Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study

Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study Yi Wang, Yu Zhang, Dengke Li, Wuyang Zhang, Shuming Wang, Xueni Zheng, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6664303/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Dec, 2025 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted 5 You are reading this latest preprint version Abstract Background This article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing mdication-related osteonecrosis of the jaw (MRONJ) through a prospective cohort study. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations. Methods Patients using anti-resorptive agents (ARAs) who required extraction of at least one tooth were included in the study. Patients’ medical history, medication history, and intraoral dental conditions were documented, and CBCT scans were performed. Following a standardized treatment protocol, patients received professional oral cleaning and antibiotics preoperatively. During surgery, minimally invasive extraction and CGF filling were performed with meticulous suturing whenever possible. Postoperatively, mouthwash was used within one month. Follow-up visits were scheduled at 10, 30, and 90 days to monitor and analyze MRONJ incidence and surgical outcomes. Results A total of 103 patients were included in the study, with 20 receiving oral ARAs for osteoporosis, 57 receiving intravenous ARAs for osteoporosis, 13 undergoing combination therapy for osteoporosis, and 13 using ARAs for malignancy. Zoledronic acid and denosumab were the most commonly used drugs. Increased bone density was observed on preoperative CBCT in 32 patients, and on postoperative CBCT at 90 days in 37 patients. In total, 253 teeth were extracted, mostly due to severe defects; periapical periodontitis and periodontitis were also major reasons for extraction. Most patients could not achieve complete and tight suturing. MRONJ developed in 2 patients (at 5 extraction sites), while the remaining patients achieved complete mucosal healing 90 days postoperatively. Notably, the two patients who developed MRONJ did not undergo our comprehensive tooth extraction procedure. Conclusion This prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and maximizes the prevention of MRONJ. Medication-related osteonecrosis of the jaw (MRONJ) Concentrated growth factor (CGF) Tooth extraction Perioperative care Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Medication-related osteonecrosis of the jaw (MRONJ) is a metabolic bone disorder characterized by necrosis of the jawbone. It predominantly develops in patients treated with anti-resorptive agents (ARAs), commonly prescribed for the management of osteoporosis and bone metastases linked to malignancy [ 1 , 2 ]. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined by three criteria: the presence of exposed necrotic bone persisting for more than eight weeks, a history of current or previous exposure to antiresorptive or antiangiogenic agents, and no prior radiation therapy or malignant disease involving the jaws [ 3 ]. MRONJ can manifest through various symptoms, including delayed wound healing, localized gingival erythema, swelling, pain, and recurrent purulent discharge. Additionally, patients may experience jawbone necrosis and, in more severe cases, exposure of necrotic bone and pathological fractures. These complications can significantly diminish a patient's quality of life [ 4 ]. Current management strategies emphasize delayed surgical interventions, such as debridement or segmental resection with reconstruction. However, these approaches are hampered by the difficulty in precisely identifying the borders of necrotic bone during surgery. This often leads to recurrence, persistent functional impairment, and an increased risk for patients with significant comorbidities [ 5 ]. Consequently, the adoption of preventive, pathogenesis-based measures is of critical clinical importance, given their potential to decrease morbidity, prevent disease progression, and preserve patients' overall well-being. MRONJ demonstrates a variable incidence depending on the patient population and dosing regimen, ranging from 0.043–0.215% among osteoporosis patients receiving low-dose ARAs for fracture prevention, and increasing substantially to 0.644–2.731% in individuals with solid tumor bone metastases or multiple myeloma managed with high-dose therapies [ 6 ]. Tooth extraction emerges as the most prevalent local precipitating factor, implicated in approximately 61% of MRONJ cases [ 7 ]; nonetheless, other dental interventions such as bone biopsies, crown lengthening, bone surgeries, implant placement, and chronic inflammatory conditions like untreated periodontitis can also provoke MRONJ by inducing trauma and creating a need for bone remodeling. This physiological process is impaired by ARAs [ 8 – 10 ]. The occurrence of MRONJ is further linked to the inhibition of osteoclast activity, which diminishes the capacity for bone repair, and the suppression of angiogenesis, resulting in reduced blood supply to affected regions [ 11 ]. Moreover, the oral cavity’s complex microbial environment and the disruption of the mucosal barrier during invasive procedures can facilitate infection of the underlying bone tissue [ 12 , 13 ]. Despite these recognized risk factors and mechanisms, the precise pathogenesis of MRONJ remains incompletely understood. If tooth extraction is necessary in patients at risk for MRONJ, several measures can effectively reduce the incidence of this complication. Improving the oral microbial environment through professional cleaning and strict oral hygiene prior to surgery prepares the tissues for optimal healing [ 14 , 15 ]. Employing gentle surgical techniques to minimize trauma, alongside perioperative administration of antimicrobial agents, further lowers the risk of infection and promotes recovery. Together, these preventative strategies provide a practical framework for safely managing tooth extractions in susceptible individuals, thereby enhancing patient outcomes and procedural safety. This article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing MRONJ through a prospective cohort study of 103 patients. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations. 2. Methods 2.1 Study design This prospective cohort study received approval from the Human Subjects Ethics Board of the Fourth Military Medical University, the Third Affiliated Hospital (Decision number: KQ-YJ-2024-086), and was conducted in compliance with the principles outlined in the Declaration of Helsinki (1975), as revised in 2013. To be eligible for inclusion, patients were required to have a history of ARAs use and to necessitate extraction of one or more teeth. Exclusion criteria comprised a history of radiation therapy to the jaws, a history of MRONJ, presence of metastatic disease involving the jaws, inability to tolerate surgical procedures due to physical condition, or failure to complete a three-month postoperative follow-up. All patients sign an informed surgical consent form prior to the procedure. 2.2 Clinical data collection Clinical data collected for each patient included name, age, indication for ARAs use, medication history, dosage and frequency of administration, indication for tooth extraction, and history of other systemic diseases. Cone-beam computed tomography (CBCT) scans were performed preoperatively and at 90 days postoperatively. Clinical intraoral examinations were conducted at 10, 30, and 90 days postoperatively to monitor for the development of MRONJ. The diagnosis of MRONJ was established based on the criteria outlined by the AAOMS guidelines [ 16 ]. 2.3 The comprehensive tooth extraction procedure The comprehensive tooth extraction protocol is depicted in Fig. 1 , with a representative case presented in Fig. 2 . Prior to extraction, patients undergo a thorough medical history evaluation and CBCT scan. One week before surgery, full-mouth dental scaling is performed to reduce oral plaque levels. Two days prior to the surgical procedure, the patient initiated prophylactic antibiotic therapy, consisting of amoxicillin 500 mg administered twice daily and metronidazole 200 mg administered twice daily, to reduce the risk of postoperative infection. With the patient's informed consent, 20 mL of venous blood is collected preoperatively to prepare concentrated growth factor (CGF). All extractions are performed by an experienced specialist. Local anesthesia is achieved with 4% articaine. Extraction instruments are selected according to the specific dental condition to ensure minimally invasive tooth removal. Granulation tissue and any sharp bone spicules are meticulously debrided. The extraction socket is irrigated with saline, after which a piece of CGF gel is placed into the socket, and an additional piece is compressed into a membrane to cover the extraction site. Primary closure of the wound is typically achieved using 4 − 0 non-absorbable sutures; if this is not feasible, wound edges are approximated as closely as possible. Postoperative management includes a five-day course of antibiotics to prevent infection. Patients are advised to rinse with chlorhexidine or tinidazole mouthwash three times daily for one month to minimize oral bacterial load. Sutures are removed 10 days after surgery, and follow-up assessments are conducted at 30 and 90 days to monitor socket healing. ARAs may be resumed one month postoperatively if indicated. 2.4 Statistical Analysis Descriptive statistics were utilized to summarize the characteristics of the patient population. All statistical analyses were conducted using SPSS software, version 29.0 (IBM, Armonk, New York, USA). Patients were categorized based on the route of administration and the therapeutic purpose of ARAs as follows: Group A, oral ARAs for osteoporosis; Group B, intravenous ARAs for osteoporosis; Group C, combination therapy for osteoporosis; and Group D, intravenous ARAs for cancer treatment. The Kruskal-Wallis test was employed to evaluate differences in mucosal healing status among these groups. 3. Results 3.1 Demographic data and medication information A total of 103 patients who received ARAs and underwent tooth extraction at the Third Affiliated Hospital of the Fourth Military Medical University between October 2013 and October 2024 were included in this study, according to specified inclusion and exclusion criteria. Among these, 20 patients took oral medications for osteoporosis, 57 received injectable medications for osteoporosis, 13 underwent combination therapy for osteoporosis, and 13 were treated for cancers via ARAs injections (Table 1 ). The majority of patients (62.13%) were aged 61–80 years, though most (61.54%) cancer-treatment patients were under 60 years. Alendronate (95.00%) was the predominant oral agent, whereas zoledronic acid (47.37%) was most frequently administered via injection. Most patients underwent a single tooth extraction, while a minority required multiple procedures. Another noteworthy observation is the increase in bone density detected through preoperative CBCT imaging in 26 patients, which was documented in 31 patients three months after tooth extraction (Fig. 3 ). These results indicate that bone remodeling and densification are not confined to the postoperative healing period but may also take place before surgical intervention. More detailed patient characteristics are listed in Table 1 . Table 1 Demographic data and medication information of the included patients Characteristic Group A( N = 20) Group B ( N = 57) Group C ( N = 13) Group D ( N = 13) Age groups, No. (%) ≤ 60 years old 6(30.00) 13(22.80) 3(23.08) 8(61.54) 61–80 years old 12(60.00) 39(68.42) 9(69.23) 4(30.77) ≥ 81 years old 2(10.00) 5(8.77) 1(7.69) 1(7.69) Sex, No. (%) Male 3(15.00) 6(10.53) 0(0.00) 3(21.43) Female 17(85.00) 51(89.47%) 13(100.00) 10(76.92) Medication, No. (%) Zoledronic acid 0(0.00) 27(47.37) 10(76.92) 10(76.92) Ibandronic acid 0(0.00) 7(12.28) 8(61.64) 0(0.00) Alendronic acid 19(95.00) 0(0.00) 6(46.15) 0(0.00) Denosumab 0(0.00) 21(36.84) 4(30.77) 0(0.00) Others 1 a (5.00) 2 b (3.51) 3 c (23.08) 3 d (23.08) Combined Dexamethasone, No. (%) Yes 1(5.00) 1(1.75) 0(0.00) 0(0.00) No 19(95.00) 56(98.25) 13(100.00) 13(100.00) Diabetes history, No. (%) Yes 1(5.00) 2(3.51) 0(0.00) 0(0.00) No 19(95.00) 55(96.49) 13(100.00) 13(100.00) Times of tooth extraction, No. (%) 1 16(80.00) 39(68.42) 12(92.31) 8(61.54) 2 4(20.00) 10(17.54) 1(7.69) 4(30.77) ≥ 3 0(0.00) 8(14.04) 0(0.00) 1(7.69) Number of teeth extracted per visit(Mean ± SD) 1.48 ± 0.70 1.65 ± 0.87 1.44 ± 0.59 1.48 ± 0.66 Scaling or not before extraction, No. (%) Yes 20(100.00) 57(100.00) 13(100.00) 11(84.62) No 0(0.00) 0(0.00) 0(0.00) 2(15.38) Types of mouthwash after the surgery, No. (%) Povidone-iodine 12(60.00) 32(56.14) 6(46.15) 13(100.00) Chlorhexidine 3(15.00) 13(22.81) 7(53.85) 0(0.00) Tinidazole 5(25.00) 12(21.05) 0(0.00) 0(0.00) Increased bone density at the extraction site before surgery, No. (%) Yes 5(25.00) 10(17.54) 5(38.46) 6(46.15) No 15(75.00) 47(82.46) 8(61.54) 7(53.85) Increased bone density at the extraction site after surgery, No. (%) Yes 5(25.00) 17(29.82) 3(23.08) 6(46.15) No 15(75.00) 40(70.18) 10(76.92) 7(53.85) *a: Risedronate;b༚Elcatonin、Clodronate༛c༚Carbocalcitonin༛Teriparatide d༚Bevacizumab、Icotinib、Incadronate 3.2 Characteristics of the extracted teeth and MRONJ A total of 253 teeth were removed across various treatment groups, with the highest number in the injectable osteoporosis therapy group (n = 164). Molars accounted for the majority of extractions, and the leading cause was irreparable residual crowns or roots (43.08%). Other significant indications included periapical pathology (22.13%) and periodontitis (20.16%). Surgical procedures frequently involved flap elevation (38.74%) and bone removal with a handpiece (24.51%). CGF was utilized in socket filling for most extractions (96.84%), while a large proportion of sites (75.10%) were not tightly sutured postoperatively. Further surgical details are summarized in Table 2 . In our study, two cancer patients with 5 teeth developed MRONJ after tooth extraction because they concealed their medication history before tooth extraction, and the comprehensive tooth extraction procedure was not followed. These two patients exhibited symptoms including unhealed oral mucosa, purulent discharge, and exposed jawbone, necessitating referral for surgical intervention. Of these two patients, one achieved recovery following a similar comprehensive procedure wherein sequestrectomy was performed instead of tooth extraction. The other required admission to the inpatient department to undergo surgical intervention. The remaining patients showed no evidence of MRONJ. Table 2 Characteristics of the extracted teeth and MRONJ(tooth number = 253) Characteristic Group A( N = 37) Group B ( N = 164) Group C ( N = 21) Group D ( N = 31) Jaws, No. (%) Maxillary 14(37.84) 98(59.76) 11(52.38) 18(58.06) Mandibular 23(62.16) 66(40.24) 10(47.62) 13(41.94) Tooth location, No. (%) Anterior teeth 6(16.22) 42(25.61) 4(19.05) 8(25.81) Premolars 8(21.62) 35(21.34) 3(14.29) 8(25.81) Molars 23(62.16) 87(53.05) 14(66.67) 15(48.39) Dental diagnosis, No. (%) Unrestorable tooth 22(59.46) 67(40.85) 7(33.33) 13(41.94) Apical pathology 7(18.92) 36(21.95) 4(19.50) 9(29.03) Periodontal disease 4(10.81) 35(21.34) 7(33.33) 5(16.13) Pulpitis 1(2.70) 12(7.32) 3(14.29) 0(0.00) Fracture of tooth 2(5.41) 14(8.54) 0(0.00) 3(9.68) Unrestorable implant 1(2.70) 0(0.00) 0(0.00) 0(0.00) Flap surgery, No. (%) Yes 15(40.54) 61(37.20) 14(66.67) 8(25.81) No 22(59.46) 103(62.80) 7(33.33) 23(74.19) Bone remove, No. (%) Yes 4(10.81) 37(22.56) 7(33.33) 14(45.16) No 33(89.19) 127(77.44) 14(66.67) 17(54.84) CGF filling, No. (%) Yes 35(94.59) 164(100.00) 21(100.00) 25(80.65) No 2(5.41) 0(0.00) 0(0.00%) 6(19.35) Tight suturing, No. (%) Yes 6(16.22) 44(26.83) 3(14.29) 10(32.26) No 31(83.78) 120(73.17) 18(85.71) 21(67.74) Postoperative MRONJ at the extraction site, No. (%) Yes 0(0.00) 0(0.00) 0(0.00) 5(16.13) No 37(100.00) 164(100.00) 21(100.00) 26(83.87) 3.3 Oral mucosal healing status of the patients At the time of suture removal, 10 days postoperatively, complete mucosal healing at the extraction sites was not observed in any patients. In group A, 17 extraction sites demonstrated basic mucosal healing. In Group B, 52 extraction sites exhibited basic healing. For patients in group C, only 4 extraction sites achieved basic mucosal healing. Notably, in group D, none of the extraction sites demonstrated satisfactory mucosal healing. Statistical analysis revealed a significant difference in the distribution of basic healing and complete non-healing among the groups (H = 19.395, P < 0.001). At the 30-day postoperative follow-up, complete mucosal healing was observed in 10.81% of extraction sites within Group A. In Group B, 25 extraction sites achieved full mucosal healing. All extraction sites in group C exhibited basically mucosal healing. In the cancer therapy group, 9.68% of extraction sites achieved full mucosal healing. Intergroup comparisons demonstrated a significant difference in the number of fully healed cases among all groups (H = 10.035, P = 0.018), with pairwise analysis indicating a significant difference between Group C and Group B. At the 90-day postoperative follow-up, all extraction sites in group A,B and C had completely healed. However, in group D, five extraction sites developed bone necrosis, with persistent lack of mucosal healing noted. Statistical analysis revealed significant differences in healing outcomes among the groups (H = 36.384, P < 0.001). The five extraction sites in Group D exhibited mucosal non-healing for over two months, with exposed bone surfaces and purulent exudate observed upon palpation. According to the AAOMS diagnostic criteria, these sites were diagnosed as MRONJ, and further surgical intervention is indicated. Details regarding mucosal healing in individual patients are illustrated in Fig. 4 . Notably, some cancer patients were able to continue anti-resorptive therapy without complication. 4. Discussion In this prospective cohort study, 103 patients on ARAs requiring tooth extraction were enrolled. We established a comprehensive tooth extraction procedure after thoroughly examining the risk factors for MRONJ. Notably, no cases of MRONJ occurred among patients who adhered to this protocol. Conversely, MRONJ developed at five extraction sites in two patients who had concealed their history of ARA usage and did not follow the recommended treatment approach. Additionally, extraction-related data were systematically collected and analyzed according to different indications and administration routes of ARAs. The incidence of MRONJ demonstrates significant variability, primarily influenced by factors such as medication type, dosage, and the route of administration, with reported rates ranging from 0.4–21%[ 17 ]. In the treatment of osteoporosis, the selection between oral and intravenous administration of ARAs generally reflects the severity of the patient’s condition, with combination therapy sometimes being indicated. Conversely, for malignancies such as breast cancer and prostate cancer, patients often require higher and more frequent doses of injectable ARAs. Previous research has established a correlation between increased cumulative doses and frequency of ARA use with a heightened risk of MRONJ development [ 18 – 20 ]. Nevertheless, the present study demonstrates that adherence to a standardized surgical protocol facilitates normal post-extraction healing in patients receiving ARAs for osteoporosis, regardless of the administration route. Although patients undergoing combination therapy or being treated for malignancy, who typically receive higher dosages and frequencies, may experience delayed mucosal healing, applying an appropriate surgical protocol appears effective in reducing the risk of MRONJ in these high-risk groups. The clinical manifestations of MRONJ are highly heterogeneous, ranging from asymptomatic presentations to severe pain, soft tissue swelling, infection, and sensory disturbances such as paresthesia [ 21 ]. The prevention of MRONJ, achieved by managing its etiological factors, is paramount for reducing patient morbidity [ 22 ]. Recognized clinical risk factors for MRONJ include both patient- and treatment-related elements, with dental risk factors being particularly prominent; among these, tooth extraction stands out as the most significant risk, followed closely by periodontal disease and pre-existing oral infections, such as periapical conditions. Several studies have highlighted these associations. For instance, Beninati et al. observed that a majority of MRONJ cases were preceded by invasive dental procedures, mainly tooth extractions [ 23 ], while Tardast et al. found a similar prevalence of recent extractions and corticosteroid use among patients with MRONJ [ 24 ]. Furthermore, evidence suggests that the presence of periapical or periodontal infections may independently elevate the risk of MRONJ, regardless of extraction status [ 13 , 25 ]. In light of these findings, our protocol places strong emphasis on infection control, incorporating rigorous preoperative dental cleaning, perioperative antibiotic therapy, the use of non-absorbable sutures, and extended postoperative mouth rinsing. Such measures are designed to minimize bacterial load and mitigate the risk of infection during the critical period before complete healing of the extraction site. Previous reports have emphasized the importance of complete wound closure following tooth extraction to prevent the penetration of bacteria and food debris into the extraction site, sometimes necessitating alveolar bone contouring [ 26 , 27 ]. However, our findings indicate that in the majority of cases (75.19%), tight suturing of extraction sites was not achievable, yet the incidence of MRONJ remained remarkably low. This suggests that, provided oral infection is well-controlled, primary closure may not be indispensable for successful healing. Furthermore, our surgical approach intentionally avoids the unnecessary removal of alveolar bone or elevation of mucoperiosteal flaps in order to maintain the blood supply to the alveolar bone, thereby reducing the likelihood of osteonecrosis. It is well-established that ARAs can negatively affect osteoclast function and bone remodeling [ 7 , 28 ], in addition to possessing anti-angiogenic effects that diminish vascular supply and heighten the risk of MRONJ [ 29 , 30 ]. Consequently, by limiting bone trauma and preserving vascular integrity during surgery, we are able to mitigate the risk of MRONJ to a certain extent. In the present study, venous blood was collected from patients prior to tooth extraction for the preparation of CGF. Following the extraction procedure, CGF was utilized to fill and cover the resultant wound, with the objective of enhancing both soft and hard tissue healing. As a fourth-generation platelet-rich plasma product, CGF has demonstrated bone regeneration potential in previous research and is frequently employed in regenerative periodontal procedures [ 31 ]. By harnessing growth factors, interleukins, and other bioactive components derived from the patient's own blood, CGF effectively fosters localized healing of soft tissues and facilitates bone regeneration. The application of CGF to the extraction socket accelerates gingival closure and thus serves as a barrier against bacterial infiltration, minimizing the risk of infection and protecting the underlying bone tissue [ 32 ]. Notably, for cases in which extraction sites could not be fully closed primarily and bone surfaces remained exposed, the CGF membrane acted as an effective physical barrier, isolating the bone from the oral environment and further promoting favorable postoperative outcomes. For patients suffering from osteoporosis or bone metastases due to malignant tumors, ARAs remain a cornerstone of effective therapy. Given the risk of MRONJ associated with ARAs, it is strongly advised that patients undergo regular dental evaluations both before and throughout the course of ARA treatment. Ideally, dental interventions such as tooth extractions should be completed prior to initiating ARAs therapy. To facilitate proper bone healing, a waiting period of at least four to six weeks, preferably no less than one month, should be observed between the extraction and the commencement of using ARAs [ 33 ]. This precautionary interval significantly reduces the likelihood of MRONJ development. Importantly, any delay in beginning ARAs should only be undertaken after thorough consultation with the patient’s oncologist, ensuring that postponing therapy does not inadvertently contribute to disease progression or other serious complications. Previous research has demonstrated that the selection of surgical techniques significantly affects the incidence rate of MRONJ [ 34 ]. The comprehensive treatment protocol established in this study has shown efficacy in preventing MRONJ, thereby enabling patients undergoing anti-resorptive therapy to receive dental care with reduced anxiety and minimizing the risk of deferring necessary oral treatments due to concerns about developing MRONJ. Nonetheless, continual monitoring of patients' oral health and the potential emergence of MRONJ in the future remains essential to fully evaluate the long-term success and reliability of this preventive approach. In this study, the majority of participants were being treated for osteoporosis, resulting in relatively low dosages and frequencies of ARAs administration. Previous literature indicates that these patients generally exhibit a reduced risk of developing MRONJ. Consequently, it is imperative that subsequent investigations encompass patients receiving anti-resorptive therapy for cancer, to more robustly assess the efficacy of the current treatment protocols. A notable limitation of the present study is the absence of a controlled design; additionally, the low incidence of MRONJ among the sample population presents challenges in elucidating factors associated with its development. Importantly, no distinctive radiographic findings were detected on CBCT imaging for patients using ARAs, regardless of the surgical intervention. Thus, in the absence of MRONJ, reliance on imaging alone does not offer reliable predictive value. Moving forward, our team intends to undertake long-term studies with larger cohorts to better identify contributors to MRONJ risk and to optimize treatment guidelines accordingly. 5. Conclusion This prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and, most importantly, maximizes the prevention of MRONJ. These findings underscore the importance of careful procedural planning and protocol-driven care in reducing adverse outcomes among vulnerable patient populations. Declarations Acknowledgements We gratefully acknowledge the financial support from the General Program of the State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration. We would also like to thank all the participating patients. Author Contributions YW: Conceptualization, data curation, formal analysis, investigation, methodology, resources, writing—original draft, writing—review and editing. YZ: Conceptualization, data curation, formal analysis, investigation, methodology, validation, writing—original draft, writing—review and editing, software. DL: Data curation, formal analysis, software, validation, writing—review and editing. WZ: Conceptualization, formal analysis, methodology, software, writing—review and editing. SW: Data curation, photography. XZ: Data curation, photography. YL: software, writing—review, and editing. TD: surgical procedure guidance, clinical trial consultation. CZ: surgical procedure guidance, clinical trial consultation. LT: surgical procedure guidance, clinical trial consultation.PL: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing—original draft, writing—review, and editing. YX: Conceptualization, surgical operation, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing—original draft, writing—review, and editing. Funding This study was funded the General Program of the State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration (No. 2024MS06). Ethics approval The studies involving human participants were approved by the Ethical Committee of the School of Stomatology at the Fourth Military Medical University in Xi'an, China. Clinical trial number Not applicable. Conflict of Interest The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest. Consent for publication Not applicable. Availability of data and materials Data used within this manuscript are available from the corresponding author on reasonable request. References King R, Tanna N, Patel V. Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab-a review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(4):289–99. Russell RGG. Bisphosphonates: the first 40 years. Bone. 2011;49(1). 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Management of Tooth Extraction in Patients Taking Antiresorptive Drugs: An Evidence Mapping Review and Meta-Analysis. J Clin Med. 2022;12(1). Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 2022;80(5):920–43. Jelin-Uhlig S, Weigel M, Ott B, Imirzalioglu C, Howaldt H-P, Böttger S et al. Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options. Int J Mol Sci. 2024;25(15). Uyanne J, Calhoun CC, Le AD. Antiresorptive drug-related osteonecrosis of the jaw. Dent Clin North Am. 2014;58(2):369–84. Chang J, Hakam AE, McCauley LK. Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw. Curr Osteoporos Rep. 2018;16(5):584–95. Ng TL, Tu MM, Ibrahim MFK, Basulaiman B, McGee SF, Srikanthan A, et al. Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review. Support Care Cancer. 2021;29(2):925–43. McGowan K, Ware RS, Acton C, Ivanovski S, Johnson NW. Both non-surgical dental treatment and extractions increase the risk of medication-related osteonecrosis of the jaw: case-control study. Clin Oral Investig. 2019;23(11):3967–75. McGowan K, McGowan T, Ivanovski S. Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral Dis. 2018;24(4):527–36. Beninati F, Pruneti R, Ficarra G. Bisphosphonate-related osteonecrosis of the jaws (Bronj). Med Oral Patol Oral Cir Bucal. 2013;18(5):e752–8. Tardast A, Sjöman R, Løes S, Abtahi J. Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention, a new way of thinking. J Appl Oral Sci. 2015;23(3):310–4. He L, Sun X, Liu Z, Qiu Y, Niu Y. Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw. Int J Oral Sci. 2020;12(1):30. Spanou A, Nelson K, Ermer MA, Steybe D, Poxleitner P, Voss PJ. Primary wound closure and perioperative antibiotic therapy for prevention of bisphosphonate-related osteonecrosis of the jaw after tooth extraction. Quintessence Int. 2020;51(3):220–8. Otto S, Tröltzsch M, Jambrovic V, Panya S, Probst F, Ristow O, et al. Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development? J Craniomaxillofac Surg. 2015;43(6):847–54. Seluki R, Seluki M, Vaitkeviciene I, Jagelaviciene E. Comparison of the Effectiveness of Conservative and Surgical Treatment of Medication-Related Osteonecrosis of the Jaw: a Systematic Review. J Oral Maxillofac Res. 2023;14(4):e1. Zhou J, Ma X, Wang T, Zhai S. Comparative efficacy of bisphosphonates in short-term fracture prevention for primary osteoporosis: a systematic review with network meta-analyses. Osteoporos Int. 2016;27(11):3289–300. Tang X, Zhang Q, Shi S, Yen Y, Li X, Zhang Y et al. Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha/VEGF signaling pathways in human breast cancer cells. Int J Cancer. 2010;126(1). Besi E, Pitros P. The role of leukocyte and platelet-rich fibrin in the prevention of medication-related osteonecrosis of the jaw, in patients requiring dental extractions: an observational study. Oral Maxillofac Surg. 2024;28(2):785–93. Parise GK, Costa BN, Nogueira ML, Sassi LM, Schussel JL. Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study. Oral Maxillofac Surg. 2023;27(3):507–12. Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(4):433–41. Mehta S, Arya R, Sproat C, Patel V. The provision of dental extractions in patients with established or a history of medication-related osteonecrosis of the jaw. Br Dent J. 2024;237(8):623–8. Cite Share Download PDF Status: Published Journal Publication published 09 Dec, 2025 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted Editorial decision: Major revision 08 Sep, 2025 Reviewers agreed at journal 26 Jul, 2025 Reviewers invited by journal 10 Jun, 2025 Editor assigned by journal 15 May, 2025 First submitted to journal 15 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6664303","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469435051,"identity":"c5cc4470-6575-4fc0-b541-53c73309f7ef","order_by":0,"name":"Yi Wang","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Wang","suffix":""},{"id":469435052,"identity":"ec8a5e28-5fc2-421f-a964-f21f68edf52f","order_by":1,"name":"Yu Zhang","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhang","suffix":""},{"id":469435053,"identity":"61fcff20-2f14-4147-8bcd-ef36b2e83d2b","order_by":2,"name":"Dengke Li","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Dengke","middleName":"","lastName":"Li","suffix":""},{"id":469435054,"identity":"8b1c1e27-6aef-467f-a051-bd01b2765016","order_by":3,"name":"Wuyang Zhang","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of 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University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Li","suffix":""},{"id":469435058,"identity":"30b3191b-378a-4d2e-b9f5-af9758389495","order_by":7,"name":"Tiange Deng","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Tiange","middleName":"","lastName":"Deng","suffix":""},{"id":469435059,"identity":"3f3faeb7-33c0-4ef9-b994-19a5d05d344b","order_by":8,"name":"Chunlin Zong","email":"","orcid":"","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":false,"prefix":"","firstName":"Chunlin","middleName":"","lastName":"Zong","suffix":""},{"id":469435060,"identity":"d4fced8d-dc29-403a-87fa-581639fe61be","order_by":9,"name":"Lei 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Xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYBADfiBmfJBQUUO8FskGBgZmgwdnjpGmhU3yYQszYaUGN5KPSfzcUSuhO+2MWUViAxsDf3t3An7TZ6SlSfaeOS5hdjvH7EbiDhkGiTNnN+DVwi+RYybB23asDqLlDBuDgUQufi1sEvnfJP+2HQPbUpDYxkxYC9AWNmnethqwFgaitEj2PDO2lm07ANSSViyRcOYYD0G/GBxPfnjzbVsdUEvyxo8/Kmrk+Nt78WsBAhYJBobDcB4PIeUgwPyBgaGOGIWjYBSMglEwUgEAmnhJLpNKzIEAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-7804-5730","institution":"Fourth Military Medical University School of Stomatology: Air Force Medical University School of Stomatology","correspondingAuthor":true,"prefix":"","firstName":"Yang","middleName":"","lastName":"Xue","suffix":""}],"badges":[],"createdAt":"2025-05-14 12:45:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6664303/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6664303/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13023-025-04138-9","type":"published","date":"2025-12-09T15:58:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84531803,"identity":"de9d5b4a-faca-4a50-bd53-3fabfdb0e235","added_by":"auto","created_at":"2025-06-13 06:18:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":515278,"visible":true,"origin":"","legend":"\u003cp\u003eThe comprehensive tooth extraction procedure for patients using ARAs medication\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6664303/v1/6520cf63c5a531adbc3a0103.png"},{"id":84531800,"identity":"7a0ab5d4-d2f3-489f-baa2-02bab8565842","added_by":"auto","created_at":"2025-06-13 06:18:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2067247,"visible":true,"origin":"","legend":"\u003cp\u003eClinical tooth extraction surgical steps and mucosal healing conditions postoperatively\u003c/p\u003e\n\u003cp\u003e(\u003cstrong\u003ea\u003c/strong\u003e) Preoperative intraoral condition. (\u003cstrong\u003eb\u003c/strong\u003e) Preoperative CBCT image of the patient. (\u003cstrong\u003ec\u003c/strong\u003e) Immediate intraoral condition after tooth extraction. (\u003cstrong\u003ed\u003c/strong\u003e) The extraction wound was sutured with 4-0 non-absorbable sutures. (\u003cstrong\u003ee\u003c/strong\u003e) Healing condition of the extraction site 10 days postoperatively. (\u003cstrong\u003ef\u003c/strong\u003e) Suture removal. (\u003cstrong\u003eg\u003c/strong\u003e) Healing condition of the extraction site 30 days postoperatively. (\u003cstrong\u003eh\u003c/strong\u003e) Healing condition of the extraction site 90 days postoperatively. (\u003cstrong\u003ei\u003c/strong\u003e)-(\u003cstrong\u003ej\u003c/strong\u003e) CBCT images of the patient at 90 days postoperatively.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6664303/v1/fef26853d6250801d07dfef2.png"},{"id":84531806,"identity":"dec3b8fa-0de2-4b90-9aaf-a39649f29833","added_by":"auto","created_at":"2025-06-13 06:18:56","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":441447,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in bone density observed in the patient's CBCT image\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Pre-extraction imaging. (b) Post-extraction imaging reveals an increase in bone density at the extraction site. (c) Pre-extraction imaging reveals an increase in bone density at the extraction site. (d) Increased bone density showed no significant change postoperatively.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6664303/v1/6f13870b6a59532254b1b989.png"},{"id":84531801,"identity":"46a3e61e-be42-44ee-8158-7707d6a7b079","added_by":"auto","created_at":"2025-06-13 06:18:56","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":68627,"visible":true,"origin":"","legend":"\u003cp\u003eMucosal healing condition of the patients\u003c/p\u003e\n\u003cp\u003eGroup A: Oral ARAs for the treatment of osteoporosis. Group B: Intravenous ARAs for the treatment of osteoporosis. Group C: Combination therapy for the treatment of osteoporosis. Group D: Intravenous ARAs for the treatment of cancers.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6664303/v1/7fbc417425a5a6f69b44698a.png"},{"id":98243998,"identity":"bb6e10b3-2c41-482e-9db6-1150a2dbf2c8","added_by":"auto","created_at":"2025-12-15 16:12:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5188281,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6664303/v1/1da556e3-3f92-4ff9-bb43-46915a65ac79.pdf"}],"financialInterests":"","formattedTitle":"Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMedication-related osteonecrosis of the jaw (MRONJ) is a metabolic bone disorder characterized by necrosis of the jawbone. It predominantly develops in patients treated with anti-resorptive agents (ARAs), commonly prescribed for the management of osteoporosis and bone metastases linked to malignancy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined by three criteria: the presence of exposed necrotic bone persisting for more than eight weeks, a history of current or previous exposure to antiresorptive or antiangiogenic agents, and no prior radiation therapy or malignant disease involving the jaws [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. MRONJ can manifest through various symptoms, including delayed wound healing, localized gingival erythema, swelling, pain, and recurrent purulent discharge. Additionally, patients may experience jawbone necrosis and, in more severe cases, exposure of necrotic bone and pathological fractures. These complications can significantly diminish a patient's quality of life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Current management strategies emphasize delayed surgical interventions, such as debridement or segmental resection with reconstruction. However, these approaches are hampered by the difficulty in precisely identifying the borders of necrotic bone during surgery. This often leads to recurrence, persistent functional impairment, and an increased risk for patients with significant comorbidities [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consequently, the adoption of preventive, pathogenesis-based measures is of critical clinical importance, given their potential to decrease morbidity, prevent disease progression, and preserve patients' overall well-being.\u003c/p\u003e \u003cp\u003eMRONJ demonstrates a variable incidence depending on the patient population and dosing regimen, ranging from 0.043\u0026ndash;0.215% among osteoporosis patients receiving low-dose ARAs for fracture prevention, and increasing substantially to 0.644\u0026ndash;2.731% in individuals with solid tumor bone metastases or multiple myeloma managed with high-dose therapies [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Tooth extraction emerges as the most prevalent local precipitating factor, implicated in approximately 61% of MRONJ cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]; nonetheless, other dental interventions such as bone biopsies, crown lengthening, bone surgeries, implant placement, and chronic inflammatory conditions like untreated periodontitis can also provoke MRONJ by inducing trauma and creating a need for bone remodeling. This physiological process is impaired by ARAs [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The occurrence of MRONJ is further linked to the inhibition of osteoclast activity, which diminishes the capacity for bone repair, and the suppression of angiogenesis, resulting in reduced blood supply to affected regions [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Moreover, the oral cavity\u0026rsquo;s complex microbial environment and the disruption of the mucosal barrier during invasive procedures can facilitate infection of the underlying bone tissue [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite these recognized risk factors and mechanisms, the precise pathogenesis of MRONJ remains incompletely understood.\u003c/p\u003e \u003cp\u003eIf tooth extraction is necessary in patients at risk for MRONJ, several measures can effectively reduce the incidence of this complication. Improving the oral microbial environment through professional cleaning and strict oral hygiene prior to surgery prepares the tissues for optimal healing [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Employing gentle surgical techniques to minimize trauma, alongside perioperative administration of antimicrobial agents, further lowers the risk of infection and promotes recovery. Together, these preventative strategies provide a practical framework for safely managing tooth extractions in susceptible individuals, thereby enhancing patient outcomes and procedural safety.\u003c/p\u003e \u003cp\u003eThis article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing MRONJ through a prospective cohort study of 103 patients. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design\u003c/h2\u003e \u003cp\u003e This prospective cohort study received approval from the Human Subjects Ethics Board of the Fourth Military Medical University, the Third Affiliated Hospital (Decision number: KQ-YJ-2024-086), and was conducted in compliance with the principles outlined in the Declaration of Helsinki (1975), as revised in 2013.\u003c/p\u003e \u003cp\u003eTo be eligible for inclusion, patients were required to have a history of ARAs use and to necessitate extraction of one or more teeth. Exclusion criteria comprised a history of radiation therapy to the jaws, a history of MRONJ, presence of metastatic disease involving the jaws, inability to tolerate surgical procedures due to physical condition, or failure to complete a three-month postoperative follow-up. All patients sign an informed surgical consent form prior to the procedure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Clinical data collection\u003c/h2\u003e \u003cp\u003eClinical data collected for each patient included name, age, indication for ARAs use, medication history, dosage and frequency of administration, indication for tooth extraction, and history of other systemic diseases. Cone-beam computed tomography (CBCT) scans were performed preoperatively and at 90 days postoperatively. Clinical intraoral examinations were conducted at 10, 30, and 90 days postoperatively to monitor for the development of MRONJ. The diagnosis of MRONJ was established based on the criteria outlined by the AAOMS guidelines [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 The comprehensive tooth extraction procedure\u003c/h2\u003e \u003cp\u003eThe comprehensive tooth extraction protocol is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, with a representative case presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Prior to extraction, patients undergo a thorough medical history evaluation and CBCT scan. One week before surgery, full-mouth dental scaling is performed to reduce oral plaque levels. Two days prior to the surgical procedure, the patient initiated prophylactic antibiotic therapy, consisting of amoxicillin 500 mg administered twice daily and metronidazole 200 mg administered twice daily, to reduce the risk of postoperative infection. With the patient's informed consent, 20 mL of venous blood is collected preoperatively to prepare concentrated growth factor (CGF). All extractions are performed by an experienced specialist. Local anesthesia is achieved with 4% articaine. Extraction instruments are selected according to the specific dental condition to ensure minimally invasive tooth removal. Granulation tissue and any sharp bone spicules are meticulously debrided. The extraction socket is irrigated with saline, after which a piece of CGF gel is placed into the socket, and an additional piece is compressed into a membrane to cover the extraction site. Primary closure of the wound is typically achieved using 4\u0026thinsp;\u0026minus;\u0026thinsp;0 non-absorbable sutures; if this is not feasible, wound edges are approximated as closely as possible. Postoperative management includes a five-day course of antibiotics to prevent infection. Patients are advised to rinse with chlorhexidine or tinidazole mouthwash three times daily for one month to minimize oral bacterial load. Sutures are removed 10 days after surgery, and follow-up assessments are conducted at 30 and 90 days to monitor socket healing. ARAs may be resumed one month postoperatively if indicated.\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were utilized to summarize the characteristics of the patient population. All statistical analyses were conducted using SPSS software, version 29.0 (IBM, Armonk, New York, USA). Patients were categorized based on the route of administration and the therapeutic purpose of ARAs as follows: Group A, oral ARAs for osteoporosis; Group B, intravenous ARAs for osteoporosis; Group C, combination therapy for osteoporosis; and Group D, intravenous ARAs for cancer treatment. The Kruskal-Wallis test was employed to evaluate differences in mucosal healing status among these groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Demographic data and medication information\u003c/h2\u003e \u003cp\u003eA total of 103 patients who received ARAs and underwent tooth extraction at the Third Affiliated Hospital of the Fourth Military Medical University between October 2013 and October 2024 were included in this study, according to specified inclusion and exclusion criteria. Among these, 20 patients took oral medications for osteoporosis, 57 received injectable medications for osteoporosis, 13 underwent combination therapy for osteoporosis, and 13 were treated for cancers via ARAs injections (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The majority of patients (62.13%) were aged 61\u0026ndash;80 years, though most (61.54%) cancer-treatment patients were under 60 years. Alendronate (95.00%) was the predominant oral agent, whereas zoledronic acid (47.37%) was most frequently administered via injection. Most patients underwent a single tooth extraction, while a minority required multiple procedures. Another noteworthy observation is the increase in bone density detected through preoperative CBCT imaging in 26 patients, which was documented in 31 patients three months after tooth extraction (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003e). These results indicate that bone remodeling and densification are not confined to the postoperative healing period but may also take place before surgical intervention. More detailed patient characteristics are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eDemographic data and medication information of the included patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup A(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup D\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eAge groups, No. (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;60 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(30.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(22.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(23.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(61.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e61\u0026ndash;80 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(68.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9(69.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(30.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;81 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(8.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(7.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1(7.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(21.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(85.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51(89.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10(76.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedication, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZoledronic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(47.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(76.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10(76.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIbandronic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(61.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlendronic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(95.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(46.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(36.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(30.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003csup\u003ea\u003c/sup\u003e(5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 \u003csup\u003eb\u003c/sup\u003e(3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 \u003csup\u003ec\u003c/sup\u003e(23.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 \u003csup\u003ed\u003c/sup\u003e(23.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCombined Dexamethasone, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(95.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56(98.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes history, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(95.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55(96.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTimes of tooth extraction, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(80.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(68.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(92.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(61.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(20.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(17.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(7.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(30.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(14.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1(7.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of teeth extracted per visit(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eScaling or not before extraction, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11(84.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2(15.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of mouthwash after the surgery, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePovidone-iodine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(56.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(46.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChlorhexidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(22.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(53.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTinidazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(21.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncreased bone density at the extraction site before surgery, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(17.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(38.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6(46.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(75.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47(82.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(61.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7(53.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncreased bone density at the extraction site after surgery, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(29.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(23.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6(46.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(75.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40(70.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(76.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7(53.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*a: Risedronate;b༚Elcatonin、Clodronate༛c༚Carbocalcitonin༛Teriparatide d༚Bevacizumab、Icotinib、Incadronate\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Characteristics of the extracted teeth and MRONJ\u003c/h2\u003e \u003cp\u003eA total of 253 teeth were removed across various treatment groups, with the highest number in the injectable osteoporosis therapy group (n\u0026thinsp;=\u0026thinsp;164). Molars accounted for the majority of extractions, and the leading cause was irreparable residual crowns or roots (43.08%). Other significant indications included periapical pathology (22.13%) and periodontitis (20.16%). Surgical procedures frequently involved flap elevation (38.74%) and bone removal with a handpiece (24.51%). CGF was utilized in socket filling for most extractions (96.84%), while a large proportion of sites (75.10%) were not tightly sutured postoperatively. Further surgical details are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eIn our study, two cancer patients with 5 teeth developed MRONJ after tooth extraction because they concealed their medication history before tooth extraction, and the comprehensive tooth extraction procedure was not followed. These two patients exhibited symptoms including unhealed oral mucosa, purulent discharge, and exposed jawbone, necessitating referral for surgical intervention. Of these two patients, one achieved recovery following a similar comprehensive procedure wherein sequestrectomy was performed instead of tooth extraction. The other required admission to the inpatient department to undergo surgical intervention. The remaining patients showed no evidence of MRONJ.\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\u003e\u003cb\u003eCharacteristics of the extracted teeth and MRONJ(tooth number\u0026thinsp;=\u0026thinsp;253)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup A(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;164)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup D\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eJaws, No. (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaxillary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(37.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98(59.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(52.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18(58.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMandibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(62.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66(40.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(47.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(41.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTooth location, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior teeth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(16.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(25.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(25.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremolars\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(21.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(21.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(25.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolars\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(62.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87(53.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15(48.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDental diagnosis, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnrestorable tooth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(59.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(40.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(41.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApical pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(18.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(21.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(19.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9(29.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriodontal disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(10.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(21.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(16.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulpitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(7.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFracture of tooth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(8.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3(9.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnrestorable implant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFlap surgery, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(40.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61(37.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8(25.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(59.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103(62.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23(74.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBone remove, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(10.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(22.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14(45.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(89.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127(77.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17(54.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCGF filling, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(94.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25(80.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6(19.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTight suturing, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(16.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44(26.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10(32.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(83.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120(73.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(85.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21(67.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative MRONJ at the extraction site, No. (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(16.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26(83.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Oral mucosal healing status of the patients\u003c/h2\u003e \u003cp\u003eAt the time of suture removal, 10 days postoperatively, complete mucosal healing at the extraction sites was not observed in any patients. In group A, 17 extraction sites demonstrated basic mucosal healing. In Group B, 52 extraction sites exhibited basic healing. For patients in group C, only 4 extraction sites achieved basic mucosal healing. Notably, in group D, none of the extraction sites demonstrated satisfactory mucosal healing. Statistical analysis revealed a significant difference in the distribution of basic healing and complete non-healing among the groups (H\u0026thinsp;=\u0026thinsp;19.395, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAt the 30-day postoperative follow-up, complete mucosal healing was observed in 10.81% of extraction sites within Group A. In Group B, 25 extraction sites achieved full mucosal healing. All extraction sites in group C exhibited basically mucosal healing. In the cancer therapy group, 9.68% of extraction sites achieved full mucosal healing. Intergroup comparisons demonstrated a significant difference in the number of fully healed cases among all groups (H\u0026thinsp;=\u0026thinsp;10.035, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018), with pairwise analysis indicating a significant difference between Group C and Group B.\u003c/p\u003e \u003cp\u003eAt the 90-day postoperative follow-up, all extraction sites in group A,B and C had completely healed. However, in group D, five extraction sites developed bone necrosis, with persistent lack of mucosal healing noted. Statistical analysis revealed significant differences in healing outcomes among the groups (H\u0026thinsp;=\u0026thinsp;36.384, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The five extraction sites in Group D exhibited mucosal non-healing for over two months, with exposed bone surfaces and purulent exudate observed upon palpation. According to the AAOMS diagnostic criteria, these sites were diagnosed as MRONJ, and further surgical intervention is indicated. Details regarding mucosal healing in individual patients are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Notably, some cancer patients were able to continue anti-resorptive therapy without complication.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this prospective cohort study, 103 patients on ARAs requiring tooth extraction were enrolled. We established a comprehensive tooth extraction procedure after thoroughly examining the risk factors for MRONJ. Notably, no cases of MRONJ occurred among patients who adhered to this protocol. Conversely, MRONJ developed at five extraction sites in two patients who had concealed their history of ARA usage and did not follow the recommended treatment approach. Additionally, extraction-related data were systematically collected and analyzed according to different indications and administration routes of ARAs.\u003c/p\u003e \u003cp\u003eThe incidence of MRONJ demonstrates significant variability, primarily influenced by factors such as medication type, dosage, and the route of administration, with reported rates ranging from 0.4\u0026ndash;21%[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In the treatment of osteoporosis, the selection between oral and intravenous administration of ARAs generally reflects the severity of the patient\u0026rsquo;s condition, with combination therapy sometimes being indicated. Conversely, for malignancies such as breast cancer and prostate cancer, patients often require higher and more frequent doses of injectable ARAs. Previous research has established a correlation between increased cumulative doses and frequency of ARA use with a heightened risk of MRONJ development [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Nevertheless, the present study demonstrates that adherence to a standardized surgical protocol facilitates normal post-extraction healing in patients receiving ARAs for osteoporosis, regardless of the administration route. Although patients undergoing combination therapy or being treated for malignancy, who typically receive higher dosages and frequencies, may experience delayed mucosal healing, applying an appropriate surgical protocol appears effective in reducing the risk of MRONJ in these high-risk groups.\u003c/p\u003e \u003cp\u003eThe clinical manifestations of MRONJ are highly heterogeneous, ranging from asymptomatic presentations to severe pain, soft tissue swelling, infection, and sensory disturbances such as paresthesia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The prevention of MRONJ, achieved by managing its etiological factors, is paramount for reducing patient morbidity [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Recognized clinical risk factors for MRONJ include both patient- and treatment-related elements, with dental risk factors being particularly prominent; among these, tooth extraction stands out as the most significant risk, followed closely by periodontal disease and pre-existing oral infections, such as periapical conditions. Several studies have highlighted these associations. For instance, Beninati et al. observed that a majority of MRONJ cases were preceded by invasive dental procedures, mainly tooth extractions [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], while Tardast et al. found a similar prevalence of recent extractions and corticosteroid use among patients with MRONJ [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Furthermore, evidence suggests that the presence of periapical or periodontal infections may independently elevate the risk of MRONJ, regardless of extraction status [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In light of these findings, our protocol places strong emphasis on infection control, incorporating rigorous preoperative dental cleaning, perioperative antibiotic therapy, the use of non-absorbable sutures, and extended postoperative mouth rinsing. Such measures are designed to minimize bacterial load and mitigate the risk of infection during the critical period before complete healing of the extraction site.\u003c/p\u003e \u003cp\u003ePrevious reports have emphasized the importance of complete wound closure following tooth extraction to prevent the penetration of bacteria and food debris into the extraction site, sometimes necessitating alveolar bone contouring [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, our findings indicate that in the majority of cases (75.19%), tight suturing of extraction sites was not achievable, yet the incidence of MRONJ remained remarkably low. This suggests that, provided oral infection is well-controlled, primary closure may not be indispensable for successful healing. Furthermore, our surgical approach intentionally avoids the unnecessary removal of alveolar bone or elevation of mucoperiosteal flaps in order to maintain the blood supply to the alveolar bone, thereby reducing the likelihood of osteonecrosis. It is well-established that ARAs can negatively affect osteoclast function and bone remodeling [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], in addition to possessing anti-angiogenic effects that diminish vascular supply and heighten the risk of MRONJ [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Consequently, by limiting bone trauma and preserving vascular integrity during surgery, we are able to mitigate the risk of MRONJ to a certain extent.\u003c/p\u003e \u003cp\u003eIn the present study, venous blood was collected from patients prior to tooth extraction for the preparation of CGF. Following the extraction procedure, CGF was utilized to fill and cover the resultant wound, with the objective of enhancing both soft and hard tissue healing. As a fourth-generation platelet-rich plasma product, CGF has demonstrated bone regeneration potential in previous research and is frequently employed in regenerative periodontal procedures [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. By harnessing growth factors, interleukins, and other bioactive components derived from the patient's own blood, CGF effectively fosters localized healing of soft tissues and facilitates bone regeneration. The application of CGF to the extraction socket accelerates gingival closure and thus serves as a barrier against bacterial infiltration, minimizing the risk of infection and protecting the underlying bone tissue [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Notably, for cases in which extraction sites could not be fully closed primarily and bone surfaces remained exposed, the CGF membrane acted as an effective physical barrier, isolating the bone from the oral environment and further promoting favorable postoperative outcomes.\u003c/p\u003e \u003cp\u003eFor patients suffering from osteoporosis or bone metastases due to malignant tumors, ARAs remain a cornerstone of effective therapy. Given the risk of MRONJ associated with ARAs, it is strongly advised that patients undergo regular dental evaluations both before and throughout the course of ARA treatment. Ideally, dental interventions such as tooth extractions should be completed prior to initiating ARAs therapy. To facilitate proper bone healing, a waiting period of at least four to six weeks, preferably no less than one month, should be observed between the extraction and the commencement of using ARAs [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. This precautionary interval significantly reduces the likelihood of MRONJ development. Importantly, any delay in beginning ARAs should only be undertaken after thorough consultation with the patient\u0026rsquo;s oncologist, ensuring that postponing therapy does not inadvertently contribute to disease progression or other serious complications.\u003c/p\u003e \u003cp\u003ePrevious research has demonstrated that the selection of surgical techniques significantly affects the incidence rate of MRONJ [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The comprehensive treatment protocol established in this study has shown efficacy in preventing MRONJ, thereby enabling patients undergoing anti-resorptive therapy to receive dental care with reduced anxiety and minimizing the risk of deferring necessary oral treatments due to concerns about developing MRONJ. Nonetheless, continual monitoring of patients' oral health and the potential emergence of MRONJ in the future remains essential to fully evaluate the long-term success and reliability of this preventive approach.\u003c/p\u003e \u003cp\u003eIn this study, the majority of participants were being treated for osteoporosis, resulting in relatively low dosages and frequencies of ARAs administration. Previous literature indicates that these patients generally exhibit a reduced risk of developing MRONJ. Consequently, it is imperative that subsequent investigations encompass patients receiving anti-resorptive therapy for cancer, to more robustly assess the efficacy of the current treatment protocols. A notable limitation of the present study is the absence of a controlled design; additionally, the low incidence of MRONJ among the sample population presents challenges in elucidating factors associated with its development. Importantly, no distinctive radiographic findings were detected on CBCT imaging for patients using ARAs, regardless of the surgical intervention. Thus, in the absence of MRONJ, reliance on imaging alone does not offer reliable predictive value. Moving forward, our team intends to undertake long-term studies with larger cohorts to better identify contributors to MRONJ risk and to optimize treatment guidelines accordingly.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and, most importantly, maximizes the prevention of MRONJ. These findings underscore the importance of careful procedural planning and protocol-driven care in reducing adverse outcomes among vulnerable patient populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the financial support from the General Program of the State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration. We would also like to thank all the participating patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYW: Conceptualization, data curation, formal analysis, investigation, methodology, resources, writing\u0026mdash;original draft, writing\u0026mdash;review and editing. YZ: Conceptualization, data curation, formal analysis, investigation, methodology, validation, writing\u0026mdash;original draft, writing\u0026mdash;review and editing, software. DL: Data curation, formal analysis, software, validation, writing\u0026mdash;review and editing. WZ: Conceptualization, formal analysis, methodology, software, writing\u0026mdash;review and editing. SW: Data curation, photography. XZ: Data curation, photography. YL: software, writing\u0026mdash;review, and editing. TD: surgical procedure guidance, clinical trial consultation. CZ: surgical procedure guidance, clinical trial consultation. LT: surgical procedure guidance, clinical trial consultation.PL: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing\u0026mdash;original draft, writing\u0026mdash;review, and editing. YX: Conceptualization, surgical operation, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing\u0026mdash;original draft, writing\u0026mdash;review, and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded the General Program of the State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration (No. 2024MS06).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were approved by the Ethical Committee of the School of Stomatology at the Fourth Military Medical University in Xi\u0026apos;an, China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData used within this manuscript are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKing R, Tanna N, Patel V. 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Br Dent J. 2024;237(8):645\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu C, Xiong Y-T, Zhu T, Liu W, Tang W, Zeng W. Management of Tooth Extraction in Patients Taking Antiresorptive Drugs: An Evidence Mapping Review and Meta-Analysis. J Clin Med. 2022;12(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 2022;80(5):920\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJelin-Uhlig S, Weigel M, Ott B, Imirzalioglu C, Howaldt H-P, B\u0026ouml;ttger S et al. Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options. Int J Mol Sci. 2024;25(15).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUyanne J, Calhoun CC, Le AD. Antiresorptive drug-related osteonecrosis of the jaw. Dent Clin North Am. 2014;58(2):369\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang J, Hakam AE, McCauley LK. Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw. Curr Osteoporos Rep. 2018;16(5):584\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNg TL, Tu MM, Ibrahim MFK, Basulaiman B, McGee SF, Srikanthan A, et al. Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review. Support Care Cancer. 2021;29(2):925\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGowan K, Ware RS, Acton C, Ivanovski S, Johnson NW. Both non-surgical dental treatment and extractions increase the risk of medication-related osteonecrosis of the jaw: case-control study. 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Oral Maxillofac Surg. 2024;28(2):785\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParise GK, Costa BN, Nogueira ML, Sassi LM, Schussel JL. Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study. Oral Maxillofac Surg. 2023;27(3):507\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(4):433\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta S, Arya R, Sproat C, Patel V. The provision of dental extractions in patients with established or a history of medication-related osteonecrosis of the jaw. Br Dent J. 2024;237(8):623\u0026ndash;8.\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":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Medication-related osteonecrosis of the jaw (MRONJ), Concentrated growth factor (CGF), Tooth extraction, Perioperative care","lastPublishedDoi":"10.21203/rs.3.rs-6664303/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6664303/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing mdication-related osteonecrosis of the jaw (MRONJ) through a prospective cohort study. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients using anti-resorptive agents (ARAs) who required extraction of at least one tooth were included in the study. Patients\u0026rsquo; medical history, medication history, and intraoral dental conditions were documented, and CBCT scans were performed. Following a standardized treatment protocol, patients received professional oral cleaning and antibiotics preoperatively. During surgery, minimally invasive extraction and CGF filling were performed with meticulous suturing whenever possible. Postoperatively, mouthwash was used within one month. Follow-up visits were scheduled at 10, 30, and 90 days to monitor and analyze MRONJ incidence and surgical outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 103 patients were included in the study, with 20 receiving oral ARAs for osteoporosis, 57 receiving intravenous ARAs for osteoporosis, 13 undergoing combination therapy for osteoporosis, and 13 using ARAs for malignancy. Zoledronic acid and denosumab were the most commonly used drugs. Increased bone density was observed on preoperative CBCT in 32 patients, and on postoperative CBCT at 90 days in 37 patients. In total, 253 teeth were extracted, mostly due to severe defects; periapical periodontitis and periodontitis were also major reasons for extraction. Most patients could not achieve complete and tight suturing. MRONJ developed in 2 patients (at 5 extraction sites), while the remaining patients achieved complete mucosal healing 90 days postoperatively. Notably, the two patients who developed MRONJ did not undergo our comprehensive tooth extraction procedure.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and maximizes the prevention of MRONJ.\u003c/p\u003e","manuscriptTitle":"Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-13 06:18:51","doi":"10.21203/rs.3.rs-6664303/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-09-08T16:40:26+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-07-26T12:36:41+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-10T20:47:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-16T01:35:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2025-05-15T09:47:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b157f3e0-1e6f-4bf1-a7f2-248d702b6ab0","owner":[],"postedDate":"June 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:04:47+00:00","versionOfRecord":{"articleIdentity":"rs-6664303","link":"https://doi.org/10.1186/s13023-025-04138-9","journal":{"identity":"orphanet-journal-of-rare-diseases","isVorOnly":false,"title":"Orphanet Journal of Rare Diseases"},"publishedOn":"2025-12-09 15:58:58","publishedOnDateReadable":"December 9th, 2025"},"versionCreatedAt":"2025-06-13 06:18:51","video":"","vorDoi":"10.1186/s13023-025-04138-9","vorDoiUrl":"https://doi.org/10.1186/s13023-025-04138-9","workflowStages":[]},"version":"v1","identity":"rs-6664303","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6664303","identity":"rs-6664303","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}