Age-specific normative values of sacral development and fusion in children and adolescents: a cross-sectional study utilizing multi-planar reconstruction computed tomography imaging

Age-specific normative values of sacral development and fusion in children and adolescents: a cross-sectional study utilizing multi-planar reconstruction computed tomography imaging | 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 Age-specific normative values of sacral development and fusion in children and adolescents: a cross-sectional study utilizing multi-planar reconstruction computed tomography imaging Kyohei Ishizuka, Satoshi Nozawa, Daichi Watanabe, Takuma Ishihara, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4544158/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Apr, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 4 You are reading this latest preprint version Abstract Background This study aimed to determine the index of the sacral vertebrae fusion period in children and adolescents to diagnose the lesion around the sacral spine accurately. Methods Patients aged 0–40 years who underwent computed tomography (CT), including the sacrum, for abdominal disorders, trauma, etc., between 2019 and 2022 were retrospectively examined. There were 402 eligible sacra (385 patients: 206 women and 179 men). We evaluated bony fusion at six parts of the sacral vertebrae (anterior or posterior of each intervertebral and both side lateral masses). The predicted probability of bony fusion obtained from the logistic regression model is depicted graphically by sex. Results The association between bony fusion in each vertebral segment and age was evaluated using a logistic regression model with a Huber–White robust sandwich estimator, including the patient as a clustering variable. Bony fusion of the sacral bodies of S1/S2 was slowest, with 80% of patients achieving bony fusion at 28.7 and 24.6 years of age for men and women, respectively. Compared to men, women exhibited earlier fusion of the intervertebral segments of the sacral vertebrae; however, no significant difference between the sexes in terms of eventual bony fusion at the lateral mass was observed, while the initiation of bony fusion occurred earlier in women. Conclusion The predicted probability of bony fusion could aid pediatricians, orthopedists, radiologists, and other physicians in understanding the normal development of the sacral spine and accurately diagnosing the lesion around the sacral spine. sacral spine development sacrum adolescent bony fusion Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background To accurately diagnose lesions around the sacral spine in pediatric patients, it is crucial to understand the normal development of the sacral spine. Insufficient fusion of the sacral vertebrae may be related to low back pain. However, most physicians are unfamiliar with the normal development of this region. Anatomy textbooks note that the sacral vertebrae are initially formed embryologically as separate structures [ 1 ]. The intervertebral spaces fuse gradually from the age of 16–18 years, and all the intervertebral spaces are considered to have fused by 30 years of age [ 1 ]. However, in clinical practice, the bony fusion timing varies even among patients of the same age. Under the circumstances, references, such as age-specific normative values of the development, could be helpful guides for physicians. To date, literature on the anatomical development of the lumbar spine, sacrum, and pelvis is extremely limited and small in size [ 2 , 3 ]. To our knowledge, there are no clear criteria for determining the progress of bony fusion of the sacral vertebrae. In this study, we present age-specific normative values for the bony fusion of the sacral vertebrae, using computed tomography (CT) images of 402 normal sacral bones from individuals aged 0–40 years. Methods Study design A retrospective cross-sectional investigation Patient selection The study comprised patients aged 0–40 years that visited or were transferred to the various departments of our hospital (e.g., pediatrics, emergency unit, internal medicine, surgery, and orthopedics) between February 2019 and November 2022 and underwent 1-mm slice thickness CT scans with sacrum evaluation. Patients with low back pain (LBP), severe fractures, bone tumors, inflammatory diseases of the pelvic region, and genetic diseases were excluded from the study. Patient variables Digital Imaging and Communications in Medicine format was used to store and read CT scans of 1-mm slice thickness. Orthopedic surgeons used the volume-rendering approach using 3D CT scans to assess bony fusion. The region of interest for bony fusion was divided into anterior–posterior at the vertebral bodies and both lateral masses, and a score at each of the six locations was maintained. The fusion criteria by Luis Rios et al. [ 2 ] were used. Briefly, the absence of bony fusion was assigned the value 0; up to 1/3 of the total area, approximately 1/2 and more than 2/3 were assigned the values 1, 2, and 3, respectively, and complete fusion was assigned the value 4. Assessments were performed by the first examiner (K.I.). To test the intra- and interexaminer reliability, the first and second observers (S.N.) assessed the images obtained from 40 patients. Statistical analysis The association between bony fusion in each vertebral segment and age was evaluated using a logistic regression model with a Huber–White robust sandwich estimator, including the patient as a clustering variable. To confirm the hypothesis that the association between sacral fusion and age varies by sex, sex and a two-way interaction term (age * sex) were included in the logistic regression model. A test of the interaction term confirmed the modifying effect of sex on the relationship between sacral fusion and age. The sex-specific predicted probability of bony fusion obtained from the logistic regression model is shown graphically. Patient characteristics were summarized using medians and interquartile ranges (IQR) for continuous variables and frequencies for categorical variables. Only one case had missing values; therefore, complete data were used for analysis. The significance level was set at a p-value of ˂ 0.05. All p-values were two-sided, and the significance level was set at a p-value of ˂ 0.05. Analyses were performed using R 4.2.2 (The R Project for Statistical Computing). Based on the findings of CT, intra- and interexaminer reliability of the bony fusion assessments was evaluated using intraclass correlation coefficients (ICC). Ethical approval Using opt-out consent, Hospital Institutional Review Board has accepted this retrospective study under study number #2022-175. The research was conducted following the tenets of the Declaration of Helsinki and its later amendments. Results Among all patients who underwent CT examinations, 2090 were eligible, and the pelvic regions of 413 of these patients were included. Of these 413 patients, 13 were scanned multiple times, which was >1 year apart; five sacra were scanned twice within a year and were included only once; and six sacra were excluded because they had apparent morphologic abnormalities owing to tumors or Marfan syndrome. Overall, 402 sacra from 385 patients were used to assess the morphology of the lumbar spine and sacrum in detail (Figure 1). The distribution of 402 sacra was as follows: 0–9-year-olds: 25 cases (6.2%); 10–14-year-olds: 32 cases (8.0%); 15–19-year-olds: 43 cases (10.7%); 20–24-year-olds: 57 cases (14.2%); 25–29-year-olds: 67 cases (16.7%); 30–34-year-olds: 70 cases (17.4%); and 35–40-year-olds: 108 cases (26.9%). The median age was 28 (IQR: 20–35). The detailed distribution of each age group is shown in Figure 2. Bony fusion was generally evaluated at the lateral mass and vertebral body separately. Intra- and interexaminer reliabilities were tested by randomly selecting 40 cases (10% of all cases). To determine bony fusion, the intraexaminer reliability was ICC 0.94 (95% confidence interval [CI], 0.93–0.94), and the interexaminer reliability was ICC 0.86 (95% CI, 0.84–0.88). The degree of fusion was associated with age at both locations (p-value = 0.001). The predicted probability of sacral fusion (score = 4) for age in each lateral mass stratified by sex is shown in Figure 3a–d. The line representing 80% of the fusion probability is represented by a dotted line. The gray zone depicts the 95% CI (Figure 3e). Most lower vertebrae showed bony fusion by age 13, with 80% of men and women showing bony fusion in all vertebrae by age 16 and 15, respectively. The S1 and S2 vertebrae showed the slowest bony fusion compared with the other vertebrae. Both S2/S3 and S4/S5 bony fusion showed significant differences between the sexes, with fusion initiating earlier in women than in men (interaction p-value of <0.001 and 0.006, respectively). Figure 4a–c demonstrates the bony fusion process of the anterior surface of the lateral masses, and Figure 4d–f depict the bony fusion process of the posterior surface of the lateral masses. In all vertebral segments, the age at the beginning, progress, and completion of bony fusion were not different between the anterior and posterior surfaces. Figure 5a–d shows the relationship between sacral fusion (score = 4) and age in the anterior region of the vertebral body of each vertebral segment, stratified by sex. The calculated age at which 80% of people attained bony fusion is shown in Figure 5e. Cranial intervertebral spaces above S3/S4 exhibited slower fusion. Results showed that women attained earlier bony fusion at all vertebral elevations. In 80% of the patients, bony fusion was confirmed at the S1/S2 vertebrae at 28.7 and 24.6 years of age for men and women, respectively. The S2/3 vertebrae and lateral masses, the association between age and bony fusion differed significantly by sex (interaction p-value = 0.022). In S3/S4 vertebrae, there was no difference in the onset of bony fusion between the sexes; however, women showed a rapid progression of bony fusion in the 10-year age group. Figure 6a–d shows the relationship between sacral fusion (score = 4) and age at the posterior segment of the vertebral body, stratified by sex. The age at which 80% of people attain bony fusion is shown in Figure 6e. Posterior fusion at the S1/S2 vertebrae and the anterior vertebrae occurs approximately 10 years of age following the bony fusion at S2/S3. A significant interaction between age and sex was not found for each posterior vertebral segment. The female group had significantly faster bony fusion progression at the S3/S4 and in the anterior vertebral body (p-value = 0.024). Based on the results, representative three-dimensional CT (3D-CT) images of the normal development of the sacrum are presented in Figure 7. In 6-year-old males, there was almost no fusion in any intervertebral space (Figure 7a). At 11 years of age, men had no fusion in any intervertebral space. In contrast, in females, fusion could be observed in many patients in the lower intervertebral spaces (Figure 7b). In 13-year-old females, fusion was observed in the lateral masses of each vertebral intervertebral space (Figure 7c), and at 16 years of age, fusion was seen in the lateral masses of all vertebral intervertebral spaces in most patients (Figure 7d). At approximately 25 years of age, most patients of both sexes exhibited fusion at all intervertebral mass sites (Figure 7e and f).[4] Utility of age -specific normative values of sacrum in diagnosing an illustrative case We encountered a case involving an 11-year-old girl who complained of LBP around the sacrum and urinary issues after intense dancing. A CT scan of the sacrum revealed incomplete fusion between the first and second sacral vertebrae (Figure 8). It was challenging to determine whether this bony development was normal. However, based on our age-specific normative values of the sacrum, we assumed that her sacral fusion was inadequate for her age, and strenuous activity was likely the cause of the LBP with bladder and bowel dysfunction. Conservative treatment, including relaxation, dance, and sports exercise, was administered for 3 months. Six months later, the patient was found to be asymptomatic. Discussion To our knowledge, this is the first study to demonstrate the age-specific normative values of sacral development and fusion based on over 400 sacra. The present study also shows the probability of bony fusion at each site for each age group. It is also shown that in the S1/S2, the most crucial level in clinical practice, bony fusion progresses gradually in the front of the vertebral body and is completed after the age of 25 years. In the lateral mass, bony fusion progresses rapidly after the age of 10 years and is completed around 15 years of age. Some reports investigate the development of primary/secondary ossification centers using small cases of the sacrum (anterior and posterior epiphysis and endplate ring epiphysis) by CT or MRI. The studies reveal that epiphyses begin to fuse at around the age of 13 and 11 in males and females, respectively, with complete bony fusion at 16–25 years of age, asymmetry in the progression of fusion, and the risk of confusion with a fracture in the state of partial fusion [5-7]. Broome et al. showed a radiographic description of the postnatal development anatomy of the sacrum with minor cases of 37 CT images (X-ray: 63 cases, MRI: 10 cases). They demonstrated that the ages of fusion are 17–24 years at intervertebral disk spaces and 11–16 years at the costal process on the S1–S2 level; 11–22 years and 2–18 years on the S2–S3 level; 8–15 years and 5–18 years on the S3–4 level, respectively. Our present study investigating 402 sacra from the fusion period aligns with their results. Cardoso et al. reported the chronological data on primary and secondary ossification centers in dry bones using 191 cases. They showed the fusion sequence follows a caudal-cranial and anterior–posterior gradient in the primary centers of ossification [8]. Meijerman et al. investigated the association between sex, socioeconomic status, and ethnicity with bony fusion. They reported the effect of socioeconomic status on bony fusion of the medial clavicular epiphysis, with slower fusion in the absence of economic wealth [9]. An earlier bony fusion in the vertebral body in women has been reported in a previous report, which is consistent with the present study [2, 8]. Reports implicate estrogens and androgens in skeletal sexual dimorphism [4]. Females undergo the growth spurt during puberty approximately two years earlier than males, a difference that we consider reflected in the earlier completion of bony fusion. It has also been suggested that the importance of bipedal walking and weight transfer through the sacrum influences sacral fusion. Bony fusion does not occur in paraplegic patients because of the lack of load on this area [10, 11]. The following reports discuss the impact of insufficient bony fusion between S1/S2 and lower back pain. According to von Brandis et al., it is important not to mistake an unfused growth plate for a fracture line when interpreting sacral images [12]. Lumbarization is the complete or incomplete fusion of the upper sacral vertebrae with the L5 [13]. Previous studies have shown a connection between insufficient fusion in the transitional vertebrae and LBP. Vinha et al. found that patients with lumbosacral transitional vertebrae (LSTV) often experience LBP [14]. Nardo et al. also noted a positive correlation between type II and LBP [15]. Insufficient bony fusion may lead to a change in normal spinal biomechanics, potentially contributing to LBP. This study found sex-specific differences in the bony fusion of S2/S3 and S4/S5 lateral masses. Sex-based differences in the sacroiliac joint (SIJ) begin at approximately 14 years of age, with males demonstrating significant differences from females [16]. In males, the center of gravity is more anterior to the SIJ, and the load on the SIJ is greater. Furthermore, S1/S2 and S2/S3 have significantly deeper curvature in men [17]. These morphological changes might affect bony fusion in their early teens. The involvement with racial variation in sacral kyphosis [18] should be the focus of future investigations. Our results should be considered alongside several study limitations. A major limitation was that the samples were derived from a single ethnic group. Second, the sample size is a relatively small amount of data, especially for patients below the age of 10, resulting in a large CI for that age group. Conclusion We have presented the age-specific normative values and predicted probability of sacral fusion based on over 400 sacra examinations. This study will help pediatricians, orthopedic surgeons, radiologists, and other physicians to better understand sacral development and related diagnoses. List Of Abbreviations CI Confidence intervals CT Computed tomography ICC Intraclass correlation coefficients LBP Low back pain SIJ Sacroiliac joint Declarations Ethics approval and consent to participate Using opt-out consent, Hospital Institutional Review Board has accepted this retrospective study under study number #2022-175. The research was conducted following the tenets of the Declaration of Helsinki and its later amendments. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors received no financial or material support for the research, authorship, and/or publication of this article. Funding This work was supported by Johnson & Johnson Medical Research Grant. Author contributions K.I. was responsible for data collection, literature extraction, manuscript description, and data interpretation. S.N. helped with research design, acquired data, and helped write manuscript. K.Y. and C.I. contributed to clinical aspects of research design and data interpretation. D.W. and T.I. interpreted data and helped write the manuscript. H.A. was responsible for final approval of the manuscript. All authors have read and approved the final submitted manuscript. Acknowledgments We would like to thank Daichi Watanabe and Takuma Ishihara, Ph.D. Centre for Advanced Medical Sciences and Clinical Research, Gifu University Hospital, for their advice on statistics. This work was supported by Johnson & Johnson Medical Research Grant. References Wilkins LW, Agur AMR. Grant’s atlas of anatomy. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 1999. Ríos L, Weisensee K, Rissech C. Sacral fusion as an aid in age estimation. Forensic Sci Int. 2008;180:e1111–7. Mahon TJ, Friedling LJ, Gordon GM. The use of ventral fusion between sacral elements S1 and S2 as an additional age-at-death indicator in a black South African skeletal sample. Forensic Sci Int. 2018;286:e2671–6. Almeida M, Laurent MR, Dubois V, Claessens F, O’Brien CA, Bouillon R, et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev. 2017;97:135–87. Broome DR, Hayman LA, Herrick RC, Braverman RM, Glass RB, Fahr LM. Postnatal maturation of the sacrum and coccyx: MR imaging, helical CT, and conventional radiography. AJR Am J Roentgenol. 1998;170:1061–6. Grissom LE, Harty MP, Guo GW, Kecskemethy HH. Maturation of pelvic ossification centers on computed tomography in normal children. Pediatr Radiol. 2018;48:1902–14. Zejden A, Jurik AG. Anatomy of the sacroiliac joints in children and adolescents by computed tomography. Pediatr Rheumatol Online J. 2017;15:82. Cardoso HFV, Pereira V, Rios L. Chronology of fusion of the primary and secondary ossification centers in the human sacrum and age estimation in child and adolescent skeletons. Am J Phys Anthropol. 2014;153:214–25. Meijerman L, Maat GJR, Schulz R, Schmeling A. Variables affecting the probability of complete fusion of the medial clavicular epiphysis. Int J Legal Med. 2007;121:463–8. Abitbol MM. Evolution of the sacrum in hominoids. Am J Phys Anthropol. 1987;74:65–81. Esses SI, Botsford DJ, Huler RJ, Rauschning W. Surgical anatomy of the sacrum. A guide for rational screw fixation. Spine. 1991;16(suppl):S283–8. von Brandis E, Zadig PK, Avenarius DFM, Flatø B, Kristian Knudsen P, Lilleby V, et al. Whole body magnetic resonance imaging in healthy children and adolescents. Bone marrow appearances of the axial skeleton. Eur J Radiol. 2022;154:110425. Murlimanju BV, Prabhu LV, Pai MM, Ganeshkumar C, Sarvepalli A. Lumbosacral transitional vertebrae: a case report and clinical implications. Int J Morphol. 2011;29:1123–5. Vinha A, Bártolo J, Lemos C, Cordeiro F, Rodrigues-Pinto R. Lumbosacral transitional vertebrae: prevalence in a southern European population and its association with low back pain. Eur Spine J. 2022;31:3647–53. Nardo L, Alizai H, Virayavanich W, Liu F, Hernandez A, Lynch JA, et al. Lumbosacral transitional vertebrae: association with low back pain. Radiology. 2012;265:497–503. Vleeming A, Schuenke MD, Masi AT, Carreiro JE, Danneels L, Willard FH. The sacroiliac joint: an overview of its anatomy, function and potential clinical implications. J Anat. 2012;221:537–67. Plochocki JH. Sexual dimorphism of anterior sacral curvature. J Forensic Sci. 2011;56:161–4. Krenn VA, Webb NM, Fornai C, Haeusler M. Sex classification using the human sacrum: geometric morphometrics versus conventional approaches. PLoS ONE. 2022;17:e0264770. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Apr, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Revision requested 17 Jun, 2024 Editor assigned by journal 14 Jun, 2024 Submission checks completed at journal 14 Jun, 2024 First submitted to journal 07 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4544158","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315491630,"identity":"39750f51-f419-4d82-9a5b-92003ee4aa1f","order_by":0,"name":"Kyohei Ishizuka","email":"","orcid":"","institution":"Gifu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kyohei","middleName":"","lastName":"Ishizuka","suffix":""},{"id":315491631,"identity":"a1e4efbd-fafd-4eeb-96a4-48c83de726f1","order_by":1,"name":"Satoshi Nozawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYLCCDwY2cgwMPDDuAcI6GGcUpBmTpoWZ48PhxAaEFgLAnL394WcGg7T0DcfPHnzwgcFOjoHxLH5rLHsOJEsXGNjkbjiTl2w4gyEZ6MJzCXi1GNxIOCA9wyAtd8OBHDNpHoYDQBeeMSCgJbH5N4/B4XSD82+I1pLMJg3UkmBwg2hbzhxjswQ6zHDmjTfGhjMMko3ZCPrlePvjGx/+2Mjznc8xfPChwk6OX4JAiMGBAlgd0ElsEmeI08Eg3wBj8fcQqWUUjIJRMApGCgAAitVKU6Vf+QMAAAAASUVORK5CYII=","orcid":"","institution":"Gifu University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Nozawa","suffix":""},{"id":315491632,"identity":"ea691605-a2ba-4dbf-a979-7f426943eb29","order_by":2,"name":"Daichi Watanabe","email":"","orcid":"","institution":"Gifu University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daichi","middleName":"","lastName":"Watanabe","suffix":""},{"id":315491633,"identity":"6c6c6641-d978-4a1a-968c-5e5e493767e1","order_by":3,"name":"Takuma Ishihara","email":"","orcid":"","institution":"Gifu University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takuma","middleName":"","lastName":"Ishihara","suffix":""},{"id":315491634,"identity":"5ad069a0-f0be-4754-848e-218475631289","order_by":4,"name":"Kazunari Yamada","email":"","orcid":"","institution":"Gifu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kazunari","middleName":"","lastName":"Yamada","suffix":""},{"id":315491635,"identity":"6cf80dc3-0a3d-41ea-a746-0a46c9b2f6ef","order_by":5,"name":"Chizuo Iwai","email":"","orcid":"","institution":"Gifu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Chizuo","middleName":"","lastName":"Iwai","suffix":""},{"id":315491636,"identity":"49f2c661-593d-41ee-9590-02c206cbb50d","order_by":6,"name":"Haruhiko Akiyama","email":"","orcid":"","institution":"Gifu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Haruhiko","middleName":"","lastName":"Akiyama","suffix":""}],"badges":[],"createdAt":"2024-06-07 07:03:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4544158/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4544158/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-025-08597-w","type":"published","date":"2025-04-10T16:05:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59515582,"identity":"489b3cba-cf33-4218-8cba-5a24572c2e86","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26997,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of patient selection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients undergoing CT between February 2019 and November 2022 were included. The data of patients who underwentimaging of the pelvic region were extracted, and some patients were excluded. Finally, 402 eligible CT images were included.\u003c/p\u003e","description":"","filename":"Fig11.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/83e332bce3b18b7a33071277.png"},{"id":59515586,"identity":"05b53f12-5654-4d8a-8eb0-ad1250541313","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25810,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSex and age distribution of the 402 sacra.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis figure depicts the sex and age data for the 402 study patients.\u003c/p\u003e","description":"","filename":"Fig21.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/5d65bb9d9b8a9fbc16f5a3a1.png"},{"id":59516838,"identity":"770cb6b4-5b17-4207-8972-cd1dc0d84b2a","added_by":"auto","created_at":"2024-07-02 17:41:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":212022,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePredicted probability of sacral fusion by age for each lateral mass.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe S1/S2 vertebrae fusion showed the slowest bony fusion progression compared with the other vertebrae. Significant changes by sex were observed in S2/S3 and S4/S5, indicating that the initiation of bony fusion is earlier in female vertebrae than in male vertebrae (interaction p-values \u0026lt;0.001and 0.006, respectively).\u003c/p\u003e","description":"","filename":"Fig31.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/9363db5eac07ab91219955aa.png"},{"id":59516839,"identity":"fdb278fe-64f3-4c4d-bcdf-4685e15ae6fe","added_by":"auto","created_at":"2024-07-02 17:41:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":192077,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePredicted probability of sacral fusion by age and lateral mass segment.\u003cbr\u003e\n \u003c/strong\u003eThe process of bony fusion of the anterior surface of the lateral masses is depicted in Figure 4a–c, while Figure 4d–f illustrates the process of bony fusion of the posterior surface of the lateral masses. In all vertebral segments, the age at the beginning, progress, and completion of bony fusion remained consistent between the anterior and posterior surfaces.\u003c/p\u003e","description":"","filename":"Fig41.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/fdf0ccc59f180655cdd27158.png"},{"id":59515579,"identity":"fb0c602a-d494-4b86-be31-644b5e507525","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":222710,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePredicted probability of sacral fusion by age for each vertebra on the anterior surface.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis figure illustrates the relationship between intervertebral space and sacral fusion rate, showing that a higher intervertebral space from S3/S4 results in slower fusion. It also demonstrates a significant interaction between age and sex, with women completing bony fusion earlier at the S2/S3 level and in the lateral masses.\u003c/p\u003e","description":"","filename":"Fig51.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/2d2dd545236c380e5e8f9151.png"},{"id":59515584,"identity":"18bde7e0-0014-4f5c-a395-6ba0a474e152","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":211998,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePredicted probability of sacral fusion by age at each vertebra on the posterior surface. \u003cbr\u003e\n \u003c/strong\u003eThe posterior and anterior vertebrae require approximately 10 years for the bony fusion of S2/S3 and S1/S2. There is no significant interaction between age and sex in either of the vertebral segments. The female group exhibitedsignificantly faster bony fusion progression in the S3/S4 vertebrae and anterior vertebral body (p = 0.024) than male group.\u003c/p\u003e","description":"","filename":"Fig61.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/7aaac494cfd75b25f3379614.png"},{"id":59515585,"identity":"5ab9ccb2-28c2-489f-9ec9-687dd8ada71f","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":891580,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThree-dimensional computed tomography (3D-CT) images depicting normal sacral development\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt 6 years of age, almost no fusion was observed in any intervertebral space in males. By 11 years of age, essentially no fusion was observed in any intervertebral space in males; however, in females, fusion was observed in many cases in the lower intervertebral spaces. At 13 years of age, fusion was observed in the lateral masses of each vertebral intervertebral space in females, and at 16 years of age, fusion was observed in the lateral masses of all vertebral intervertebral spaces in most patients. At approximately 25 years of age, most patients of both sexes exhibited fusion at all sites of intervertebral masses.\u003c/p\u003e","description":"","filename":"FIg71.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/70c5047ca59f2baee1da527e.png"},{"id":59515583,"identity":"4ee056f0-64b4-4bda-b6aa-0b39b5ea2845","added_by":"auto","created_at":"2024-07-02 17:33:51","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":556911,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUtility of age-specific normative values of the sacrum in diagnosing an illustrative case\u003cbr\u003e\n \u003c/strong\u003eAn 11-year-old girl presenting with complaints of low back pain (LBP) around the sacrum and urinary disturbance after strenuous dancing. A computed tomography scan revealed incomplete bony fusion at S1/S2 and S2/S3 (arrowhead). Based on our age-specific normative values of the sacrum, we assumed that her sacral fusion was inadequate for her age. She is currently receiving conservative treatment with no exercise; she no longer complains of pain 6 months later.\u003c/p\u003e","description":"","filename":"Fig81.png","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/ba009efa1bf1be604ba5b95e.png"},{"id":80558616,"identity":"a6d3d374-8db3-40ff-8d8a-1f37f0d57379","added_by":"auto","created_at":"2025-04-14 16:15:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3177903,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4544158/v1/71b78ac4-c206-4ee6-8cd5-eed178c93c96.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Age-specific normative values of sacral development and fusion in children and adolescents: a cross-sectional study utilizing multi-planar reconstruction computed tomography imaging","fulltext":[{"header":"Background","content":"\u003cp\u003eTo accurately diagnose lesions around the sacral spine in pediatric patients, it is crucial to understand the normal development of the sacral spine. Insufficient fusion of the sacral vertebrae may be related to low back pain. However, most physicians are unfamiliar with the normal development of this region. Anatomy textbooks note that the sacral vertebrae are initially formed embryologically as separate structures [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The intervertebral spaces fuse gradually from the age of 16\u0026ndash;18 years, and all the intervertebral spaces are considered to have fused by 30 years of age [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, in clinical practice, the bony fusion timing varies even among patients of the same age. Under the circumstances, references, such as age-specific normative values of the development, could be helpful guides for physicians. To date, literature on the anatomical development of the lumbar spine, sacrum, and pelvis is extremely limited and small in size [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo our knowledge, there are no clear criteria for determining the progress of bony fusion of the sacral vertebrae. In this study, we present age-specific normative values for the bony fusion of the sacral vertebrae, using computed tomography (CT) images of 402 normal sacral bones from individuals aged 0\u0026ndash;40 years.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eA retrospective cross-sectional investigation\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eThe study comprised patients aged 0\u0026ndash;40 years that visited or were transferred to the various departments of our hospital (e.g., pediatrics, emergency unit, internal medicine, surgery, and orthopedics) between February 2019 and November 2022 and underwent 1-mm slice thickness CT scans with sacrum evaluation. Patients with low back pain (LBP), severe fractures, bone tumors, inflammatory diseases of the pelvic region, and genetic diseases were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatient variables\u003c/h2\u003e \u003cp\u003eDigital Imaging and Communications in Medicine format was used to store and read CT scans of 1-mm slice thickness. Orthopedic surgeons used the volume-rendering approach using 3D CT scans to assess bony fusion. The region of interest for bony fusion was divided into anterior\u0026ndash;posterior at the vertebral bodies and both lateral masses, and a score at each of the six locations was maintained. The fusion criteria by Luis Rios et al. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] were used. Briefly, the absence of bony fusion was assigned the value 0; up to 1/3 of the total area, approximately 1/2 and more than 2/3 were assigned the values 1, 2, and 3, respectively, and complete fusion was assigned the value 4. Assessments were performed by the first examiner (K.I.). To test the intra- and interexaminer reliability, the first and second observers (S.N.) assessed the images obtained from 40 patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe association between bony fusion in each vertebral segment and age was evaluated using a logistic regression model with a Huber\u0026ndash;White robust sandwich estimator, including the patient as a clustering variable. To confirm the hypothesis that the association between sacral fusion and age varies by sex, sex and a two-way interaction term (age * sex) were included in the logistic regression model. A test of the interaction term confirmed the modifying effect of sex on the relationship between sacral fusion and age. The sex-specific predicted probability of bony fusion obtained from the logistic regression model is shown graphically. Patient characteristics were summarized using medians and interquartile ranges (IQR) for continuous variables and frequencies for categorical variables. Only one case had missing values; therefore, complete data were used for analysis. The significance level was set at a p-value of ˂ 0.05. All p-values were two-sided, and the significance level was set at a p-value of ˂ 0.05. Analyses were performed using R 4.2.2 (The R Project for Statistical Computing). Based on the findings of CT, intra- and interexaminer reliability of the bony fusion assessments was evaluated using intraclass correlation coefficients (ICC).\u003c/p\u003e \u003c/div\u003e\n\u003ch2\u003eEthical approval\u003c/h2\u003e\n\u003cp\u003eUsing opt-out consent, Hospital Institutional Review Board has accepted this retrospective study under study number #2022-175. The research was conducted following the tenets of the Declaration of Helsinki and its later amendments.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAmong all patients who underwent CT examinations, 2090 were eligible, and the pelvic regions of 413 of these patients were included. Of these 413 patients, 13 were scanned\u0026nbsp;multiple times, which was \u0026gt;1 year apart; five sacra were scanned twice within a year and were included only once; and six sacra were excluded because they had apparent morphologic abnormalities owing to\u0026nbsp;tumors or Marfan syndrome. Overall, 402 sacra\u0026nbsp;from 385 patients\u0026nbsp;were used to assess the morphology of the lumbar spine and sacrum in detail (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe distribution of\u0026nbsp;402 sacra\u0026nbsp;was as follows: 0\u0026ndash;9-year-olds: 25 cases (6.2%); 10\u0026ndash;14-year-olds: 32 cases (8.0%); 15\u0026ndash;19-year-olds: 43 cases (10.7%); 20\u0026ndash;24-year-olds: 57 cases (14.2%); 25\u0026ndash;29-year-olds: 67 cases (16.7%); 30\u0026ndash;34-year-olds: 70 cases (17.4%); and 35\u0026ndash;40-year-olds: 108 cases (26.9%).\u0026nbsp;The median age was 28 (IQR: 20\u0026ndash;35). The detailed distribution of each age group is shown in Figure 2.\u003c/p\u003e\n\u003cp\u003eBony fusion was generally evaluated at the lateral mass and vertebral body separately.\u003c/p\u003e\n\u003cp\u003eIntra- and interexaminer reliabilities were tested by randomly selecting 40 cases (10% of all cases). To determine bony fusion, the intraexaminer reliability was ICC 0.94 (95% confidence interval [CI], 0.93\u0026ndash;0.94), and the interexaminer reliability was ICC 0.86 (95% CI, 0.84\u0026ndash;0.88). The degree of\u0026nbsp;fusion was associated with age at both locations (p-value = 0.001).\u0026nbsp;The predicted probability of sacral fusion (score = 4) for age in each lateral mass stratified by sex is shown in Figure 3a\u0026ndash;d. The line representing 80% of the fusion probability is represented by a dotted line. The\u0026nbsp;gray\u0026nbsp;zone depicts the 95% CI (Figure 3e). Most lower vertebrae showed bony fusion by age 13, with 80% of men and women showing bony fusion in all vertebrae by age 16 and 15, respectively. The S1 and S2\u0026nbsp;vertebrae showed the slowest bony fusion compared with the other vertebrae. Both S2/S3 and S4/S5 bony fusion showed significant differences between the sexes, with fusion initiating earlier in women than in men (interaction p-value of \u0026lt;0.001 and 0.006, respectively).\u003c/p\u003e\n\u003cp\u003eFigure 4a\u0026ndash;c demonstrates the bony fusion process of the anterior surface of the lateral masses, and Figure 4d\u0026ndash;f depict the bony fusion process of the posterior surface of the lateral masses. In all vertebral segments, the age at the beginning, progress, and completion of bony fusion were not different between the anterior and posterior surfaces. Figure 5a\u0026ndash;d shows the relationship between sacral fusion (score = 4) and age in the anterior region of the vertebral body of each vertebral segment, stratified by sex. The calculated age at which 80% of people attained bony fusion is shown in Figure 5e. Cranial intervertebral spaces above S3/S4 exhibited slower fusion. Results showed that women attained earlier bony fusion at all vertebral elevations. In 80% of the patients, bony fusion was confirmed at the S1/S2 vertebrae at 28.7 and 24.6 years of age for men and women, respectively. The S2/3 vertebrae and lateral masses, the association between age and bony fusion differed significantly by sex (interaction p-value = 0.022). In S3/S4 vertebrae, there was no difference in the onset of bony fusion between the sexes; however, women showed a rapid progression of bony fusion in the 10-year age group.\u003c/p\u003e\n\u003cp\u003eFigure 6a\u0026ndash;d shows the relationship between sacral fusion\u0026nbsp;(score = 4)\u0026nbsp;and age\u0026nbsp;at the posterior segment of the vertebral body, stratified by sex. The age\u0026nbsp;at which 80% of people attain bony fusion is shown in\u0026nbsp;Figure 6e. Posterior fusion at the S1/S2 vertebrae and the anterior vertebrae occurs approximately 10 years of age following the bony fusion\u0026nbsp;at S2/S3. A significant interaction between age and sex\u0026nbsp;was not found for each posterior vertebral segment. The female group had significantly faster bony fusion progression at the S3/S4 and in the anterior vertebral body (p-value = 0.024).\u003c/p\u003e\n\u003cp\u003eBased on the results, representative three-dimensional CT (3D-CT) images of the normal development of the sacrum are presented in Figure 7. In 6-year-old males, there was almost no fusion in any intervertebral space (Figure 7a). At 11 years of age, men had no fusion in any intervertebral space. In contrast, in females, fusion could be observed in many patients in the lower intervertebral spaces (Figure 7b). In 13-year-old females, fusion was observed in the lateral masses of each vertebral intervertebral space (Figure 7c), and at 16 years of age, fusion was seen in the lateral masses of all vertebral intervertebral spaces in most patients (Figure 7d). At approximately 25 years of age, most patients of both sexes exhibited fusion at all intervertebral mass sites (Figure 7e and f).[4]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUtility of age\u003c/strong\u003e\u003cstrong\u003e-specific normative values of sacrum in diagnosing an illustrative case\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe encountered a case involving an 11-year-old girl who complained of LBP around the sacrum and urinary issues after intense dancing. A CT scan of the sacrum revealed incomplete fusion between the first and second sacral vertebrae (Figure 8). It was challenging to determine whether this bony development was normal. However, based on our age-specific normative values of the sacrum, we assumed that her sacral fusion was inadequate for her age, and strenuous activity was likely the cause of the LBP with bladder and bowel dysfunction. Conservative treatment, including relaxation, dance, and sports exercise, was administered for 3 months. Six months later, the patient was found to be asymptomatic.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study to demonstrate the age-specific normative values of sacral development and fusion based on over 400 sacra. The present study also shows the probability of bony fusion at each site for each age group. It is also shown that in the S1/S2, the most crucial level in clinical practice, bony fusion progresses gradually in the front of the vertebral body and is completed after the age of 25 years. In the lateral mass, bony fusion progresses rapidly after the age of 10 years and is completed around 15 years of age.\u003c/p\u003e\n\u003cp\u003eSome reports investigate the development of primary/secondary ossification centers using small cases of the sacrum (anterior and posterior epiphysis and endplate ring epiphysis) by CT or MRI. The studies reveal that epiphyses begin to fuse at around the age of 13 and 11 in males and females, respectively, with complete bony fusion at 16\u0026ndash;25 years of age, asymmetry in the progression of fusion, and the risk of confusion with a fracture in the state of partial fusion\u0026nbsp;[5-7].\u0026nbsp;Broome et al. showed a radiographic description of the postnatal development anatomy of the sacrum with minor cases of 37 CT images (X-ray: 63 cases, MRI: 10 cases). They demonstrated that the ages of fusion are 17\u0026ndash;24 years at intervertebral disk spaces and 11\u0026ndash;16 years at the costal process on the S1\u0026ndash;S2 level; 11\u0026ndash;22 years and 2\u0026ndash;18 years on the S2\u0026ndash;S3 level; 8\u0026ndash;15 years and 5\u0026ndash;18 years on the S3\u0026ndash;4 level, respectively. Our present study investigating 402 sacra from the fusion period aligns with their results. Cardoso et al. reported the chronological data on primary and secondary ossification centers in dry bones using 191 cases. They showed the fusion sequence follows a caudal-cranial and anterior\u0026ndash;posterior gradient in the primary centers of ossification\u0026nbsp;[8].\u003c/p\u003e\n\u003cp\u003eMeijerman et al. investigated the association between sex, socioeconomic status, and ethnicity with bony fusion. They reported the effect of socioeconomic status on bony fusion of the medial clavicular epiphysis, with slower fusion in the absence of economic wealth\u0026nbsp;[9]. An earlier bony fusion in the vertebral body in women has been reported in a previous report, which is consistent with the present study\u0026nbsp;[2, 8].\u0026nbsp;Reports implicate estrogens and androgens in skeletal sexual dimorphism [4]. Females undergo the growth spurt during puberty approximately two years earlier than males, a difference that we consider reflected in the earlier completion of bony fusion. It has also been suggested that the importance of bipedal walking and weight transfer through the sacrum influences sacral fusion. Bony fusion does not occur in paraplegic patients because of the lack of load on this area\u0026nbsp;[10, 11].\u003c/p\u003e\n\u003cp\u003eThe following reports discuss the impact of insufficient bony fusion between S1/S2 and lower back pain. According to von Brandis et al., it is important not to mistake an unfused growth plate for a fracture line when interpreting sacral images [12]. Lumbarization is the complete or incomplete fusion of the upper sacral vertebrae with the L5 [13]. Previous studies have shown a connection between insufficient fusion in the transitional vertebrae and LBP. Vinha et al. found that patients with lumbosacral transitional vertebrae (LSTV) often experience LBP [14]. Nardo et al. also noted a positive correlation between type II and LBP [15]. Insufficient bony\u0026nbsp;fusion may lead to a change in normal spinal biomechanics, potentially contributing to LBP.\u003c/p\u003e\n\u003cp\u003eThis study found sex-specific differences in the bony fusion of S2/S3 and S4/S5 lateral masses. Sex-based differences in the sacroiliac joint (SIJ) begin at approximately 14 years of age, with males demonstrating significant differences from females\u0026nbsp;[16].\u0026nbsp;In males, the center of gravity is more anterior to the SIJ, and the load on the SIJ is greater. Furthermore, S1/S2 and S2/S3 have significantly deeper curvature in men\u0026nbsp;[17]. These morphological changes might affect bony fusion in their early teens. The involvement with racial variation in sacral kyphosis\u0026nbsp;[18]\u0026nbsp;should be the focus of future investigations.\u003c/p\u003e\n\u003cp\u003eOur results should be considered alongside several study limitations. A major limitation was that the samples were derived from a single ethnic group. Second, the sample size is a relatively small amount of data, especially for patients below the age of 10, resulting in a large CI for that age group.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have presented the age-specific normative values and predicted probability of sacral fusion based on over 400 sacra examinations. This study will help pediatricians, orthopedic surgeons, radiologists, and other physicians to better understand sacral development and related diagnoses.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eCI Confidence intervals\u003c/p\u003e \u003cp\u003eCT Computed tomography\u003c/p\u003e \u003cp\u003eICC Intraclass correlation coefficients\u003c/p\u003e \u003cp\u003eLBP Low back pain\u003c/p\u003e \u003cp\u003eSIJ Sacroiliac joint\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing opt-out consent, Hospital Institutional Review Board has accepted this retrospective study under study number #2022-175. The research was conducted following the tenets of the Declaration of Helsinki and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial or material support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Johnson\u0026nbsp;\u0026amp;\u0026nbsp;Johnson Medical Research Grant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.I.\u0026nbsp;was responsible for data collection, literature extraction, manuscript description, and data interpretation. S.N. helped with research design, acquired data, and helped write manuscript. K.Y. and C.I. contributed to clinical aspects of research design and data interpretation. D.W. and T.I. interpreted data and helped write the manuscript. H.A. was responsible for final approval of the manuscript. All authors have read and approved the final submitted manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Daichi Watanabe and Takuma Ishihara, Ph.D. Centre for Advanced Medical Sciences and Clinical Research, Gifu University Hospital, for their advice on statistics.\u003c/p\u003e\n\u003cp\u003eThis work was supported by Johnson \u0026amp; Johnson Medical Research Grant.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWilkins LW, Agur AMR. Grant\u0026rsquo;s atlas of anatomy. 10th ed. Philadelphia: Lippincott Williams \u0026amp; Wilkins; 1999.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026iacute;os L, Weisensee K, Rissech C. Sacral fusion as an aid in age estimation. Forensic Sci Int. 2008;180:e1111\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMahon TJ, Friedling LJ, Gordon GM. The use of ventral fusion between sacral elements S1 and S2 as an additional age-at-death indicator in a black South African skeletal sample. Forensic Sci Int. 2018;286:e2671\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmeida M, Laurent MR, Dubois V, Claessens F, O\u0026rsquo;Brien CA, Bouillon R, et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev. 2017;97:135\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBroome DR, Hayman LA, Herrick RC, Braverman RM, Glass RB, Fahr LM. Postnatal maturation of the sacrum and coccyx: MR imaging, helical CT, and conventional radiography. AJR Am J Roentgenol. 1998;170:1061\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrissom LE, Harty MP, Guo GW, Kecskemethy HH. Maturation of pelvic ossification centers on computed tomography in normal children. Pediatr Radiol. 2018;48:1902\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZejden A, Jurik AG. Anatomy of the sacroiliac joints in children and adolescents by computed tomography. Pediatr Rheumatol Online J. 2017;15:82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCardoso HFV, Pereira V, Rios L. Chronology of fusion of the primary and secondary ossification centers in the human sacrum and age estimation in child and adolescent skeletons. Am J Phys Anthropol. 2014;153:214\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeijerman L, Maat GJR, Schulz R, Schmeling A. Variables affecting the probability of complete fusion of the medial clavicular epiphysis. Int J Legal Med. 2007;121:463\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbitbol MM. Evolution of the sacrum in hominoids. Am J Phys Anthropol. 1987;74:65\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsses SI, Botsford DJ, Huler RJ, Rauschning W. Surgical anatomy of the sacrum. A guide for rational screw fixation. Spine. 1991;16(suppl):S283\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Brandis E, Zadig PK, Avenarius DFM, Flat\u0026oslash; B, Kristian Knudsen P, Lilleby V, et al. Whole body magnetic resonance imaging in healthy children and adolescents. Bone marrow appearances of the axial skeleton. Eur J Radiol. 2022;154:110425.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurlimanju BV, Prabhu LV, Pai MM, Ganeshkumar C, Sarvepalli A. Lumbosacral transitional vertebrae: a case report and clinical implications. Int J Morphol. 2011;29:1123\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVinha A, B\u0026aacute;rtolo J, Lemos C, Cordeiro F, Rodrigues-Pinto R. Lumbosacral transitional vertebrae: prevalence in a southern European population and its association with low back pain. Eur Spine J. 2022;31:3647\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNardo L, Alizai H, Virayavanich W, Liu F, Hernandez A, Lynch JA, et al. Lumbosacral transitional vertebrae: association with low back pain. Radiology. 2012;265:497\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVleeming A, Schuenke MD, Masi AT, Carreiro JE, Danneels L, Willard FH. The sacroiliac joint: an overview of its anatomy, function and potential clinical implications. J Anat. 2012;221:537\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePlochocki JH. Sexual dimorphism of anterior sacral curvature. J Forensic Sci. 2011;56:161\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrenn VA, Webb NM, Fornai C, Haeusler M. Sex classification using the human sacrum: geometric morphometrics \u003cem\u003eversus\u003c/em\u003e conventional approaches. PLoS ONE. 2022;17:e0264770.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"sacral spine development, sacrum, adolescent, bony fusion","lastPublishedDoi":"10.21203/rs.3.rs-4544158/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4544158/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aimed to determine the index of the sacral vertebrae fusion period in children and adolescents to diagnose the lesion around the sacral spine accurately.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients aged 0\u0026ndash;40 years who underwent computed tomography (CT), including the sacrum, for abdominal disorders, trauma, etc., between 2019 and 2022 were retrospectively examined. There were 402 eligible sacra (385 patients: 206 women and 179 men). We evaluated bony fusion at six parts of the sacral vertebrae (anterior or posterior of each intervertebral and both side lateral masses). The predicted probability of bony fusion obtained from the logistic regression model is depicted graphically by sex.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe association between bony fusion in each vertebral segment and age was evaluated using a logistic regression model with a Huber\u0026ndash;White robust sandwich estimator, including the patient as a clustering variable. Bony fusion of the sacral bodies of S1/S2 was slowest, with 80% of patients achieving bony fusion at 28.7 and 24.6 years of age for men and women, respectively. Compared to men, women exhibited earlier fusion of the intervertebral segments of the sacral vertebrae; however, no significant difference between the sexes in terms of eventual bony fusion at the lateral mass was observed, while the initiation of bony fusion occurred earlier in women.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe predicted probability of bony fusion could aid pediatricians, orthopedists, radiologists, and other physicians in understanding the normal development of the sacral spine and accurately diagnosing the lesion around the sacral spine.\u003c/p\u003e","manuscriptTitle":"Age-specific normative values of sacral development and fusion in children and adolescents: a cross-sectional study utilizing multi-planar reconstruction computed tomography imaging","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-02 17:33:46","doi":"10.21203/rs.3.rs-4544158/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-17T15:02:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-14T05:12:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-14T05:11:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2024-06-07T07:02:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"afb34d88-8ee4-4baa-b271-8ce066251c54","owner":[],"postedDate":"July 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-14T16:09:48+00:00","versionOfRecord":{"articleIdentity":"rs-4544158","link":"https://doi.org/10.1186/s12891-025-08597-w","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2025-04-10 16:05:27","publishedOnDateReadable":"April 10th, 2025"},"versionCreatedAt":"2024-07-02 17:33:46","video":"","vorDoi":"10.1186/s12891-025-08597-w","vorDoiUrl":"https://doi.org/10.1186/s12891-025-08597-w","workflowStages":[]},"version":"v1","identity":"rs-4544158","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4544158","identity":"rs-4544158","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}