{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T17:41:46Z","timestamp":1772559706649,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,9,29]],"date-time":"2017-09-29T00:00:00Z","timestamp":1506643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Community","award":["HEALTHF2-2008-201626"],"award-info":[{"award-number":["HEALTHF2-2008-201626"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Both vitamin D and collagen have roles in osteocartilaginous homeostasis. We evaluated the association between the circulating 25-hydroxyvitamin D (25(OH)D) type I and II collagen degradation products (CTx-I, and CTx-II), and four vitamin D receptor gene (VDR) polymorphisms, in Italian males affected by low back pain (LBP) due to herniation\/discopathy and\/or vertebral osteochondrosis. FokI, BsmI, ApaI, and TaqI VDR-polymorphisms were detected through PCR\u2013restriction fragment length polymorphism (RFLP), and circulating 25(OH)D, CTx-I and CTx-II were measured by immunoassays in 79 patients (of which 26 had osteochondrosis) and 79 age-, sex- and body mass index (BMI)-matched healthy controls. Among all 158 subjects, carriers of FF and Ff genotypes showed lower 25(OH)D than ff, which suggested a higher depletion of vitamin D in F allele carriers. Higher CTx-I concentrations were observed in TT versus Tt among controls, and Tt versus tt among LBP cases, which suggested a higher bone-cartilaginous catabolism in subjects bearing the T allele. Higher CTx-II concentrations were observed in patients with osteochondrosis bearing FF, bb, TT, or Aa genotypes in comparison with hernia\/discopathy patients and healthy controls. Vertebral osteochondrosis shows peculiar genotypic and biochemical features related to vitamin D and the osteocartilaginous metabolism. Vitamin D has roles in the pathophysiology of osteochondrosis.<\/jats:p>","DOI":"10.3390\/ijms18102073","type":"journal-article","created":{"date-parts":[[2017,9,29]],"date-time":"2017-09-29T12:24:04Z","timestamp":1506687844000},"page":"2073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["High Levels of Circulating Type II Collagen Degradation Marker (CTx-II) Are Associated with Specific VDR Polymorphisms in Patients with Adult Vertebral Osteochondrosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Sabina","family":"Cauci","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-6564","authenticated-orcid":false,"given":"Marco","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Girolamo","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"De Luca","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Perucca Orfei","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Banfi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-985X","authenticated-orcid":false,"given":"Giovanni","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Brayda-Bruno","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Spine Surgery III-Scoliosis Unit, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-3424","authenticated-orcid":false,"given":"Alessandra","family":"Colombini","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Colombini, A., Brayda-Bruno, M., Lombardi, G., Croiset, S.J., Vrech, V., Maione, V., Banfi, G., and Cauci, S. (2014). FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: A case-control study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097027"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.3390\/ijms16023722","article-title":"Gender differences in the VDR-FokI polymorphism and conventional non-genetic risk factors in association with lumbar spine pathologies in an Italian case-control study","volume":"16","author":"Colombini","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/00003086-198101000-00023","article-title":"Juvenile kyphosis (Scheuermann\u2019s disease): Radiography, histology, and pathogenesis","volume":"154","author":"Aufdermaur","year":"1981","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_4","first-page":"5","article-title":"The classic: Kyphosis dorsalis juvenilis","volume":"128","author":"Scheuermann","year":"1977","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000116327","article-title":"Thoracic disk herniation and Scheuermann\u2019s disease","volume":"26","author":"Lesoin","year":"1987","journal-title":"Eur. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1097\/00007632-198711000-00015","article-title":"Lumbar Scheuermann\u2019s. A clinical series and classification","volume":"12","author":"Blumenthal","year":"1987","journal-title":"Spine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/BF00204096","article-title":"Spinal stenosis subsequent to juvenile lumbar osteochondrosis","volume":"19","author":"Tallroth","year":"1990","journal-title":"Skelet. Radiol."},{"key":"ref_8","first-page":"14","article-title":"Adult Scheuermann\u2019s disease as cause of mechanic dorsalgia","volume":"60","author":"Trotta","year":"2008","journal-title":"Reumatismo"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.5435\/00124635-199801000-00004","article-title":"Scheuermann\u2019s kyphosis in adolescents and adults: Diagnosis and management","volume":"6","author":"Tribus","year":"1998","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/00007632-198908000-00017","article-title":"End-plate lesions of the lumbar spine","volume":"14","author":"McFadden","year":"1989","journal-title":"Spine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"940","DOI":"10.2106\/00004623-199072060-00026","article-title":"Scheuermann disease","volume":"72","author":"Lowe","year":"1990","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1097\/BRS.0000000000000479","article-title":"Radiological signs of Scheuermann disease and low back pain: Retrospective categorization of 188 hospital staff members with 6-year follow-up","volume":"39","author":"Liu","year":"2014","journal-title":"Spine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1302\/0301-620X.61B1.154522","article-title":"Scheuermann\u2019s disease or spinal osteochondrosis: Its frequency and relationship with spondylosis","volume":"61","author":"Stoddard","year":"1979","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/jor.1100040408","article-title":"Pathogenesis of osteochondrosis juvenilis Scheuermann","volume":"4","author":"Aufdermaur","year":"1986","journal-title":"J. Orthop. Res. Off. Publ. Orthop. Res. Soc."},{"key":"ref_15","first-page":"211","article-title":"The vulnerable, rapidly growing thoracic spine of the adolescent","volume":"78","author":"Dommisse","year":"1990","journal-title":"S. Afr. Med. J. S.-Afr. Tydskr. Geneeskd."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E485","DOI":"10.1097\/00007632-200211150-00020","article-title":"Classical Scheuermann disease in male monozygotic twins: Further support for the genetic etiology hypothesis","volume":"27","author":"Graat","year":"2002","journal-title":"Spine"},{"key":"ref_17","first-page":"2133","article-title":"Prevalence, concordance, and heritability of Scheuermann kyphosis based on a study of twins","volume":"88","author":"Damborg","year":"2006","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_18","first-page":"1105","article-title":"Dominant inheritance of Scheuermann\u2019s juvenile kyphosis","volume":"132","author":"Halal","year":"1978","journal-title":"Am. J. Dis. Child."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1136\/jmg.29.1.41","article-title":"Familial Scheuermann disease: A genetic and linkage study","volume":"29","author":"McKenzie","year":"1992","journal-title":"J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jsbmb.2013.03.001","article-title":"Relationship between vitamin D receptor gene (VDR) polymorphisms, vitamin D status, osteoarthritis and intervertebral disc degeneration","volume":"138","author":"Colombini","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cca.2017.05.028","article-title":"Plasma vitamin D and osteo-cartilaginous markers in Italian males affected by intervertebral disc degeneration: Focus on seasonal and pathological trend of type II collagen degradation","volume":"471","author":"Vigano","year":"2017","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1679\/aohc.55.77","article-title":"Intracellular localization and translocation of 1 alpha, 25-dihydroxyvitamin D3 receptor in osteoblasts","volume":"55","author":"Amizuka","year":"1992","journal-title":"Arch. Histol. Cytol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/BRS.0b013e3181695d59","article-title":"1,25(OH)2-vitamin D3 inhibits proliferation and decreases production of monocyte chemoattractant protein-1, thrombopoietin, VEGF, and angiogenin by human annulus cells in vitro","volume":"33","author":"Gruber","year":"2008","journal-title":"Spine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.biocel.2012.03.012","article-title":"Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc","volume":"44","author":"Colombini","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jos.2016.11.009","article-title":"Association between vitamin D receptor gene polymorphisms and intervertebral disc degeneration: A meta-analysis","volume":"22","author":"Chen","year":"2017","journal-title":"J. Orthop. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00586-016-4771-2","article-title":"Vitamin D receptor gene polymorphisms and lumbar disc degeneration: A systematic review and meta-analysis","volume":"26","author":"Jiang","year":"2017","journal-title":"Eur. Spine J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Colombini, A., Brayda-Bruno, M., Lombardi, G., Croiset, S.J., Ceriani, C., Buligan, C., Barbina, M., Banfi, G., and Cauci, S. (2016). BsmI, ApaI and TaqI Polymorphisms in the Vitamin D Receptor Gene (VDR) and Association with Lumbar Spine Pathologies: An Italian Case-Control Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155004"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.biocel.2007.12.011","article-title":"Pathophysiology of the human intervertebral disc","volume":"40","author":"Colombini","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1056\/NEJMp1500523","article-title":"A new initiative on precision medicine","volume":"372","author":"Collins","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rescigno, T., Micolucci, L., Tecce, M.F., and Capasso, A. (2017). Bioactive nutrients and nutrigenomics in age-related diseases. Molecules, 22.","DOI":"10.3390\/molecules22010105"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cca.2012.09.004","article-title":"Vitamin D in exercise: Physiologic and analytical concerns","volume":"415","author":"Lanteri","year":"2013","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.gene.2004.05.014","article-title":"Genetics and biology of vitamin D receptor polymorphisms","volume":"338","author":"Uitterlinden","year":"2004","journal-title":"Gene"},{"key":"ref_33","unstructured":"Marques, V.V., Aguiar, J.P.N., Donizetti, S.T., de Oliveira, J., Marques, P.C.A., Vitor, F.A., and Manoukian, F.N. (2017). Genetic polymorphisms of vitamin D metabolism genes and serum level of vitamin D in colorectal cancer. Int. J. Biol. Markers."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.1097\/00007632-200102010-00003","article-title":"The relative roles of intragenic polymorphisms of the vitamin d receptor gene in lumbar spine degeneration and bone density","volume":"26","author":"Videman","year":"2001","journal-title":"Spine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.20892\/j.issn.2095-3941.2017.0020","article-title":"Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms","volume":"14","author":"Stinco","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/asj.12000","article-title":"Effects of 25-hydroxy-cholecalciferol on the development of osteochondrosis in swine","volume":"84","author":"Sugiyama","year":"2013","journal-title":"Anim. Sci. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jsbmb.2016.12.013","article-title":"Integrative genomic approaches to dissect clinically-significant relationships between the VDR cistrome and gene expression in primary colon cancer","volume":"173","author":"Long","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Singh, P.K., van den Berg, P.R., Long, M.D., Vreugdenhil, A., Grieshober, L., Ochs-Balcom, H.M., Wang, J., Delcambre, S., Heikkinen, S., and Carlberg, C. (2017). Integration of VDR genome wide binding and GWAS genetic variation data reveals co-occurrence of VDR and NF-kappaB binding that is linked to immune phenotypes. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3481-4"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbiomolbio.2016.09.011","article-title":"Preface to from the century of the genome to the century of the organism: New theoretical approaches","volume":"122","author":"Soto","year":"2016","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"504","DOI":"10.2337\/diabetes.49.3.504","article-title":"Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans","volume":"49","author":"Pani","year":"2000","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1373\/clinchem.2016.261461","article-title":"Short-term Variability of Vitamin D-Related Biomarkers","volume":"62","author":"Lutsey","year":"2016","journal-title":"Clin. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2073\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:46:13Z","timestamp":1760208373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,29]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["ijms18102073"],"URL":"https:\/\/doi.org\/10.3390\/ijms18102073","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,29]]}}}