Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report

Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report | 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 Case Report Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report Farzad Aghdashi, Maryam Armanfar, Farshid Bastami This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7786327/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Ehlers-Danlos Syndrome (EDS) is a heterogeneous disorder characterized by defects in collagen maturation. Patients with EDS commonly exhibit joint hypermobility, skin hyperextensibility, and tissue fragility. The syndrome can affect oral health, the vascular system, bones, teeth, periodontium, as well as the neuromuscular and joint systems. Due to reduced bone density, some EDS patients may receive antiresorptive medications, which can increase the risk of medication-related osteonecrosis of the jaw (MRONJ). Case Presentation : We report a case of a 25-year-old Iranian female with EDS and a history of denosumab therapy. She underwent bimaxillary orthognathic surgery to correct skeletal malocclusion. The procedure presented multiple challenges, including inherent bone abnormalities, prior denosumab use, and altered collagen structure, all contributing to unpredictable bone healing. Conclusion: Despite these challenges, the patient was successfully treated with bimaxillary orthognathic surgery, achieving a highly satisfactory outcome in terms of both functional rehabilitation and aesthetic improvement. Ehler-Danlos Syndrome Orthognathic Surgery Medication Related of The Jaw Denosumab Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Ehlers-Danlos Syndrome (EDS) is a heterogeneous hereditary connective tissue disorder. The Dutch surgeon Job Van Meek'ren was first described the EDS in 1668, who had observed a 23-year-old man with "extraordinary elasticity of the skin". The term of "Ehlers-Danlos syndrome" refers to a case presentation given by Edward Ehlers and Henry Danlos in 1901 and 1908 respectively. However, a formal description of Ehlers-Danlos syndrome was provided by an English dermatologist, F P Weber in 1936 [ 1 ]. Individuals with EDS often exhibit clinical manifestations include joint hypermobility, skin hyperextensibility, and tissue fragility [ 2 ]. Additionally, these patients may experience vascular, ocular, and visceral involvement, each associated with specific modes of inheritance [ 3 ]. These involvement lead to the symptoms in multiple organ systems including musculoskeletal pain, cardiac manifestations, mast cell activation disorders, Neurological and spinal manifestations, Psychological and Psychiatric problems [ 4 ]. Additionally, urogynaecology services symptoms can be exhibit in EDS patients including vaginal prolapse, bladder pain syndrome, recurrent urinary tracts infections [ 5 ]. The age range of affected individuals is highly diverse. Previous studies estimate the prevalence of EDS at approximately 1 in 5,000 births, with classical and hypermobile EDS accounting for 90% of cases [ 6 ]. EDS is classified into 14 subtypes based on clinical symptoms, including classical EDS, cardiac-valvular EDS, vascular EDS, arthrochalasia EDS, myopathic EDS, classical-like EDS, classical-like EDS type 2, dermatosparaxis EDS, kyphoscoliotic EDS, brittle cornea syndrome, spondylodysplastic EDS, musculocontractural EDS, periodontal EDS, and hypermobile EDS [ 7 ]. These types are caused by 20 different gene variants, most of which encode fibrillar collagen types I, III, and V, processing or modifying enzymes, and enzymes that modify the glycosaminoglycan chains of proteoglycans. The causative gene of hypermobile type of EDS remain unknown [ 8 ]. Patients with EDS often experience a reduced oral health-related quality of life due to physical pain, psychological issues, and other disabling concerns [ 9 ]. Oral and maxillofacial manifestations are common across all types of Ehlers-Danlos Syndrome. Collagen abnormalities compromise oral health, impacting the vascular system, bones, teeth, periodontium, and the neuromuscular and joint systems [ 10 ]. Dental issues associated with EDS include fragile oral mucosa, early-onset periodontal defects, unusual missing of the inferior labial and lingual frenum, dental crown anatomy, crown fractures, stunted roots or dilacerations, aberrant dentinal tubules, pulpal vascular pathology and denticles, hypermobile temporomandibular joints (TMJ), and easy movement of teeth in response to orthodontic treatment [ 11 ]. Previous studies have revealed decreased bone mineral density in patients with EDS, though the mechanism remains unclear [ 12 ]. Eller vainicher et al, also show an impaired bone quality and increased prevalence of vertebral and non-vertebral fragility fractures in EDS patients [ 13 ]. The primary medications used in antiresorptive therapy for osteoporosis are bisphosphonates and denosumab (Prolia), which inhibit osteoclast-mediated bone resorption and prevent future fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a very rare side effect of these antiresorptive agents in patients with osteoporosis [ 14 ]. Patients with a history of bisphosphonate use who are candidates for orthognathic surgery are at risk of developing MRONJ, which can impede tooth movement [ 15 ]. In this study, we present a case of a patient with EDS who had a history of intravenous denosumab injection for the treatment of osteoporosis and subsequently underwent orthognathic surgery to correct dentofacial deformity. Case Presentation In accordance with the case report (CARE) guidelines [16], this report describes a patient with Ehler Danlos syndrome who had facial deformity. This patient underwent Bimaxillary orthognathic surgery and open septo-rihnoplasty in the Department of Oral and Maxillofacial Surgery at Imam Hossein Hospital. Chief Complain A 20-year-old Iranian female was referred to the Department of Oral and Maxillofacial Surgery at Imam Hossein Hospital in December 2022 with the chief complaint of dentofacial deformity. Patient Information According to her medical history, she had been diagnosed with Ehlers-Danlos Syndrome (EDS). The patient reported difficulty breathing in an extended head position and exhibited asymmetric breaths. She also had finger joint hypermobility, and clinical dermatological examination revealed soft, velvety, and hyperextensible skin. In her medical history, the patient reported a facial trauma followed the car accident and then mandibular symphysis fracture and dentoalveolar fracture. In order to treatment, close reduction was performed. (Fig 1) the patient mentioned receiving two injections of Prolia 60mg (denosumab) for osteoporosis, the first in May 2021 and the second four months later. Her cardiological examination was unremarkable. The challenges to orthognathic surgery in this patient included inherent bony abnormalities, a history of denosumab administration, and altered collagen structure, all of which contributed to an unpredictable bone healing process. The patient had been undergoing fixed orthodontic treatment for approximately one year before the consultation for orthognathic surgery. Clinical Finding The patient extra-oral examination in the frontal view revealed a short face, a deep mentolabial fold, and paranasal deficiency. The malar eminences were flat. In the smile view, tooth exposure was minimal, close to zero. The examination of facial lateral view showed a concave profile and mandibular prognathism (Fig 2). During the oral examination, it was noted that her inferior labial and lingual frenulum were absent. Additionally, the first maxillary premolar was missing. Her occlusal relationships were Class III on both the right and left sides in the centric position. The maxillary dental midline was shifted 1.1 mm to the right, while the mandibular dental midline and chin midline were deviated 5.3 mm to the right. The reverse overjet measured 11 mm, and the overbite was 2 mm. A posterior crossbite was evident in the right posterior region (Fig 3). The temporomandibular joint showed no history of hypermobility or luxation. The patient presented with mild gingivitis but no recession. Pre-surgical orthodontic treatment achieved good intra-arch dental alignment and arch coordination. Diagnosis Assessment Cephalometric analysis revealed a skeletal Class III relationship with maxillary retrusion and mandibular prognathism (Table 1, Fig 4). Table 1: The results of cephalometric analysis Name Measured value Normal range SNA 78.8 80 - 84 SNB 88.1 75 - 80 ANB 9.4 1 - 5 SA-Pog 156.7 ANS-Me 51.4 Maxillary cant (Canine to FP) Maxillary midline shift 1.1 mm to right Mandibular midline shift 5.2 mm to right Chin shift 5.3 mm to right Therapeutic intervention Under general anesthesia and nasal intubation, the patient underwent orthognathic surgery, which included maxillary anterior-inferior repositioning of 4 mm, advancement of 9 mm, and rotation to the left by 1 mm through Le Fort I osteotomy. Mandibular autorotation and a setback of 3 mm were achieved by bilateral sagittal split osteotomy. Maxillary fixation was performed at both the piriform and zygomatic buttresses using miniplates. Mandibular fixation was completed with a trocar and four screws on the right side and a miniplate on the left side. In December 2023, the patient underwent cosmetic open septo-rhinoplasty. Healing was uneventfully and the results were satisfactory for both the patients and surgeon. (Fig 7) Follow up and outcomes A satisfactory result was achieved in this patient. Clinical and radiographic records were obtained after surgery (Fig 5 and 6). Postoperatively, healing was uneventful, and bone remodeling occurred perfectly. No immediate postoperative complications, such as bleeding, wound infection, breathing problems, hematoma, or persistent paresthesia, were noted. Additionally, no late complications, such as non-union at the osteotomy site, were observed. Clinical trial number : not applicable Discussion EDS are hereditary connective tissue disorders with symptoms such as tissue fragility, skin hyperextensibility, and joint hypermobility, affecting approximately 1 in 5,000 births [ 17 ]. EDS results from mutations in collagen-related genes, impacting bone health and leading to conditions like osteoporosis [ 18 ]. Patients with EDS may experience reduced bone mineral density, making them susceptible to fractures, which is managed with antiresorptive drugs such as bisphosphonates and denosumab [ 12 ]. Oral and maxillofacial issues in EDS patients include TMJ instability, fragile oral mucosa, early periodontal disease, and abnormal dental anatomy [ 11 ]. These factors complicate surgical procedures, raising concerns about delayed healing and postoperative complications [ 19 ]. However, recent studies suggest that orthognathic surgery can be safely performed in EDS patients, even those on bisphosphonate therapy. For example, research by Arnaud Gleizal found that patients on bisphosphonates experienced normal bone and mucosal healing without osteonecrosis or periodontal issues [ 20 ]. Similarly, Tengku Shaeran and colleagues reported successful bimaxillary surgery in a patient with a history of oral bisphosphonates by incorporating a drug holiday [ 21 ]. In this case, the patient with EDS and a history of intravenous denosumab underwent successful bimaxillary orthognathic surgery. Despite concerns about collagen synthesis affecting bone healing, the surgery was completed without major complications, demonstrating that with careful planning, such surgical interventions can be effectively managed in EDS patients. Conclusion This case demonstrates that with careful planning, bimaxillary orthognathic surgery can be successfully performed in patients with EDS, even those with a history of denosumab administration. Despite the challenges of altered collagen structure and bone healing, the patient experienced a smooth recovery with no major complications, highlighting the potential for effective surgical correction of dentofacial deformities in EDS patients. Declarations The author have no financial interests to disclose. Acknowledgements Not applicable Author contributions Conception: Farzad Aghdashi Design of the work: Farzad Aghdashi Analysis, or interpretation of data: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami Writing original draft: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami Writing—revising & editing: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami Funding None. Ethics Approval and consent to participate Not applicable Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal Competing interest There are no conflicts of interest. References Olubajo F, Kaliaperumal C, Choudhari KA: Vascular Ehlers-Danlos Syndrome: Literature review and surgical management of intracranial vascular complications. Clin Neurol Neurosurg 2020, 193: 105775. Maraj B, Harding-Theobald E, Karaki F: Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature. J Gen Intern Med 2018, 33: 1192-1195. Melamed Y, Barkai G, Frydman M: Multiple supernumerary teeth (MSNT) and Ehlers-Danlos syndrome (EDS): a case report. J Oral Pathol Med 1994, 23: 88-91. Riley B: The Many Facets of Hypermobile Ehlers-Danlos Syndrome. J Am Osteopath Assoc 2020, 120: 30-32. Patel M, Khullar V: Urogynaecology and Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet 2021, 187: 579-585. Ghali N, Sobey G, Burrows N: Ehlers-Danlos syndromes. Bmj 2019, 366: l4966. Yoshizawa T, Kosho T: Mouse Models of Musculocontractural Ehlers-Danlos Syndrome. Genes (Basel) 2023, 14 . Malfait F, Castori M, Francomano CA, Giunta C, Kosho T, Byers PH: The Ehlers-Danlos syndromes. Nat Rev Dis Primers 2020, 6: 64. Lepperdinger U, Zschocke J, Kapferer-Seebacher I: Oral manifestations of Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet 2021, 187: 520-526. Di Giacomo P, Celli M, Ierardo G, Polimeni A, Di Paolo C: Evaluation of Temporomandibular Disorders and Comorbidities in Patients with Ehler--Danlos: Clinical and Digital Findings. J Int Soc Prev Community Dent 2018, 8: 333-338. Arun T, Nalbantgil D, Sayinsu K: Orthodontic treatment protocol of Ehlers-Danlos syndrome type VI. Angle Orthod 2006, 76: 177-183. Yasukawa S, Uehara M, Suzuki T, Nakano M, Kosho T, Nakamura Y, Takahashi J: The first experience of denosumab therapy on patients with Ehlers-Danlos syndrome and osteoporosis: detailed observation of two patients. Mod Rheumatol Case Rep 2021, 5: 377-383. Eller-Vainicher C, Bassotti A, Imeraj A, Cairoli E, Ulivieri FM, Cortini F, Dubini M, Marinelli B, Spada A, Chiodini I: Bone involvement in adult patients affected with Ehlers-Danlos syndrome. Osteoporos Int 2016, 27: 2525-2531. Hauer L, Jambura J, Hrusak D, Chalupova M, Posta P, Rusnak S, Vyskocil V: Surgical therapy for medication-related osteonecrosis of the jaw in osteoporotic patients treated with antiresorptive agents. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020, 164: 100-107. Sondeijker CFW, Apperloo RC, Kalaykova SI, Baan F, Maertens JKM: Combined orthodontic and surgical treatment for a patient with Hallermann-Streiff-Francois syndrome, severe obstructive sleep apnea, and history of antiresorptive medication. Am J Orthod Dentofacial Orthop 2021, 159: 97-107. Riley DS, Barber MS, Kienle GS, Aronson JK, von Schoen-Angerer T, Tugwell P, Kiene H, Helfand M, Altman DG, Sox H, et al: CARE guidelines for case reports: explanation and elaboration document. J Clin Epidemiol 2017, 89: 218-235. Hoshijima M, Kawanabe N, Iida S, Yamashiro T, Kamioka H: Camouflage Treatment for Skeletal Maxillary Protrusion and Lateral Deviation with Classic-Type Ehlers-Danlos Syndrome. Acta Med Okayama 2021, 75: 205-212. Basalom S, Rauch F: Bone Disease in Patients with Ehlers-Danlos Syndromes. Curr Osteoporos Rep 2020, 18: 95-102. DeLeonibus A, Bogart J, Gharb BB, Rampazzo A: Orthognathic Surgery in Ehlers-Danlos Syndrome: Review of the Literature and Case Report. The Cleft Palate Craniofacial Journal 2023, 61: 1061-1070. Gleizal A, Meon A, Asselborn M, Chauvel-Picard J: Orthognathic surgery in patients treated with bisphosphonates: A case series. Journal of Cranio-Maxillofacial Surgery 2023, 51: 521-527. Tengku Shaeran TA, Msf M, Purmal K, A P, Alam M, Samsudin A: Oral Bisphosphonate and Orthognathic Surgery: A Case Report and Literature Review. International Medical Journal (1994) 2014, 21: 424-427. Additional Declarations No competing interests reported. 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07:38:43","extension":"xml","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55393,"visible":true,"origin":"","legend":"","description":"","filename":"ab31256d23d34b2185e7bfd87a7048c01structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/3583eda56279cbceb3fdd49a.xml"},{"id":96250744,"identity":"55d638f4-a1bf-4305-9884-568be85538d7","added_by":"auto","created_at":"2025-11-19 07:38:56","extension":"html","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":62547,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/dc8138ddc6caa82500c82c2d.html"},{"id":96117172,"identity":"00c6ee9e-7670-43bd-ac9c-d87df543a6aa","added_by":"auto","created_at":"2025-11-17 19:21:58","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":943341,"visible":true,"origin":"","legend":"\u003cp\u003eClose reduction of mandibular fracture\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/258d42588e29d4c814a70f38.jpeg"},{"id":96117176,"identity":"6e48cc21-cc47-49a1-afe9-471858df0704","added_by":"auto","created_at":"2025-11-17 19:21:58","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1329354,"visible":true,"origin":"","legend":"\u003cp\u003ePre-operative extraoral photographs\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/c4cb996b56a19b15bddc3740.jpeg"},{"id":96117174,"identity":"c4dcd238-b76c-4028-8f6d-188687b27111","added_by":"auto","created_at":"2025-11-17 19:21:58","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1071802,"visible":true,"origin":"","legend":"\u003cp\u003ePre-operative intraoral photographs\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/29daa6c82ddeb665251e86d6.jpeg"},{"id":96250506,"identity":"4ba4b809-0105-44c4-ae06-cd603d80786f","added_by":"auto","created_at":"2025-11-19 07:38:32","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1179243,"visible":true,"origin":"","legend":"\u003cp\u003ePre operative radiographic analysis\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/8e36cd8a0fe1651ecc951528.jpeg"},{"id":96247387,"identity":"9c91ae7f-741b-4321-aee3-0f6cb811787e","added_by":"auto","created_at":"2025-11-19 07:27:26","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1085884,"visible":true,"origin":"","legend":"\u003cp\u003ePost-operative OPG showing skeletal correction\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/5b5fc79308e9e4d5f8e8c37a.jpeg"},{"id":96117180,"identity":"57c28135-a4be-47fe-8aa0-cb32ed791b75","added_by":"auto","created_at":"2025-11-17 19:21:58","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1215977,"visible":true,"origin":"","legend":"\u003cp\u003ePost orthognathic surgery frontal view of the patient showing improved facial symmetry\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/1270f790864b87fe23975328.jpeg"},{"id":96248853,"identity":"f3a94553-aa67-4159-ab35-438cb24fa77c","added_by":"auto","created_at":"2025-11-19 07:29:30","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1973243,"visible":true,"origin":"","legend":"\u003cp\u003ePost septo-rihnoplasty frontal and profile views showing satisfactory esthetic results.\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/e1e2a9baf69d9d3472c1bbfa.jpeg"},{"id":101849039,"identity":"29846ad2-fded-4237-b286-4dd0c1115d2c","added_by":"auto","created_at":"2026-02-04 09:43:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10066142,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7786327/v1/028b9ffe-6828-47e1-bfa3-a65b6ca6e7bd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEhlers-Danlos Syndrome (EDS) is a heterogeneous hereditary connective tissue disorder. The Dutch surgeon Job Van Meek'ren was first described the EDS in 1668, who had observed a 23-year-old man with \"extraordinary elasticity of the skin\". The term of \"Ehlers-Danlos syndrome\" refers to a case presentation given by Edward Ehlers and Henry Danlos in 1901 and 1908 respectively. However, a formal description of Ehlers-Danlos syndrome was provided by an English dermatologist, F P Weber in 1936 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIndividuals with EDS often exhibit clinical manifestations include joint hypermobility, skin hyperextensibility, and tissue fragility [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Additionally, these patients may experience vascular, ocular, and visceral involvement, each associated with specific modes of inheritance [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These involvement lead to the symptoms in multiple organ systems including musculoskeletal pain, cardiac manifestations, mast cell activation disorders, Neurological and spinal manifestations, Psychological and Psychiatric problems [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, urogynaecology services symptoms can be exhibit in EDS patients including vaginal prolapse, bladder pain syndrome, recurrent urinary tracts infections [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The age range of affected individuals is highly diverse. Previous studies estimate the prevalence of EDS at approximately 1 in 5,000 births, with classical and hypermobile EDS accounting for 90% of cases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEDS is classified into 14 subtypes based on clinical symptoms, including classical EDS, cardiac-valvular EDS, vascular EDS, arthrochalasia EDS, myopathic EDS, classical-like EDS, classical-like EDS type 2, dermatosparaxis EDS, kyphoscoliotic EDS, brittle cornea syndrome, spondylodysplastic EDS, musculocontractural EDS, periodontal EDS, and hypermobile EDS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These types are caused by 20 different gene variants, most of which encode fibrillar collagen types I, III, and V, processing or modifying enzymes, and enzymes that modify the glycosaminoglycan chains of proteoglycans. The causative gene of hypermobile type of EDS remain unknown [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePatients with EDS often experience a reduced oral health-related quality of life due to physical pain, psychological issues, and other disabling concerns [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Oral and maxillofacial manifestations are common across all types of Ehlers-Danlos Syndrome. Collagen abnormalities compromise oral health, impacting the vascular system, bones, teeth, periodontium, and the neuromuscular and joint systems [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDental issues associated with EDS include fragile oral mucosa, early-onset periodontal defects, unusual missing of the inferior labial and lingual frenum, dental crown anatomy, crown fractures, stunted roots or dilacerations, aberrant dentinal tubules, pulpal vascular pathology and denticles, hypermobile temporomandibular joints (TMJ), and easy movement of teeth in response to orthodontic treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Previous studies have revealed decreased bone mineral density in patients with EDS, though the mechanism remains unclear [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Eller vainicher et al, also show an impaired bone quality and increased prevalence of vertebral and non-vertebral fragility fractures in EDS patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe primary medications used in antiresorptive therapy for osteoporosis are bisphosphonates and denosumab (Prolia), which inhibit osteoclast-mediated bone resorption and prevent future fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a very rare side effect of these antiresorptive agents in patients with osteoporosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Patients with a history of bisphosphonate use who are candidates for orthognathic surgery are at risk of developing MRONJ, which can impede tooth movement [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this study, we present a case of a patient with EDS who had a history of intravenous denosumab injection for the treatment of osteoporosis and subsequently underwent orthognathic surgery to correct dentofacial deformity.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eIn accordance with the case report (CARE) guidelines [16], this report describes a patient with Ehler Danlos syndrome who had facial deformity. This patient underwent Bimaxillary orthognathic surgery and open septo-rihnoplasty in the Department of Oral and Maxillofacial Surgery at Imam Hossein Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChief Complain\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 20-year-old Iranian female was referred to the Department of Oral and Maxillofacial Surgery at Imam Hossein Hospital in December 2022 with the chief complaint of dentofacial deformity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;According to her medical history, she had been diagnosed with Ehlers-Danlos Syndrome (EDS). The patient reported difficulty breathing in an extended head position and exhibited asymmetric breaths. She also had finger joint hypermobility, and clinical dermatological examination revealed soft, velvety, and hyperextensible skin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn her medical history, the patient reported a facial trauma followed the car accident and then mandibular symphysis fracture and dentoalveolar fracture. In order to treatment, close reduction was performed. (Fig 1) \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ethe patient mentioned receiving two injections of Prolia 60mg (denosumab) for osteoporosis, the first in May 2021 and the second four months later. Her cardiological examination was unremarkable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe challenges to orthognathic surgery in this patient included inherent bony abnormalities, a history of denosumab administration, and altered collagen structure, all of which contributed to an unpredictable bone healing process. The patient had been undergoing fixed orthodontic treatment for approximately one year before the consultation for orthognathic surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Finding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient extra-oral examination in the frontal view revealed a short face, a deep mentolabial fold, and paranasal deficiency. The malar eminences were flat. In the smile view, tooth exposure was minimal, close to zero. The examination of facial lateral view showed a concave profile and mandibular prognathism (Fig 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring the oral examination, it was noted that her inferior labial and lingual frenulum were absent. Additionally, the first maxillary premolar was missing. Her occlusal relationships were Class III on both the right and left sides in the centric position. The maxillary dental midline was shifted 1.1 mm to the right, while the mandibular dental midline and chin midline were deviated 5.3 mm to the right. The reverse overjet measured 11 mm, and the overbite was 2 mm. A posterior crossbite was evident in the right posterior region (Fig 3).\u003c/p\u003e\n\u003cp\u003eThe temporomandibular joint showed no history of hypermobility or luxation. The patient presented with mild gingivitis but no recession. Pre-surgical orthodontic treatment achieved good intra-arch dental alignment and arch coordination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis Assessment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCephalometric analysis revealed a skeletal Class III relationship with maxillary retrusion and mandibular prognathism (Table 1, Fig 4).\u003c/p\u003e\n\u003cp\u003eTable 1: The results of cephalometric analysis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eName\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasured value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal range\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSNA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e78.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e80 - 84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSNB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e88.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e75 - 80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eANB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1 - 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSA-Pog\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e156.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eANS-Me\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e51.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaxillary cant (Canine to FP)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaxillary midline shift\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1.1 mm to right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMandibular midline shift\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e5.2 mm to right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChin shift\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e5.3 mm to right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnder general anesthesia and nasal intubation, the patient underwent orthognathic surgery, which included maxillary anterior-inferior repositioning of 4 mm, advancement of 9 mm, and rotation to the left by 1 mm through Le Fort I osteotomy. Mandibular autorotation and a setback of 3 mm were achieved by bilateral sagittal split osteotomy. Maxillary fixation was performed at both the piriform and zygomatic buttresses using miniplates. Mandibular fixation was completed with a trocar and four screws on the right side and a miniplate on the left side.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn December 2023, the patient underwent cosmetic open septo-rhinoplasty. Healing was uneventfully and the results were satisfactory for both the patients and surgeon. (Fig 7)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow up and outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA satisfactory result was achieved in this patient. Clinical and radiographic records were obtained after surgery (Fig 5 and 6).\u003c/p\u003e\n\u003cp\u003ePostoperatively, healing was uneventful, and bone remodeling occurred perfectly. No immediate postoperative complications, such as bleeding, wound infection, breathing problems, hematoma, or persistent paresthesia, were noted. Additionally, no late complications, such as non-union at the osteotomy site, were observed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEDS are hereditary connective tissue disorders with symptoms such as tissue fragility, skin hyperextensibility, and joint hypermobility, affecting approximately 1 in 5,000 births [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. EDS results from mutations in collagen-related genes, impacting bone health and leading to conditions like osteoporosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Patients with EDS may experience reduced bone mineral density, making them susceptible to fractures, which is managed with antiresorptive drugs such as bisphosphonates and denosumab [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOral and maxillofacial issues in EDS patients include TMJ instability, fragile oral mucosa, early periodontal disease, and abnormal dental anatomy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These factors complicate surgical procedures, raising concerns about delayed healing and postoperative complications [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, recent studies suggest that orthognathic surgery can be safely performed in EDS patients, even those on bisphosphonate therapy. For example, research by Arnaud Gleizal found that patients on bisphosphonates experienced normal bone and mucosal healing without osteonecrosis or periodontal issues [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Similarly, Tengku Shaeran and colleagues reported successful bimaxillary surgery in a patient with a history of oral bisphosphonates by incorporating a drug holiday [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this case, the patient with EDS and a history of intravenous denosumab underwent successful bimaxillary orthognathic surgery. Despite concerns about collagen synthesis affecting bone healing, the surgery was completed without major complications, demonstrating that with careful planning, such surgical interventions can be effectively managed in EDS patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case demonstrates that with careful planning, bimaxillary orthognathic surgery can be successfully performed in patients with EDS, even those with a history of denosumab administration. Despite the challenges of altered collagen structure and bone healing, the patient experienced a smooth recovery with no major complications, highlighting the potential for effective surgical correction of dentofacial deformities in EDS patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe author have no financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception: Farzad Aghdashi\u003c/p\u003e\n\u003cp\u003eDesign of the work: Farzad Aghdashi\u003c/p\u003e\n\u003cp\u003eAnalysis, or interpretation of data: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami\u003c/p\u003e\n\u003cp\u003eWriting original draft: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami\u003c/p\u003e\n\u003cp\u003eWriting\u0026mdash;revising \u0026amp; editing: Farzad Aghdashi, Maryam Armanfar, Farshid Bastami\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOlubajo F, Kaliaperumal C, Choudhari KA: \u003cstrong\u003eVascular Ehlers-Danlos Syndrome: Literature review and surgical management of intracranial vascular complications.\u003c/strong\u003e \u003cem\u003eClin Neurol Neurosurg \u003c/em\u003e2020, \u003cstrong\u003e193:\u003c/strong\u003e105775.\u003c/li\u003e\n\u003cli\u003eMaraj B, Harding-Theobald E, Karaki F: \u003cstrong\u003eVascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.\u003c/strong\u003e \u003cem\u003eJ Gen Intern Med \u003c/em\u003e2018, \u003cstrong\u003e33:\u003c/strong\u003e1192-1195.\u003c/li\u003e\n\u003cli\u003eMelamed Y, Barkai G, Frydman M: 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Ehlers-Danlos Syndrome: Review of the Literature and Case Report.\u003c/strong\u003e \u003cem\u003eThe Cleft Palate Craniofacial Journal \u003c/em\u003e2023, \u003cstrong\u003e61:\u003c/strong\u003e1061-1070.\u003c/li\u003e\n\u003cli\u003eGleizal A, Meon A, Asselborn M, Chauvel-Picard J: \u003cstrong\u003eOrthognathic surgery in patients treated with bisphosphonates: A case series.\u003c/strong\u003e \u003cem\u003eJournal of Cranio-Maxillofacial Surgery \u003c/em\u003e2023, \u003cstrong\u003e51:\u003c/strong\u003e521-527.\u003c/li\u003e\n\u003cli\u003eTengku Shaeran TA, Msf M, Purmal K, A P, Alam M, Samsudin A: \u003cstrong\u003eOral Bisphosphonate and Orthognathic Surgery: A Case Report and Literature Review.\u003c/strong\u003e \u003cem\u003eInternational Medical Journal (1994) \u003c/em\u003e2014, \u003cstrong\u003e21:\u003c/strong\u003e424-427.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ehler-Danlos Syndrome, Orthognathic Surgery, Medication Related of The Jaw, Denosumab","lastPublishedDoi":"10.21203/rs.3.rs-7786327/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7786327/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Ehlers-Danlos Syndrome (EDS) is a heterogeneous disorder characterized by defects in collagen maturation. Patients with EDS commonly exhibit joint hypermobility, skin hyperextensibility, and tissue fragility. The syndrome can affect oral health, the vascular system, bones, teeth, periodontium, as well as the neuromuscular and joint systems. Due to reduced bone density, some EDS patients may receive antiresorptive medications, which can increase the risk of medication-related osteonecrosis of the jaw (MRONJ).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e: We report a case of a 25-year-old Iranian female with EDS and a history of denosumab therapy. She underwent bimaxillary orthognathic surgery to correct skeletal malocclusion. The procedure presented multiple challenges, including inherent bone abnormalities, prior denosumab use, and altered collagen structure, all contributing to unpredictable bone healing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Despite these challenges, the patient was successfully treated with bimaxillary orthognathic surgery, achieving a highly satisfactory outcome in terms of both functional rehabilitation and aesthetic improvement.\u003c/p\u003e","manuscriptTitle":"Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-17 19:21:53","doi":"10.21203/rs.3.rs-7786327/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"72e343a3-ffcf-47aa-8a55-233ddc4cb546","owner":[],"postedDate":"November 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-04T09:42:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-17 19:21:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7786327","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7786327","identity":"rs-7786327","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}