Denosumab Usage in Rare Cemento-Osseous Dysplasia Involves the Whole Mandible, Including the Bilateral Condyle—A Case Report

Denosumab Usage in Rare Cemento-Osseous Dysplasia Involves the Whole Mandible, Including the Bilateral Condyle—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 Denosumab Usage in Rare Cemento-Osseous Dysplasia Involves the Whole Mandible, Including the Bilateral Condyle—A Case Report Chieh Ling Chiang, Tzu Huan Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5135664/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2025 Read the published version in BMC Oral Health → Version 1 posted 13 You are reading this latest preprint version Abstract Background Cemento-osseous dysplasia is the most common type of apical radiopaque lesion in the tooth-bearing area. However, large destructive lesions are rare. We report a case in which the lesion extended to the bilateral condyle and whole mandible and was managed with denosumab instead of surgical resection. Case Presentation: A 45-year-old woman with destructive progressing large cemento-osseous dysplasia involve the whole mandible, including the bilateral condyle and bony expansion, which led to facial deformity and malocclusion. She was hesitant about the surgical option of resection of the whole mandible and turned to the off-label use of denosumab. After 9 months of administration, rapid ossification of the osteolytic lesion was observed, but there was no obvious change in volume. A bone scan with SPE-CT revealed stable disease with no progression. Conclusion: Denosumab may be considered a potential medical treatment option to prevent the progression of severe destructive cemento-osseous dysplasia in patients with limited surgical options. Cemento-osseous dysplasia Fibro-osseous lesion Denosumab Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Cemento-osseous dysplasia (COD) is the most common radiopacity lesion of the jaw bone. Predominantly occurring in middle-aged black women. Some investigators suggest that cemento-osseous dysplasia originates from periodontal ligament cell or bone remodeling triggered by local trauma, such as clenching or bruxism[ 1 ]. Most CODs are asymptomatic and are unexpectedly discovered via dental radiographic examination. Surgical treatment and unnecessary biopsy should be avoid. Traditionally, COD involves the tooth-bearing area and is normally asymptomatic with no bony expansion. COD usually appears to be associated with the root apex or previous tooth extraction site. There are three subtypes of COD: focal, periapical, and florid types. Florid-type COD may involve multiple quadrants and exhibit bony expansion in rare circumstances with tenderness, causing chronic osteomyelitis and delayed healing if infected[ 2 ]. Case Report A woman with a chief complaint of lower tooth swelling and purulent discharge visited our department for help. The initial panoramic film revealed diffuse mixed radiopaque and radiolucent lesions from the right mandibular body to the left mandibular body (Fig. 1 ). She denied chin numbness and underwent normal neurological examination of the inferior alveolar nerve. Some suppurative discharge from periodontal tissue was noted without tenderness. She had mandibular removable partial dentures fabricated at a dental clinic several years ago but became unfit over time. Clinically, the patient showed mandibular bony expansion with a protrusive mandible and class III lateral profile, while she had a straight profile according to the photo taken at her young age. CT revealed moderate bony expansion with peripheral sclerotic changes at the periosteum at the focal area and mixed radiopaque and radiolucency extending to the whole mandible, including the bilateral condyle, bilateral ascending ramus and body to the symphysis area; no obvious intralesional contrast media were noted (Fig. 2 ). A bone scan with SPE-CT revealed high signal uptake at the whole mandible with no uptake at other parts of the body (Fig. 3 ). The initial impression was a fibro-osseous lesion, including the whole mandible, with chronic suppurative osteomyelitis. The infection was controlled via the use of augmentin with local debridement and tooth extraction. Some intrabony tissue was sent for pathological examination. Microscopically, a hypercellular fibroblastic stroma with some bands of osteoid or cementum-like calcification was distributed throughout the lesion (Fig. 4 ). The bony trabeculae were surrounded by plump osteoblasts. The pathological diagnosis was ossifying fibroma. The patient was lost to follow-up since the infection subsided. Two years later, she came to our department again due to progressive mandible expansion with poor chewing ability. However, owing to the large extent of the lesion, total mandibulectomy with two fibular flaps with dental implants was simulated via ProPlan CMF (Fig. 5 ). However, owing to the length of the defect, using bilateral fibula simultaneously and TMJ function using fibula bone stock for joint reconstruction was uncertain. The patient hesitated about the treatment plan. Hence, we discuss off-label use of denosumab with patients since many studies have investigated other fibro-osseous lesions, such as fibrous dysplasia. We performed the second tissue biopsy and sent it to an oral pathologist. The present case involved a fibro-osseous lesion, favoring florid-type cemento-osseous dysplasia. Microscopically, there is cellular fibrovascular connective tissue with scattered hemorrhage and a variable mixture of woven bone, lamellar bone and irregularly shaped cementum-like particles. Since there is no protocol for treating osseous dysplasia or ossifying fibroma with denosumab, we followed the most commonly used protocol for treating fibrous dysplasia according to the literature[ 3 ]: 60 mg of denosumab every 3 months. After 3 regimens, there were no obvious changes in the facial profile. However, rapid calcification of the bone lesion, including the bilateral condyle, ramus, and symphysis areas, was noted on CT. A bone scan with SPE-CT still revealed Tc-99 uptake at the whole mandible but decreased signal intensity at the condylar area. Our intent is to maintain denosumab usage until stable disease conditions are reached and consider resecting the mandible from body to body, preserving the diseased subcondyle region, and reconstructing it with one fibula flap for implant-supported dentures. The condition of the diseased condyle was closely monitored. The TMJ total joint prosthesis to replace the bilateral diseased condyle if the disease progresses and when the device is legally available in Taiwan. Discussion and conclusion Fibro-osseous lesions can be categorized into three diseases: fibrous dysplasia (FD), cemento-ossifying fibroma (COF) and cemento-osseous dysplasia (COD). Microscopically, FD shows irregularly shaped trabeculae of immature bone in a cellular fibrous tissue. The trabeculae tend to be curvilinear shaped, such as a Chinese character without osteoblastic rimming, which could be easily distinguished from COF and COD. However, the COFs and CODs are nearly the same histologically. They both have fibrovascular connective tissue with mineralized products, such as immature woven bone, lamellar bone and cementum-like particles. Peripheral osteoid or osteoblastic rimming is usually present in both lesions. However, COFs have less significant intralesional hemorrhage, whereas CODs tend to have “ginger root” bone trabeculae. To the best of our knowledge, there are no reports of florid-type COD that spreads beyond the tooth-bearing area and extends to the bilateral condyles. The pattern of the presented case is so rare that we consider familial gigantiform cementoma (FGC) as another possible diagnosis. Histologically, FGC and COD show the same spectrum of changes under a microscope. We can only diagnose this disease clinically and radiographically. According to the 5th edition of the World Health Organization for odontogenic maxillary facial bone tumors[ 4 ], FGC normally develops in young patients, such as adolescents, who exhibit rapid expansion of all four quadrants of the jaw with facial deformities and who are not predisposed by sex or ethnic group. On the other hand, approximately 90% of those with COD are middle-aged females. Most of the population is African American women, followed by East Asians and Whites[ 5 ]. Both florid-type COD and gigantiform cementoma can be familial or sporadic[ 6 ]. However, our case involved only the mandible of a middle-aged female and had no family history of jawbone lesions. Moreover, the lesion progresses slowly for decades, whereas FGC grows rapidly, which is different from traditional gigantiform cementoma. FGC is an autosomal dominant mutation in the ANO5 gene that is absent in familial COD, ossifying fibroma, and polyostotic fibrous dysplasia[ 7 ]. Cemento-ossifying fibroma (COF) is typically recognized as a neoplasm with a clear margin between the tumor and normal bone[ 8 ]. During biopsy, a firm mass can be identified. On the other hand, COD patients exhibit fragile fragmented dreg tissue during biopsy and are more likely to experience hemorrhage in the mixed radiographic stage, similar to the case we present here. Syndromic ossifying fibroma (also called hyperparathyroidism jaw tumor) often presents with mutations in the tumor suppressor gene HRPT2, known as CDC73 [ 9 ]. Our patient presented with normal parathyroid function. In addition to conventional ossifying fibroma, more aggressive subtypes, such as psammomatoid ossifying fibroma and trabecular ossifying fibroma, are diseases that restrict in childhood and are classified as juvenile ossifying fibroma. Hence, we prefer florid-type COD with condyle involvement as the final diagnosis. Most of the time, focal COD requires no biopsy or treatment. For such extensive COD with limited surgical options, there is no standard medical treatment protocol. However, many reports and case series have demonstrated the benefit of denosumab usage in fibrous dysplasia, giant cell bone tumors and aneurysm bone cysts[ 10 – 12 ]. The pathophysiology of FD involves the replacement of normal bone tissue with fibrous tissue resulting from GNAS mutation, which is restricted to fibrous dysplasia and can distinguish other fibro-osseous lesions, such as CODs and COFs[ 13 , 14 ]. GNAS mutation results in the release of osteoblastic factors that form immature osteoblasts. These osteoblasts release osteoclastic factors such as RANKL, OPG, M-CSF, and IL-6, which induce proinflammatory macrophages and osteoclast differentiation[ 15 ]. Denosumab is a human monoclonal anti-RANKL antibody that reduces the activity of fibrous dysplasia. However, COD shares different pathophysiologies and is restricted to the jaw bone only. Some researchers believe that occlusal parafunction and overload may result in periapical osteosclerosis. The craniofacial bone originates from neural crest mesenchymal cells and undergoes a variety of signaling pathways, such as the Wnt and bone morphogenic protein (BMP) pathways, during bone formation[ 16 ]. Other studies regard COD as a disease driven by RAS-MAPK mutation[ 17 ], although only 28% of the patients (5 out of 18 patients) had RAS-MAPK pathway mutations in this study. Treatment options for such extensive cemento-osseous dysplasia extending to the whole mandible are limited, and very few clinical reports in the literature can be found. Denosumab usage in bone lesions, such as fibrous dysplasia, aneurysm, bone cysts or giant cell tumors, has been documented[ 18 , 19 ] and has shown some encouraging results, such as pain, tumor volume control and ossification of the bone lesion. Although the pathophysiology of these bone diseases differs, blocking the RANKL pathway to affect the bone turnover rate still has benefits. For giant cell granulomas, denosumab is the only approved medical agent for inoperable giant cell granulomas or adjuvant treatment for operable cases according to an open-label phase II trial[ 20 ]. For fibrous dysplasia and aneurysm bone cysts, few clinical trials exist, but some case series support the treatment outcome of Denosumab[ 3 , 21 ]. Our case also revealed mineralization of the destructive bone in a large case of cemento-osseous dysplasia as an alternative treatment. There are no previous reports focusing on the use of denosumab in treating COD. Further research in pathophysiology and clinical trials is needed. Abbreviations COD: Cemento-osseous dysplasia COF: Cemento-ossifying fibroma FD: Fibrous dysplasia Declarations Availability of data and materials The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request. Consent to Publish declaration: A written informed consent was obtained from the patient for publication of this Case report and any accompanying images. There was no Funding to declare Clinical trial number: not applicable. Competing interests The authors declare that they have no competing interes Author Information: First author: Chieh Ling Chiang, Mackay Memorial Hospital, Hsinchu Branch Corresponding Author: Tzu Huan Huang, Mackay Memorial Hospital Chieh Ling Chiang wrote the main manuscript and Tzu Huan Huang prepare the figures, review the article. All authors reviewed the manuscript. References Waldron CA, Giansanti JS: Benign fibro-osseous lesions of the jaws: a clinical-radiologic-histologic review of sixty-five cases. II. Benign fibro-osseous lesions of periodontal ligament origin . Oral Surg Oral Med Oral Pathol 1973, 35 (3):340-350. Cavalcante MB, de Oliveira Lima AL, Júnior MA, Santos MB: Florid Cemento-Osseous Dysplasia Simultaneous the Chronic Suppurative Osteomyelitis in Mandible . J Craniofac Surg 2016, 27 (8):2173-2176. Majoor BCJ, Papapoulos SE, Dijkstra PDS, Fiocco M, Hamdy NAT, Appelman-Dijkstra NM: Denosumab in Patients With Fibrous Dysplasia Previously Treated With Bisphosphonates . J Clin Endocrinol Metab 2019, 104 (12):6069-6078. Vered M, Wright JM: Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Odontogenic and Maxillofacial Bone Tumours . Head Neck Pathol 2022, 16 (1):63-75. El-Mofty SK: Fibro-Osseous Lesions of the Craniofacial Skeleton: An Update . Head Neck Pathol 2014, 8 (4):432-444. MacDonald DS: Maxillofacial fibro-osseous lesions . Clin Radiol 2015, 70 (1):25-36. Zhou Z, Zhang Y, Zhu L, Cui Y, Gao Y, Zhou CX: Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review . Molecular genetics & genomic medicine 2024, 12 (1):e2277. Woo SB: Central Cemento-Ossifying Fibroma: Primary Odontogenic or Osseous Neoplasm? J Oral Maxillofac Surg 2015, 73 (12 Suppl):S87-93. Aldred MJ, Talacko AA, Savarirayan R, Murdolo V, Mills AE, Radden BG, Alimov A, Villablanca A, Larsson C: Dental findings in a family with hyperparathyroidism–jaw tumor syndrome and a novel HRPT2 gene mutation . Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2006, 101 (2):212-218. Meier ME, van der Bruggen W, van de Sande MAJ, Appelman-Dijkstra NM: Regression of fibrous dysplasia in response to denosumab therapy: A report of two cases . Bone reports 2021, 14 :101058. Maximen J, Robin F, Tronchot A, Rossetti A, Ropars M, Guggenbuhl P: Denosumab in the management of Aneurysmal bone cyst . Joint Bone Spine 2022, 89 (1):105260. Borkowska AM, Szumera-Ciećkiewicz A, Szostakowski B, Pieńkowski A, Rutkowski PL: Denosumab in Giant Cell Tumor of Bone: Multidisciplinary Medical Management Based on Pathophysiological Mechanisms and Real-World Evidence . Cancers (Basel) 2022, 14 (9). Patel MM, Wilkey JF, Abdelsayed R, D'Silva NJ, Malchoff C, Mallya SM: Analysis of GNAS mutations in cemento-ossifying fibromas and cemento-osseous dysplasias of the jaws . Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010, 109 (5):739-743. Tabareau-Delalande F, Collin C, Gomez-Brouchet A, Decouvelaere AV, Bouvier C, Larousserie F, Marie B, Delfour C, Aubert S, Rosset P et al : Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions . Mod Pathol 2013, 26 (7):911-921. Kim HY, Shim JH, Heo CY: A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects . Int J Mol Sci 2023, 24 (21). Günhan Ö, Kahraman D, Yalçın ÜK: The possible pathogenesis of cemento-osseous dysplasia: A case series and discussion . Advances in Oral and Maxillofacial Surgery 2021, 3 . Haefliger S, Turek D, Andrei V, Alborelli I, Calgua B, Ameline B, Harder D, Baumhoer D: Cemento-osseous dysplasia is caused by RAS-MAPK activation . Pathology 2023, 55 (3):324-328. Trojani MC, Gensburger D, Bagouet F, Cortet B, Couture G, Marcelli C, Mehsen Cetre N, Breuil V, Chapurlat R: Denosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study . Bone 2023, 174 :116819. Pan KS, Boyce AM: Denosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia-Risks and Benefits . Current osteoporosis reports 2021, 19 (2):141-150. Chawla S, Blay JY, Rutkowski P, Le Cesne A, Reichardt P, Gelderblom H, Grimer RJ, Choy E, Skubitz K, Seeger L et al : Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study . Lancet Oncol 2019, 20 (12):1719-1729. Alhumaid I, Abu-Zaid A: Denosumab Therapy in the Management of Aneurysmal Bone Cysts: A Comprehensive Literature Review . Cureus 2019, 11 (1):e3989. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2025 Read the published version in BMC Oral Health → Version 1 posted Editorial decision: Revision requested 22 Nov, 2024 Reviews received at journal 20 Nov, 2024 Reviewers agreed at journal 11 Nov, 2024 Reviews received at journal 06 Nov, 2024 Reviewers agreed at journal 06 Nov, 2024 Reviews received at journal 26 Oct, 2024 Reviewers agreed at journal 26 Oct, 2024 Reviewers agreed at journal 25 Oct, 2024 Reviewers invited by journal 01 Oct, 2024 Editor invited by journal 01 Oct, 2024 Editor assigned by journal 28 Sep, 2024 Submission checks completed at journal 28 Sep, 2024 First submitted to journal 23 Sep, 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5135664","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":381518619,"identity":"269d730b-cf5d-4937-ac0e-e36a88c81d9f","order_by":0,"name":"Chieh Ling Chiang","email":"","orcid":"","institution":"Mackay Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chieh","middleName":"Ling","lastName":"Chiang","suffix":""},{"id":381518620,"identity":"25a4602a-6896-4a4f-9d53-482640997985","order_by":1,"name":"Tzu Huan Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYJAC5j8VEjxs7M3HwDw2dmL08JyxkOHjOZbGwJAA1MJMjBbelgobOYkcM7AWBkJa+GefPfhAsgHoMImcbw8+/tgmz8fMwPjhYw5uLRLn8pINDHcAtfC83W44I+G2YRszA7PkzG14rDnDYyaReAbk/dxt0jwJtxmBWtiYefFokQdpOdgG1MKQ8wykxZ6gFgOgFslGkBaOHDaQlkSCWgzP8BgbM4AcxnPMTHJG2u3kNmbGZrx+kTvDY/iYoaLOXr69+ZnEB5vbtvPbmw9++IjP+1gAYwNp6kfBKBgFo2AUYAAAEkxFWdXko4gAAAAASUVORK5CYII=","orcid":"","institution":"Mackay Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tzu","middleName":"Huan","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2024-09-23 06:40:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5135664/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5135664/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12903-025-05514-4","type":"published","date":"2025-01-30T15:57:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71692660,"identity":"b2dbc499-e347-4b7f-8526-734d2fa62725","added_by":"auto","created_at":"2024-12-17 18:35:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1344406,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/eafd6ea3965eaa747f281c26.png"},{"id":71692656,"identity":"7ef41a3e-553a-4da6-8da9-603c9c034f30","added_by":"auto","created_at":"2024-12-17 18:35:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1447003,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/6f707f6702b5e89878169924.png"},{"id":71692658,"identity":"134e6de7-a1e4-4b02-8400-d627398021ac","added_by":"auto","created_at":"2024-12-17 18:35:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1278701,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/c83a3e77f6db22caba9ae09b.png"},{"id":71692661,"identity":"d7d764ae-03a3-4079-8220-dca862a4f2f7","added_by":"auto","created_at":"2024-12-17 18:35:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2834095,"visible":true,"origin":"","legend":"\u003cp\u003eA. Curvilinear trabeculae of lamellar bone with rimming of osteoblasts\u003c/p\u003e\n\u003cp\u003eB. Curvilinear trabeculae of lamellar bone (right side) and cementum-like tissue (left side) in a fibrotic stroma.\u003c/p\u003e\n\u003cp\u003eC. Irregularly shaped cementum-like particles (secondary biopsy)\u003c/p\u003e\n\u003cp\u003eD. Woven bone with scattered hemorrhage (secondary biopsy)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/ae433ec8a41132cc64101b44.png"},{"id":71693366,"identity":"066e2d50-7175-452f-b98f-1b0ce405cfc3","added_by":"auto","created_at":"2024-12-17 18:43:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1021893,"visible":true,"origin":"","legend":"\u003cp\u003eA regularly sized mandible from another patient was used as a template to simulate the position of the fibula flap from the bilateral leg.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/25f1b11d995a09dae76bf0c4.png"},{"id":75351270,"identity":"aeb42ded-4179-4fe0-b9ae-61987ba34f3d","added_by":"auto","created_at":"2025-02-03 16:08:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10686416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5135664/v1/5b908207-207a-4e92-a6b8-c42678f7d444.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Denosumab Usage in Rare Cemento-Osseous Dysplasia Involves the Whole Mandible, Including the Bilateral Condyle—A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eCemento-osseous dysplasia (COD) is the most common radiopacity lesion of the jaw bone. Predominantly occurring in middle-aged black women. Some investigators suggest that cemento-osseous dysplasia originates from periodontal ligament cell or bone remodeling triggered by local trauma, such as clenching or bruxism[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Most CODs are asymptomatic and are unexpectedly discovered via dental radiographic examination. Surgical treatment and unnecessary biopsy should be avoid. Traditionally, COD involves the tooth-bearing area and is normally asymptomatic with no bony expansion. COD usually appears to be associated with the root apex or previous tooth extraction site. There are three subtypes of COD: focal, periapical, and florid types. Florid-type COD may involve multiple quadrants and exhibit bony expansion in rare circumstances with tenderness, causing chronic osteomyelitis and delayed healing if infected[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Report ","content":"\u003cp\u003eA woman with a chief complaint of lower tooth swelling and purulent discharge visited our department for help. The initial panoramic film revealed diffuse mixed radiopaque and radiolucent lesions from the right mandibular body to the left mandibular body (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). She denied chin numbness and underwent normal neurological examination of the inferior alveolar nerve. Some suppurative discharge from periodontal tissue was noted without tenderness. She had mandibular removable partial dentures fabricated at a dental clinic several years ago but became unfit over time. Clinically, the patient showed mandibular bony expansion with a protrusive mandible and class III lateral profile, while she had a straight profile according to the photo taken at her young age. CT revealed moderate bony expansion with peripheral sclerotic changes at the periosteum at the focal area and mixed radiopaque and radiolucency extending to the whole mandible, including the bilateral condyle, bilateral ascending ramus and body to the symphysis area; no obvious intralesional contrast media were noted (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). A bone scan with SPE-CT revealed high signal uptake at the whole mandible with no uptake at other parts of the body (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The initial impression was a fibro-osseous lesion, including the whole mandible, with chronic suppurative osteomyelitis. The infection was controlled via the use of augmentin with local debridement and tooth extraction. Some intrabony tissue was sent for pathological examination. Microscopically, a hypercellular fibroblastic stroma with some bands of osteoid or cementum-like calcification was distributed throughout the lesion (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The bony trabeculae were surrounded by plump osteoblasts. The pathological diagnosis was ossifying fibroma. The patient was lost to follow-up since the infection subsided. Two years later, she came to our department again due to progressive mandible expansion with poor chewing ability. However, owing to the large extent of the lesion, total mandibulectomy with two fibular flaps with dental implants was simulated via ProPlan CMF (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). However, owing to the length of the defect, using bilateral fibula simultaneously and TMJ function using fibula bone stock for joint reconstruction was uncertain. The patient hesitated about the treatment plan. Hence, we discuss off-label use of denosumab with patients since many studies have investigated other fibro-osseous lesions, such as fibrous dysplasia. We performed the second tissue biopsy and sent it to an oral pathologist. The present case involved a fibro-osseous lesion, favoring florid-type cemento-osseous dysplasia. Microscopically, there is cellular fibrovascular connective tissue with scattered hemorrhage and a variable mixture of woven bone, lamellar bone and irregularly shaped cementum-like particles. Since there is no protocol for treating osseous dysplasia or ossifying fibroma with denosumab, we followed the most commonly used protocol for treating fibrous dysplasia according to the literature[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]: 60 mg of denosumab every 3 months. After 3 regimens, there were no obvious changes in the facial profile. However, rapid calcification of the bone lesion, including the bilateral condyle, ramus, and symphysis areas, was noted on CT. A bone scan with SPE-CT still revealed Tc-99 uptake at the whole mandible but decreased signal intensity at the condylar area. Our intent is to maintain denosumab usage until stable disease conditions are reached and consider resecting the mandible from body to body, preserving the diseased subcondyle region, and reconstructing it with one fibula flap for implant-supported dentures. The condition of the diseased condyle was closely monitored. The TMJ total joint prosthesis to replace the bilateral diseased condyle if the disease progresses and when the device is legally available in Taiwan.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Discussion and conclusion","content":"\u003cp\u003eFibro-osseous lesions can be categorized into three diseases: fibrous dysplasia (FD), cemento-ossifying fibroma (COF) and cemento-osseous dysplasia (COD). Microscopically, FD shows irregularly shaped trabeculae of immature bone in a cellular fibrous tissue. The trabeculae tend to be curvilinear shaped, such as a Chinese character without osteoblastic rimming, which could be easily distinguished from COF and COD. However, the COFs and CODs are nearly the same histologically. They both have fibrovascular connective tissue with mineralized products, such as immature woven bone, lamellar bone and cementum-like particles. Peripheral osteoid or osteoblastic rimming is usually present in both lesions. However, COFs have less significant intralesional hemorrhage, whereas CODs tend to have “ginger root” bone trabeculae.\u003c/p\u003e\u003cp\u003eTo the best of our knowledge, there are no reports of florid-type COD that spreads beyond the tooth-bearing area and extends to the bilateral condyles. The pattern of the presented case is so rare that we consider familial gigantiform cementoma (FGC) as another possible diagnosis. Histologically, FGC and COD show the same spectrum of changes under a microscope. We can only diagnose this disease clinically and radiographically. According to the 5th edition of the World Health Organization for odontogenic maxillary facial bone tumors[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], FGC normally develops in young patients, such as adolescents, who exhibit rapid expansion of all four quadrants of the jaw with facial deformities and who are not predisposed by sex or ethnic group. On the other hand, approximately 90% of those with COD are middle-aged females. Most of the population is African American women, followed by East Asians and Whites[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Both florid-type COD and gigantiform cementoma can be familial or sporadic[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, our case involved only the mandible of a middle-aged female and had no family history of jawbone lesions. Moreover, the lesion progresses slowly for decades, whereas FGC grows rapidly, which is different from traditional gigantiform cementoma. FGC is an autosomal dominant mutation in the ANO5 gene that is absent in familial COD, ossifying fibroma, and polyostotic fibrous dysplasia[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCemento-ossifying fibroma (COF) is typically recognized as a neoplasm with a clear margin between the tumor and normal bone[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. During biopsy, a firm mass can be identified. On the other hand, COD patients exhibit fragile fragmented dreg tissue during biopsy and are more likely to experience hemorrhage in the mixed radiographic stage, similar to the case we present here. Syndromic ossifying fibroma (also called hyperparathyroidism jaw tumor) often presents with mutations in the tumor suppressor gene HRPT2, known as CDC73 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Our patient presented with normal parathyroid function. In addition to conventional ossifying fibroma, more aggressive subtypes, such as psammomatoid ossifying fibroma and trabecular ossifying fibroma, are diseases that restrict in childhood and are classified as juvenile ossifying fibroma. Hence, we prefer florid-type COD with condyle involvement as the final diagnosis.\u003c/p\u003e\u003cp\u003eMost of the time, focal COD requires no biopsy or treatment. For such extensive COD with limited surgical options, there is no standard medical treatment protocol. However, many reports and case series have demonstrated the benefit of denosumab usage in fibrous dysplasia, giant cell bone tumors and aneurysm bone cysts[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e–\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The pathophysiology of FD involves the replacement of normal bone tissue with fibrous tissue resulting from GNAS mutation, which is restricted to fibrous dysplasia and can distinguish other fibro-osseous lesions, such as CODs and COFs[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. GNAS mutation results in the release of osteoblastic factors that form immature osteoblasts. These osteoblasts release osteoclastic factors such as RANKL, OPG, M-CSF, and IL-6, which induce proinflammatory macrophages and osteoclast differentiation[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Denosumab is a human monoclonal anti-RANKL antibody that reduces the activity of fibrous dysplasia. However, COD shares different pathophysiologies and is restricted to the jaw bone only. Some researchers believe that occlusal parafunction and overload may result in periapical osteosclerosis. The craniofacial bone originates from neural crest mesenchymal cells and undergoes a variety of signaling pathways, such as the Wnt and bone morphogenic protein (BMP) pathways, during bone formation[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Other studies regard COD as a disease driven by RAS-MAPK mutation[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], although only 28% of the patients (5 out of 18 patients) had RAS-MAPK pathway mutations in this study.\u003c/p\u003e\u003cp\u003eTreatment options for such extensive cemento-osseous dysplasia extending to the whole mandible are limited, and very few clinical reports in the literature can be found. Denosumab usage in bone lesions, such as fibrous dysplasia, aneurysm, bone cysts or giant cell tumors, has been documented[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and has shown some encouraging results, such as pain, tumor volume control and ossification of the bone lesion. Although the pathophysiology of these bone diseases differs, blocking the RANKL pathway to affect the bone turnover rate still has benefits. For giant cell granulomas, denosumab is the only approved medical agent for inoperable giant cell granulomas or adjuvant treatment for operable cases according to an open-label phase II trial[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. For fibrous dysplasia and aneurysm bone cysts, few clinical trials exist, but some case series support the treatment outcome of Denosumab[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our case also revealed mineralization of the destructive bone in a large case of cemento-osseous dysplasia as an alternative treatment. There are no previous reports focusing on the use of denosumab in treating COD. Further research in pathophysiology and clinical trials is needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOD: Cemento-osseous dysplasia\u003c/p\u003e\n\u003cp\u003eCOF: Cemento-ossifying fibroma\u003c/p\u003e\n\u003cp\u003eFD: Fibrous dysplasia\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eConsent to Publish declaration: A written informed consent was obtained from the patient for publication of this Case report and any accompanying images.\u003cbr\u003e\u0026nbsp;There was no Funding to declare\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interes\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor Information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst author: Chieh Ling Chiang, Mackay Memorial Hospital, Hsinchu Branch\u003c/p\u003e\n\u003cp\u003eCorresponding Author: Tzu Huan Huang, Mackay Memorial Hospital\u003c/p\u003e\n\u003cp\u003eChieh Ling Chiang wrote the main manuscript and Tzu Huan Huang prepare the figures, review the article. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWaldron CA, Giansanti JS: \u003cstrong\u003eBenign fibro-osseous lesions of the jaws: a clinical-radiologic-histologic review of sixty-five cases. II. Benign fibro-osseous lesions of periodontal ligament origin\u003c/strong\u003e. \u003cem\u003eOral Surg Oral Med Oral Pathol \u003c/em\u003e1973, \u003cstrong\u003e35\u003c/strong\u003e(3):340-350.\u003c/li\u003e\n\u003cli\u003eCavalcante MB, de Oliveira Lima AL, J\u0026uacute;nior MA, Santos MB: \u003cstrong\u003eFlorid Cemento-Osseous Dysplasia Simultaneous the Chronic Suppurative Osteomyelitis in Mandible\u003c/strong\u003e. \u003cem\u003eJ Craniofac Surg \u003c/em\u003e2016, \u003cstrong\u003e27\u003c/strong\u003e(8):2173-2176.\u003c/li\u003e\n\u003cli\u003eMajoor BCJ, Papapoulos SE, Dijkstra PDS, Fiocco M, Hamdy NAT, Appelman-Dijkstra NM: \u003cstrong\u003eDenosumab in Patients With Fibrous Dysplasia Previously Treated With Bisphosphonates\u003c/strong\u003e. \u003cem\u003eJ Clin Endocrinol Metab \u003c/em\u003e2019, \u003cstrong\u003e104\u003c/strong\u003e(12):6069-6078.\u003c/li\u003e\n\u003cli\u003eVered M, Wright JM: \u003cstrong\u003eUpdate from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Odontogenic and Maxillofacial Bone Tumours\u003c/strong\u003e. \u003cem\u003eHead Neck Pathol \u003c/em\u003e2022, \u003cstrong\u003e16\u003c/strong\u003e(1):63-75.\u003c/li\u003e\n\u003cli\u003eEl-Mofty SK: \u003cstrong\u003eFibro-Osseous Lesions of the Craniofacial Skeleton: An Update\u003c/strong\u003e. \u003cem\u003eHead Neck Pathol \u003c/em\u003e2014, \u003cstrong\u003e8\u003c/strong\u003e(4):432-444.\u003c/li\u003e\n\u003cli\u003eMacDonald DS: \u003cstrong\u003eMaxillofacial fibro-osseous lesions\u003c/strong\u003e. \u003cem\u003eClin Radiol \u003c/em\u003e2015, \u003cstrong\u003e70\u003c/strong\u003e(1):25-36.\u003c/li\u003e\n\u003cli\u003eZhou Z, Zhang Y, Zhu L, Cui Y, Gao Y, Zhou CX: \u003cstrong\u003eFamilial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review\u003c/strong\u003e. \u003cem\u003eMolecular genetics \u0026amp; genomic medicine \u003c/em\u003e2024, \u003cstrong\u003e12\u003c/strong\u003e(1):e2277.\u003c/li\u003e\n\u003cli\u003eWoo SB: \u003cstrong\u003eCentral Cemento-Ossifying Fibroma: Primary Odontogenic or Osseous Neoplasm?\u003c/strong\u003e \u003cem\u003eJ Oral Maxillofac Surg \u003c/em\u003e2015, \u003cstrong\u003e73\u003c/strong\u003e(12 Suppl):S87-93.\u003c/li\u003e\n\u003cli\u003eAldred MJ, Talacko AA, Savarirayan R, Murdolo V, Mills AE, Radden BG, Alimov A, Villablanca A, Larsson C: \u003cstrong\u003eDental findings in a family with hyperparathyroidism\u0026ndash;jaw tumor syndrome and a novel HRPT2 gene mutation\u003c/strong\u003e. \u003cem\u003eOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology \u003c/em\u003e2006, \u003cstrong\u003e101\u003c/strong\u003e(2):212-218.\u003c/li\u003e\n\u003cli\u003eMeier ME, van der Bruggen W, van de Sande MAJ, Appelman-Dijkstra NM: \u003cstrong\u003eRegression of fibrous dysplasia in response to denosumab therapy: A report of two cases\u003c/strong\u003e. \u003cem\u003eBone reports \u003c/em\u003e2021, \u003cstrong\u003e14\u003c/strong\u003e:101058.\u003c/li\u003e\n\u003cli\u003eMaximen J, Robin F, Tronchot A, Rossetti A, Ropars M, Guggenbuhl P: \u003cstrong\u003eDenosumab in the management of Aneurysmal bone cyst\u003c/strong\u003e. \u003cem\u003eJoint Bone Spine \u003c/em\u003e2022, \u003cstrong\u003e89\u003c/strong\u003e(1):105260.\u003c/li\u003e\n\u003cli\u003eBorkowska AM, Szumera-Ciećkiewicz A, Szostakowski B, Pieńkowski A, Rutkowski PL: \u003cstrong\u003eDenosumab in Giant Cell Tumor of Bone: Multidisciplinary Medical Management Based on Pathophysiological Mechanisms and Real-World Evidence\u003c/strong\u003e. \u003cem\u003eCancers (Basel) \u003c/em\u003e2022, \u003cstrong\u003e14\u003c/strong\u003e(9).\u003c/li\u003e\n\u003cli\u003ePatel MM, Wilkey JF, Abdelsayed R, D\u0026apos;Silva NJ, Malchoff C, Mallya SM: \u003cstrong\u003eAnalysis of GNAS mutations in cemento-ossifying fibromas and cemento-osseous dysplasias of the jaws\u003c/strong\u003e. \u003cem\u003eOral Surg Oral Med Oral Pathol Oral Radiol Endod \u003c/em\u003e2010, \u003cstrong\u003e109\u003c/strong\u003e(5):739-743.\u003c/li\u003e\n\u003cli\u003eTabareau-Delalande F, Collin C, Gomez-Brouchet A, Decouvelaere AV, Bouvier C, Larousserie F, Marie B, Delfour C, Aubert S, Rosset P\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eDiagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions\u003c/strong\u003e. \u003cem\u003eMod Pathol \u003c/em\u003e2013, \u003cstrong\u003e26\u003c/strong\u003e(7):911-921.\u003c/li\u003e\n\u003cli\u003eKim HY, Shim JH, Heo CY: \u003cstrong\u003eA Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects\u003c/strong\u003e. \u003cem\u003eInt J Mol Sci \u003c/em\u003e2023, \u003cstrong\u003e24\u003c/strong\u003e(21).\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;nhan \u0026Ouml;, Kahraman D, Yal\u0026ccedil;ın \u0026Uuml;K: \u003cstrong\u003eThe possible pathogenesis of cemento-osseous dysplasia: A case series and discussion\u003c/strong\u003e. \u003cem\u003eAdvances in Oral and Maxillofacial Surgery \u003c/em\u003e2021, \u003cstrong\u003e3\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eHaefliger S, Turek D, Andrei V, Alborelli I, Calgua B, Ameline B, Harder D, Baumhoer D: \u003cstrong\u003eCemento-osseous dysplasia is caused by RAS-MAPK activation\u003c/strong\u003e. \u003cem\u003ePathology \u003c/em\u003e2023, \u003cstrong\u003e55\u003c/strong\u003e(3):324-328.\u003c/li\u003e\n\u003cli\u003eTrojani MC, Gensburger D, Bagouet F, Cortet B, Couture G, Marcelli C, Mehsen Cetre N, Breuil V, Chapurlat R: \u003cstrong\u003eDenosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study\u003c/strong\u003e. \u003cem\u003eBone \u003c/em\u003e2023, \u003cstrong\u003e174\u003c/strong\u003e:116819.\u003c/li\u003e\n\u003cli\u003ePan KS, Boyce AM: \u003cstrong\u003eDenosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia-Risks and Benefits\u003c/strong\u003e. \u003cem\u003eCurrent osteoporosis reports \u003c/em\u003e2021, \u003cstrong\u003e19\u003c/strong\u003e(2):141-150.\u003c/li\u003e\n\u003cli\u003eChawla S, Blay JY, Rutkowski P, Le Cesne A, Reichardt P, Gelderblom H, Grimer RJ, Choy E, Skubitz K, Seeger L\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eDenosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study\u003c/strong\u003e. \u003cem\u003eLancet Oncol \u003c/em\u003e2019, \u003cstrong\u003e20\u003c/strong\u003e(12):1719-1729.\u003c/li\u003e\n\u003cli\u003eAlhumaid I, Abu-Zaid A: \u003cstrong\u003eDenosumab Therapy in the Management of Aneurysmal Bone Cysts: A Comprehensive Literature Review\u003c/strong\u003e. \u003cem\u003eCureus \u003c/em\u003e2019, \u003cstrong\u003e11\u003c/strong\u003e(1):e3989.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cemento-osseous dysplasia, Fibro-osseous lesion, Denosumab","lastPublishedDoi":"10.21203/rs.3.rs-5135664/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5135664/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCemento-osseous dysplasia is the most common type of apical radiopaque lesion in the tooth-bearing area. However, large destructive lesions are rare. We report a case in which the lesion extended to the bilateral condyle and whole mandible and was managed with denosumab instead of surgical resection.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA 45-year-old woman with destructive progressing large cemento-osseous dysplasia involve the whole mandible, including the bilateral condyle and bony expansion, which led to facial deformity and malocclusion. She was hesitant about the surgical option of resection of the whole mandible and turned to the off-label use of denosumab. After 9 months of administration, rapid ossification of the osteolytic lesion was observed, but there was no obvious change in volume. A bone scan with SPE-CT revealed stable disease with no progression.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eDenosumab may be considered a potential medical treatment option to prevent the progression of severe destructive cemento-osseous dysplasia in patients with limited surgical options.\u003c/p\u003e","manuscriptTitle":"Denosumab Usage in Rare Cemento-Osseous Dysplasia Involves the Whole Mandible, Including the Bilateral Condyle—A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-17 18:35:42","doi":"10.21203/rs.3.rs-5135664/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-22T17:08:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-21T03:39:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310313788779391645629126218833463710299","date":"2024-11-11T11:09:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-06T11:41:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327965134999776687120240735527152394727","date":"2024-11-06T09:44:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-26T22:01:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241895609868390954293260453327685085937","date":"2024-10-26T21:52:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34490179193857020017693029245861858149","date":"2024-10-25T11:14:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-01T06:52:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-01T05:20:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-28T06:48:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-28T06:47:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2024-09-23T06:38:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d88eb5ac-cc88-46d4-bd35-a3c3926beb6c","owner":[],"postedDate":"December 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:02:25+00:00","versionOfRecord":{"articleIdentity":"rs-5135664","link":"https://doi.org/10.1186/s12903-025-05514-4","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2025-01-30 15:57:33","publishedOnDateReadable":"January 30th, 2025"},"versionCreatedAt":"2024-12-17 18:35:42","video":"","vorDoi":"10.1186/s12903-025-05514-4","vorDoiUrl":"https://doi.org/10.1186/s12903-025-05514-4","workflowStages":[]},"version":"v1","identity":"rs-5135664","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5135664","identity":"rs-5135664","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}