{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:02:06Z","timestamp":1788444126324,"version":"build-2803163510"},"reference-count":157,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Scheuermann\u2019s kyphosis (SK) is a rigid dorsal kyphosis of unclear pathophysiological origin. The aim of this review is to summarise current theories and both clinical and experimental findings regarding the underlying mechanisms of SK. Emerging evidence highlights the significant role of excessive mechanical loading as a major contributor to defective growth of the cartilaginous vertebral endplate. This is associated with the formation of Schmorl\u2019s nodes, disruption of the ring apophysis, and compromised intervertebral disc integrity\u2014ultimately resulting in vertebral body wedging and thickening of the anterior longitudinal ligament. In addition, numerous studies have investigated the genetic contribution and underlying molecular mechanisms involved in the pathogenesis of SK. Recent in vivo findings suggest an association between asymmetric mechanosensory activation of cerebrospinal fluid (CSF), contacting neurons, and defective Reissner fibre signalling, which may contribute to abnormal spinal morphogenesis in the sagittal thoracic plane. These findings indicate a potential link between altered CSF dynamics and the development of SK. Taken together, the evidence supports a multifactorial aetiology, with both genetic and biomechanical factors playing central roles in the development of Scheuermann\u2019s kyphosis. The interpretation of the underlying pathophysiological mechanism could result in the early detection of the subjects that may have genetical predisposition for SK appearance and the development of target molecular treatments in order to counter the progression of the deformity.<\/jats:p>","DOI":"10.3390\/biom16010056","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insights into the Pathophysiology of Scheuermann\u2019s Kyphosis: From Structural Deformities to Genetic Predisposition and Underlying Signalling Pathways"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-5522","authenticated-orcid":false,"given":"Angelos","family":"Kaspiris","sequence":"first","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5670-933X","authenticated-orcid":false,"given":"Ioannis","family":"Spyrou","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Marougklianis","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridoula Roberta","family":"Afrati","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Sakellariou","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4371-9857","authenticated-orcid":false,"given":"Iordanis","family":"Varsamos","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-5475","authenticated-orcid":false,"given":"Panagiotis","family":"Karampinas","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-5250","authenticated-orcid":false,"given":"Elias","family":"Vasiliadis","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiros G.","family":"Pneumaticos","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, National and Kapodistrian University of Athens, \u201cKAT\u201d General Hospital, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1055\/s-0043-1771334","article-title":"Scheuermann\u2019s Disease","volume":"27","author":"Kaur","year":"2023","journal-title":"Semin. 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