Risk Factors for Dry Socket After Mandibular Third Molar Extraction: A Prospective Cohort Study

Risk Factors for Dry Socket After Mandibular Third Molar Extraction: 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 Risk Factors for Dry Socket After Mandibular Third Molar Extraction: A Prospective Cohort Study Ziang Zhuo, Renhuan Huang, Jiaruo Qin, Chengmin Lin, Liyan Lu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7749745/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Dry socket (DS) is one of the most distressing complications following tooth extraction, particularly after surgical removal of mandibular third molars. The etiology of DS remains unclear and involves a complex interplay of infection, immune responses, and multiple contributing factors. Therefore, the primary objective of this study was to investigate the risk factors associated with DS. Material and Methods This prospective, single-center, case-control study enrolled adult patients requiring mandibular third molar extraction. A series of questionnaires were administered to collect data on demographics, calculus index (CI), smoking habits, menstrual cycle, medication use, molar status, operative duration, as well as sleep duration and regularity. Associations were analyzed using the Chi-Square Test. Result The study included 579 mandibular third molars from 559 patients. Among these, 36 sites (6.2%) developed DS. Factors such as gender, CI, smoking habits, menstrual cycle, medication use, molar status, and operation duration were not significantly associated with DS. However, patients with insufficient and irregular sleep exhibited a significantly higher incidence of DS (P ≤ 0.01). Conclusions Sleep insufficiency and irregularity may be risk factors for DS, though the underlying physiological mechanisms require further investigation. Mandibular Third Molar Dry socket Sleep Insufficiency Sleep Irregularity Prospective Cohort Study Figures Figure 1 Figure 2 Figure 3 Introduction Dry socket (DS), also known as alveolar osteitis or fibrinolytic osteitis, is one of the most suffering complications following tooth extraction in dental practice. DS typically occurs within one to four days after extraction [ 1 – 3 ] . The incidence of DS ranges from 1% to 5% in routine extraction practice, with a higher prevalence in the mandible than in the maxilla—particularly after surgical extraction of third molars, where the incidence can reach up to 30% [ 4 , 5 ] . Clinical manifestations include an empty socket with exposed alveolar bone, severe pain radiating to the neck and head—often worsening at night—with or without halitosis and lymph node enlargement. The pain associated with DS is frequently refractory to common analgesics, causing patients to wake frequently during the night [ 6 – 8 ] . The pathophysiology of alveolar osteitis is highly complex and not fully understood. The most widely accepted theory is fibrinolysis theory [ 9 ] , wherein excessive release of tissue-type plasminogen activator (tPA), due to trauma or inflammation, activates plasminogen to form plasmin, which degrades fibrin within the blood clot. This results in exposure of the alveolar bone and superficial osteitis. The absence, abnormal formation, or premature disintegration of the blood clot via fibrinolysis is considered the primary mechanism [ 10 – 12 ] . DS is attributed to various factors, including overall health status, lifestyle habits, and oral infection. Multiple risk factors have been reported, such as gender, menstrual cycle, age, smoking, oral contraceptive use, bacterial profile, extraction site, procedure complexity, surgical technique, poor oral hygiene, vasoconstrictor use, anesthesia volume, inadequate intraoperative irrigation, and patient non-compliance, though some remain controversial [ 12 – 22 ] . Fibrinolytic activity may also be influenced by periodontal bacteria such as Treponema denticola, Streptococcusspp., Prevotella, Bacteroides, and Peptostreptococcus [ 23 , 24 ] . Patients who developed alveolar osteitis after dental extractions are reported to harbor a different microbiota compared to those without postoperative complications [ 4 ] . Several studies have indicated that both topical and systemic applications of antibiotics and antiseptics can significantly reduce the incidence of this complication [ 21 , 25 , 26 ] , though the role of bacteria remains inconclusive. The initiating factor for fibrinolytic activation is unclear. In our clinical practice, we have observed a lower incidence of DS than that reported in the literature. Interestingly, many DS patients reported insufficient sleep duration and irregular sleep patterns within 0–2 days after extraction. Previous studies have shown that insufficient sleep is associated with reduced nitric oxide-mediated endothelium-dependent vasodilation and endothelial tPA release in hypertensive adults [ 27 ] . We therefore hypothesized that short sleep duration and irregular sleep following tooth extraction may be associated with DS. Thus, the primary aim of this study was to investigate the association between various risk factors and DS, with a specific focus on sleep duration and regularity. Material and Methods Subjects We conducted a prospective, single-center, case-control study to investigate potential risk factors for DS in patients undergoing mandibular third molar extraction at the Department of Stomatology, Shanghai Tenth People's Hospital. The study protocol was reviewed and approved by the Ethics Committee of Shanghai Tenth People's Hospital (No. SHSY-ICE-5.0/24k149/P01) and registered with the Chinese Clinical Trial Registry (No. ChiCTR2200056556). This study conforms with the ethical standards as laid out in the 1964 Declaration of Helsinki and its later amendments, and compliant with the Strengthening the Reporting of Observational Studies (STROBE) guidelines[28]. Participants provided written informed consent prior to taking part in the study (Appendix 1).The flowchart is presented in Fig. 1 . Patients aged over 18 years who were scheduled for mandibular third molar extraction were consecutively enrolled between September 1, 2024, and January 31, 2025. Exclusion criteria were as follows: Patients unwilling or unable to return for follow-up or participate in telephone interviews; Women who were pregnant or breastfeeding; Patients taking medications that may impair wound healing (e.g., immunosuppressants, steroids, bisphosphonates); Presence of a cyst at the extraction site, considering curettage may cause additional trauma; Acute pulpitis in adjacent teeth. Criteria for DS DS was diagnosed [ 15 , 29 ] based on patient complaints and clinical examination: Severe pain around the extraction site, typically more intense than on the first postoperative day and often worsening at night, with or without radiation to the neck and head; With or without halitosis; Empty socket with exposed bone walls. Pre-operation Comprehensive epidemiological data were collected preoperatively, including age, gender, smoking habits, menstrual cycle (for women), and medication use. Oral hygiene was assessed using the calculus index (CI). Questionnaires were presented in Appendix 1. The status of the mandibular third molar was evaluated via clinical and radiographic examination and classified into three categories: fully or partially erupted (Class I), fully soft tissue impacted (Class II), and fully bone impacted (Class III), as illustrated in Fig. 2 . Surgical complexity generally increases from Class I to Class III. Intraoperation All procedures were performed by the same dentist to minimize bias. Operative duration and complexity were recorded. Key surgical techniques including 1) flap elevation, 2) odontosection and 3) osteotomy, were applied individually or in combination as needed: Combination A: none of the three techniques; Combination B: flap elevation only; Combination C: odontosection only; Combination D: flap elevation and odontosection; Combination E: all three techniques. Post-operation All patients were prescribed cephalosporin (0.25g, orally, four times daily), ibuprofen (0.3g, orally, as needed), and compound chlorhexidine mouthwash (5mL, gargle, three times daily). Detailed postoperative care instructions were provided. Pain (using a visual analogue scale, VAS) and swelling were recorded via follow-up phone calls on postoperative days 1, 3, and 7. Patients were also asked to recall their sleep onset time and total sleep duration on the first and second nights after surgery. Sleep duration of less than 7 hours per night was considered insufficient [ 48 ] , and sleep onset delayed by more than 2 hours relative to the usual time was considered irregular [ 49 ] . Daily sufficient sleep was scored as 0, insufficient as 1; regular sleep as 0, irregular as 1, respectively. Total scores for sleep duration and regularity on postoperative days 1 and 2 were recorded and analyzed. Patients with suspected DS, bleeding, inflammation, or other complications were scheduled for follow-up as needed until complete resolution. Treatment of DS In cases of DS, the socket was irrigated alternately with hydrogen peroxide and sterile saline, then coated with Periocline ointment (Lederle, USA). Data and Analysis Data recording was performed by a nurse, and statistical analysis was conducted independently by another dentist. Data were analyzed using SPSS version 25 (IBM, USA). Descriptive statistics (frequencies and percentages) were used to characterize the study population. The Chi-Square test and Fisher's Exact test were applied for categorical variables (e.g., age, gender, smoking, tooth status, surgical variables, menstrual cycle, CI, operative duration). A p-value ≤ 0.05 was considered statistically significant. Result A total of 559 patients with 579 mandibular third molars were included (20 patients underwent bilateral extractions during the same visit). Among these, 439 molars (75.8%) were from female patients and 140 (24.2%) from male patients. The mean age was 30.7 years (range: 18–69). DS occurred at 36 extraction sites (6.2%). Among the 40 extraction sites from bilateral procedures, 3 sites (7.5%) in 3 patients developed DS. No patient developed bilateral DS. Epidemiological data are summarized in Table 1 . Table 1 Epidemiological data of the study. Variable Molars(%) DS P Sex Male 140 6(4.3%) 0.277 Female 439 30(6.8%) Age 18-34y 472 31(6.6%) 0.800 35-49y 89 3(3.4%) 50-64y 15 1(6.7%) 65y- 3 0(0.0%) Smoking Yes 25 1(4.0%) 0.963 No 554 35(6.3%) Contraceptive (only women) Yes 1 1(100.0%) 0.068 No 438 29(6,6%) Menstrual Cycles follicular phase 153 10(6.5%) 0.486 ovulatory phase 58 4(6.9%) luteal phase 159 9(5.7%) irregular menstruation 57 5(8.8%) Postpartum amenorrhea 2 0(0.0%) pausimenia 10 2(2.0%) CI 0 219 12(5.8%) 0.041 1 201 19(9.5%) 2 159 5(3.1%) Classification of The Mandibular Third Molar Ⅰ(fully or partially erupted) 383 24(6.3%) 0.983 Ⅱ( fully tissue impacted) 135 8(5.9%) Ⅲ(fully bone impacted) 61 4(6.6%) Technique Complexity None 122 8(6.6%) 0.819 flap elevation 54 5(9.3%) odontosection 119 6(5.0%) flap elevation + odontosection 181 12(6.6%) flap elevation + odontosection + oste-otomy 103 5(4,9%) Operation Duration ≤ 5min 362 21(5.8%) 0.417 6 ~ 10min 129 7(5.4%) 11-20min 75 8(10.7%) 21 ~ 30min 12 0(0.0%) ≥ 31min 1 0(0.0%) Sleep Duration 0 515 19(3.7%) < 0.001 1 23 3(13.0%) 2 41 14(34.1%) Sleep Regularity 0 527 22(4.2%) < 0.001 1 31 2(6.5%) 2 21 12(57.1%) Following treatment, 35 patients experienced significant pain relief without requiring additional visits; only one female patient required a second dressing. Among the 439 sites in female patients, 30 developed DS (incidence 6.8%). Among the 140 sites in male patients, 6 developed DS (incidence 4.3%). The difference was not statistically significant (P = 0.277). Only one female patient reported using oral contraceptives, and she developed DS. Although DS occurrence was higher in women, suggesting a possible hormonal influence, sub-analysis of menstrual cycle phases (follicular, ovulatory, luteal, irregular menstruation, postpartum amenorrhea, and postmenopause) showed no significant association with DS (P = 0.486). One of the 25 sites from smokers developed DS, compared to 35 of the 554 sites from non-smokers. The difference was not statistically significant (P = 0.963). Molars were categorized by surgical difficulty. Operation duration ranged from 1 to 40 minutes (mean 5.8 minutes). None of the surgical variables showed a significant association with DS. Regarding sleep duration, DS occurred in 3 of 24 sites (13.0%) with a score of 1, and 14 of 41 sites (34.0%) with a score of 2—significantly higher than in the score 0 group (P < 0.01). Similarly, sleep irregularity was associated with a higher incidence of DS. Results are summarized in Table 2 . Table 2 Sleep duration and irregularity scores and DS occurrence. Variable DS(n = 543) Healthy socket(n = 36) p-value Sleep duration 0 496 19 / 1 20 3 0.027 2 27 14 < 0.001 Sleep regularity 0 505 22 / 1 29 2 0.537 2 9 12 < 0.001 Other variables, including age, surgical technique, and operation duration, showed no significant association with DS. Discussion This study collected basic epidemiological data and possible risk factors related to DS. For the first time, we identified a significant association between DS and both sleep duration and irregularity following mandibular third molar extraction. The incidence of DS in our study was 6.2%, consistent with recent reports [ 29 ] . Previous studies indicate that DS occurs in 1–5% of routine extractions, with incidence after mandibular third molar extraction ranging from 4.6% to 17% [ 4 , 29 – 31 ] . This variability may be due to differences in assessment methods, patient characteristics, and multifactorial influences on bone healing [ 20 ] . No significant gender difference was observed, consistent with some previous studies [ 8 ] , though others have reported conflicting results [ 32 – 34 ] . The discrepancy may be due to unaccounted variables such as menstrual cycle, hormonal levels, or specific medications [ 11 ] . Oral contraceptives are believed to increase DS risk [ 35 , 36 ] .Only one patient in our study used them, and she developed DS. Interestingly, she had also experienced DS after a previous extraction at our hospital over two years ago. Although menstrual cycle has been proposed to influence DS risk via fluctuation of estrogen level [ 37 ] , we found no significant association. Smoking is widely reported to impair wound healing [ 2 , 11 , 38 ] via mechanisms possibly involving nicotine, cotinine, carbon monoxide, and hydrogen cyanide. Contrary to expectations, our results showed a slightly higher—though not significant—DS incidence among non-smokers. Rakhshan [ 11 ] believed that smoking may confound gender effects due to higher smoking rates among men. Surgical trauma and difficulty were often cited as risk factors [ 39 ] . Contrary to our hypothesis, we found no significant association between DS and surgical difficulty. This may be due to better soft tissue coverage, suturing, and socket closure in more complex cases. No relationship was found between CI and DS. The role of bacteria in DS warrants further investigation [ 1 , 40 ] . Sleep plays a critical role in circadian rhythm and overall health. Cellular circadian dynamics have been shown to influence wound healing via fibroblast activity [ 41 ] . Sleep duration and regularity are key indicators of sleep quality [ 42 ] . Adequate and regular sleep improves memory, emotional regulation, metabolic function, energy balance, and immune response [ 43 – 47 ] , and helps maintain stress-recovery balance via the hypothalamic-pituitary-adrenal axis [ 47 ] . Sleep duration less than seven hours was considered insufficient sleep [ 48 ] , and sleep onset time two hours later than usual was considered irregular sleep [ 49 ] .Sleep deprivation has been shown to impair endothelial tPA release via nitric oxide-mediated pathways [ 50 ] . Given that increased fibrinolytic activity due to tPA is a key mechanism in DS, sleep disturbances may disrupt circadian rhythms and impede healing. Our results suggest that insufficient and irregular sleep are associated with higher DS incidence. However, the molecular mechanisms require further study. Limitations of this study include a relatively small sample size and imbalanced gender distribution, which may introduce bias. Future studies with larger samples are needed. Additionally, sleep data were self-reported and subject to recall bias. Objective measures such as polysomnography should be used in future research. Conclusion In summary, this prospective, single-center, case-control study suggests that sleep insufficiency and irregularity may be risk factors for DS. The physiological mechanisms underlying this association require further exploration Declarations Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Disclosure of interest The authors report there are no competing interests to declare. Funding This work was supported by Shanghai Municipal Health Commission Hygiene Industry Clinical Research Project(202240133); Program for Research-oriented Physician of Shanghai Tenth People's Hospital(2023YJXYSB005 and YNCR2C002); Tongji University Medicine-X Interdisciplinary Research Initiative (2025-0553-ZD-04); Cultivation grant for clinical and basic integration research of Shanghai Tenth People's Hospital, (No.SYYYRH2025025 and No.SYYYRH2025027) . Author Contribution Ziang Zhuo performed clinical treatment, collected data and prepared figures 1-3; Renhuan Huang recruited clinical participants; Jiaruo Qin recruited clinical participant, analyzed data and prepared table 1-2; Chengmin Lin and Liyan Lu organized clinical follow-up; Peng Wang and Yiyang Qu assisted data organization; Jieyin Huang and Haixia Liu revised manuscript; Hang Yuan wrote manuscript; Yiming Zhang wrote manuscript and provide funding; Yuanzhi Xu designed researching project. 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Huang","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Renhuan","middleName":"","lastName":"Huang","suffix":""},{"id":533987848,"identity":"63903136-0c11-47d5-8b11-e44ae81ad366","order_by":2,"name":"Jiaruo Qin","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Jiaruo","middleName":"","lastName":"Qin","suffix":""},{"id":533987849,"identity":"588b20cf-8105-48fd-bd59-b58ff46518e1","order_by":3,"name":"Chengmin Lin","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Chengmin","middleName":"","lastName":"Lin","suffix":""},{"id":533987850,"identity":"62978c21-3022-4267-97b2-c096e2d93059","order_by":4,"name":"Liyan 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People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Jieying","middleName":"","lastName":"Huang","suffix":""},{"id":533987854,"identity":"6af4e2d0-e19b-4c1a-9a61-abf582b8fd9f","order_by":8,"name":"Haixia Liu","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Haixia","middleName":"","lastName":"Liu","suffix":""},{"id":533987855,"identity":"5f359d73-b4af-49e5-9867-e86bca140c46","order_by":9,"name":"Hang Yuan","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Hang","middleName":"","lastName":"Yuan","suffix":""},{"id":533987856,"identity":"e7ebcf6e-d9b2-40f6-9e92-754bbde24575","order_by":10,"name":"Yiming Zhang","email":"","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Yiming","middleName":"","lastName":"Zhang","suffix":""},{"id":533987857,"identity":"2af9bc58-3d0e-469d-9b9a-ce43c3201ac3","order_by":11,"name":"Yuanzhi Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBCDBDb2BhDNxgMkDIjUwnOYVC0MEslwDn4tBjdyzCR+7qjL45N8f/BxwS8+GQb25m0SDDV3cGqRnJFjJtl7hq2YTTqZ2XhmH9BhPMfKJBiOPcOphV8CaAtvG09im3QymzRvD1ALSISx4TBOLWxABZJ/2yQS2yQPQ7XIv8GvBWSLNG+bQWKbBDObNM8PkC08+LVI9jwrtpZtS0hs40k2NuZtYONh40krtkg4hluLwfHkjTffttUlzm8/+PAxz59j9vzshzfe+FCDWwsDAwdSLDC2HWNgAzES8GhgYGB/gMT5U4NX7SgYBaNgFIxMAADzk0a1OAIO2gAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Tenth People's Hospital, Medicine School of Tongji University","correspondingAuthor":true,"prefix":"","firstName":"Yuanzhi","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-09-30 09:24:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7749745/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7749745/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94825476,"identity":"8436be15-82e2-4174-883e-9cd1fc526d4d","added_by":"auto","created_at":"2025-10-31 06:50:21","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2742656,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptv15.docx","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/917729e1f9744a78b1fcf752.docx"},{"id":94781510,"identity":"047d3ff8-4410-44c3-94bd-ae0d70f667ed","added_by":"auto","created_at":"2025-10-30 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06:49:24","extension":"xml","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101712,"visible":true,"origin":"","legend":"","description":"","filename":"dc0ef377c2524e46bd4d4e21166cac1d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/35e574470aef1d9d1a42edce.xml"},{"id":94781524,"identity":"b0851608-542f-4fa2-9df7-b4fe6ce9995f","added_by":"auto","created_at":"2025-10-30 15:47:07","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":111273,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/b88aaee6593ab3b434481408.html"},{"id":94825384,"identity":"84c4abbb-f227-450f-8fe8-6b2a19fb3547","added_by":"auto","created_at":"2025-10-31 06:50:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84936,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow diagram according to STROBE\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/a65cbcec9bce546aeea86572.png"},{"id":94781513,"identity":"6aee35c9-8a78-4e07-b461-aece7d7fcd3c","added_by":"auto","created_at":"2025-10-30 15:47:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":150377,"visible":true,"origin":"","legend":"\u003cp\u003eThe classification of the mandibular third molar status. A: Fully or partially erupted (Class I); B: Fully soft tissue impacted (Class II); C: Fully bone impacted (Class III)\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/70d5eb794d3c4c221f271466.png"},{"id":94781516,"identity":"d1add850-5fbc-49f2-8b88-b10eb12812e3","added_by":"auto","created_at":"2025-10-30 15:47:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":873322,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment approach to DS. A: Dry socket after irrigation； B: A periocline ointment dressing was placed loosely into the socket.\u003c/p\u003e","description":"","filename":"floatimage35.png","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/ed629d63e92cff2732b4a558.png"},{"id":107518213,"identity":"40ca27fa-e801-4a1a-9836-95b8ee2e4130","added_by":"auto","created_at":"2026-04-22 08:43:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2047326,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/973d460e-e033-4a17-b2cc-d27d45f2e6ea.pdf"},{"id":94781520,"identity":"02799402-85b9-4bd3-8f75-afbad46fffd0","added_by":"auto","created_at":"2025-10-30 15:47:06","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":36889,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7749745/v1/fa8edf18c1345ab9b9fa3e45.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk Factors for Dry Socket After Mandibular Third Molar Extraction: A Prospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDry socket (DS), also known as alveolar osteitis or fibrinolytic osteitis, is one of the most suffering complications following tooth extraction in dental practice. DS typically occurs within one to four days after extraction\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. The incidence of DS ranges from 1% to 5% in routine extraction practice, with a higher prevalence in the mandible than in the maxilla\u0026mdash;particularly after surgical extraction of third molars, where the incidence can reach up to 30%\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eClinical manifestations include an empty socket with exposed alveolar bone, severe pain radiating to the neck and head\u0026mdash;often worsening at night\u0026mdash;with or without halitosis and lymph node enlargement. The pain associated with DS is frequently refractory to common analgesics, causing patients to wake frequently during the night\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The pathophysiology of alveolar osteitis is highly complex and not fully understood. The most widely accepted theory is fibrinolysis theory\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, wherein excessive release of tissue-type plasminogen activator (tPA), due to trauma or inflammation, activates plasminogen to form plasmin, which degrades fibrin within the blood clot. This results in exposure of the alveolar bone and superficial osteitis. The absence, abnormal formation, or premature disintegration of the blood clot via fibrinolysis is considered the primary mechanism\u003csup\u003e[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDS is attributed to various factors, including overall health status, lifestyle habits, and oral infection. Multiple risk factors have been reported, such as gender, menstrual cycle, age, smoking, oral contraceptive use, bacterial profile, extraction site, procedure complexity, surgical technique, poor oral hygiene, vasoconstrictor use, anesthesia volume, inadequate intraoperative irrigation, and patient non-compliance, though some remain controversial \u003csup\u003e[\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Fibrinolytic activity may also be influenced by periodontal bacteria such as Treponema denticola, Streptococcusspp., Prevotella, Bacteroides, and Peptostreptococcus\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Patients who developed alveolar osteitis after dental extractions are reported to harbor a different microbiota compared to those without postoperative complications\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Several studies have indicated that both topical and systemic applications of antibiotics and antiseptics can significantly reduce the incidence of this complication\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, though the role of bacteria remains inconclusive. The initiating factor for fibrinolytic activation is unclear.\u003c/p\u003e\u003cp\u003eIn our clinical practice, we have observed a lower incidence of DS than that reported in the literature. Interestingly, many DS patients reported insufficient sleep duration and irregular sleep patterns within 0\u0026ndash;2 days after extraction. Previous studies have shown that insufficient sleep is associated with reduced nitric oxide-mediated endothelium-dependent vasodilation and endothelial tPA release in hypertensive adults\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. We therefore hypothesized that short sleep duration and irregular sleep following tooth extraction may be associated with DS.\u003c/p\u003e\u003cp\u003eThus, the primary aim of this study was to investigate the association between various risk factors and DS, with a specific focus on sleep duration and regularity.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSubjects\u003c/h2\u003e\u003cp\u003eWe conducted a prospective, single-center, case-control study to investigate potential risk factors for DS in patients undergoing mandibular third molar extraction at the Department of Stomatology, Shanghai Tenth People's Hospital. The study protocol was reviewed and approved by the Ethics Committee of Shanghai Tenth People's Hospital (No. SHSY-ICE-5.0/24k149/P01) and registered with the Chinese Clinical Trial Registry (No. ChiCTR2200056556). This study conforms with the ethical standards as laid out in the 1964 Declaration of Helsinki and its later amendments, and compliant with the Strengthening the Reporting of Observational Studies (STROBE) guidelines[28]. Participants provided written informed consent prior to taking part in the study (Appendix 1).The flowchart is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePatients aged over 18 years who were scheduled for mandibular third molar extraction were consecutively enrolled between September 1, 2024, and January 31, 2025. Exclusion criteria were as follows:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePatients unwilling or unable to return for follow-up or participate in telephone interviews;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eWomen who were pregnant or breastfeeding;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePatients taking medications that may impair wound healing (e.g., immunosuppressants, steroids, bisphosphonates);\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePresence of a cyst at the extraction site, considering curettage may cause additional trauma;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAcute pulpitis in adjacent teeth.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCriteria for DS\u003c/h3\u003e\n\u003cp\u003eDS was diagnosed\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e based on patient complaints and clinical examination:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eSevere pain around the extraction site, typically more intense than on the first postoperative day and often worsening at night, with or without radiation to the neck and head;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eWith or without halitosis;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eEmpty socket with exposed bone walls.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\n\u003ch3\u003ePre-operation\u003c/h3\u003e\n\u003cp\u003eComprehensive epidemiological data were collected preoperatively, including age, gender, smoking habits, menstrual cycle (for women), and medication use. Oral hygiene was assessed using the calculus index (CI). Questionnaires were presented in Appendix 1. The status of the mandibular third molar was evaluated via clinical and radiographic examination and classified into three categories: fully or partially erupted (Class I), fully soft tissue impacted (Class II), and fully bone impacted (Class III), as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Surgical complexity generally increases from Class I to Class III.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eIntraoperation\u003c/h3\u003e\n\u003cp\u003eAll procedures were performed by the same dentist to minimize bias. Operative duration and complexity were recorded. Key surgical techniques including 1) flap elevation, 2) odontosection and 3) osteotomy, were applied individually or in combination as needed:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eCombination A: none of the three techniques;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCombination B: flap elevation only;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCombination C: odontosection only;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCombination D: flap elevation and odontosection;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCombination E: all three techniques.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003ePost-operation\u003c/h3\u003e\n\u003cp\u003eAll patients were prescribed cephalosporin (0.25g, orally, four times daily), ibuprofen (0.3g, orally, as needed), and compound chlorhexidine mouthwash (5mL, gargle, three times daily). Detailed postoperative care instructions were provided. Pain (using a visual analogue scale, VAS) and swelling were recorded via follow-up phone calls on postoperative days 1, 3, and 7. Patients were also asked to recall their sleep onset time and total sleep duration on the first and second nights after surgery.\u003c/p\u003e\u003cp\u003eSleep duration of less than 7 hours per night was considered insufficient \u003csup\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e, and sleep onset delayed by more than 2 hours relative to the usual time was considered irregular \u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/sup\u003e. Daily sufficient sleep was scored as 0, insufficient as 1; regular sleep as 0, irregular as 1, respectively. Total scores for sleep duration and regularity on postoperative days 1 and 2 were recorded and analyzed. Patients with suspected DS, bleeding, inflammation, or other complications were scheduled for follow-up as needed until complete resolution.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eTreatment of DS\u003c/h2\u003e\u003cp\u003eIn cases of DS, the socket was irrigated alternately with hydrogen peroxide and sterile saline, then coated with Periocline ointment (Lederle, USA). \u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData and Analysis\u003c/h3\u003e\n\u003cp\u003eData recording was performed by a nurse, and statistical analysis was conducted independently by another dentist. Data were analyzed using SPSS version 25 (IBM, USA). Descriptive statistics (frequencies and percentages) were used to characterize the study population. The Chi-Square test and Fisher's Exact test were applied for categorical variables (e.g., age, gender, smoking, tooth status, surgical variables, menstrual cycle, CI, operative duration). A p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eA total of 559 patients with 579 mandibular third molars were included (20 patients underwent bilateral extractions during the same visit). Among these, 439 molars (75.8%) were from female patients and 140 (24.2%) from male patients. The mean age was 30.7 years (range: 18\u0026ndash;69). DS occurred at 36 extraction sites (6.2%). Among the 40 extraction sites from bilateral procedures, 3 sites (7.5%) in 3 patients developed DS. No patient developed bilateral DS. Epidemiological data are summarized 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\u003eEpidemiological data of the study.\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eMolars(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6(4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e439\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30(6.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18-34y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e472\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31(6.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.800\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35-49y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3(3.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50-64y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(6.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65y-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.963\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e554\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35(6.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eContraceptive\u003c/p\u003e\u003cp\u003e(only women)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(100.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e438\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29(6,6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003eMenstrual Cycles\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003efollicular phase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e153\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10(6.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003e0.486\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eovulatory phase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4(6.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eluteal phase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e159\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9(5.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eirregular menstruation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5(8.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePostpartum amenorrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epausimenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(2.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e219\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12(5.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e201\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19(9.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e159\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5(3.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eClassification of\u003c/p\u003e\u003cp\u003eThe Mandibular Third Molar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅠ(fully or partially erupted)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e383\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24(6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.983\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅡ( fully tissue impacted)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(5.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅢ(fully bone impacted)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4(6.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003eTechnique Complexity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(6.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e0.819\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eflap elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5(9.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eodontosection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6(5.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eflap elevation\u0026thinsp;+\u0026thinsp;odontosection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e181\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12(6.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eflap elevation\u0026thinsp;+\u0026thinsp;odontosection\u0026thinsp;+\u0026thinsp;oste-otomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5(4,9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003eOperation Duration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;5min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21(5.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e0.417\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u0026thinsp;~\u0026thinsp;10min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7(5.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11-20min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(10.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u0026thinsp;~\u0026thinsp;30min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;31min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSleep Duration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e515\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19(3.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3(13.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14(34.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSleep Regularity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e527\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22(4.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(6.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12(57.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFollowing treatment, 35 patients experienced significant pain relief without requiring additional visits; only one female patient required a second dressing.\u003c/p\u003e\u003cp\u003eAmong the 439 sites in female patients, 30 developed DS (incidence 6.8%). Among the 140 sites in male patients, 6 developed DS (incidence 4.3%). The difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.277).\u003c/p\u003e\u003cp\u003eOnly one female patient reported using oral contraceptives, and she developed DS. Although DS occurrence was higher in women, suggesting a possible hormonal influence, sub-analysis of menstrual cycle phases (follicular, ovulatory, luteal, irregular menstruation, postpartum amenorrhea, and postmenopause) showed no significant association with DS (P\u0026thinsp;=\u0026thinsp;0.486).\u003c/p\u003e\u003cp\u003eOne of the 25 sites from smokers developed DS, compared to 35 of the 554 sites from non-smokers. The difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.963).\u003c/p\u003e\u003cp\u003eMolars were categorized by surgical difficulty. Operation duration ranged from 1 to 40 minutes (mean 5.8 minutes). None of the surgical variables showed a significant association with DS.\u003c/p\u003e\u003cp\u003eRegarding sleep duration, DS occurred in 3 of 24 sites (13.0%) with a score of 1, and 14 of 41 sites (34.0%) with a score of 2\u0026mdash;significantly higher than in the score 0 group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Similarly, sleep irregularity was associated with a higher incidence of DS. Results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSleep duration and irregularity scores and DS occurrence.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDS(n\u0026thinsp;=\u0026thinsp;543)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHealthy socket(n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep duration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e496\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\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\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.027\u003c/p\u003e\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\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSleep regularity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e505\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\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\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.537\u003c/p\u003e\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\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOther variables, including age, surgical technique, and operation duration, showed no significant association with DS.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study collected basic epidemiological data and possible risk factors related to DS. For the first time, we identified a significant association between DS and both sleep duration and irregularity following mandibular third molar extraction.\u003c/p\u003e\u003cp\u003eThe incidence of DS in our study was 6.2%, consistent with recent reports \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Previous studies indicate that DS occurs in 1\u0026ndash;5% of routine extractions, with incidence after mandibular third molar extraction ranging from 4.6% to 17%\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. This variability may be due to differences in assessment methods, patient characteristics, and multifactorial influences on bone healing \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNo significant gender difference was observed, consistent with some previous studies \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, though others have reported conflicting results\u003csup\u003e[\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. The discrepancy may be due to unaccounted variables such as menstrual cycle, hormonal levels, or specific medications \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Oral contraceptives are believed to increase DS risk \u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e.Only one patient in our study used them, and she developed DS. Interestingly, she had also experienced DS after a previous extraction at our hospital over two years ago. Although menstrual cycle has been proposed to influence DS risk via fluctuation of estrogen level \u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e, we found no significant association.\u003c/p\u003e\u003cp\u003eSmoking is widely reported to impair wound healing\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e via mechanisms possibly involving nicotine, cotinine, carbon monoxide, and hydrogen cyanide. Contrary to expectations, our results showed a slightly higher\u0026mdash;though not significant\u0026mdash;DS incidence among non-smokers. Rakhshan\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e believed that smoking may confound gender effects due to higher smoking rates among men.\u003c/p\u003e\u003cp\u003eSurgical trauma and difficulty were often cited as risk factors\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Contrary to our hypothesis, we found no significant association between DS and surgical difficulty. This may be due to better soft tissue coverage, suturing, and socket closure in more complex cases. No relationship was found between CI and DS. The role of bacteria in DS warrants further investigation \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSleep plays a critical role in circadian rhythm and overall health. Cellular circadian dynamics have been shown to influence wound healing via fibroblast activity \u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e. Sleep duration and regularity are key indicators of sleep quality \u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e. Adequate and regular sleep improves memory, emotional regulation, metabolic function, energy balance, and immune response \u003csup\u003e[\u003cspan additionalcitationids=\"CR44 CR45 CR46\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/sup\u003e, and helps maintain stress-recovery balance via the hypothalamic-pituitary-adrenal axis\u003csup\u003e[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/sup\u003e. Sleep duration less than seven hours was considered insufficient sleep\u003csup\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e, and sleep onset time two hours later than usual was considered irregular sleep\u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/sup\u003e.Sleep deprivation has been shown to impair endothelial tPA release via nitric oxide-mediated pathways\u003csup\u003e[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e. Given that increased fibrinolytic activity due to tPA is a key mechanism in DS, sleep disturbances may disrupt circadian rhythms and impede healing. Our results suggest that insufficient and irregular sleep are associated with higher DS incidence. However, the molecular mechanisms require further study.\u003c/p\u003e\u003cp\u003eLimitations of this study include a relatively small sample size and imbalanced gender distribution, which may introduce bias. Future studies with larger samples are needed. Additionally, sleep data were self-reported and subject to recall bias. Objective measures such as polysomnography should be used in future research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this prospective, single-center, case-control study suggests that sleep insufficiency and irregularity may be risk factors for DS. The physiological mechanisms underlying this association require further exploration\u003c/p\u003e"},{"header":"Declarations","content":"\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePatient and public involvement\u003c/h2\u003e\u003cp\u003ePatients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.\u003c/p\u003e\u003c/div\u003e\u003ch2\u003eDisclosure of interest\u003c/h2\u003e\u003cp\u003eThe authors report there are no competing interests to declare.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by Shanghai Municipal Health Commission Hygiene Industry Clinical Research Project(202240133); Program for Research-oriented Physician of Shanghai Tenth People's Hospital(2023YJXYSB005 and YNCR2C002); Tongji University Medicine-X Interdisciplinary Research Initiative (2025-0553-ZD-04); Cultivation grant for clinical and basic integration research of Shanghai Tenth People's Hospital, (No.SYYYRH2025025 and No.SYYYRH2025027) .\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZiang Zhuo performed clinical treatment, collected data and prepared figures 1-3; Renhuan Huang recruited clinical participants; Jiaruo Qin recruited clinical participant, analyzed data and prepared table 1-2; Chengmin Lin and Liyan Lu organized clinical follow-up; Peng Wang and Yiyang Qu assisted data organization; Jieyin Huang and Haixia Liu revised manuscript; Hang Yuan wrote manuscript; Yiming Zhang wrote manuscript and provide funding; Yuanzhi Xu designed researching project.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analyzed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCHOW O, WANG R. Alveolar Osteitis: A Review of Current Concepts [J]. J oral maxillofacial surgery: official J Am Association Oral Maxillofacial Surg. 2020;78(8):1288\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZAHID T, GHAFOOR S. Molecular events in the clinicopathological diagnosis of alveolar osteitis [J]. JPMA The Journal of the Pakistan Medical Association, 2021, 71(2(a)): 508\u0026thinsp;\u0026ndash;\u0026thinsp;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGAROLA F, GILLIGAN G, PANICO R et al. Clinical management of alveolar osteitis. A systematic review [J]. Medicina oral, patologia oral y cirugia bucal, 2021, 26(6): e691\u0026ndash;702.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAGUILAR-DUR\u0026aacute;N L, FIGUEIREDO R, SEMINAGO R, et al. A metagenomic study of patients with alveolar osteitis after tooth extraction. A preliminary case-control study [J]. 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Effects of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on dry socket incidence and postsurgical pain: a double-blind split-mouth randomized controlled clinical trial [J]. J Orofac Pain. 2013;27(3):256\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHEDSTR\u0026ouml;M L, SJ\u0026ouml;GREN P. Effect estimates and methodological quality of randomized controlled trials about prevention of alveolar osteitis following tooth extraction: a systematic review [J]. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics, 2007, 103(1): 8\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSTOCKELMAN K A, BAIN A R, GOULDING A, Negative Influence of Insufficient Sleep on Endothelial Vasodilator and Fibrinolytic Function in Hypertensive Adults [J]., Hypertension et al. Dallas, Tex: (1979), 2021, 78(6): 1829-40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVON ELM E, ALTMAN D G, EGGER M, et al. 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Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons, 1991, 49(2): 141-5; discussion 5\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCOHEN M E, SIMECEK JW. Effects of gender-related factors on the incidence of localized alveolar osteitis [J]. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics, 1995, 79(4): 416\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUPADHYAYA C, HUMAGAIN H. Prevalence of dry socket following extraction of permanent teeth at Kathmandu University Teaching Hospital (KUTH), Dhulikhel, Kavre,Nepal: a study [J]. Kathmandu Univ Med J. 2010;8(29):18\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOGUNLEWE M O, ADEYEMO W L, LADEINDE A L, et al. Incidence and pattern of presentation of dry socket following non-surgical tooth extraction [J]. Nigerian Q J Hosp Med. 2007;17(4):126\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBIENEK D R, FILLIBEN JJ. Risk assessment and sensitivity meta-analysis of alveolar osteitis occurrence in oral contraceptive users [J]. Journal of the American Dental Association (1939), 2016, 147(6): 394\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXU JL, SUN L, LIU C, et al. Effect of oral contraceptive use on the incidence of dry socket in females following impacted mandibular third molar extraction: a meta-analysis [J]. Int J Oral Maxillofac Surg. 2015;44(9):1160\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHARAJI A. Single-dose intra-alveolar chlorhexidine gel application, easier surgeries, and younger ages are associated with reduced dry socket risk [J]. J oral maxillofacial surgery: official J Am Association Oral Maxillofacial Surg. 2014;72(2):259\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKUŚNIEREK W, BRZEZIŃSKA K, NIJAKOWSKI K et al. Smoking as a Risk Factor for Dry Socket: A Systematic Review [J]. Dentistry J, 2022, 10(7).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMACGREGOR AJ. Aetiology of dry socket: a clinical investigation [J]. Br J oral Surg. 1968;6(1):49\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCARDOSO C L, RODRIGUES M T FERREIRA, J\u0026uacute;NIOR O, et al. Clinical concepts of dry socket [J]. J oral maxillofacial surgery: official J Am Association Oral Maxillofacial Surg. 2010;68(8):1922\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHOYLE N P, SEINKMANE E, PUTKER M et al. Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing [J]. 2017, 9(415): eaal2774.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFISCHER D, MCHILL A W SANOA et al. Irregular sleep and event schedules are associated with poorer self-reported well-being in US college students [J]. Sleep, 2020, 43(6).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLEONG R L F, CHENG G H, CHEE M W L, et al. The effects of sleep on prospective memory: A systematic review and meta-analysis [J]. Sleep Med Rev. 2019;47:18\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBAGLIONI C, SPIEGELHALDER K, LOMBARDO C, et al. Sleep and emotions: a focus on insomnia [J]. Sleep Med Rev. 2010;14(4):227\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDUAN D, KIM L J, JUN JC, et al. Connecting insufficient sleep and insomnia with metabolic dysfunction [J]. Volume 1519. Annals of the New York Academy of Sciences; 2023. pp. 94\u0026ndash;117. 1.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBESEDOVSKY L, LANGE T. The Sleep-Immune Crosstalk in Health and Disease [J]. Physiol Rev. 2019;99(3):1325\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVAN DALFSEN J H, MARKUS C R. The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review [J]. Sleep Med Rev. 2018;39:187\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHIJMANS J G, LEVY M. Insufficient sleep is associated with a pro-atherogenic circulating microRNA signature [J]. Exp Physiol. 2019;104(6):975\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFULL K M, HUANG T, SHAH N A, et al. Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis [J]. J Am Heart Association. 2023;12(4):e027361.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSTOCKELMAN K A, BAIN A R, GOULDING A et al. Negative Influence of Insufficient Sleep on Endothelial Vasodilator and Fibrinolytic Function in Hypertensive Adults [J]. 2021, 78(6): 1829\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Mandibular Third Molar, Dry socket, Sleep Insufficiency, Sleep Irregularity, Prospective Cohort Study","lastPublishedDoi":"10.21203/rs.3.rs-7749745/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7749745/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eDry socket (DS) is one of the most distressing complications following tooth extraction, particularly after surgical removal of mandibular third molars. The etiology of DS remains unclear and involves a complex interplay of infection, immune responses, and multiple contributing factors. Therefore, the primary objective of this study was to investigate the risk factors associated with DS.\u003c/p\u003e\u003ch2\u003eMaterial and Methods\u003c/h2\u003e\u003cp\u003eThis prospective, single-center, case-control study enrolled adult patients requiring mandibular third molar extraction. A series of questionnaires were administered to collect data on demographics, calculus index (CI), smoking habits, menstrual cycle, medication use, molar status, operative duration, as well as sleep duration and regularity. Associations were analyzed using the Chi-Square Test.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e\u003cp\u003eThe study included 579 mandibular third molars from 559 patients. Among these, 36 sites (6.2%) developed DS. Factors such as gender, CI, smoking habits, menstrual cycle, medication use, molar status, and operation duration were not significantly associated with DS. However, patients with insufficient and irregular sleep exhibited a significantly higher incidence of DS (P\u0026thinsp;\u0026le;\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eSleep insufficiency and irregularity may be risk factors for DS, though the underlying physiological mechanisms require further investigation.\u003c/p\u003e","manuscriptTitle":"Risk Factors for Dry Socket After Mandibular Third Molar Extraction: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 15:47:02","doi":"10.21203/rs.3.rs-7749745/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6a80c97d-7222-45a2-84e0-5e6fa452a4d9","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-22T08:43:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 15:47:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7749745","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7749745","identity":"rs-7749745","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}