{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:36:40Z","timestamp":1793317000213,"version":"4.5.0"},"reference-count":87,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1), which is the most common phacomatoses, is an autosomal dominant disorder characterized by clinical presentations in various tissues and organs, such as the skin, eyes and nervous and skeletal systems. The musculoskeletal implications of NF1 include a variety of deformities, including scoliosis, kyphoscoliosis, spondylolistheses, congenital bony bowing, pseudarthrosis and bone dysplasia. Scoliosis is the most common skeletal problem, affecting 10\u201330% of NF1 patients. Although the pathophysiology of spinal deformities has not been elucidated yet, defects in bone metabolism have been implicated in the progression of scoliotic curves. Measurements of Bone Mineral Density (BMD) in the lumbar spine by using dual energy absorptiometry (DXA) and quantitative computer tomography (QCT) have demonstrated a marked reduction in Z-score and osteoporosis. Additionally, serum bone metabolic markers, such as vitamin D, calcium, phosphorus, osteocalcin and alkaline phosphatase, have been found to be abnormal. Intraoperative and histological vertebral analysis confirmed that alterations of the trabecular microarchitecture are associated with inadequate bone turnover, indicating generalized bone metabolic defects. At the molecular level, loss of function of neurofibromin dysregulates Ras and Transforming Growth factor-\u03b21 (TGF-\u03b21) signaling and leads to altered osteoclastic proliferation, osteoblastic activity and collagen production. Correlation between clinical characteristics and molecular pathways may provide targets for novel therapeutic approaches in NF1.<\/jats:p>","DOI":"10.3390\/jcm11020444","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Current Aspects on the Pathophysiology of Bone Metabolic Defects during Progression of Scoliosis in Neurofibromatosis Type 1"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-5522","authenticated-orcid":false,"given":"Angelos","family":"Kaspiris","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Division for Orthopaedic Research, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-6565","authenticated-orcid":false,"given":"Olga D.","family":"Savvidou","sequence":"additional","affiliation":[{"name":"First Department of Orthopaedic Surgery, \u201cATTIKON\u201d University Hospital, School of Medicine, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-5250","authenticated-orcid":false,"given":"Elias S.","family":"Vasiliadis","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, \u201cKAT\u201d General Hospital, School of Medicine, National and Kapodistrian University of Athens, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-3421","authenticated-orcid":false,"given":"Argyris C.","family":"Hadjimichael","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, \u201cKAT\u201d General Hospital of Athens-NHS, Nikis 2, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Melissaridou","sequence":"additional","affiliation":[{"name":"First Department of Orthopaedic Surgery, \u201cATTIKON\u201d University Hospital, School of Medicine, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Iliopoulou-Kosmadaki","sequence":"additional","affiliation":[{"name":"First Department of Orthopaedic Surgery, \u201cATTIKON\u201d University Hospital, School of Medicine, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4814-1449","authenticated-orcid":false,"given":"Ilias D.","family":"Iliopoulos","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, \u201cRion\u201d University Hospital and Medical School, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-4325","authenticated-orcid":false,"given":"Evangelia","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Division for Orthopaedic Research, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios","family":"Chronopoulos","sequence":"additional","affiliation":[{"name":"Laboratory for Research of the Musculoskeletal System, School of Medicine, National and Kapodistrian University of Athens, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1001\/archderm.141.1.71","article-title":"Prevalence of neurofibromatosis 1 in German children at elementary school enrollment","volume":"141","author":"Lammert","year":"2005","journal-title":"Arch. 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