Bone Flap Resorption After Autologous Cranioplasty in Traumatic Brain Injury: A Case-control Study in Vietnam  

Bone Flap Resorption After Autologous Cranioplasty in Traumatic Brain Injury: A Case-control Study in Vietnam | 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 Bone Flap Resorption After Autologous Cranioplasty in Traumatic Brain Injury: A Case-control Study in Vietnam Huy Ngoc Pham, Nguyen Cong Tien Anh, Linh Khanh Nguyen, Son Hong Ha, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9394702/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Introduction Autologous bone is a commonly used material for cranioplasty following decompressive craniectomy; however, it is accompanied by the inherent risk of resorption. This study aimed to identify factors associated with bone flap resorption (BFR) in patients undergoing autologous cranioplasty after decompressive craniectomy for traumatic brain injury. Methods A matched case-control study was conducted at Viet Duc University Hospital between January 2022 and July 2025. Cases were defined as patients who developed severe BFR requiring revision surgery. Each case was matched with two controls without BFR based on cranioplasty date and follow-up duration. The association of demographic, general health, trauma historyand peri-cranioplasty characteristics with BFR was assessed using conditional logistic regression. Results A total of 71 cases and 142 matched controls were included. BFR that required surgical revision occurred predominantly within two years after cranioplasty (90%). The mean time interval from cranioplasty to complication diagnosis was 444 ± 212 days. Large-sized bone flap (OR: 3.96, 95% CI: 1.86 - 8.43), fragmented bone flap (OR: 7.84, 95% CI: 1.38 - 44.53), and chronic viral hepatitis (either B or C) (OR: 4.32, 95% CI: 1.54 - 12.15) were independent associated factors of BFR. Young age (<18), frontal sinus fracture and ventriculoperitoneal shunt implantation showed a trend to increase risk of BFR but failed to reach statistical significance in multivariate analysis. Conclusions In our study, bone fragmentation, large bone flap size, and chronic viral hepatitis were associated with increased risk of bone flap resorption after autologous cranioplasty in TBI patients. Further studies are necessary to confirm these findings, especially the role of chronic viral hepatitis. cranioplasty bone resorption autologous bone traumatic brain injury risk factors Figures Figure 1 Figure 2 Introduction Bone flap resorption is a concerning complication in autologous cranioplasty following decompressive craniectomy. It causes thinning, weakening, or even complete lysis of the flap, thereby compromising skull integrity and might necessitate revision surgery. A study in Finland found up to 90% of cases experience BFR to some extent with a mean follow-up interval of 52 months 1 while several studies reported around 20% of patients developing severe BFR. 2 – 9 Traumatic brain injury (TBI) is the most common indication for decompressive craniectomy. Higher rates of post-cranioplasty BFR are also found in TBI group compared to stroke or tumor. 10 , 11 . Several factors predisposing patients to bone necrosis have been suggested such as young age, 1–3,6,8,12 bone fragmentation, 2,3,6,7,13 distance between the graft-bone border, 14 large cranial defect, 15 delay to cranioplasty, 3,9,16 and the presence of a ventriculoperitoneal shunt. 17 However, conflicting results from other studies still exist. For instance, Korhonen et al. 12 and Bowers et al. 13 found no significant association between BFR and the time interval between decompressive craniectomy and cranioplasty. A Turkish study did not identify a statistically significant link between defect size and BFR risk. 14 Additionally, evidence from Vietnamese cohorts remains limited. Therefore, we conducted this study to identify associated factors of bone flap resorption following autologous cranioplasty for patients with traumatic brain injury in Vietnam. Methods Design and Setting A matched case-control study was conducted analyzing patients who underwent autologous cranioplasty following decompressive craniectomy for traumatic brain injury at Viet Duc University Hospital between January 2022 and July 2025. Cases were patients who developed bone resorption requiring revision cranioplasty as of July 2025. Controls were patients without clinical or radiological evidence of bone resorption. The case-control ratio was 1:2, with matching criteria including the time of cranioplasty and follow-up duration. Controls had to be operated on the same or nearest day as the matched case and must have had a follow-up period that was the same length or longer than that of the case. Bone Flap Preservation and Cranioplasty Surgery After decompressive craniectomy (DC), the bone flaps were immediately sent to the hospital's tissue bank for a sterile cryopreservation process. They were first cleared of blood and soft tissue, then placed in the biomedical freezer at − 80°C with continuous temperature monitoring. During storage, routine quality checks were carried out, and any bone flap showing signs of contamination was excluded from later reimplantation. On the day of CP, the bone flap was defrosted and had the final assessment before implantation. Cranioplasty (CP) was conducted in an elective setting by qualified attending neurosurgeons. The same skin incision as in the decompressive craniectomy was used, and the underlying fascia and muscle layers were dissected to expose the skull defect requiring cranioplasty. The bone flap retrieved from the tissue bank was reimplanted into the cranial defect and fixed by non-absorbable sutures or titanium miniplates and screws. A subgaleal drain was routinely placed, and the wound was closed in anatomical layers. Postoperative CT imaging was undertaken within 48 hours to detect early complications, and surgical drains were generally removed on postoperative day three. The first postoperative CT scan will also be used as a reference to assess future bone resorption complications. Post-cranioplasty management After CP, the integration and stability of the implanted bone flap were assessed through physical examination and head CT imaging. Clinical signs such as palpable skull defects and localized softening or visible sinking of the flap were suggestive of bone resorption. The CT scan image of the bone flap was compared with the first postoperative imaging. BFR was classified into type I defined as partial thinning and localized resorption of the bone flap without complete structural collapse or type II in the presence of complete osteolysis involving both the inner and outer tables. (Dünisch et al.) Patients with type II BFR were indicated for revision surgeries. Variables and Data Collection Data was extracted from the hospital computer system including all patient medical records during hospitalization and follow-up examination notes. These documented all the clinical evaluation, imaging results, surgical report and treatment process. Regarding demographic and general health features, we investigated age, sex (male or female), body mass index (BMI), current smoking status (during the past 3 months), current alcohol use (units per day in the past 3 months) and comorbidities. Trauma history was also collected including the mechanism of injury and post-craniectomy complications. Examined peri-cranioplasty characteristics were preoperative Glasgow Outcome Scale Extended (GOSE) score, time interval between DC and CP, bone flap features (size, fragmentation and presence of frontal fracture), fixation method of the bone flap (plates and screws or sutures). Using Computed Tomography results, the surface area of the bone flaps was calculated by the elliptic formula (a x b x 3.14/4), in which (a) and (b) were vertical and horizontal diameters, respectively. Post-cranioplasty complications were analyzed with respect to epidural fluid collection (thickness greater than 10 mm) and surgical site infection. Data Analysis Continuous variables were presented as means and standard deviations and compared between cases and controls using t-tests. The categorical factors were reported as percentages and group differences were assessed by Chi-square tests and Fisher's exact tests. Conditional logistic regression models were used to analyze the association of factors and the odds of having infection. Variables that yielded a P-value < 0.2 in univariate analysis were included in the multivariate adjusted logistic regression model. Results are presented as odd ratios with 95% confidence intervals. Statistical analyses were performed using Stata 17.0 (College Station, TX: StataCorp LP). Ethical Considerations This study was approved by the Institutional Review Board at Viet Duc University Hospital. Written informed consent was provided by the patients and family members who participated in this study. Results Table 1 Univariate analysis of association between demographic, general health characteristics, trauma history and bone flap resorption. Age ( 25) 8 (11.3) 14 (9.9) 0.75 Current smoke 8 (11.3) 12 (8.5) 0.51 Alcohol (> 2 unit/day) 11 (15.5) 18 (12.7) 0.57 Comorbidities Diabetes 4 (5.6) 11 (7.8) 0.57 Hypertension 19 (26.8) 36 (25.4) 0.83 Dyslipidemia 1 (1.4) 3 (2.1) 0.59 Chronic hepatitis B and C 10 (14.1) 8 (5.6) 0.04 Chronic kidney disease 0 (0.0) 3 (2.1) 0.29 TBI cause Traffic accident 60(84.5) 111(78.2) 0.35 Fall 10(14.1) 30(21.3) Violence 1(1.4) 1(0.7) Complications after DC Meningitis 6(8.5) 13(9.2) 0.54 CSF - leakage 2(2.8) 3(2.1) 0.54 Surgical site infection 0(0.0) 1(0.7) 0.67 VP shunt 9(12.7) 7(4.9) 0.04 Pneumocephalus 5(7,0) 8(5,6) 0,69 Demographic and general health characteristics and trauma history in the case and control groups are illustrated in Table 1 . Patients younger than 18 years and those with hepatitis were more common in the case group (19.7% vs. 12.0% and 14.1% vs. 5.6%, respectively). No significant differences were observed for BMI, smoking status, alcohol abuse, or comorbidities. Regarding trauma history, VP shunt implantation occurred more frequently among cases (12.7% vs. 4.9%, p = 0.04) while TBI etiology and other post-decompressive craniectomy complications did not differ significantly between groups. Table 2 Univariate analysis of association between peri-cranioplasty characteristics and bone flap resorption. GOSE score before cranioplasty (> 4) Case (n = 71) n (%) Control (n = 142) n (%) p-value 55 (77.5) 111(78.2) 0.91 Late cranioplasty (> 180 days) 5(7.0) 7(4,9) 0,53 Bone flap size (> 110 cm 2 ) 12(16.9) 11(7.8) 0,04 Site of DC Unilateral hemicraniectomy 64(90,1) 119(83.8) 0,52 Bifrontal craniectomy 4(5,6) 20(14.1) Bilateral hemicraniectomy 3(4,2) 3(2,1) Fragmented bone flap 21(29,6) 11(7,8) < 0,01 Frontal sinus fracture 5(7.0) 3(2.1) 0,07 Bone flap fixation Screws and plates 63(88.7) 121(85.2) 0.48 Suture 8(11,3) 21(14.8) Postoperative complications Epidural fluid collection 3(4,2) 3(2,1) 0,38 Surgical site infection 0(0.0) 0(0.0) Perioperative features of the two groups and univariate analysis were presented in Table 2 . Regarding bone flap features, the proportions of large graft size and fragmented flaps were greater in the case group compared to the control group (16.9% versus 7.8%, p = 0.04 and 29.6% versus 7.8%, p < 0.01, respectively). On preoperative CT-scan imaging, the rate of frontal sinus fracture was also higher in the case group (7.0% versus 2.1%; p = 0.07). No significant differences were observed for other variables including pre-op GOSE scores, late cranioplasty, bilateral craniectomy, epidural fluid collection and surgical site infection after cranioplasty. Table 3 Multivariate regression Factors Odds Ratio 95% CI p-value Young age 1,90 0.79–4,57 0.15 Hepatitis 3,30 1,06–10,24 0.04 Large bone flap 3,09 1.05–9,08 0,04 Fragmented bone flap 5,28 2,04–13.65 < 0.01 Frontal sinus fracture 3,31 0,65–16,94 0.15 VP shunt 2,00 0.63–6,33 0.24 Six variables yielded a p-value < 0.2 in the univariate analysis and were included in the multivariate statistical model including young age, chronic hepatitis, large-sized bone flap, fragmented bone flap, frontal sinus fracture and VP shunt implantation (Table 3 ). In multivariate analysis, three factors were identified as independent risk factors of aseptic bone resorption, including large-sized bone flap (OR: 3.96, 95% CI: 1.86–8.43), fragmented bone flap (OR: 7.84, 95% CI: 1.38–44.53), and chronic hepatitis (OR: 4.32, 95% CI: 1.54–12.15). Discussion Cranioplasty using autologous bone is considered a special form of autologous transplantation because the bone flap has typically been cryopreserved and most of its cellular components are non-viable at the time of reimplantation. 18 , 19 The reintegration of bone flap greatly depends on the balance between the osteoblastic bone formation and osteoclastic bone resorption. 20 – 23 When osteoclastic activity predominates, the flap progressively thins, ultimately leading to cranioplasty failure. 23 BFR is a slow and progressive process that emerges shortly after reimplantation. Although early radiological signs may be detectable on CT scans within a few months, significant resorption requiring revision is often diagnosed much later. 24 In our cases, BFR-related cranioplasty failures were found at around 444 ± 212 days (≈ 14.8 ± 7.0 months) after surgery; this finding was comparable with other previous studies. Schuss et al. reported a mean onset of 20 ± 17 months, 25 whereas Honeybul et al. observed cases around 12 months postoperatively. 26 In the present study, fragmented bone flaps, large flap size, and chronic hepatitis were identified as independent predictors of postoperative bone resorption. Fragmented bone flap Fragmentation often occurs in the setting of high-energy head trauma or when the bone flap is removed in multiple pieces during decompressive craniectomy. In our study, patients with fragmented flaps exhibited a significantly higher incidence of bone flap resorption (BFR) compared with those with single-piece flaps, which is consistent with prior reports. 3 , 6 , 13 , 27 , 28 Dünisch et al., in a retrospective study of 372 patients, reported that bone flaps broken into two pieces increased the odds of necrosis by 3.35-fold, whereas fragmentation into three or more pieces raised the risk by 24-fold compared with intact flaps. 6 Brommeland et al. also found flap fragmentation as a strong independent predictor of bone flap resorption, yielding an odds ratio of 14.3 (p = 0.005). 27 In cryopreserved autografts (which lack viable osteoblasts), survival depends on revascularization and contacts of bone with dura and periosteum. 29 Fragmentation creates gaps, thereby impeding vascular invasion and osteoprogenitor cell migration to the bone flap, ultimately preventing osseous union with the native calvarium. 27 Moreover, unstable fragments permit subtle micromotion under the scalp, which continuously stimulates bone remodeling. 30 Given the risk of BFR in extensively fragmented cases, the use of synthetic materials should be considered. Furthermore, thorough surgical planning can reduce the need for removing multiple fragments intraoperatively. Bone flap size In this study, bone flap size (≥ 110 cm²) was identified as a risk factor of BFR after autologous cranioplasty. This finding aligns with a previous study by Schoekler and Trummer, concluding that large bone flaps were more susceptible to BFR. 31 Similarly, in a retrospective cohort study, Kim et al. also reported an increased risk of resorption in patients with bone flaps larger than 110 cm². 15 Many theories have been hypothesized to explain the impact of this factor on the survival of the implanted flap. After the cryopreservation period, larger bone flaps tend to accumulate greater amounts of devitalized and necrotic tissue, which amplifies local inflammatory responses. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) stimulate osteoclast differentiation and activity while suppressing osteoblast function. 32 , 33 In addition, the reconstruction of a wide cranial defect is often associated with greater soft-tissue disruption and a higher likelihood of vascular injury, both of which impair neovascularization and bony reintegration. 34 Although a large decompressive craniectomy is of pivotal importance for effective intracranial pressure control in emergency settings, the risk of BFR may be reduced by good surgical techniques. Preservation of the main vessel of the scalp as well as proper management of soft tissue should be achieved during surgery. 35 Viral hepatitis In the present study, up to 8.5% of patients are infected with chronic viral hepatitis (HBV and HCV). This figure partially reflects the prevalence of viral hepatitis in Vietnam, with HBV’s pool estimate of roughly 11% of the general population, 50 markedly exceeding the global average of around 3%. 51 In contrast, HCV prevalence is lower (1%) than HBV and highly concentrated in high-risk groups such as people who inject drugs. 51 Chronic viral hepatitis (HBV and HCV) was associated with an increased risk of bone flap resorption after cranioplasty in our cohort. To our knowledge, this association has not been previously reported in the context of cranioplasty outcomes; however, the connection between chronic viral hepatitis and bone health is being established. Hepatitis, particularly in its chronic viral forms (HBV, HCV), is reported to increase the risk of osteoporosis. 36 – 40 The presence of hepatitis viruses can be a chronic trigger of cytokine release. The circulating cytokines, especially tumor necrosis factor (TNF), might promote osteoclastic activity inside the bone mineralized matrix, thereby accelerating bone resorption. 41–43 Moreover, viral hepatitis was also linked to the decrease in vitamin D 40,44 and insulin-like growth factor 1 45 as well as the dysregulation in the RANK–RANKL–OPG signaling pathway, 46 all of which further disrupt bone remodeling homeostasis. Given that successful cranioplasty relies on revascularization, osteoblast survival, and balanced bone remodeling, the systemic pro-resorptive environment observed in chronic viral hepatitis may compromise bone flap incorporation and accelerate resorptive processes. Antiviral treatments, particularly nucleotide analogues such as tenofovir, have been associated with reduced bone mineral density and may further contribute to bone fragility 47 – 49 . Unfortunately, treatment status and duration of infection could not be fully evaluated in the present study. Future prospective studies incorporating bone metabolic markers, vitamin D levels, liver function indices, and antiviral treatment data are warranted to clarify causality and to identify high-risk patients who may benefit from alternative reconstructive strategies. Strengths and Limitations This study benefits from its high number of cases which allowed multivariate analysis. However, the study still faces limitations due to its retrospective nature with potential information bias. Additionally, as a case-control study, it cannot establish causality, and the findings require confirmation through further research with stronger study designs. Furthermore, the study population included only severe cases, which may limit the generalizability of the results to the broader population with bone resorption. Conclusions Bone fragmentation, bone flap size and hepatitis were associated with a higher rate of bone flap resorption after cranioplasty. Further studies are necessary to confirm these findings, especially the role of chronic viral hepatitis. Abbreviations TBI: traumatic brain injury; CP: cranioplasty; DC: decompressive cranioplasty; BMI: body mass index; GOSE: Glasgow Outcome Scale – Extended; CSF: cerebrospinal fluid; EFC: epidural fluid collection; BFR: bone flap resorption; VP: ventriculoperitoneal; CT: computed tomography; LOS: Length of stay; OR: odds ratio; CI: confidence interval; HBV: hepatitis B virus; HCV: hepatitis C virus Declarations Author Contribution The authors sincerely acknowledge all participants of this study for their valuable contributions and cooperation throughout the research process. Their participation and support were essential to the successful completion of this work. The authors also wish to thank the medical and technical staff at the Department of Neurosurgery in Viet Duc University Hospital for their assistance in data collection and patient care during the study period. The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. None of the authors have any financial, personal, or professional relationships that could be construed as influencing the work presented in this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The study was entirely self-supported by the authors without external financial assistance. Ethical approval for this study was obtained from the Institutional Review Board of Viet Duc University Hospital. All procedures were conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration. Informed consent was obtained from all individual participants included in the study. Conflict of interest We declare no conflict of interest. Acknowledgements We are grateful to all patients for participating in the study. Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The study received no financial support from any organization References Korhonen TK, Salokorpi N, Niinimäki J, Serlo W, Lehenkari P, Tetri S (2019) Quantitative and qualitative analysis of bone flap resorption in patients undergoing cranioplasty after decompressive craniectomy. J Neurosurg 130(1):312–321. 10.3171/2017.8.JNS171857 Di Rienzo A, Colasanti R, Dobran M et al (2024) Bone Flap Resorption After Cranioplasty: Risk Factors and Proposal of the Flap Integrity Score. 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BMC Infect Dis 16(1):507. 10.1186/s12879-016-1836-0 Gallego-Rojo FJ, Gonzalez-Calvin JL, Muñoz-Torres M, Mundi JL, Fernandez-Perez R, Rodrigo-Moreno D (1998) Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis. Hepatol Baltim Md 28(3):695–699. 10.1002/hep.510280315 Moschen AR, Kaser A, Stadlmann S et al (2005) The RANKL/OPG system and bone mineral density in patients with chronic liver disease. J Hepatol 43(6):973–983. 10.1016/j.jhep.2005.05.034 Baranek B, Wang S, Cheung AM, Mishra S, Tan DH (2020) The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis. Antivir Ther 25(1):21–32. 10.3851/IMP3346 Gill US, Zissimopoulos A, Al-Shamma S et al (2015) Assessment of bone mineral density in tenofovir-treated patients with chronic hepatitis B: can the fracture risk assessment tool identify those at greatest risk? J Infect Dis 211(3):374–382. 10.1093/infdis/jiu471 Yip TCF, Lai JCT, Yam TF et al (2024) Long-term use of tenofovir disoproxil fumarate increases fracture risk in elderly patients with chronic hepatitis B. J Hepatol 80(4):553–563. 10.1016/j.jhep.2023.12.001 Flower B, Du Hong D, Vu Thi Kim H et al (2022) Seroprevalence of Hepatitis B, C and D in Vietnam: A systematic review and meta-analysis. Lancet Reg Health West Pac 24:100468. 10.1016/j.lanwpc.2022.100468 Burki T (2024) WHO’s 2024 global hepatitis report. Lancet Infect Dis 24(6):e362–e363. 10.1016/S1473-3099(24)00307-4 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 10 May, 2026 Reviewers agreed at journal 21 Apr, 2026 Reviewers invited by journal 16 Apr, 2026 Editor assigned by journal 13 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 12 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9394702","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626929481,"identity":"8d16513f-a8e4-422b-baf2-9d96f433f2a1","order_by":0,"name":"Huy Ngoc Pham","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYDCCAwwMzEBKDsx+QIoWYzA7gRQtiQ0gDlFa+I73mD0uqNmWPj/s8EOgLXZyug0EtEieOZZuPOPY7dyNt9MMgFqSjc0OENBicCP5mDQPG1DL7ASQlgOJ2whrSWyT5vl3O91wdvoHYrUAbeFtu50gL51DpC1gv/D23TbcIJ1TcCDBgAi/gEOM59ttefnZ6Zs/fKiwkyOoBQjYIC4EqzQgrByhRb6BONWjYBSMglEwAgEANchJ2IcEed8AAAAASUVORK5CYII=","orcid":"","institution":"Viet Duc Hospital","correspondingAuthor":true,"prefix":"","firstName":"Huy","middleName":"Ngoc","lastName":"Pham","suffix":""},{"id":626929482,"identity":"27c0f5ff-f8b6-424d-a54a-e731ab415068","order_by":1,"name":"Nguyen Cong Tien Anh","email":"","orcid":"","institution":"Hanoi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Nguyen","middleName":"Cong Tien","lastName":"Anh","suffix":""},{"id":626929483,"identity":"a9641a8b-d7fa-456c-9c11-c2ebb082ab4f","order_by":2,"name":"Linh Khanh Nguyen","email":"","orcid":"","institution":"Hanoi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Linh","middleName":"Khanh","lastName":"Nguyen","suffix":""},{"id":626929484,"identity":"57f83fa8-e77d-4b84-91e3-237bbcc1bd2c","order_by":3,"name":"Son Hong Ha","email":"","orcid":"","institution":"Hanoi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Son","middleName":"Hong","lastName":"Ha","suffix":""},{"id":626929485,"identity":"4199adff-59bc-4a03-bd91-cbb32a8fc62e","order_by":4,"name":"Dinh Van Tran","email":"","orcid":"","institution":"Viet Duc Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dinh","middleName":"Van","lastName":"Tran","suffix":""},{"id":626929486,"identity":"c3c155f6-2932-4799-9383-264a85f94817","order_by":5,"name":"Tuan Anh Le","email":"","orcid":"","institution":"Hanoi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tuan","middleName":"Anh","lastName":"Le","suffix":""},{"id":626929487,"identity":"1b2fdb0c-349b-47d5-a7c1-d8ce1b08d237","order_by":6,"name":"Ha Dai Duong","email":"","orcid":"","institution":"Hanoi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ha","middleName":"Dai","lastName":"Duong","suffix":""},{"id":626929488,"identity":"55ee4ce3-c821-491b-bf2c-7e0d7598c5b3","order_by":7,"name":"He Van Dong","email":"","orcid":"","institution":"Viet Duc Hospital","correspondingAuthor":false,"prefix":"","firstName":"He","middleName":"Van","lastName":"Dong","suffix":""}],"badges":[],"createdAt":"2026-04-12 13:53:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9394702/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9394702/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107637195,"identity":"85914ada-f93e-4bbb-8daa-464a3618a356","added_by":"auto","created_at":"2026-04-23 12:41:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":115734,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParticipant flow chart\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study population included 71 cases matched with 142 controls who fulfilled inclusion and exclusion criteria (Figure 1). The case group was comprised of 56 (78.9%) males and 15 (21.1%) females with a mean age of 36.8 ± 15.2 while the control group had 113 (79.6%) males and 29 (20.4%) females with a mean age of 40.4 ± 17.6 (Table 1). Traffic accidents were the cause of TBI in the majority of cases (80.3%), followed by falls (18.8%) and violence (0.9%)\u003c/p\u003e","description":"","filename":"floatimage114.png","url":"https://assets-eu.researchsquare.com/files/rs-9394702/v1/ba13d6fd8733c49ecfbfea3a.png"},{"id":107637194,"identity":"217858b0-8919-49a3-80c7-757c1b9b9b6e","added_by":"auto","created_at":"2026-04-23 12:41:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80917,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime interval from cranioplasty surgery to infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA majority of severe bone resorption (Type II) cases occurred in the first and second postoperative years with 27 (38%) and 37 (52%) cases respectively (Figure 2). In particular, the mean time to diagnosis was 444 ± 212 days ranging from 180 to 910 days.\u003c/p\u003e","description":"","filename":"floatimage26.png","url":"https://assets-eu.researchsquare.com/files/rs-9394702/v1/3da65816d161be1c60f5a53c.png"},{"id":107637253,"identity":"88f73b85-f4ad-4246-afcc-0ab638cbb01e","added_by":"auto","created_at":"2026-04-23 12:41:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":488152,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9394702/v1/510dc24e-8fb0-4a9d-8fbe-82c93395f15a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bone Flap Resorption After Autologous Cranioplasty in Traumatic Brain Injury: A Case-control Study in Vietnam ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBone flap resorption is a concerning complication in autologous cranioplasty following decompressive craniectomy. It causes thinning, weakening, or even complete lysis of the flap, thereby compromising skull integrity and might necessitate revision surgery. A study in Finland found up to 90% of cases experience BFR to some extent with a mean follow-up interval of 52 months\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e while several studies reported around 20% of patients developing severe BFR.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Traumatic brain injury (TBI) is the most common indication for decompressive craniectomy. Higher rates of post-cranioplasty BFR are also found in TBI group compared to stroke or tumor.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral factors predisposing patients to bone necrosis have been suggested such as young age,\u003csup\u003e1–3,6,8,12\u003c/sup\u003e bone fragmentation,\u003csup\u003e2,3,6,7,13\u003c/sup\u003e distance between the graft-bone border,\u003csup\u003e14\u003c/sup\u003e large cranial defect,\u003csup\u003e15\u003c/sup\u003e delay to cranioplasty,\u003csup\u003e3,9,16\u003c/sup\u003e and the presence of a ventriculoperitoneal shunt.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e However, conflicting results from other studies still exist. For instance, Korhonen et al. \u003csup\u003e12\u003c/sup\u003e and Bowers et al. \u003csup\u003e13\u003c/sup\u003e found no significant association between BFR and the time interval between decompressive craniectomy and cranioplasty. A Turkish study did not identify a statistically significant link between defect size and BFR risk. \u003csup\u003e14\u003c/sup\u003e Additionally, evidence from Vietnamese cohorts remains limited. Therefore, we conducted this study to identify associated factors of bone flap resorption following autologous cranioplasty for patients with traumatic brain injury in Vietnam.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eDesign and Setting\u003c/p\u003e\u003cp\u003eA matched case-control study was conducted analyzing patients who underwent autologous cranioplasty following decompressive craniectomy for traumatic brain injury at Viet Duc University Hospital between January 2022 and July 2025. Cases were patients who developed bone resorption requiring revision cranioplasty as of July 2025. Controls were patients without clinical or radiological evidence of bone resorption. The case-control ratio was 1:2, with matching criteria including the time of cranioplasty and follow-up duration. Controls had to be operated on the same or nearest day as the matched case and must have had a follow-up period that was the same length or longer than that of the case.\u003c/p\u003e\u003cp\u003eBone Flap Preservation and Cranioplasty Surgery\u003c/p\u003e\u003cp\u003eAfter decompressive craniectomy (DC), the bone flaps were immediately sent to the hospital's tissue bank for a sterile cryopreservation process. They were first cleared of blood and soft tissue, then placed in the biomedical freezer at − 80°C with continuous temperature monitoring. During storage, routine quality checks were carried out, and any bone flap showing signs of contamination was excluded from later reimplantation. On the day of CP, the bone flap was defrosted and had the final assessment before implantation.\u003c/p\u003e\u003cp\u003eCranioplasty (CP) was conducted in an elective setting by qualified attending neurosurgeons. The same skin incision as in the decompressive craniectomy was used, and the underlying fascia and muscle layers were dissected to expose the skull defect requiring cranioplasty. The bone flap retrieved from the tissue bank was reimplanted into the cranial defect and fixed by non-absorbable sutures or titanium miniplates and screws. A subgaleal drain was routinely placed, and the wound was closed in anatomical layers. Postoperative CT imaging was undertaken within 48 hours to detect early complications, and surgical drains were generally removed on postoperative day three. The first postoperative CT scan will also be used as a reference to assess future bone resorption complications.\u003c/p\u003e\u003cp\u003ePost-cranioplasty management\u003c/p\u003e\u003cp\u003eAfter CP, the integration and stability of the implanted bone flap were assessed through physical examination and head CT imaging. Clinical signs such as palpable skull defects and localized softening or visible sinking of the flap were suggestive of bone resorption. The CT scan image of the bone flap was compared with the first postoperative imaging. BFR was classified into type I defined as partial thinning and localized resorption of the bone flap without complete structural collapse or type II in the presence of complete osteolysis involving both the inner and outer tables. (Dünisch et al.) Patients with type II BFR were indicated for revision surgeries.\u003c/p\u003e\u003cp\u003eVariables and Data Collection\u003c/p\u003e\u003cp\u003eData was extracted from the hospital computer system including all patient medical records during hospitalization and follow-up examination notes. These documented all the clinical evaluation, imaging results, surgical report and treatment process.\u003c/p\u003e\u003cp\u003eRegarding demographic and general health features, we investigated age, sex (male or female), body mass index (BMI), current smoking status (during the past 3 months), current alcohol use (units per day in the past 3 months) and comorbidities. Trauma history was also collected including the mechanism of injury and post-craniectomy complications. Examined peri-cranioplasty characteristics were preoperative Glasgow Outcome Scale Extended (GOSE) score, time interval between DC and CP, bone flap features (size, fragmentation and presence of frontal fracture), fixation method of the bone flap (plates and screws or sutures). Using Computed Tomography results, the surface area of the bone flaps was calculated by the elliptic formula (a x b x 3.14/4), in which (a) and (b) were vertical and horizontal diameters, respectively. Post-cranioplasty complications were analyzed with respect to epidural fluid collection (thickness greater than 10 mm) and surgical site infection.\u003c/p\u003e\u003ch2\u003eData Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were presented as means and standard deviations and compared between cases and controls using t-tests. The categorical factors were reported as percentages and group differences were assessed by Chi-square tests and Fisher's exact tests. Conditional logistic regression models were used to analyze the association of factors and the odds of having infection. Variables that yielded a P-value \u0026lt; 0.2 in univariate analysis were included in the multivariate adjusted logistic regression model. Results are presented as odd ratios with 95% confidence intervals. Statistical analyses were performed using Stata 17.0 (College Station, TX: StataCorp LP).\u003c/p\u003e\u003cp\u003eEthical Considerations\u003c/p\u003e\u003cp\u003eThis study was approved by the Institutional Review Board at Viet Duc University Hospital. Written informed consent was provided by the patients and family members who participated in this study.\u003c/p\u003e"},{"header":"Results","content":" \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\u003eUnivariate analysis of association between demographic, general health characteristics, trauma history and bone flap resorption.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eAge (\u0026lt;\u0026thinsp;18)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142) \u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (19.7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (12.0)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.13\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\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\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113 (79.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (20.4)\u003c/p\u003e \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\u003e(\u0026gt;\u0026thinsp;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent smoke\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol (\u0026gt;\u0026thinsp;2 unit/day)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\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\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \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\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \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\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \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\u003eChronic hepatitis B and C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \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\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTBI cause\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eTraffic accident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60(84.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111(78.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.35\u003c/p\u003e \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\u003eFall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30(21.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eViolence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplications after DC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eMeningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13(9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \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\u003eCSF - leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \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\u003eSurgical site infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u003c/p\u003e \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\u003eVP shunt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \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\u003ePneumocephalus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(5,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,69\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\u003eDemographic and general health characteristics and trauma history in the case and control groups are illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients younger than 18 years and those with hepatitis were more common in the case group (19.7% vs. 12.0% and 14.1% vs. 5.6%, respectively). No significant differences were observed for BMI, smoking status, alcohol abuse, or comorbidities. Regarding trauma history, VP shunt implantation occurred more frequently among cases (12.7% vs. 4.9%, p\u0026thinsp;=\u0026thinsp;0.04) while TBI etiology and other post-decompressive craniectomy complications did not differ significantly between groups.\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\u003eUnivariate analysis of association between peri-cranioplasty characteristics and bone flap resorption.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGOSE score before cranioplasty (\u0026gt;\u0026thinsp;4)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;71) \u003c/p\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142) \u003c/p\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (77.5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111(78.2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLate cranioplasty (\u0026gt;\u0026thinsp;180 days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(4,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBone flap size (\u0026gt;\u0026thinsp;110 cm\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSite of DC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eUnilateral hemicraniectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64(90,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e119(83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0,52\u003c/p\u003e \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\u003eBifrontal craniectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(5,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(14.1)\u003c/p\u003e \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\u003eBilateral hemicraniectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(4,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(2,1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFragmented bone flap\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(29,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(7,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFrontal sinus fracture\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,07\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBone flap fixation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\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\u003eScrews and plates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121(85.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \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\u003eSuture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(11,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative\u003c/b\u003e complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eEpidural fluid collection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(4,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(2,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,38\u003c/p\u003e \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\u003eSurgical site infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePerioperative features of the two groups and univariate analysis were presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Regarding bone flap features, the proportions of large graft size and fragmented flaps were greater in the case group compared to the control group (16.9% versus 7.8%, p\u0026thinsp;=\u0026thinsp;0.04 and 29.6% versus 7.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, respectively). On preoperative CT-scan imaging, the rate of frontal sinus fracture was also higher in the case group (7.0% versus 2.1%; p\u0026thinsp;=\u0026thinsp;0.07).\u003c/p\u003e \u003cp\u003eNo significant differences were observed for other variables including pre-op GOSE scores, late cranioplasty, bilateral craniectomy, epidural fluid collection and surgical site infection after cranioplasty.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate regression\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=\"char\" char=\".\" 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\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYoung age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u0026ndash;4,57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHepatitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3,30\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,06\u0026ndash;10,24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLarge bone flap\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3,09\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05\u0026ndash;9,08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0,04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFragmented bone flap\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e5,28\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,04\u0026ndash;13.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrontal sinus fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3,31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,65\u0026ndash;16,94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVP shunt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2,00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.63\u0026ndash;6,33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\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\u003eSix variables yielded a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.2 in the univariate analysis and were included in the multivariate statistical model including young age, chronic hepatitis, large-sized bone flap, fragmented bone flap, frontal sinus fracture and VP shunt implantation (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In multivariate analysis, three factors were identified as independent risk factors of aseptic bone resorption, including large-sized bone flap (OR: 3.96, 95% CI: 1.86\u0026ndash;8.43), fragmented bone flap (OR: 7.84, 95% CI: 1.38\u0026ndash;44.53), and chronic hepatitis (OR: 4.32, 95% CI: 1.54\u0026ndash;12.15).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCranioplasty using autologous bone is considered a special form of autologous transplantation because the bone flap has typically been cryopreserved and most of its cellular components are non-viable at the time of reimplantation.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The reintegration of bone flap greatly depends on the balance between the osteoblastic bone formation and osteoclastic bone resorption.\u003csup\u003e\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e When osteoclastic activity predominates, the flap progressively thins, ultimately leading to cranioplasty failure.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBFR is a slow and progressive process that emerges shortly after reimplantation. Although early radiological signs may be detectable on CT scans within a few months, significant resorption requiring revision is often diagnosed much later.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e In our cases, BFR-related cranioplasty failures were found at around 444\u0026thinsp;\u0026plusmn;\u0026thinsp;212 days (\u0026asymp;\u0026thinsp;14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0 months) after surgery; this finding was comparable with other previous studies. Schuss et al. reported a mean onset of 20\u0026thinsp;\u0026plusmn;\u0026thinsp;17 months,\u003csup\u003e25\u003c/sup\u003e whereas Honeybul et al. observed cases around 12 months postoperatively.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the present study, fragmented bone flaps, large flap size, and chronic hepatitis were identified as independent predictors of postoperative bone resorption.\u003c/p\u003e\n\u003ch3\u003eFragmented bone flap\u003c/h3\u003e\n\u003cp\u003eFragmentation often occurs in the setting of high-energy head trauma or when the bone flap is removed in multiple pieces during decompressive craniectomy. In our study, patients with fragmented flaps exhibited a significantly higher incidence of bone flap resorption (BFR) compared with those with single-piece flaps, which is consistent with prior reports.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e D\u0026uuml;nisch et al., in a retrospective study of 372 patients, reported that bone flaps broken into two pieces increased the odds of necrosis by 3.35-fold, whereas fragmentation into three or more pieces raised the risk by 24-fold compared with intact flaps.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Brommeland et al. also found flap fragmentation as a strong independent predictor of bone flap resorption, yielding an odds ratio of 14.3 (p\u0026thinsp;=\u0026thinsp;0.005). \u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn cryopreserved autografts (which lack viable osteoblasts), survival depends on revascularization and contacts of bone with dura and periosteum.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Fragmentation creates gaps, thereby impeding vascular invasion and osteoprogenitor cell migration to the bone flap, ultimately preventing osseous union with the native calvarium.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Moreover, unstable fragments permit subtle micromotion under the scalp, which continuously stimulates bone remodeling.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGiven the risk of BFR in extensively fragmented cases, the use of synthetic materials should be considered. Furthermore, thorough surgical planning can reduce the need for removing multiple fragments intraoperatively.\u003c/p\u003e\n\u003ch3\u003eBone flap size\u003c/h3\u003e\n\u003cp\u003eIn this study, bone flap size (\u0026ge;\u0026thinsp;110 cm\u0026sup2;) was identified as a risk factor of BFR after autologous cranioplasty. This finding aligns with a previous study by Schoekler and Trummer, concluding that large bone flaps were more susceptible to BFR.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Similarly, in a retrospective cohort study, Kim et al. also reported an increased risk of resorption in patients with bone flaps larger than 110 cm\u0026sup2;.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMany theories have been hypothesized to explain the impact of this factor on the survival of the implanted flap. After the cryopreservation period, larger bone flaps tend to accumulate greater amounts of devitalized and necrotic tissue, which amplifies local inflammatory responses. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) stimulate osteoclast differentiation and activity while suppressing osteoblast function.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e In addition, the reconstruction of a wide cranial defect is often associated with greater soft-tissue disruption and a higher likelihood of vascular injury, both of which impair neovascularization and bony reintegration.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough a large decompressive craniectomy is of pivotal importance for effective intracranial pressure control in emergency settings, the risk of BFR may be reduced by good surgical techniques. Preservation of the main vessel of the scalp as well as proper management of soft tissue should be achieved during surgery.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003eViral hepatitis\u003c/h3\u003e\n\u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eIn the present study, up to 8.5% of patients are infected with chronic viral hepatitis\u003c/span\u003e (HBV and HCV). \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThis figure partially reflects the prevalence\u003c/span\u003e of viral hepatitis in Vietnam, with HBV\u0026rsquo;s pool estimate of roughly 11% of the general population,\u003csup\u003e50\u003c/sup\u003e markedly exceeding the global average of around 3%.\u003csup\u003e51\u003c/sup\u003e In contrast, HCV prevalence is lower (1%) than HBV and highly concentrated in high-risk groups such as people who inject drugs.\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eChronic viral hepatitis\u003c/span\u003e (HBV and HCV) \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ewas associated with an\u003c/span\u003e increased risk of bone flap resorption after cranioplasty in our cohort. To our knowledge, this association has not been previously reported in the context of cranioplasty outcomes; however, the connection between chronic viral hepatitis and bone health is being established.\u003c/p\u003e \u003cp\u003eHepatitis, particularly in its chronic viral forms (HBV, HCV), is reported to increase the risk of osteoporosis.\u003csup\u003e\u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e The presence of hepatitis viruses can be a chronic trigger of cytokine release. The circulating cytokines, especially tumor necrosis factor (TNF), might promote osteoclastic activity inside the bone mineralized matrix, thereby accelerating bone resorption. \u003csup\u003e41\u0026ndash;43\u003c/sup\u003e Moreover, viral hepatitis was also linked to the decrease in vitamin D\u003csup\u003e40,44\u003c/sup\u003e and insulin-like growth factor 1 \u003csup\u003e45\u003c/sup\u003e as well as the dysregulation in the RANK\u0026ndash;RANKL\u0026ndash;OPG signaling pathway,\u003csup\u003e46\u003c/sup\u003e all of which further disrupt bone remodeling homeostasis.\u003c/p\u003e \u003cp\u003eGiven that successful cranioplasty relies on revascularization, osteoblast survival, and balanced bone remodeling, the systemic pro-resorptive environment observed in chronic viral hepatitis may compromise bone flap incorporation and accelerate resorptive processes. Antiviral treatments, particularly nucleotide analogues such as tenofovir, have been associated with reduced bone mineral density and may further contribute to bone fragility\u003csup\u003e\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Unfortunately, treatment status and duration of infection could not be fully evaluated in the present study.\u003c/p\u003e \u003cp\u003eFuture prospective studies incorporating bone metabolic markers, vitamin D levels, liver function indices, and antiviral treatment data are warranted to clarify causality and to identify high-risk patients who may benefit from alternative reconstructive strategies.\u003c/p\u003e \u003cp\u003eStrengths and Limitations\u003c/p\u003e \u003cp\u003eThis study benefits from its high number of cases which allowed multivariate analysis. However, the study still faces limitations due to its retrospective nature with potential information bias. Additionally, as a case-control study, it cannot establish causality, and the findings require confirmation through further research with stronger study designs. Furthermore, the study population included only severe cases, which may limit the generalizability of the results to the broader population with bone resorption.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBone fragmentation, bone flap size and hepatitis were associated with a higher rate of bone flap resorption after cranioplasty. Further studies are necessary to confirm these findings, especially the role of chronic viral hepatitis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTBI: traumatic brain injury; CP: cranioplasty; DC: decompressive cranioplasty; BMI: body mass index; GOSE: Glasgow Outcome Scale \u0026ndash; Extended; CSF: cerebrospinal fluid; EFC: epidural fluid collection; BFR: bone flap resorption; VP: ventriculoperitoneal; CT: computed tomography; LOS: Length of stay; OR: odds ratio; CI: confidence interval; HBV: hepatitis B virus; HCV: hepatitis C virus\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe authors sincerely acknowledge all participants of this study for their valuable contributions and cooperation throughout the research process. Their participation and support were essential to the successful completion of this work. The authors also wish to thank the medical and technical staff at the Department of Neurosurgery in Viet Duc University Hospital for their assistance in data collection and patient care during the study period. The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. None of the authors have any financial, personal, or professional relationships that could be construed as influencing the work presented in this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The study was entirely self-supported by the authors without external financial assistance. Ethical approval for this study was obtained from the Institutional Review Board of Viet Duc University Hospital. All procedures were conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eWe declare no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eWe are grateful to all patients for participating in the study.\u003c/p\u003e\n\u003ch2\u003eData availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated during and/or\u0026nbsp;analyzed\u0026nbsp;during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eDeclaration of Conflicting Interests\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThe study received no financial support from any organization\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKorhonen TK, Salokorpi N, Niinim\u0026auml;ki J, Serlo W, Lehenkari P, Tetri S (2019) Quantitative and qualitative analysis of bone flap resorption in patients undergoing cranioplasty after decompressive craniectomy. 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Lancet Infect Dis 24(6):e362\u0026ndash;e363. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1473-3099(24)00307-4\u003c/span\u003e\u003cspan address=\"10.1016/S1473-3099(24)00307-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cranioplasty, bone resorption, autologous bone, traumatic brain injury, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-9394702/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9394702/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\n\u003cp\u003eAutologous bone is a commonly used material for cranioplasty following decompressive craniectomy; however, it is accompanied by the inherent risk of resorption. This study aimed to identify factors associated with bone flap resorption (BFR) in patients undergoing autologous cranioplasty after decompressive craniectomy for traumatic brain injury.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eA matched case-control study was conducted at Viet Duc University Hospital between January 2022 and July 2025. Cases were defined as patients who developed severe BFR requiring revision surgery. Each case was matched with two controls without BFR based on cranioplasty date and follow-up duration. The association of demographic, general health, trauma historyand peri-cranioplasty characteristics with BFR was assessed using conditional logistic regression.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eA total of 71 cases and 142 matched controls were included. BFR that required surgical revision occurred predominantly within two years after cranioplasty (90%). The mean time interval from cranioplasty to complication diagnosis was 444 ± 212 days. Large-sized bone flap (OR: 3.96, 95% CI: 1.86 - 8.43), fragmented bone flap (OR: 7.84, 95% CI: 1.38 - 44.53), and chronic viral hepatitis (either B or C) (OR: 4.32, 95% CI: 1.54 - 12.15) were independent associated factors of BFR. Young age (\u0026lt;18), frontal sinus fracture and ventriculoperitoneal shunt implantation showed a trend to increase risk of BFR but failed to reach statistical significance in multivariate analysis.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eIn our study, bone fragmentation, large bone flap size, and chronic viral hepatitis were associated with increased risk of bone flap resorption after autologous cranioplasty in TBI patients. Further studies are necessary to confirm these findings, especially the role of chronic viral hepatitis.\u003c/p\u003e","manuscriptTitle":"Bone Flap Resorption After Autologous Cranioplasty in Traumatic Brain Injury: A Case-control Study in Vietnam ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 12:41:10","doi":"10.21203/rs.3.rs-9394702/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-10T15:28:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"210556788918730399878012564997741385104","date":"2026-04-21T09:48:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-16T07:22:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-14T00:01:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-14T00:00:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Neurochirurgica","date":"2026-04-12T13:49:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2945433e-8559-4c20-9517-28641ac1aa9f","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-10T15:28:42+00:00","index":11,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T12:41:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 12:41:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9394702","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9394702","identity":"rs-9394702","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}