{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:22:45Z","timestamp":1779103365377,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteogenesis imperfecta (OI) is a rare, heritable, skeletal disorder resulting in defective bone formation. Clinical presentation is heterogeneous. This study aims to provide an overview of the clinical manifestations by disease severity and age in a large cohort of Italian patients with OI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with OI who received care at the IRCCS Istituto Ortopedico Rizzoli from 2005 to 2024 were enrolled in the Registry of Osteogenesis Imperfecta database and analyzed for this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 628 patients with OI were included in the study (51.1% had Type I, 5.1% Type III, 6.7% Type IV, 0.3% Type V, and 36.8% unknown type). Patient height was reduced with increasing disease severity (Type I had mildly reduced height and Type III had marked height reduction). Fractures were common across all OI groups. The annualized fracture rates were highest in younger patients (288.31 per 1,000 person years) and patients with Type III, Type IV OI and unknown type. Skeletal deformities were present across all OI types and in every age group, with trunk deformities being most frequently reported. An estimated 10\u201330% of all patients suffered from functional limitations. Extraskeletal manifestations (skin abnormalities, hearing loss, valvulopathies, scleral discoloration, joint hyperlaxity, and dental abnormalities) were common.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Various parameters including height, weight, fractures, and skeletal and extraskeletal deformities vary by OI type and patient age. These findings support the need for phenotype-informed, life-course care planning with the need for adaptations for age-related patterns to optimize patient care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1823717","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:40:11Z","timestamp":1779100811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Osteogenesis imperfecta: a registry-based study of the clinical symptoms of disease in a large cohort of Italian patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Marina","family":"Mordenti","sequence":"first","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli","place":["Bologna, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Clancy","sequence":"additional","affiliation":[{"name":"Mereo BioPharma Group Plc","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Dyer","sequence":"additional","affiliation":[{"name":"Mereo BioPharma Group Plc","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manila","family":"Boarini","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli","place":["Bologna, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Banchelli","sequence":"additional","affiliation":[{"name":"Independent researcher","place":["Bologna, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive","family":"Whitcher","sequence":"additional","affiliation":[{"name":"Mereo BioPharma Group Plc","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Lanza","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli","place":["Bologna, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli","place":["Bologna, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.81","article-title":"Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta","volume":"23","author":"Lindahl","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1210\/endrev\/bnab017","article-title":"Osteogenesis imperfecta: Mechanisms and signaling pathways connecting classical and rare OI types","volume":"43","author":"Jovanovic","year":"2022","journal-title":"Endocr Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.02.004","article-title":"Genetic causes and mechanisms of osteogenesis imperfecta","volume":"102","author":"Lim","year":"2017","journal-title":"Bone"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1530\/ey.20.3.8","article-title":"Nosology of genetic skeletal disorders: 2023 revision","volume":"191","author":"Unger","year":"2023","journal-title":"Am J Med Genet A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R95","DOI":"10.1530\/eje-20-0299","article-title":"Osteogenesis imperfecta: an update on clinical features and therapies","volume":"183","author":"Marom","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1006\/rwgn.2001.0941","article-title":"Genetic heterogeneity in osteogenesis imperfecta","volume":"16","author":"Sillence","year":"1979","journal-title":"J Med Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejmg.2009.10.007","article-title":"Classification of osteogenesis imperfecta revisited","volume":"53","author":"Van Dijk","year":"2010","journal-title":"Eur J Med Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36545","article-title":"Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment","author":"Van Dijk","year":"2014","journal-title":"Am J Med Genet A"},{"key":"B9","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13023-020-01404-w","article-title":"Reproductive options for families at risk of osteogenesis imperfecta: a review","volume":"15","author":"Zhytnik","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s13023-024-03341-4","article-title":"SATURN: assessing the feasibility of utilising existing registries for real-world evidence data collection to meet patients, regulatory, health technology assessment and payer requirements","volume":"19","author":"Sangiorgi","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2479","article-title":"Real-world evidence in EU medicines regulation: Enabling use and establishing value","volume":"111","author":"Arlett","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"B12","article-title":"Real-world evidence","year":"2025"},{"key":"B13","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13023-024-03185-y","article-title":"Project SATURN- a real-world evidence data collaboration with existing European datasets in osteogenesis imperfecta to support future therapies","volume":"19","author":"Sangiorgi","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1299232","article-title":"Osteogenesis imperfecta: a cross-sectional study of skeletal and extraskeletal features in a large cohort of Italian patients","volume":"14","author":"Mordenti","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/bf03344156","article-title":"Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr)","volume":"29","author":"Cacciari","year":"2006","journal-title":"J Endocrinol Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.869604","article-title":"Prevalence and hospital admissions in patients with osteogenesis imperfecta in The Netherlands: a nationwide registry study","volume":"13","author":"Storoni","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3709-1","article-title":"DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum","volume":"27","author":"Bardai","year":"2016","journal-title":"Osteoporos Int"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01200","article-title":"Genotype-phenotype association analysis reveals new pathogenic factors for osteogenesis imperfecta disease","volume":"10","author":"Shi","year":"2019","journal-title":"Front Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000000013","article-title":"Genotype-phenotype relationship in a large cohort of osteogenesis imperfecta patients with COL1A1 mutations revealed by a new scoring system","volume":"132","author":"Li","year":"2019","journal-title":"Chin Med J (Engl)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3653-0","article-title":"Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1\/COL1A2 genotype and collagen structure","volume":"27","author":"Hald","year":"2016","journal-title":"Osteoporos Int"},{"key":"B21","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1186\/s13023-024-03433-1","article-title":"Height prediction of individuals with osteogenesis imperfecta by machine learning","volume":"19","author":"Yang","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1186\/s12887-025-05838-8","article-title":"Growth trajectories of children and adolescents with osteogenesis imperfecta in a reference center in Rio de Janeiro, Brazil","volume":"25","author":"Pereira","year":"2025","journal-title":"BMC Pediatr"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0045-1","article-title":"Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study","volume":"21","author":"Jain","year":"2019","journal-title":"Genet Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/jbmrpl\/ziaf124","article-title":"Real-world data of fracture rates and musculoskeletal disorders for patients living with osteogenesis imperfecta","volume":"9","author":"Yang","year":"2025","journal-title":"JBMR Plus"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1308\/rcsann.2019.0002","article-title":"Fracture admission trends in England over a ten-year period","volume":"101","author":"Jennison","year":"2019","journal-title":"Ann R Coll Surg Engl"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2920","article-title":"Fracture rates and fracture sites in patients with osteogenesis imperfecta: a nationwide register-based cohort study","volume":"32","author":"Folkestad","year":"2017","journal-title":"J Bone Miner Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10782","article-title":"The natural history of symptomatic fractures in children and adolescents with osteogenesis imperfecta type 1: a cohort study from Western Australia","volume":"7","author":"Joshi","year":"2023","journal-title":"JBMR Plus"},{"key":"B28","doi-asserted-by":"publisher","first-page":"117607","DOI":"10.2139\/ssrn.5254756","article-title":"Mortality and fracture risk in children with osteogenesis imperfecta: results from the French nationwide hospital discharge database","volume":"200","author":"Philippoteaux","year":"2025","journal-title":"Bone"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae791","article-title":"Genetics and bone mineral density predict the fractures in adults with osteogenesis imperfecta: a prospective study","volume":"110","author":"Blandin","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2024.104926","article-title":"Imaging in osteogenesis imperfecta: Where we are and where we are going","volume":"68","author":"Gazzotti","year":"2024","journal-title":"Eur J Med Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2022.07.002","article-title":"Functional status of individuals with osteogenesis imperfecta: data from a reference center","volume":"99","author":"Carvalho","year":"2023","journal-title":"J Pediatr (Rio J)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0491-4","article-title":"Mobility in osteogenesis imperfecta: a multicenter North American study","volume":"21","author":"Kruger","year":"2019","journal-title":"Genet Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2024.100757","article-title":"Type 1 collagen: Synthesis, structure and key functions in bone mineralization","volume":"136","author":"Selvaraj","year":"2024","journal-title":"Differentiation"},{"key":"B34","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1186\/s13023-025-04073-9","article-title":"Health-related quality of life in individuals with osteogenesis imperfecta in the United States: a cross-sectional study","volume":"20","author":"Derocher","year":"2025","journal-title":"Orphanet J Rare Dis"},{"key":"B35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13023-023-02643-3","article-title":"Systematic review of health related-quality of life in adults with osteogenesis imperfecta","volume":"18","author":"Mc Donald","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-024-01213-4","article-title":"Extra-skeletal manifestations in osteogenesis imperfecta mouse models","volume":"115","author":"Crawford","year":"2024","journal-title":"Calcif Tissue Int"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14882","article-title":"Ocular characteristics and complications in patients with osteogenesis imperfecta: a systematic review","volume":"100","author":"Treurniet","year":"2022","journal-title":"Acta Ophthalmol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-15-428","article-title":"Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric osteogenesis imperfecta patients: a retrospective cross-sectional study","volume":"15","author":"Arponen","year":"2014","journal-title":"BMC Musculoskelet Disord"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-024-01293-2","article-title":"Dental abnormalities in osteogenesis imperfecta: a systematic review","volume":"115","author":"Ventura","year":"2024","journal-title":"Calcif Tissue Int"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2025.08.032","article-title":"Oral health-related quality of life in patients with osteogenesis imperfecta in Taiwan","volume":"21","author":"Hsu","year":"2026","journal-title":"J Dental Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"17125","DOI":"10.1038\/s41598-022-20169-9","article-title":"Treatments for hearing loss in osteogenesis imperfecta: a systematic review and meta-analysis on their efficacy","volume":"12","author":"Ugarteburu","year":"2022","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s13023-015-0362-2","article-title":"Initial report of the osteogenesis imperfecta adult natural history initiative","volume":"10","author":"Tosi","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.09.107","article-title":"Cardiovascular disease in patients with osteogenesis imperfecta - a nationwide, register-based cohort study","volume":"225","author":"Folkestad","year":"2016","journal-title":"Int J Cardiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2895","article-title":"Mortality and causes of death in patients with osteogenesis imperfecta: a register-based nationwide cohort study","volume":"31","author":"Folkestad","year":"2016","journal-title":"J Bone Miner Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.8.627","article-title":"Causes of death in osteogenesis imperfecta","volume":"49","author":"McAllion","year":"1996","journal-title":"J Clin Pathol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1186\/s13023-025-03973-0","article-title":"Somewhere to go: a position paper on addressing gaps in transition care for adults with childhood-onset rare diseases","volume":"20","author":"Tosi","year":"2025","journal-title":"Orphanet J Rare Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1823717\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:40:13Z","timestamp":1779100813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1823717\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":46,"alternative-id":["10.3389\/fendo.2026.1823717"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1823717","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]},"article-number":"1823717"}}