kishimoto, H. & Moridera, K. Position paper on medication-related osteonecrosis of the jaw 2023 update—Key points for revision—. Jpn J. Oral Maxillofac. Surg. 70 , 278–285. 10.5794/jjoms.70.278 (2024). El-Rabbany, M. et al. Surgical therapy in patients with medication-related osteonecrosis of the jaw is associated with disease resolution and improved quality of life: A prospective cohort study. J. Oral Maxillofac. Surg. 80 , 1084–1093. 10.1016/j.joms.2022.01.012 (2022). Oteri, G. et al. Oral-health-related quality of life after surgical treatment of osteonecrosis of the jaws. J. Craniofac. Surg. 29 , 403–408. 10.1097/SCS.0000000000004087 (2018). Murphy, J. & Mannion, C. J. Medication-related osteonecrosis of the jaws and quality of life: review and structured analysis. Br. J. Oral Maxillofac. Surg. 58 , 619–624. 10.1016/j.bjoms.2020.03.010 (2020). Moll, S. et al. Patients’ quality of life improves after surgical intervention of stage III medication-related osteonecrosis of the jaw. Oral Maxillofac. Surg. 25 , 359–366. 10.1007/s10006-020-00927-7 (2021). Chen, S., Ren, H., He, Y., An, J. & Zhang, Y. Recurrence-related factors of medication-related osteonecrosis of the jaw: A five-year experience. J. Oral Maxillofac. Surg. 79 , 2472–2481. 10.1016/j.joms.2021.07.029 (2021). Vasikaran, S. D., Glendenning, P. & Morris, H. A. The role of biochemical markers of bone turnover in osteoporosis management in clinical practice. Clin. Biochem. Rev. 27 , 119–121 (2006). McGowan, K., McGowan, T. & Ivanovski, S. Risk factors for medication-related osteonecrosis of the jaw: A systematic review. Oral Dis. 24 , 527–536. 10.1111/odi.12640 (2018). Dawes, C. et al. The functions of human saliva: a review sponsored by the World Workshop on Oral Medicine VI. Arch. Oral Biol. 60 , 863–874. 10.1016/j.archoralbio.2015.03.004 (2015). Migliorati, C. A., Brennan, M. T. & Peterson, D. E. Medication-related osteonecrosis of the jaws. J. Natl. Cancer Inst. Monogr. lgz009 (2019). (2019). 10.1093/jncimonographs/lgz009 Sarkar, S. et al. Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J. Bone Min. Res. 19 , 394–401. 10.1359/JBMR.0301243 (2004). Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.docx SupplementaryTable0224.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 22 Apr, 2026 Reviews received at journal 19 Apr, 2026 Reviews received at journal 09 Apr, 2026 Reviews received at journal 07 Apr, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviewers invited by journal 19 Mar, 2026 Editor invited by journal 17 Mar, 2026 Editor assigned by journal 14 Mar, 2026 Submission checks completed at journal 14 Mar, 2026 First submitted to journal 12 Mar, 2026 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-9101394","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":609070080,"identity":"6e6102dd-db37-425c-b088-38adbd96215a","order_by":0,"name":"Sachiko YAMASAKI","email":"data:image/png;base64,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","orcid":"","institution":"Hiroshima University","correspondingAuthor":true,"prefix":"","firstName":"Sachiko","middleName":"","lastName":"YAMASAKI","suffix":""},{"id":609070093,"identity":"53b9caa9-ccdd-4686-9b4f-15da1f8b044b","order_by":1,"name":"Tomoaki SHINTANI","email":"","orcid":"","institution":"Hiroshima University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomoaki","middleName":"","lastName":"SHINTANI","suffix":""},{"id":609070095,"identity":"96793ec3-f83a-4602-b792-e689f0811c63","order_by":2,"name":"Kota MORISHITA","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Kota","middleName":"","lastName":"MORISHITA","suffix":""},{"id":609070098,"identity":"9edcae89-8da9-4125-89fa-ea86280c187f","order_by":3,"name":"Fumitaka OBAYASHI","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Fumitaka","middleName":"","lastName":"OBAYASHI","suffix":""},{"id":609070107,"identity":"ae894002-2f71-4073-b897-6b2c289ec40c","order_by":4,"name":"Nami OBAYASHI","email":"","orcid":"","institution":"Hiroshima University 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University","correspondingAuthor":false,"prefix":"","firstName":"Nanako","middleName":"","lastName":"ITO","suffix":""},{"id":609070125,"identity":"9a12aff5-40bc-45bc-9645-fa51630d4174","order_by":11,"name":"Koichi KOIZUMI","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Koichi","middleName":"","lastName":"KOIZUMI","suffix":""},{"id":609070126,"identity":"cbe9d918-bf8d-4f9f-b34d-8d92f408837b","order_by":12,"name":"Mikihito KAJIYA","email":"","orcid":"","institution":"Hiroshima University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mikihito","middleName":"","lastName":"KAJIYA","suffix":""},{"id":609070127,"identity":"0f65e5ca-6519-48c3-8918-62a2bab0690e","order_by":13,"name":"Souichi YANAMOTO","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Souichi","middleName":"","lastName":"YANAMOTO","suffix":""}],"badges":[],"createdAt":"2026-03-12 07:23:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9101394/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9101394/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105319232,"identity":"c63c0a91-1d57-41bf-99c6-f0ee7f30c882","added_by":"auto","created_at":"2026-03-24 16:59:46","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120551,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eChanges in the Quality of Life (QOL) before and after surgical treatment for medication-related osteonecrosis of the jaw (MRONJ).\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOverview of Assessment (a–f): Surgical intervention significantly improved both the total QOL score and individual subdomains in patients with MRONJ (n = 43).\u003c/p\u003e\n\u003cp\u003eBox-and-whisker plots illustrate the distribution of scores, where boxes represent the median and interquartile range (IQR).\u003c/p\u003e\n\u003cp\u003eTotal QOL Score (a): The median (IQR) total QOL score increased significantly from 1060 (IQR 925–1150) to 1140 (IQR 1035–1230) (\u003cem\u003ep \u003c/em\u003e= 0.0002). The mean improvement was +84.8 points (95% CI: 40.2–129.3, \u003cem\u003ep \u003c/em\u003e= 0.0004).\u003c/p\u003e\n\u003cp\u003eSubdomain Improvements (b–f): Significant improvements were observed across all evaluated subdomains (all \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001 via Wilcoxon signed-rank test):\u003c/p\u003e\n\u003cp\u003eAnxiety (b): Showed the most substantial clinical gain, with the median (IQR) score rising sharply from 30 (IQR 30–70) to 100 (IQR 70–100).\u003c/p\u003e\n\u003cp\u003ePain (c): Median score improved from 75 to 100.\u003c/p\u003e\n\u003cp\u003eHalitosis (d): Median score reached the maximum of 100 postoperatively, reflecting a marked reduction in halitosis-related impairment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eChanges in the oral functional and environmental parameters over time.\u003c/strong\u003e\u003c/em\u003e\u003cbr\u003e\nChanges in (a) occlusal force, (b) masticatory function, (c) swallowing function, (d) oral mucosal moisture, (e) salivary flow volume, and (f) tongue pressure were evaluated preoperatively and at 3 months (3M) and 6 months (6M) postoperatively using paired data. For visualization of within-subject changes, values were centered by subject (block). Friedman test analysis revealed no significant differences across time points for occlusal force (\u003cem\u003ep \u003c/em\u003e= 0.289), masticatory function (\u003cem\u003ep\u003c/em\u003e = 0.296), swallowing function (\u003cem\u003ep\u003c/em\u003e= 0.973), oral bacterial count (\u003cem\u003ep\u003c/em\u003e = 0.747), salivary flow volume (\u003cem\u003ep\u003c/em\u003e= 0.542), or tongue pressure (\u003cem\u003ep\u003c/em\u003e = 0.546).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9101394/v1/bbd501eabad93de884797be3.jpg"},{"id":105319230,"identity":"249e9634-4186-4f5e-909e-811c9f621800","added_by":"auto","created_at":"2026-03-24 16:59:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":131780,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eForest plot of medication-related osteonecrosis of the jaw recurrence.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate Cox proportional hazards analysis of oral recurrence related factors.\u003c/p\u003e\n\u003cp\u003eError bars represent the range from the lower 95% confidence interval (CI) to the upper 95% CI. Values shown on the right indicate hazard ratios (HRs) with corresponding 95% CIs.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9101394/v1/2e186330ecd0f538c13b3c3f.jpg"},{"id":105569740,"identity":"7dcc44f4-1ed9-4dd7-889d-850f1720a044","added_by":"auto","created_at":"2026-03-27 13:13:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1614865,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9101394/v1/15e9a638-1c01-4334-a494-b516819f06d9.pdf"},{"id":105564960,"identity":"455e402b-28f1-411f-9eeb-e0f1f64da0a2","added_by":"auto","created_at":"2026-03-27 12:51:27","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":21588,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9101394/v1/5d26053b189c5704accbabe3.docx"},{"id":105319231,"identity":"3b4bcb16-aa25-443d-bbc0-26b6c6360069","added_by":"auto","created_at":"2026-03-24 16:59:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":43874,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable0224.docx","url":"https://assets-eu.researchsquare.com/files/rs-9101394/v1/66b2fdb0da254a0460ab2e48.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surgical management of medication-related osteonecrosis of the jaw improves quality of life without deterioration in oral function","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMedication-related osteonecrosis of the jaw (MRONJ) represents a complex interface between systemic pharmacologic therapy and localized bone pathology [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although contemporary management strategies emphasize mucosal closure and radiographic resolution, structural healing alone does not fully reflect therapeutic success. Quality of life (QOL) constitutes a critical clinical endpoint in MRONJ, as the substantial burden of pain, infection, halitosis, and functional impairment impact the daily activities and psychosocial well-being of patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOral health\u0026ndash;related QOL in MRONJ is frequently compromised because the disease disrupts essential functions such as mastication and swallowing [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although surgical outcomes are commonly evaluated by structural resolution, these measures do not necessarily capture functional recovery or patient-centered benefit [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The 2022 American Association of Oral and Maxillofacial Surgeons (AAOMS) position paper highlights QOL improvement as a key therapeutic goal [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Similarly, the 2023 Japanese position paper has supported proactive surgical management in selected patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, longitudinal studies integrating patient-reported outcomes with objective functional parameters remain limited. Therefore, whether surgical eradication of necrotic bone compromises or restores stomatognathic function remains unclear.\u003c/p\u003e \u003cp\u003eBeyond its clinical manifestations, MRONJ represents a disruption of the delicate balance between bone remodeling, mucosal integrity, and mechanical loading within the stomatognathic system. While antiresorptive therapy suppresses osteoclastic activity and reduces skeletal turnover, the jaw is uniquely exposed to repetitive functional stress and microbial challenge. How these systemic and local forces interact to influence postoperative recovery and recurrence remains poorly understood. In particular, whether restoration of structural continuity translates into recovery of biomechanical and environmental homeostasis has not been systematically examined.\u003c/p\u003e \u003cp\u003eRecurrence has traditionally been attributed to systemic risk factors and incomplete resection. Nevertheless, postoperative functional loading and oral environmental stability may also influence recurrence dynamics. Accordingly, this study longitudinally evaluated patient-reported QOL and objective oral functional parameters following surgical management of MRONJ and explored their association with recurrence.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and study design\u003c/h2\u003e \u003cp\u003e This prospective cohort study was conducted and reported in accordance with the STROBE guidelines. The study was approved by the Ethics Committee of Hiroshima University (Approval number: E-2022-0176) and prospectively registered in the UMIN Clinical Trials Registry (UMIN000048986). Written informed consent was obtained from all participants. Eligible participants included patients diagnosed with MRONJ who underwent surgical treatment at the Department of Oral and Maxillofacial Surgery, Hiroshima University Hospital (Japan), between October 2022 and December 2025. MRONJ diagnosis was established based on the AAOMS position paper criteria [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA total of 48 consecutive patients who underwent surgical treatment for MRONJ at our institution were included in the study cohort. All patients were enrolled in a prospective clinical follow-up program and were scheduled for postoperative evaluation at regular intervals. Participants completed QOL questionnaires prior to surgical treatment and at approximately 6 months postoperatively. Detailed oral functional examinations were performed preoperatively and at 3 and 6 months after surgery. Postoperative QOL assessments were scheduled at 6 months after surgery in accordance with the institutional follow-up protocol. Among the 48 patients, 43 had available paired preoperative and postoperative QOL data at the 6-month time point and were therefore included in the longitudinal paired QOL analyses. The remaining five patients had not yet reached the 6-month postoperative time point or were unable to complete postoperative QOL assessment due to death or difficulty attending follow-up visits. These patients were included in the baseline and perioperative analyses but were excluded from paired QOL analyses due to unavailable follow-up data (Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eQOL measurements and data collection\u003c/h3\u003e\n\u003cp\u003eQOL was assessed using a validated MRONJ-specific questionnaire derived from the University of Washington QOL questionnaire, the EORTC QLQ-H\u0026amp;N35, and the Functional Assessment of Cancer Therapy\u0026ndash;Head and Neck, as previously reported in the literature [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and approved by the Hiroshima University Ethics Committee. The questionnaire comprised 13 items assessing the following domains: pain, appearance, daily activity, recreation, swallowing, chewing, speech, taste, halitosis, salivary function, mood, and anxiety. Responses were recorded using 4- or 5-point Likert-type scales. For ease of interpretation, all domain scores were transformed to a standardized 0\u0026ndash;100 scale, with higher scores indicating better QOL. The total QOL score, defined as the sum of the standardized domain scores, was prespecified as the primary outcome. Individual QOL subdomains were analyzed as secondary and exploratory outcomes. Analyses of the QOL changes were conducted using data from participants who completed QOL assessments at least 6 months postoperatively. This approach reflects real-world clinical practice in this population and enhances the generalizability of the findings.\u003c/p\u003e\n\u003ch3\u003eClinical variables and oral functional assessment\u003c/h3\u003e\n\u003cp\u003eBaseline clinical and demographic data were collected for each patient, including age, sex, body mass index (BMI), smoking history, alcohol consumption, history of antiresorptive agent (ARA) use (type, duration, and indication), medical comorbidities (malignancy, diabetes mellitus, autoimmune disease), history of chemotherapy and steroid use, MRONJ stage, lesion site, and clinical manifestations (infection, bone exposure, extraoral fistula, sensory disturbance, and pathological fracture). Surgical procedures were categorized as sequestrectomy with peripheral ostectomy, partial maxillectomy, marginal mandibulectomy, segmental mandibulectomy, or hemimandibulectomy. The number of remaining teeth and presence or absence of MRONJ recurrence were also recorded. To minimize potential sources of bias, surgical indications and procedures were determined by departmental consensus prior to treatment. All operations were performed by board-certified oral and maxillofacial surgeons with more than 15 years of clinical experience, and outcome assessments were conducted using standardized criteria. Consecutive patient enrollment and predefined follow-up protocols were employed to reduce selection and information bias. Oral functional examinations included assessment of: (1) the degree of tongue coating, (2) oral bacterial count, (3) salivary flow volume, (4) oral mucosal moisture, (5) occlusal force, (6) lip motor function, (7) tongue pressure, (8) masticatory function, and (9) swallowing function. These parameters capture complementary dimensions of stomatognathic performance: biomechanical loading (occlusal force, masticatory performance, tongue pressure), neuromotor coordination (oral diadochokinesis), and oral environmental stability (salivary flow, mucosal moisture, bacterial count). This approach evaluates whether surgical intervention alters the functional ecosystem beyond structural healing alone. Moreover, periodontal parameters\u0026mdash;including periodontal inflamed surface area (PISA), bleeding on probing, periodontal epithelial surface area, and probing pocket depth\u0026mdash;were also evaluated. Objective oral function assessments were performed by calibrated examiners with more than 15 years of experience, ensuring inter-rater reliability. Measurements of occlusal force and tongue pressure were conducted using validated instruments (Dental Prescale II, JMS Co., Ltd., Tokyo, Japan), and reproducibility was confirmed with repeated measurements in a subset of patients (intraclass correlation coefficient\u0026thinsp;\u0026gt;\u0026thinsp;0.90). This methodological rigor enhances confidence in longitudinal comparisons.\u003c/p\u003e\n\u003ch3\u003eDefinition of healing\u003c/h3\u003e\n\u003cp\u003eHealing of MRONJ was defined as the absence of exposed bone and inflammatory signs, including drainage, gingival redness, or pain. Patients were followed for recurrence from the date of surgical treatment until January 30, 2026, providing a uniform observation period for the assessment of MRONJ recurrence.\u003c/p\u003e\n\u003ch3\u003eHandling of missing data\u003c/h3\u003e\n\u003cp\u003eDue to the inclusion of elderly and oncologic patients, some follow-up data were missing because of death or difficulty attending follow-up visits (e.g., fracture or deterioration of general condition). Therefore, complete-case analyses were primarily performed. As sensitivity analyses, nonparametric methods accommodating incomplete observations were also applied, and results were compared to assess the robustness of the findings.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThis prospective cohort study followed 48 patients with Stage 2\u0026ndash;3 MRONJ undergoing surgery from October 2022 to January 30, 2026. Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range), as appropriate. Categorical variables are expressed as frequencies and percentages. Paired comparisons of QOL scores were performed using the Wilcoxon signed-rank test. Longitudinal changes in oral functional parameters were analyzed using the Friedman test for repeated nonparametric measures with post-hoc Steel tests for multiple comparisons.\u003c/p\u003e \u003cp\u003eAssociations between clinical variables and recurrence were evaluated using chi-square or Fisher\u0026rsquo;s exact tests for categorical variables and nonparametric tests for continuous variables. For time-to-event analyses, Cox proportional hazards models were constructed to identify factors associated with recurrence. Variables considered clinically relevant based on prior literature were entered into multivariable models to address potential confounding. The proportional hazards assumption was verified by inspection of Schoenfeld residuals.\u003c/p\u003e \u003cp\u003eSubgroup analyses were performed in dentate patients to examine the association between periodontal inflammatory burden and recurrence. Interaction terms were not formally tested due to the limited number of events.\u003c/p\u003e \u003cp\u003eMissing follow-up data due to death or loss to follow-up were primarily handled using complete-case analyses. Sensitivity analyses using nonparametric methods including all available observations were performed to confirm the robustness of results. Continuous oral functional variables were dichotomized based on receiver-operating characteristic (ROC) curve\u0026ndash;derived cut-off values when appropriate. The median follow-up period was estimated using the reverse Kaplan\u0026ndash;Meier method. A two-sided p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using JMP Pro version 18.0 (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient cohort and follow-up\u003c/h2\u003e \u003cp\u003eA total of 48 patients were included in the study, comprising 27 and 21 patients with underlying malignancies and osteoporosis, respectively. Based on the AAOMS staging, 31 patients (64.6%) presented with Stage 2 MRONJ and 17 (35.4%) with Stage 3. The mandible was the most frequent site of involvement (62.5%), and denosumab was the most commonly used antiresorptive agent (54.2%). Of the initial cohort, 43 patients (89.6%) completed the 6-month postoperative follow-up including QOL assessments. The median follow-up period for the entire cohort was 14 (1\u0026ndash;38) months (Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eChanges in the QOL scores (Primary and Secondary Outcomes)\u003c/h2\u003e \u003cp\u003eThe primary outcome, the total QOL score, demonstrated a significant improvement following surgical treatment (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean total score increased from 956.7\u0026thinsp;\u0026plusmn;\u0026thinsp;189.5 preoperatively to 1041.5\u0026thinsp;\u0026plusmn;\u0026thinsp;127.3 at 6 months postoperatively, representing a mean paired difference of 84.8 (95% CI: 40.2\u0026ndash;129.3; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002, Wilcoxon signed-rank test) (Fig.\u0026nbsp;1-1a). Detailed analysis of the individual subdomains revealed that the most substantial gains occurred in psychological and symptom-related areas. Specifically, the anxiety score exhibited a dramatic increase, with a mean paired improvement of 34.0 (95% confidence interval [CI]: 21.7\u0026ndash;46.2; \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.0001), representing the largest magnitude of change among all evaluated domains (Fig.\u0026nbsp;1-1b). Significant postoperative gains were also observed in pain, which improved by a mean of 16.3 (95% CI: 10.0\u0026ndash;22.5; \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.0001) (Fig.\u0026nbsp;1-1c), and halitosis, which showed a mean increase of 12.0 (95% CI: 5.0\u0026ndash;18.9; \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0004) (Fig.\u0026nbsp;1-1d).\u003c/p\u003e \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 \u003cp\u003eChanges in the quality of life (QOL) scores before and after surgical treatment for medication-related osteonecrosis of the jaw (MRONJ) (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePreoperative score\u003c/p\u003e \u003cp\u003eMedian [IQR]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostoperative score (6 months)\u003c/p\u003e \u003cp\u003eMedian [IQR]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value (Wilcoxon)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal QOL score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1060 (925\u0026ndash;1150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1140 (1035\u0026ndash;1230)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0069\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePain\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100(75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppearance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (50\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0776\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaily activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (50\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecreation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (50\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwallowing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChewing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (50\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (50\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1850\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpeech\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (70\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaste\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (70\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (70\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSaliva\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHalitosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (70\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (100\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWorry/Anxiety\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (30\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (70\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as median [interquartile range]. Preoperative and postoperative (6-month) QOL scores were compared using the Wilcoxon signed-rank test. A \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The total QOL score represents the sum of all domain scores, with higher scores indicating better QOL.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIQR: interquartile range\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eContrary to these symptomatic improvements, domains related to physical oral functions remained stable without signs of surgical compromise. No significant deterioration was observed in chewing (mean difference: \u0026minus;\u0026thinsp;7.0; 95% CI: \u0026minus;\u0026thinsp;16.2 to 2.3; \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.1353) (Fig.\u0026nbsp;1-1e) or swallowing (mean difference: \u0026minus;\u0026thinsp;2.3; 95% CI: \u0026minus;\u0026thinsp;7.7 to 3.0; \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.5126) (Fig.\u0026nbsp;1-1f). Similarly, taste perception demonstrated no significant change following the intervention (mean difference: 1.7; 95% CI: \u0026minus;\u0026thinsp;7.3 to 10.7; \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.7675). Pain and psychological domains improved significantly, while functional domains remained stable (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eChanges in Objective Oral Function\u003c/h2\u003e \u003cp\u003eComprehensive examinations of objective oral function were conducted to evaluate the longitudinal impact of surgical intervention. Friedman test analyses in patients with complete paired data across three time points revealed that the majority of oral functional parameters remained stable throughout the evaluation period (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eResults of the Friedman test for oral functional parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eχ\u0026sup2; (df\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwallowing function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of tongue coating\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral bacterial count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.813\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral bacterial level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.584\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.747\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalivary flow volume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.542\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral mucosal moisture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.861\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcclusal force\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMasticatory function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwallowing function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip motor function /pa/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip motor function /ta/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip motor function /ka/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eFriedman test results for oral functional parameters measured at three time points (preoperative, 3 months, and 6 months after surgery). No significant temporal changes were observed in any parameters.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eConsistent findings were observed in the supplementary Steel test analyses comparing baseline values with each follow-up time point using all available data, which are presented in Supplementary Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e. Specifically, no significant longitudinal changes were observed in the occlusal force (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;2.848, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.289), masticatory function (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;2.438, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.296), or swallowing function (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.054, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.973). Similarly, indicators of the oral environment and minor motor functions, including oral bacterial count (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;3.813, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.149), salivary flow volume (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;1.226, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.542), oral mucosal moisture (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.299, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.861), and tongue pressure (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;1.211, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.546), exhibited no significant deterioration (Fig.\u0026nbsp;1\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e Oral diadochokinesis was employed to assess specific motor functions: the syllable /pa/ for lip closure (related to food spillage), /ta/ for anterior tongue elevation (related to bolus transport), and /ka/ for posterior tongue movement (related to the initiation of swallowing). While /pa/ (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;4.483, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.106) and /ka/ (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.455, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.796) remained unchanged, tongue motor function /ta/ exhibited a statistically significant longitudinal change (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;9.156, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eRisk Factors Associated with MRONJ Recurrence\u003c/h2\u003e \u003cp\u003eDuring the observation period, MRONJ recurrence was documented in 10 of 48 patients (20.8%). Univariate analyses revealed that demographic and lifestyle factors were not significantly associated with recurrence (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\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 \u003cp\u003eComprehensive univariate analyses of factors associated with medication-related osteonecrosis of the jaw (MRONJ) recurrence\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\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRecurrence (n\u0026thinsp;=\u0026thinsp;10) Median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-recurrence (n\u0026thinsp;=\u0026thinsp;37) Median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStatistical test\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDemographics\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.5 (64.25\u0026ndash;77.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.0 (64.0\u0026ndash;80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2757\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.24 (20.75\u0026ndash;28.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.06 (19.91\u0026ndash;24.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLifestyle factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol consumption, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7775\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease-related factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMRONJ stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7907\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJaw location (mandible), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesion site (molar region), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (81.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedication-related factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiresorptive type (denosumab), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2894\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHigh-dose therapy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (43.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0391\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInjectable administration, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0193\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroid use, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (43.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (54.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical procedure (segmental resection), n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (70.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2; test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0134\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOral condition\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemaining teeth (number)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.5 (5.75\u0026ndash;27.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.0 (15.5\u0026ndash;27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7538\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDegree of Tongue coating (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.1 (47.2\u0026ndash;68.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.9 (11.1\u0026ndash;58.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0600\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral bacterial count (x 10\u003csup\u003e4\u003c/sup\u003e CFU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e585.5 (221\u0026ndash;1197.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e581 (314\u0026ndash;1885)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral bacterial level score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.5\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalivary flow volume (g/2 min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.81 (1.19\u0026ndash;3.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.32 (1.77\u0026ndash;4.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3427\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral mucosal moisture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.35 (27.13\u0026ndash;31.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.10 (27.55\u0026ndash;31.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6304\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOral function\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcclusal force (N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e437.4 (46.4\u0026ndash;593.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e281.4 (104.6\u0026ndash;587.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9482\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.65 (22.1\u0026ndash;39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.4 (19.5\u0026ndash;34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4747\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMasticatory performance function (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210.8 (72.9\u0026ndash;264.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147.0 (107.8\u0026ndash;195.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwallowing function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeriodontal burden\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePISA (mm\u0026sup2;)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159.4 (119.4\u0026ndash;297.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.0 (22.1\u0026ndash;126.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWilcoxon rank-sum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.055\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are presented as \u003cb\u003emedian (interquartile range)\u003c/b\u003e unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eP\u003c/em\u003e values were calculated using Wilcoxon rank-sum tests or Fisher\u0026rsquo;s exact tests, as appropriate.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eBold values\u003c/b\u003e indicate variables with statistical significance or borderline significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.10).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003e*\u003c/b\u003e PISA values were available in a limited subset of patients and were analyzed in an exploratory manner.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026dagger; Due to limited sample size, PISA results should be interpreted cautiously.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIQR: interquartile range, BMI: body mass index, MRONJ: medication-related osteonecrosis of the jaw, CFU: colony forming unit, PISA: periodontal inflamed surface area.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn contrast, treatment-related factors emerged as prominent determinants. Patients receiving high-dose antiresorptive therapy exhibited a significantly higher recurrence rate compared to those on low-dose therapy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039, Pearson chi-square and Cochran\u0026ndash;Armitage trend tests), with an odds ratio (OR) of 5.25 (95% CI: 0.98\u0026ndash;28.18).\u003c/p\u003e \u003cp\u003eRegarding surgical intervention, marginal or partial resection was associated with higher recurrence rates compared with segmental procedures (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013, likelihood ratio test). Despite the need for extensive resection in selected cases, postoperative total QOL scores improved significantly, and essential oral functions were preserved. This suggests that a carefully planned surgical strategy, supported by comprehensive preoperative imaging, can achieve an optimal balance between curative resection and the preservation of patient-centered outcomes.\u003c/p\u003e \u003cp\u003eAmong oral functional parameters, degree of tongue coating demonstrated a trend toward association with recurrence in univariate testing (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.060). Additionally, in the subset of 18 dentate patients, higher PISA values tended to be associated with recurrence (Supplementary Table S3). Consistent with previous reports, high-dose antiresorptive therapy, injectable administration, and concomitant chemotherapy were significantly associated with recurrence. In contrast, several oral functional and periodontal parameters did not reach statistical significance but demonstrated directional trends, suggesting potential additional influences beyond established systemic risk factors.\u003c/p\u003e \u003cp\u003eMultivariable logistic regression analyses were performed using two complementary models to evaluate independent predictors (Supplementary Table S4). In both models, concomitant chemotherapy was consistently and independently associated with an increased risk of recurrence (Model 1: OR 5.30; Model 2: OR 10.4). In Model 1, which focused on oral function, reduced masticatory performance demonstrated a trend toward association with recurrence; however, it did not reach statistical significance. In Model 2, marginal/partial resection remained significantly associated with recurrence (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013).\u003c/p\u003e \u003cp\u003eIn univariate analyses, treatment-related factors demonstrated stronger associations with recurrence than local oral functional parameters. Concomitant chemotherapy was significantly associated with earlier recurrence in univariate Cox proportional hazards analysis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, log-rank test). Injectable administration of antiresorptive agents was also associated with a significantly increased risk of recurrence (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) (Supplementary Table S5).\u003c/p\u003e \u003cp\u003eROC curve analyses were performed to explore potential cut-off values for selected oral functional parameters (Supplementary Table S6). However, the discriminative ability of these parameters was modest, and dichotomized variables based on these cut-offs did not demonstrate statistically significant associations with recurrence.\u003c/p\u003e \u003cp\u003eSeveral oral functional parameters demonstrated consistent trends toward a shorter time to recurrence in univariate Cox proportional hazards analyses; however, these associations did not reach conventional levels of statistical significance. In the present study, high masticatory function, high occlusal force, and high tongue pressure\u0026mdash;each reflecting a vigorous stomatognathic function\u0026mdash;were associated with an increased risk of recurrence (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.10). These findings suggest that higher mechanical loading on the surgical site during mastication may adversely affect bone stability in patients with MRONJ. This is consistent with the frequent clinical observation of tori (torus mandibularis or palatinus) in this patient population, signifying a history of excessive occlusal stress. Additionally, a decreased salivary flow volume rate was identified as a potential risk factor, while degree of tongue coating and oral mucosal moisture demonstrated no significant association (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table S7).\u003c/p\u003e \u003cp\u003eDue to the limited number of recurrences, multivariable Cox proportional hazards modeling including selected clinical and treatment-related variables did not identify any independent predictors of recurrence. Therefore, recurrence-related factors were primarily evaluated using univariate Cox analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study demonstrated that surgical management of MRONJ is associated with restoration of symptomatic and functional balance rather than functional deterioration. Although previous reports have suggested that surgical resection of jaw pathology may result in long-term improvements in the QOL following resolution of inflammation and pathological burden [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], longitudinal objective evaluation following MRONJ surgery remains limited. In the present cohort, despite bone resection and tooth loss, objective measures remained stable over time, while patient-reported QOL improved significantly. These functional parameters reflect different components of stomatognathic performance and are widely used as objective indicators of oral functional status in clinical and epidemiological research. Functional impairment in MRONJ is presumably driven more by inflammatory burden than structural loss.\u003c/p\u003e \u003cp\u003eThe pathophysiology of MRONJ involves chronic inflammatory processes and compromised bone remodeling associated with antiresorptive agents, which are believed to interfere with mucosal integrity and neuromuscular coordination [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These findings indicate that functional impairment in MRONJ may be driven more strongly by persistent inflammatory burden rather than structural deficit alone. Chronic infection, nociceptive input, and mucosal instability likely interfere with neuromuscular coordination and adaptive oral function. Surgical necrotic bone removal may therefore attenuate inhibitory inflammatory signaling, permitting functional recalibration within the stomatognathic system. Within this framework, surgery can be interpreted not solely as tissue removal, but as an intervention that facilitates re-establishment of biological and functional equilibrium.\u003c/p\u003e \u003cp\u003eRecurrence analyses revealed a layered pattern of risk. Systemic factors\u0026mdash;particularly concomitant chemotherapy\u0026mdash;were the strongest determinants of recurrence occurrence. The reproducibility of these established systemic risk factors strengthens the internal validity of the cohort. Against this background, the directional associations observed for oral functional and periodontal parameters suggest that local mechanical and environmental conditions may further modulate recurrence dynamics beyond systemic susceptibility alone. In contrast, functional parameters were not independent predictors but demonstrated directional trends in time-to-event analyses. Higher occlusal force, greater masticatory performance, and increased tongue pressure were associated with shorter recurrence-free intervals; however, statistical significance was limited by event number. These observations suggest the potential role of mechanical loading in modulating bone stability under pharmacologically suppressed remodeling conditions; however, causal relationships cannot be established in this observational study [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The coexistence of antiresorptive-induced suppression of bone turnover and localized mechanical strain may create a vulnerability window in which adaptive remodeling capacity is exceeded. This mechanobiological interaction warrants further investigation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Reduced salivary flow was significantly associated with earlier recurrence, underscoring the importance of oral environmental stability. Saliva contributes to mucosal defense, microbial homeostasis, and wound healing, and its impairment has been linked to delayed healing and persistent inflammation in head and neck conditions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. To our knowledge, the relationship between reduced salivary flow and MRONJ recurrence has not been specifically examined in previous studies. Collectively, these findings suggest that recurrence dynamics may reflect the interaction among systemic vulnerability, mechanical stress, and environmental homeostasis rather than any single determinant.\u003c/p\u003e \u003cp\u003eCertain limitations should be acknowledged, including the modest sample size and single-center design, which constrained multivariable time-to-event modeling and render mechanistic interpretations hypothesis-generating. Nevertheless, the prospective longitudinal integration of patient-reported and objective functional outcomes provides a clinically relevant framework that may extend beyond this specific cohort. Validation in multicenter settings is warranted. Although the observed associations suggest a potential influence of mechanical loading on postoperative bone stability, the present study was not designed to determine causal mechanisms, and further experimental and biomechanical studies are required.\u003c/p\u003e \u003cp\u003eSurgical MRONJ management restores functional and symptomatic balance. These findings highlight the importance of integrating functional assessment into surgical decision-making and postoperative management strategies for patients with MRONJ. Recurrence dynamics are influenced by systemic vulnerability, mechanical loading, and oral environmental stability. Multidimensional assessment integrating patient-reported outcomes and objective function is recommended. Mechanobiological frameworks can inform individualized postoperative strategies to optimize long-term outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting Interests Statement\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing financial interests.\u003c/p\u003e\n\u003ch2\u003eFunding information\u003c/h2\u003e\n\u003cp\u003eThis research was partially supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (No. 23K093981A).\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contributions\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSachiko YAMASAKI: Contributed to conception, design, data acquisition, analysis, and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eTomoaki SHINTANI: Contributed to design, acquisition, and analysis, critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eKota MORISHITA: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eFumitaka OBAYASHI: Contributed to conception and acquisition, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eNami OBAYASHI: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eTamamo MATSUYAMA: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eNatsuki EBOSHIDA: Contributed to conception and analysis, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eKensaku MATSUI: Contributed to conception and analysis, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eMirai HIGAKI: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eAtsuko HAMADA: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eNanako ITO: Contributed to conception and analysis, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eKoichi KOIZUMI: Contributed to conception and acquisition, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eMikihito KAJIYA: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eSouichi YANAMOTO: Contributed to conception and interpretation, drafted and critically revised manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors gave their final approval and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe would like to thank Dr. Hiromi Nishi for patient referrals and treatment support.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to ethical and privacy restrictions but are available from the corresponding author on reasonable request and with approval of the institutional ethics committee.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOtto, S., Pautke, C., Opelz, C., Niepel, D. \u0026amp; Schi\u0026oslash;dt, M. 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Res.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e, 394\u0026ndash;401. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1359/JBMR.0301243\u003c/span\u003e\u003cspan address=\"10.1359/JBMR.0301243\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2004).\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Osteonecrosis, Quality of Life, Mastication, Saliva, Occlusion, Risk Factors","lastPublishedDoi":"10.21203/rs.3.rs-9101394/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9101394/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAlthough medication-related osteonecrosis of the jaw (MRONJ) is frequently treated surgically, bone resection and tooth loss may compromise oral function. This study longitudinally evaluated patient-reported quality of life (QOL) and objective oral functional parameters following surgical management of MRONJ and explored biological and mechanical factors associated with recurrence. Forty-eight patients with Stage 2\u0026ndash;3 MRONJ underwent surgical management and were prospectively followed. QOL was assessed using a validated MRONJ-specific instrument preoperatively and at 6 months. Objective oral functional parameters were evaluated preoperatively and at 3 and 6 months. Longitudinal changes were analyzed using nonparametric repeated-measures models, and recurrence-related factors were explored using regression analyses.\u003c/p\u003e \u003cp\u003eTotal QOL significantly improved at 6 months. Despite invasive resection procedures, key oral functional parameters remained stable without significant deterioration. Recurrence occurred in 20.8% of patients and was strongly associated with systemic factors, particularly concomitant chemotherapy. Higher masticatory performance, occlusal force, and tongue pressure demonstrated trends toward shorter recurrence-free intervals, suggesting a potential role of mechanical loading. Reduced salivary flow volume was significantly associated with earlier recurrence. These findings suggest that surgical treatment may contribute to restoration of functional equilibrium while highlighting potential biological and mechanical determinants of recurrence.\u003c/p\u003e","manuscriptTitle":"Surgical management of medication-related osteonecrosis of the jaw improves quality of life without deterioration in oral function","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-24 16:59:37","doi":"10.21203/rs.3.rs-9101394/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-22T05:00:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-20T02:44:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-09T20:41:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T22:33:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"273044704249429271628688576729846278782","date":"2026-03-19T18:16:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258230234238322224154524368372706793991","date":"2026-03-19T17:34:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55870165954562799827601176407699583372","date":"2026-03-19T17:12:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T17:07:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-17T16:19:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-14T11:19:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-14T11:18:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-12T07:08:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f7d661a-41ee-4456-89a7-f543639afb6d","owner":[],"postedDate":"March 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64811069,"name":"Health sciences/Diseases"},{"id":64811070,"name":"Health sciences/Health care"},{"id":64811071,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-04-27T11:24:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-24 16:59:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9101394","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9101394","identity":"rs-9101394","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}