{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:03:13Z","timestamp":1787166193610,"version":"build-2736575974"},"reference-count":119,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of Health","award":["5RO1 AR080416-02"],"award-info":[{"award-number":["5RO1 AR080416-02"]}]},{"DOI":"10.13039\/501100004721","name":"The University of Tokyo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004721","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Osteoporos Rep"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose of Review<\/jats:title>\n                    <jats:p>The study aims to provide updated information on the genetic factors associated with the diagnoses \u2018Diffuse Idiopathic Skeletal Hyperostosis\u2019 (DISH), \u2018Ossification of the Posterior Longitudinal Ligament\u2019 (OPLL), and in patients with spinal ligament ossification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>\n                      Recent studies have advanced our knowledge of genetic factors associated with DISH, OPLL, and other spinal ossification (ossification of the anterior longitudinal ligament [OALL] and the yellow ligament [OYL]). Several case studies of individuals afflicted with monogenic disorders, such as X-linked hypophosphatemia (XLH), demonstrate the strong association of fibroblast growth factor 23-related hypophosphatemia with OPLL, suggesting that pathogenic variants in\n                      <jats:italic>PHEX<\/jats:italic>\n                      ,\n                      <jats:italic>ENPP1<\/jats:italic>\n                      , and\n                      <jats:italic>DMP1<\/jats:italic>\n                      are associated with FGF23-phosphate wasting phenotype and strong genetic factors placing patients at risk for OPLL. Moreover, emerging evidence demonstrates that heterozygous and compound heterozygous\n                      <jats:italic>ENPP1<\/jats:italic>\n                      pathogenic variants inducing \u2018Autosomal Recessive Hypophosphatemic Rickets Type 2\u2019 (ARHR2) also place patients at risk for DISH and OPLL, possibly due to the loss of inhibitory plasma pyrophosphate (PP\n                      <jats:sub>i<\/jats:sub>\n                      ) which suppresses ectopic calcification and enthesis mineralization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      Our findings emphasize the importance of genetic and plasma biomarker screening in the clinical evaluation of DISH and OPLL patients, with plasma PP\n                      <jats:sub>i<\/jats:sub>\n                      constituting an important new biomarker for the identification of DISH and OPLL patients whose disease course may be responsive to ENPP1 enzyme therapy, now in clinical trials for rare calcification disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11914-023-00814-6","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T03:01:59Z","timestamp":1690945319000},"page":"552-566","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments"],"prefix":"10.1007","volume":"21","author":[{"given":"Hajime","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrios T.","family":"Braddock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-5372","authenticated-orcid":false,"given":"Nobuaki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"814_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/BRS.0b013e318241ad33","volume":"37","author":"S Matsunaga","year":"2012","unstructured":"Matsunaga S, Sakou T. Ossification of the posterior longitudinal ligament of the cervical spine: etiology and natural history. Spine (Phila Pa 1976). 2012;37:309\u201314.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR2","doi-asserted-by":"publisher","first-page":"E394","DOI":"10.1097\/BRS.0000000000000791","volume":"40","author":"T Fujimori","year":"2015","unstructured":"Fujimori T, Le H, Hu SS, Chin C, Pekmezci M, Schairer W, et al. Ossification of the posterior longitudinal ligament of the cervical spine in 3161 patients: a CT-based study. Spine (Phila Pa 1976). 2015;40:E394-403.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1055\/s-0035-1556580","volume":"6","author":"R Abiola","year":"2015","unstructured":"Abiola R, Rubery P, Mesfin A. Ossification of the posterior longitudinal ligament: etiology, diagnosis, and outcomes of nonoperative and operative management. Global Spine J. 2015;6:195\u2013204.","journal-title":"Global Spine J"},{"key":"814_CR4","doi-asserted-by":"publisher","first-page":"E1216","DOI":"10.1097\/BRS.0b013e31829e018b","volume":"38","author":"K Mori","year":"2013","unstructured":"Mori K, Kasahara T, Mimura T, Nishizawa K, Murakami Y, Matsusue Y, et al. Prevalence, distribution, and morphology of thoracic ossification of the yellow ligament in Japanese; results of CT-based cross-sectional study. Spine (Phila Pa 1976). 2013;38:E1216-22.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR5","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/s00586-012-2492-8","volume":"22","author":"N Lang","year":"2013","unstructured":"Lang N, Yuan HS, Wang HL, Liao J, Li M, Guo FX, et al. Epidemiological survey of ossification of the ligamentum flavum in thoracic spine: CT imaging observation of 993 cases. Eur Spine J. 2013;22:857\u201362.","journal-title":"Eur Spine J"},{"key":"814_CR6","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3340\/jkns.2015.58.2.112","volume":"58","author":"BJ Moon","year":"2015","unstructured":"Moon BJ, Kuh SU, Kim S, Kim KS, Cho YE, Chin DK. Prevalence, distribution, and significance of incidental thoracic ossification of the ligamentum flavum in Korean patients with back or leg pain: MR-based cross sectional study. J Korean Neurosurg Soc. 2015;58:112\u20138.","journal-title":"J Korean Neurosurg Soc"},{"key":"814_CR7","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1259\/0007-1285-66-792-1193","volume":"66","author":"QW Arafat","year":"1993","unstructured":"Arafat QW, Jackowski A, Chavda SV, West RJ. Case report: ossification of the thoracic ligamenta flava in a Caucasian: a rare cause of myelopathy. Br J Radiol. 1993;66:1193\u20136.","journal-title":"Br J Radiol"},{"key":"814_CR8","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1097\/00007632-199807150-00019","volume":"23","author":"H Pascal-Mousselard","year":"1998","unstructured":"Pascal-Mousselard H, Smadja D, Cabre P, Raynaud M, Catonne Y. Ossification of the ligamenta flava with severe myelopathy in a black patient. A case report. Spine (Phila Pa 1976). 1998;23:1607\u20138.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR9","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1097\/00007632-199903010-00019","volume":"24","author":"RJ Van Oostenbrugge","year":"1999","unstructured":"Van Oostenbrugge RJ, Herpers MJ, De Kruijk JR. Spinal cord compression caused by unusual location and extension of ossified ligamenta flava in a Caucasian male. A case report and literature review. Spine (Phila Pa 1976). 1999;24:486\u20138.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR10","first-page":"1313","volume":"27","author":"F Debiais","year":"2000","unstructured":"Debiais F, Bataille B, Debiais P, Azais I, Bontoux D, Alcalay M. Femoral neuropathy secondary to ossification of the ligamentum flavum. J Rheumatol J Rheumatol. 2000;27:1313\u20134.","journal-title":"J Rheumatol J Rheumatol"},{"key":"814_CR11","first-page":"96","volume":"46","author":"P Celli","year":"2002","unstructured":"Celli P, Caroli E, Trill\u00f2 G, Ferrante L, Mariatos P. Ossification of the ligamentum flavum in a Caucasian. Case report J Neurosurg Sci. 2002;46:96\u20139.","journal-title":"Case report J Neurosurg Sci"},{"key":"814_CR12","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/sj.sc.3101953","volume":"45","author":"DP Tokala","year":"2007","unstructured":"Tokala DP, Lam KS, Prince HG. Ossification of the proximal thoracic ligamenta flava causing acute myelopathy in a Caucasian: case report and literature review. Spinal Cord. 2007;45:310\u20133.","journal-title":"Spinal Cord"},{"key":"814_CR13","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3171\/SPI.2008.9.11.427","volume":"9","author":"R Xu","year":"2008","unstructured":"Xu R, Sciubba DM, Gokaslan ZL, Bydon A. Ossification of the ligamentum flavum in a Caucasian man. J Neurosurg Spine. 2008;9:427\u201337.","journal-title":"J Neurosurg Spine"},{"key":"814_CR14","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41394-021-00422-5","volume":"7","author":"GA Ricciardi","year":"2021","unstructured":"Ricciardi GA, Garfinkel IG, Carrioli GG, Ricciardi DO. Thoracic ligamentum flavum ossification: a rare cause of spinal cord injury without tomographic evidence of trauma in a Caucasian patient. Case report and literature review. Spinal Cord Ser Cases. 2021;7:57.","journal-title":"Spinal Cord Ser Cases."},{"key":"814_CR15","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1136\/ard.9.4.321","volume":"9","author":"J Forestier","year":"1950","unstructured":"Forestier J, Rotes-Querol J. Senile ankylosing hyperostosis of the spine. Ann Rheum Dis. 1950;9:321\u201330.","journal-title":"Ann Rheum Dis"},{"key":"814_CR16","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1148\/15.3.513","volume":"115","author":"D Resnick","year":"1975","unstructured":"Resnick D, Shaul SR, Robins JM. Diffuse idiopathic skeletal hyperostosis (DISH): Forestier\u2019s disease with extraspinal manifestations. Radiology. 1975;115:513\u201324.","journal-title":"Radiology"},{"key":"814_CR17","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s00586-008-0764-0","volume":"18","author":"LA Westerveld","year":"2009","unstructured":"Westerveld LA, Verlaan JJ, Oner FC. Spinal fractures in patients with ankylosing spinal disorders: a systematic review of the literature on treatment, neurological status and complications. Eur Spine J. 2009;18:145\u201356.","journal-title":"Eur Spine J"},{"key":"814_CR18","doi-asserted-by":"publisher","first-page":"E458","DOI":"10.1097\/BRS.0b013e3181cc764f","volume":"35","author":"T Caron","year":"2010","unstructured":"Caron T, Bransford R, Nguyen Q, Agel J, Chapman J, Bellabarba C. Spine fractures in patients with ankylosing spinal disorders. Spine (Phila Pa 1976). 2010;35:E458-64.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR19","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1097\/BRS.0b013e3182474d8b","volume":"37","author":"P Liu","year":"2012","unstructured":"Liu P, Yao Y, Liu MY, Fan WL, Chao R, Wang ZG, et al. Spinal trauma in Mainland China from 2001 to 2007: an epidemiological study based on a nationwide database. Spine (Phila Pa 1976). 2012;37:1310\u20135.","journal-title":"Spine (Phila Pa 1976)"},{"key":"814_CR20","doi-asserted-by":"publisher","first-page":"S122","DOI":"10.4103\/2152-7806.130675","volume":"5","author":"FA Nascimento","year":"2014","unstructured":"Nascimento FA, Gatto LAM, Lages RO, Neto HM, Demartini ZD, Koppe GL. Diffuse idiopathic skeletal hyperostosis: a review. Surg Neurol Int. 2014;5:S122\u20135.","journal-title":"Surg Neurol Int"},{"key":"814_CR21","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.3390\/ijms22084255","volume":"22","author":"M Dabrowski","year":"2021","unstructured":"Dabrowski M, Kubaszewski \u0141. Diffuse idiopathic skeletal hyperostosis of cervical spine with dysphagia-molecular and clinical aspects. Int J Mol Sci. 2021;22:4255.","journal-title":"Int J Mol Sci"},{"key":"814_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.03.009","volume":"103","author":"A Rothenbuhler","year":"2020","unstructured":"Rothenbuhler A, Schnabel D, H\u00f6gler W, Linglart A. Diagnosis, treatment-monitoring and follow-up of children and adolescents with X-linked hypophosphatemia (XLH). Metabolism. 2020;103: 153892.","journal-title":"Metabolism"},{"key":"814_CR23","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1148\/radiology.171.2.2539609","volume":"171","author":"DC Hardy","year":"1989","unstructured":"Hardy DC, Murphy WA, Siegel BA, Reid IR, Whyte MP. X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features. Radiology. 1989;171:403\u201314.","journal-title":"Radiology"},{"key":"814_CR24","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00223-009-9270-6","volume":"85","author":"G Liang","year":"2009","unstructured":"Liang G, Katz LD, Insogna KL, Carpenter TO, Macica CM. Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice. Calcif Tissue Int. 2009;85:235\u201346.","journal-title":"Calcif Tissue Int"},{"key":"814_CR25","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1530\/EJE-15-0661","volume":"174","author":"H Che","year":"2016","unstructured":"Che H, Roux C, Etcheto A, Rothenbuhler A, Kamenicky P, Linglart A, et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016;174:325\u201333.","journal-title":"Eur J Endocrinol"},{"key":"814_CR26","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1007\/s10545-018-0147-6","volume":"41","author":"D Chesher","year":"2018","unstructured":"Chesher D, Oddy M, Darbar U, Sayal P, Casey A, Ryan A, et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis. 2018;41:865\u201376.","journal-title":"J Inherit Metab Dis"},{"key":"814_CR27","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1210\/js.2018-00365","volume":"3","author":"A Skrinar","year":"2019","unstructured":"Skrinar A, Dvorak-Ewell M, Evins A, Macica C, Linglart A, Imel EA, et al. The lifelong impact of X-linked hypophosphatemia: results from a burden of disease survey. J Endocr Soc. 2019;3:1321\u201334.","journal-title":"J Endocr Soc"},{"key":"814_CR28","doi-asserted-by":"publisher","first-page":"E3682","DOI":"10.1210\/clinem\/dgab282","volume":"106","author":"H Kato","year":"2021","unstructured":"\u2022\u2022 Kato H, Koga M, Kinoshita Y, Taniguchi Y, Kobayashi H, Fukumoto S, et al. Incidence of complications in 25 adult patients with X-linked hypophosphatemia. J Clin Endocrinol Metab. 2021;106:E3682\u201392. An important study documenting that the prevalence of spinal ligament ossifications and osteoarthritis is higher among adult patients with XLH than that among Japanese general population.","journal-title":"J Clin Endocrinol Metab"},{"key":"814_CR29","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1002\/jbmr.105","volume":"25","author":"O M\u00e4kitie","year":"2010","unstructured":"M\u00e4kitie O, Pereira RC, Kaitila I, Turan S, Bastepe M, Laine T, et al. Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation. J Bone Miner Res. 2010;25:2165\u201374.","journal-title":"J Bone Miner Res"},{"key":"814_CR30","doi-asserted-by":"publisher","first-page":"5906","DOI":"10.1210\/en.2012-1551","volume":"153","author":"AC Karaplis","year":"2012","unstructured":"Karaplis AC, Bai X, Falet JP, Macica CM. Mineralizing enthesopathy is a common feature of renal phosphate-wasting disorders attributed to FGF23 and is exacerbated by standard therapy in hyp mice. Endocrinology. 2012;153:5906\u201317.","journal-title":"Endocrinology"},{"key":"814_CR31","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.bone.2014.08.014","volume":"68","author":"MH Gannag\u00e9-Yared","year":"2014","unstructured":"Gannag\u00e9-Yared MH, Makrythanasis P, Chouery E, Sobacchi C, Mehawej C, Santoni FA, et al. Exome sequencing reveals a mutation in DMP1 in a family with familial sclerosing bone dysplasia. Bone. 2014;68:142\u20135.","journal-title":"Bone"},{"key":"814_CR32","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.bone.2011.06.029","volume":"49","author":"T Saito","year":"2011","unstructured":"Saito T, Shimizu Y, Hori M, Taguchi M, Igarashi T. Case Report A patient with hypophosphatemic rickets and ossi fi cation of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene. Bone. 2011;49:913\u20136.","journal-title":"Bone"},{"key":"814_CR33","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ijscr.2016.08.038","volume":"27","author":"Y Hirao","year":"2016","unstructured":"Hirao Y, Chikuda H, Oshima Y, Matsubayashi Y, Tanaka S. Extensive ossification of the paraspinal ligaments in a patient with vitamin D-resistant rickets: case report with literature review. Int J Surg Case Rep. 2016;27:125\u20138.","journal-title":"Int J Surg Case Rep"},{"key":"814_CR34","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1136\/jmg.30.8.687","volume":"30","author":"JM Connor","year":"1993","unstructured":"Connor JM, Skirton H, Lunt PW. A three generation family with fibrodysplasia ossificans progressiva. J Med Genet. 1993;30:687\u20139.","journal-title":"J Med Genet"},{"key":"814_CR35","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1002\/ajmg.a.34003","volume":"155A","author":"CP Barnett","year":"2011","unstructured":"Barnett CP, Dugar M, Haan EA. Late-onset variant fibrodysplasia ossificans progressiva leading to misdiagnosis of ankylosing spondylitis. Am J Med Genet A. 2011;155A:1492\u20135.","journal-title":"Am J Med Genet A."},{"key":"814_CR36","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1002\/ajmg.a.61274","volume":"179","author":"A Gupta","year":"2019","unstructured":"\u2022 Gupta A, Zimmermann MT, Wang H, Broski SM, Sigafoos AN, Macklin SK, et al. Molecular characterization of known and novel ACVR1 variants in phenotypes of aberrant ossification. Am J Med Genet A. 2019;179:1764\u201377. An interesting study reporting the novel ACVR1 variants in patients with DISH.","journal-title":"Am J Med Genet A"},{"key":"814_CR37","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/ng1868","volume":"38","author":"B Lorenz-Depiereux","year":"2006","unstructured":"Lorenz-Depiereux B, Bastepe M, Benet-Pag\u00e8s A, Amyere M, Wagenstaller J, M\u00fcller-Barth U, et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet. 2006;38:1248\u201350.","journal-title":"Nat Genet"},{"key":"814_CR38","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1038\/ng1905","volume":"38","author":"JQ Feng","year":"2006","unstructured":"Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006;38:1310\u20135.","journal-title":"Nat Genet"},{"key":"814_CR39","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/956","volume":"19","author":"A Okawa","year":"1998","unstructured":"Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet. 1998;19:271\u20133.","journal-title":"Nat Genet"},{"key":"814_CR40","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41436-020-00983-0","volume":"23","author":"CR Ferreira","year":"2021","unstructured":"Ferreira CR, Hackbarth ME, Ziegler SG, Pan KS, Roberts MS, Rosing DR, et al. Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI). Genet Med. 2021;23:396\u2013407.","journal-title":"Genet Med"},{"key":"814_CR41","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/jbmr.4487","volume":"37","author":"CR Ferreira","year":"2022","unstructured":"\u2022 Ferreira CR, Ansh J, Nester C, O\u2019Brien C, Stabach P, Murtada S, et al. Musculoskeletal comorbidities and quality of life in ENPP1-deficient adults and the response of enthesopathy to enzyme replacement therapy in murine models. J Bone Miner Res. 2022;37:494\u2013504. An interesting study evaluating the epreventive effect of ENPP1 replacement therapy on ENPP1 deficient mice.","journal-title":"J Bone Miner Res"},{"key":"814_CR42","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1359\/JBMR.050305","volume":"20","author":"L Serrano De La Pe\u00f1a","year":"2005","unstructured":"Serrano De La Pe\u00f1a L, Billings PC, Fiori JL, Ahn J, Kaplan FS, Shore EM. Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA. J Bone Miner Res. 2005;20:1168\u201376.","journal-title":"J Bone Miner Res"},{"key":"814_CR43","doi-asserted-by":"publisher","first-page":"115410","DOI":"10.1016\/j.bone.2020.115410","volume":"137","author":"S Tsukamoto","year":"2020","unstructured":"Tsukamoto S, Kuratani M, Katagiri T. Functional characterization of a unique mutant of ALK2, p.K400E, that is associated with a skeletal disorder, diffuse idiopathic skeletal hyperostosis. Bone. 2020;137:115410.","journal-title":"Bone."},{"key":"814_CR44","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1002\/jbmr.1826","volume":"28","author":"S Warraich","year":"2013","unstructured":"Warraich S, Bone DBJ, Quinonez D, Ii H, Choi DS, Holdsworth DW, et al. Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans. J Bone Miner Res. 2013;28:1135\u201349.","journal-title":"J Bone Miner Res"},{"key":"814_CR45","doi-asserted-by":"publisher","first-page":"3651","DOI":"10.1182\/blood-2015-03-631598","volume":"125","author":"G Daniels","year":"2015","unstructured":"Daniels G, Ballif BA, Helias V, Saison C, Grimsley S, Mannessier L, et al. Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization. Blood. 2015;125:3651\u20134.","journal-title":"Blood"},{"key":"814_CR46","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.bone.2016.05.008","volume":"90","author":"H Ii","year":"2016","unstructured":"Ii H, Warraich S, Tenn N, Quinonez D, Holdsworth DW, Hammond JR, et al. Disruption of biomineralization pathways in spinal tissues of a mouse model of diffuse idiopathic skeletal hyperostosis. Bone. 2016;90:37\u201349.","journal-title":"Bone"},{"key":"814_CR47","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.jocn.2012.10.033","volume":"20","author":"RF Schmidt","year":"2013","unstructured":"Schmidt RF, Goldstein IM, Liu JK. Ossified ligamentum flavum causing spinal cord compression in a patient with acromegaly. J Clin Neurosci. 2013;20:1599\u2013603.","journal-title":"J Clin Neurosci"},{"key":"814_CR48","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s12891-021-04232-6","volume":"22","author":"D Kamakura","year":"2021","unstructured":"Kamakura D, Fukutake K, Nakamura K, Tsuge S, Hasegawa K, Tochigi N, et al. Acromegaly presenting with myelopathy due to ossification of posterior longitudinal ligament: a case report. BMC Musculoskelet Disord. 2021;22:353.","journal-title":"BMC Musculoskelet Disord"},{"key":"814_CR49","first-page":"99","volume":"4","author":"GO Littlejohn","year":"1986","unstructured":"Littlejohn GO, Hall S, Brand CA, Davidson A. New bone formation in acromegaly: pathogenetic implications for diffuse idiopathic skeletal hyperostosis. Clin Exp Rheumatol. 1986;4:99\u2013104.","journal-title":"Clin Exp Rheumatol"},{"key":"814_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2022.101628","volume":"17","author":"Y Hoshino","year":"2022","unstructured":"Hoshino Y, Hidaka N, Kato H, Koga M, Taniguchi Y, Kobayashi H, et al. Incidence of ossification of the spinal ligaments in acromegaly patients. Bone Rep. 2022;17: 101628.","journal-title":"Bone Rep"},{"key":"814_CR51","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41574-018-0114-1","volume":"14","author":"A Beckers","year":"2018","unstructured":"Beckers A, Petrossians P, Hanson J, Daly AF. The causes and consequences of pituitary gigantism. Nat Rev Endocrinol. 2018;14:705\u201320.","journal-title":"Nat Rev Endocrinol"},{"key":"814_CR52","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1136\/jnnp.27.5.459","volume":"27","author":"DR Cullen","year":"1964","unstructured":"Cullen DR, Pearce JM. Spinal cord compression in pseudohypoparathyroidism. J Neurol Neurosurg Psychiatry. 1964;27:459\u201362.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"814_CR53","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1007\/BF00355355","volume":"13","author":"H Firooznia","year":"1985","unstructured":"Firooznia H, Golimbu C, Rafii M. Case report 312. Diagnosis: progressive paraparesis in a woman with pseudohypoparathyroidism (PHP) with ossification of the posterior longitudinal ligament from C4 to T5. Skeletal Radiol. 1985;13:310\u20133.","journal-title":"Skeletal Radiol."},{"key":"814_CR54","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S0009-9260(89)80101-1","volume":"40","author":"RG Lambert","year":"1989","unstructured":"Lambert RG, Becker EJ. Diffuse skeletal hyperostosis in idiopathic hypoparathyroidism. Clin Radiol. 1989;40:212\u20135.","journal-title":"Clin Radiol"},{"key":"814_CR55","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1177\/030006059702500607","volume":"25","author":"Y Yamamoto","year":"1997","unstructured":"Yamamoto Y, Noto Y, Saito M, Ichizen H, Kida H. Spinal cord compression by heterotopic ossification associated with pseudohypoparathyroidism. J Int Med Res. 1997;25:364\u20138.","journal-title":"J Int Med Res"},{"key":"814_CR56","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1007\/s00415-002-0822-1","volume":"249","author":"T Iwase","year":"2002","unstructured":"Iwase T, Nokura K, Mizuno T, Inagaki T. Spastic tetraparesis in a patient with pseudopseudohypoparathyroidism. J Neurol. 2002;249:1457\u20138.","journal-title":"J Neurol"},{"key":"814_CR57","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1007\/BF03347265","volume":"28","author":"H Chen","year":"2005","unstructured":"Chen H, Tseng F, Su D, Chen H, Tsai K. Multiple intracranial calcifications and spinal compressions: rare complications of type la pseudohypoparathyroidism. J Endocrinol Invest. 2005;28:646\u201350.","journal-title":"J Endocrinol Invest"},{"key":"814_CR58","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1097\/RHU.0b013e3181bb9865","volume":"15","author":"S \u00dcnverdi","year":"2009","unstructured":"\u00dcnverdi S, \u00d6zt\u00fcrk MA, Inal S, Selek H, G\u00f6ker B, Haznedaroglu \u00c7, et al. Idiopathic hypoparathyroidism mimicking diffuse idiopathic skeletal hyperostosis. J Clin Rheumatol. 2009;15:361\u20132.","journal-title":"J Clin Rheumatol"},{"key":"814_CR59","doi-asserted-by":"publisher","first-page":"E1355","DOI":"10.1097\/BRS.0b013e3181e53726","volume":"35","author":"Y Jiang","year":"2010","unstructured":"Jiang Y, Hu H, Ye X, Peng J, He H, Xu G, et al. Multilevel myelopathy associated with pseudohypoparathyroidism simulating diffuse skeletal hyperostosis: a case report and literature review. Spine. 2010;35:E1355\u20138.","journal-title":"Spine"},{"key":"814_CR60","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jocn.2010.04.029","volume":"18","author":"P Li","year":"2011","unstructured":"Li P, Huang L, Zhao Z, Ye X, Liu Z. Spinal-cord compression related to pseudohypoparathyroidism. J Clin Neurosci. 2011;18:143\u20135.","journal-title":"J Clin Neurosci"},{"key":"814_CR61","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1097\/MAJ.0b013e31828b663b","volume":"346","author":"AM Rivas","year":"2013","unstructured":"Rivas AM, Lado-Abeal J. Diffuse idiopathic skeletal hyperostosis and familial hypocalciuric hypercalcemia: a unique association in a young female. Am J Med Sci. 2013;346:247\u20139.","journal-title":"Am J Med Sci"},{"key":"814_CR62","doi-asserted-by":"publisher","first-page":"42","DOI":"10.12659\/PJR.896104","volume":"81","author":"DR John","year":"2016","unstructured":"John DR, Suthar PP. Radiological features of long-standing hypoparathyroidism. Pol J Radiol. 2016;81:42\u20135.","journal-title":"Pol J Radiol."},{"key":"814_CR63","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/0026-0495(84)90209-9","volume":"33","author":"T Okazaki","year":"1984","unstructured":"Okazaki T, Takuwa Y, Yamamoto M, Matsumoto T, Igarashi T, Kurokawa T, et al. Ossification of the paravertebral ligaments: a frequent complication of hypoparathyroidism. Metabolism. 1984;33:710\u20133.","journal-title":"Metabolism"},{"key":"814_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5535\/arm.2014.38.1.1","volume":"38","author":"DH Kim","year":"2014","unstructured":"Kim DH, Yun DH, Kim HS, Min SK, Yoo SD, Lee KH, et al. The insertion\/deletion polymorphism of angiotensin I converting enzyme gene is associated with ossification of the posterior longitudinal ligament in the Korean population. Ann Rehabil Med. 2014;38:1\u20135.","journal-title":"Ann Rehabil Med"},{"key":"814_CR65","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s00439-006-0170-9","volume":"119","author":"T Horikoshi","year":"2006","unstructured":"Horikoshi T, Maeda K, Kawaguchi Y, Chiba K, Mori K, Koshizuka Y, et al. A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Hum Genet. 2006;119:611\u20136.","journal-title":"Hum Genet"},{"key":"814_CR66","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1007\/s11033-013-2933-4","volume":"41","author":"J Chon","year":"2014","unstructured":"Chon J, Hong JH, Kim J, Han YJ, Lee BW, Kim SC, et al. Association between BH3 interacting domain death agonist (BID) gene polymorphism and ossification of the posterior longitudinal ligament in Korean population. Mol Biol Rep. 2014;41:895\u20139.","journal-title":"Mol Biol Rep"},{"key":"814_CR67","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1097\/00029330-200809020-00010","volume":"121","author":"W Hao","year":"2008","unstructured":"Hao W, Zhao-hui Y, Dong-mei L, Ling W, Xiang-long M, Bao-peng T. Association between two polymorphisms of the bone morpho-genetic protein-2 gene with genetic susceptibility to ossification of the posterior longitudinal ligament of the cervical spine and its severity. Chin Med J. 2008;121:1806\u201310.","journal-title":"Chin Med J"},{"key":"814_CR68","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1007\/s00586-008-0651-8","volume":"17","author":"H Wang","year":"2008","unstructured":"Wang H, Liu D, Yang Z, Tian B, Li J, Meng X, et al. Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients. Eur Spine J. 2008;17:956\u201364.","journal-title":"Eur Spine J"},{"key":"814_CR69","first-page":"2341","volume":"123","author":"L Yan","year":"2010","unstructured":"Yan L, Zhao WG, Li JJ, Yang H, Wang H, Lin X. Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients. Chin Med J. 2010;123:2341\u20136.","journal-title":"Chin Med J"},{"key":"814_CR70","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.3760\/cma.j.issn.0366-6999.20123323","volume":"126","author":"L Yan","year":"2013","unstructured":"Yan L, Chang Z, Liu Y, Li YB, He BR, Hao DJ. A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T>G) affects the Smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine. Chin Med J. 2013;126:1112\u20138.","journal-title":"Chin Med J"},{"key":"814_CR71","first-page":"2537","volume":"123","author":"XL Meng","year":"2010","unstructured":"Meng XL, Wang H, Yang H, Hai Y, Tian BP, Lin X. T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population. Chin Med J. 2010;123:2537\u201342.","journal-title":"Chin Med J"},{"key":"814_CR72","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1002\/jor.21586","volume":"30","author":"Y Ren","year":"2012","unstructured":"Ren Y, Feng J, Liu ZZ, Wan H, Li JH, Lin X. A new haplotype in BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. J Orthop Res. 2012;30:748\u201356.","journal-title":"J Orthop Res"},{"key":"814_CR73","doi-asserted-by":"publisher","first-page":"e40587","DOI":"10.1371\/journal.pone.0040587","volume":"7","author":"Y Ren","year":"2012","unstructured":"Ren Y, Liu Z, Feng J, Wan H, Li J, Wang H, et al. Association of a bmp9 haplotype with ossification of the posterior longitudinal ligament (OPLL) in a chinese population. PLoS One. 2012;7:e40587.","journal-title":"PLoS One"},{"key":"814_CR74","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12891-018-1966-1","volume":"19","author":"H Wang","year":"2018","unstructured":"Wang H, Jin W, Li H. Genetic polymorphisms in bone morphogenetic protein receptor type IA gene predisposes individuals to ossification of the posterior longitudinal ligament of the cervical spine via the smad signaling pathway. BMC Musculoskelet Disord. 2018;19:61.","journal-title":"BMC Musculoskelet Disord"},{"key":"814_CR75","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1038\/ng.3045","volume":"46","author":"M Nakajima","year":"2014","unstructured":"\u2022 Nakajima M, Takahashi A, Tsuji T, Karasugi T, Baba H, Uchida K, et al. A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine. Nat Genet. 2014;46:1012\u20136. This study performs the largest scale GWAS for the susceptibility gene of OPLL.","journal-title":"Nat Genet"},{"key":"814_CR76","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1086\/378593","volume":"73","author":"T Tanaka","year":"2003","unstructured":"Tanaka T, Ikari K, Furushima K, Okada A, Tanaka H, Furukawa K-I, et al. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2003;73:812\u201322.","journal-title":"Am J Hum Genet"},{"key":"814_CR77","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.1097\/BRS.0b013e31815b761c","volume":"32","author":"Q Kong","year":"2007","unstructured":"Kong Q, Ma X, Li F, Guo Z, Qi Q, Li W, et al. COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament. Spine. 2007;32:2834\u20138.","journal-title":"Spine"},{"key":"814_CR78","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.4238\/2014.March.31.4","volume":"13","author":"KH Kim","year":"2014","unstructured":"Kim KH, Kuh SU, Park JY, Lee SJ, Park HS, Chin DK, et al. Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Korean patients and family members. Genet Mol Res. 2014;13:2240\u20137.","journal-title":"Genet Mol Res"},{"key":"814_CR79","doi-asserted-by":"crossref","unstructured":"Wang P, Liu X, Zhu B, Ma Y, Yong L, Teng Z, et al. Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients. J Orthop Surg Res. 2018;13:109.","DOI":"10.1186\/s13018-018-0817-y"},{"key":"814_CR80","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1086\/301868","volume":"62","author":"H Koga","year":"1998","unstructured":"Koga H, Sakou T, Taketomi E, Hayashi K, Numasawa T, Harata S, et al. Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 1998;62:1460\u20137.","journal-title":"Am J Hum Genet"},{"key":"814_CR81","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1359\/jbmr.2001.16.5.948","volume":"16","author":"S Maeda","year":"2001","unstructured":"Maeda S, Ishidou Y, Koga H, Taketomi E, Ikari K, Komiya S, et al. Functional impact of human collagen \u03b12(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res. 2001;16:948\u201357.","journal-title":"J Bone Miner Res"},{"key":"814_CR82","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.4238\/2014.March.17.7","volume":"13","author":"W Wei","year":"2014","unstructured":"Wei W, He HL, Chen CY, Zhao Y, Jiang HL, Liu WT, et al. Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients. Genet Mol Res. 2014;13:1794\u2013804.","journal-title":"Genet Mol Res"},{"key":"814_CR83","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1007\/s004390050993","volume":"104","author":"I Nakamura","year":"1999","unstructured":"Nakamura I, Ikegawa S, Okawa A, Okuda S, Koshizuka Y, Kawaguchi H, et al. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Hum Genet. 1999;104:492\u20137.","journal-title":"Hum Genet"},{"key":"814_CR84","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1359\/jbmr.2002.17.1.138","volume":"17","author":"Y Koshizuka","year":"2002","unstructured":"Koshizuka Y, Kawaguchi H, Ogata N, Ikeda T, Mabuchi A, Seichi A, et al. Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res. 2002;17:138\u201344.","journal-title":"J Bone Miner Res"},{"key":"814_CR85","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1097\/00007632-200208150-00015","volume":"27","author":"N Ogata","year":"2002","unstructured":"Ogata N, Koshizuka Y, Miura T, Iwasaki M, Hosoi T, Shiraki M, et al. Association of bone metabolism regulatory factor gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity. Spine. 2002;27:1765\u201371.","journal-title":"Spine"},{"key":"814_CR86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4184\/jkss.2012.19.1.1","volume":"19","author":"KT Kim","year":"2012","unstructured":"Kim KT, Lee SH, Kwack YH, Son ES, Park KJ, Kim DH. Association of estrogen receptor 2 (ESR 2) gene polymorphisms with ossification of the posterior longitudinal ligament of the spine. J Korean Soc Spine Surg. 2012;19:1\u20137.","journal-title":"J Korean Soc Spine Surg"},{"key":"814_CR87","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3340\/jkns.2012.52.1.7","volume":"52","author":"JK Jun","year":"2012","unstructured":"Jun JK, Kim SM. Association study of fibroblast growth factor 2 and fibroblast growth factor receptors gene polymorphism in Korean ossification of the posterior longitudinal ligament patients. J Korean Neurosurg Soc. 2012;52:7\u201313.","journal-title":"J Korean Neurosurg Soc"},{"key":"814_CR88","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1097\/00007632-199111000-00001","volume":"16","author":"T Sakou","year":"1991","unstructured":"Sakou T, Taketomi E, Matsunaga S, Yamaguchi M, Sonoda S, Yashiki S. Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leukocyte antigen haplotype. Spine. 1991;16:1249\u201352.","journal-title":"Spine"},{"key":"814_CR89","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1097\/00007632-199905150-00002","volume":"24","author":"S Matsunaga","year":"1999","unstructured":"Matsunaga S, Yamaguchi M, Hayashi K, Sakou T. Genetic analysis of ossification of the posterior longitudinal ligament. Spine. 1999;24:937\u20139.","journal-title":"Spine"},{"key":"814_CR90","doi-asserted-by":"publisher","first-page":"876","DOI":"10.3109\/08820139.2012.714437","volume":"41","author":"KT Kim","year":"2012","unstructured":"Kim KT, Kim DH, Chung JY, Lee S, Joo J, Nah SS, et al. Association of interferon gamma polymorphism with ossification of the posterior longitudinal ligament in the korean population. Immunol Invest. 2012;41:876\u201387.","journal-title":"Immunol Invest"},{"key":"814_CR91","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.cyto.2011.05.016","volume":"55","author":"DH Kim","year":"2011","unstructured":"Kim DH, Jeong YS, Chon J, Yoo SD, Kim HS, Kang SW, et al. Association between interleukin 15 receptor, alpha (IL15RA) polymorphism and Korean patients with ossification of the posterior longitudinal ligament. Cytokine. 2011;55:343\u20136.","journal-title":"Cytokine"},{"key":"814_CR92","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13018-014-0103-6","volume":"9","author":"Q Guo","year":"2014","unstructured":"Guo Q, Lv S-Z, Wu S-W, Tian X, Li Z-Y. Association between single nucleotide polymorphism of IL15RA gene with susceptibility to ossification of the posterior longitudinal ligament of the spine. J Orthop Surg Res. 2014;9:103.","journal-title":"J Orthop Surg Res"},{"key":"814_CR93","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159756","volume":"11","author":"JJ Lim","year":"2016","unstructured":"Lim JJ, Shin DA, Jeon YJ, Kumar H, Sohn S, Min HS, et al. Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine. PLoS ONE. 2016;11: e0159756.","journal-title":"PLoS ONE"},{"key":"814_CR94","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1016\/j.spinee.2021.07.005","volume":"21","author":"CH Lee","year":"2021","unstructured":"Lee CH, Kim KT, Kim CH, Lee EY, Lee SG, Seo ME, et al. Unveiling the genetic variation of severe continuous\/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis. Spine J. 2021;21:1847\u201356.","journal-title":"Spine J"},{"key":"814_CR95","doi-asserted-by":"publisher","first-page":"3333","DOI":"10.1007\/s11999-010-1511-5","volume":"468","author":"Y Liu","year":"2010","unstructured":"Liu Y, Zhao Y, Chen Y, Shi G, Yuan W. RUNX2 polymorphisms associated with OPLL and OLF in the Han population. Clin Orthop Relat Res. 2010;468:3333\u201341.","journal-title":"Clin Orthop Relat Res"},{"key":"814_CR96","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22068","volume":"31","author":"F Chang","year":"2017","unstructured":"Chang F, Li L, Gao G, Ding S, Yang J, Zhang T, et al. Role of Runx2 polymorphisms in risk and prognosis of ossification of posterior longitudinal ligament. J Clin Lab Anal. 2017;31: e22068.","journal-title":"J Clin Lab Anal"},{"key":"814_CR97","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1359\/jbmr.1999.14.4.500","volume":"14","author":"T Numasawa","year":"1999","unstructured":"Numasawa T, Koga H, Ueyama K, Maeda S, Sakou T, Harata S, et al. Human retinoic X receptor \u03b2: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine. J Bone Miner Res. 1999;14:500\u20138.","journal-title":"J Bone Miner Res"},{"key":"814_CR98","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1097\/00007632-200106010-00017","volume":"26","author":"M Kamiya","year":"2001","unstructured":"Kamiya M, Harada A, Mizuno M, Iwata H, Yamada Y. Association between a polymorphism of the transforming growth factor-beta1 gene and genetic susceptibility to ossification of the posterior longitudinal ligament in Japanese patients. Spine. 2001;26:1264\u20136.","journal-title":"Spine"},{"key":"814_CR99","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jocn.2012.05.031","volume":"20","author":"DW Jekarl","year":"2013","unstructured":"Jekarl DW, Paek CM, An YJ, Kim YJ, Kim M, Kim Y, et al. TGFBR2 gene polymorphism is associated with ossification of the posterior longitudinal ligament. J Clin Neurosci. 2013;20:453\u20136.","journal-title":"J Clin Neurosci"},{"key":"814_CR100","doi-asserted-by":"publisher","first-page":"E553","DOI":"10.1097\/BRS.0b013e31817e9de2","volume":"33","author":"G Kobashi","year":"2008","unstructured":"Kobashi G, Ohta K, Washio M, Okamoto K, Sasaki S, Yokoyama T, et al. FokI variant of vitamin D receptor gene and factors related to atherosclerosis associated with ossification of the posterior longitudinal ligament of the spine: a multi-hospital case-control study. Spine. 2008;33:E553\u20138.","journal-title":"Spine"},{"key":"814_CR101","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1007\/s00701-013-1747-4","volume":"155","author":"DK Chin","year":"2013","unstructured":"Chin DK, Han IB, Ropper AE, Jeon YJ, Kim DH, Kim YS, et al. Association of VKORC1-1639G>A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study. Acta Neurochir. 2013;155:1937\u201342.","journal-title":"Acta Neurochir"},{"key":"814_CR102","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1097\/01.brs.0000182318.47343.6d","volume":"30","author":"S Tsukahara","year":"2005","unstructured":"Tsukahara S, Miyazawa N, Akagawa H, Forejtova S, Pavelka K, Tanaka T, et al. COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine. 2005;30:2321\u20134.","journal-title":"Spine"},{"key":"814_CR103","first-page":"116","volume":"45","author":"B Parreira","year":"2020","unstructured":"Parreira B, Couto AR, Rocha F, Sousa M, Faustino V, Power DM, et al. Whole exome sequencing of patients with diffuse idiopathic skeletal hyperostosis and calcium pyrophosphate crystal chondrocalcinosis. Acta Reumatol Port. 2020;45:116\u201326.","journal-title":"Acta Reumatol Port"},{"key":"814_CR104","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1359\/jbmr.2002.17.1.128","volume":"17","author":"K Furushima","year":"2002","unstructured":"Furushima K, Shimo-Onoda K, Maeda S, Nobukuni T, Ikari K, Koga H, et al. Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res. 2002;17:128\u201337.","journal-title":"J Bone Miner Res"},{"key":"814_CR105","doi-asserted-by":"publisher","first-page":"4807","DOI":"10.4238\/2013.February.28.26","volume":"12","author":"IB Han","year":"2013","unstructured":"Han IB, Ropper AE, Jeon YJ, Park HS, Shin DA, Teng YD, et al. Association of transforming growth factor-beta 1 gene polymorphism with genetic susceptibility to ossification of the posterior longitudinal ligament in Korean patients. Genet Mol Res. 2013;12:4807\u201316.","journal-title":"Genet Mol Res"},{"key":"814_CR106","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1097\/01.BRS.0000068245.27017.9F","volume":"28","author":"Y Kawaguchi","year":"2003","unstructured":"Kawaguchi Y, Furushima K, Sugimori K, Inoue I, Kimura T. Association between polymorphism of the transforming growth factor-beta1 gene with the radiologic characteristic and ossification of the posterior longitudinal ligament. Spine. 2003;28:1424\u20136.","journal-title":"Spine"},{"key":"814_CR107","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/jbmr.4550","volume":"37","author":"H Kato","year":"2022","unstructured":"\u2022\u2022 Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, et al. Identification of ENPP1 haploinsufficiency in patients with diffuse idiopathic skeletal hyperostosis and early-onset osteoporosis. J Bone Miner Res. 2022;37:1125\u201335. An important study documenting that heterozygous or compound heterozygous ENPP1 pathogenic variant could be the genetic factor for development of OPLL, DISH and early-onset osteoporosis.","journal-title":"J Bone Miner Res"},{"key":"814_CR108","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1002\/jbmr.3911","volume":"35","author":"R Oheim","year":"2020","unstructured":"\u2022\u2022 Oheim R, Zimmerman K, Maulding ND, St\u00fcrznickel J, von Kroge S, Kavanagh D, et al. Human heterozygous ENPP1 deficiency is associated with early onset osteoporosis, a phenotype recapitulated in a mouse model of Enpp1 deficiency. J Bone Miner Res. 2020;35:528\u201339. An important study documenting that heterozygous ENPP1 pathogenic variant could be the genetic factor for development of early-onset osteoporosis.","journal-title":"J Bone Miner Res"},{"key":"814_CR109","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.3171\/2010.11.FOCUS10276","volume":"30","author":"K Saetia","year":"2011","unstructured":"Saetia K, Cho D, Lee S, Kim DH, Kim SD. Ossification of the posterior longitudinal ligament: a review. Neurosurg Focus. 2011;30:E1.","journal-title":"Neurosurg Focus"},{"key":"814_CR110","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0174881","volume":"12","author":"Y Kawaguchi","year":"2017","unstructured":"Kawaguchi Y, Nakano M, Yasuda T, Seki S, Suzuki K, Yahara Y, et al. Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): inflammation in OPLL. PLoS ONE. 2017;12:1\u201313.","journal-title":"PLoS ONE"},{"key":"814_CR111","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1177\/2192568218801015","volume":"9","author":"Y Kawaguchi","year":"2019","unstructured":"\u2022\u2022 Kawaguchi Y, Kitajima I, Nakano M, Yasuda T, Seki S, Suzuki K, et al. Increase of the serum FGF-23 in ossification of the posterior longitudinal ligament. Global Spine J. 2019;9:492\u20138. An interesting study evaluating the association between serum FGF23 levels and OPLL.","journal-title":"Global Spine J"},{"key":"814_CR112","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1002\/jbmr.4640","volume":"37","author":"K Zimmerman","year":"2022","unstructured":"Zimmerman K, Liu X, von Kroge S, Stabach P, Lester ER, Chu EY, et al. Catalysis-independent ENPP1 protein signaling regulates mammalian bone mass. J Bone Miner Res. 2022;37:1733\u201349.","journal-title":"J Bone Miner Res."},{"key":"814_CR113","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115656","volume":"142","author":"ND Maulding","year":"2021","unstructured":"Maulding ND, Kavanagh D, Zimmerman K, Coppola G, Carpenter TO, Jue NK, et al. Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization. Bone. 2021;142: 115656.","journal-title":"Bone"},{"key":"814_CR114","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1111\/exd.14587","volume":"31","author":"IJ Jacobs","year":"2022","unstructured":"Jacobs IJ, Cheng Z, Ralph D, O\u2019Brien K, Flaman L, Howe J, et al. INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6\u2212\/\u2212 mouse model of Pseudoxanthoma elasticum. Exp Dermatol Exp Dermatol. 2022;31:1095\u2013101.","journal-title":"Exp Dermatol Exp Dermatol"},{"key":"814_CR115","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1097\/00007632-199310000-00007","volume":"18","author":"S Ikegawa","year":"1993","unstructured":"Ikegawa S, Kurokawa T, Hizuka N, Hoshino Y, Ohnishi I, Shizumet K. Increase of serum growth hormone-binding protein in patients with ossification of the posterior longitudinal ligament of the spine. Spine. 1993;18:1757\u201360.","journal-title":"Spine"},{"key":"814_CR116","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s002239900410","volume":"62","author":"K Goto","year":"1998","unstructured":"Goto K, Yamazaki M, Tagawa M, Goto S, Kon T, Moriya H, et al. Involvement of insulin-like growth factor I in development of ossification of the posterior longitudinal ligament of the spine. Calcif Tissue Int. 1998;62:158\u201365.","journal-title":"Calcif Tissue Int"},{"key":"814_CR117","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s100380170117","volume":"46","author":"S Maeda","year":"2001","unstructured":"Maeda S, Koga H, Matsunaga S, Numasawa T, Ikari K, Furushima K, et al. Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine. J Hum Genet. 2001;46:1\u20134.","journal-title":"J Hum Genet"},{"key":"814_CR118","doi-asserted-by":"publisher","first-page":"10006","DOI":"10.1038\/ncomms10006","volume":"6","author":"RA Albright","year":"2015","unstructured":"Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, et al. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nat Commun. 2015;6:10006.","journal-title":"Nat Commun"},{"key":"814_CR119","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1210\/clinem\/dgab615","volume":"107","author":"E Bernhard","year":"2022","unstructured":"Bernhard E, Nitschke Y, Khursigara G, Sabbagh Y, Wang Y, Rutsch F. A reference range for plasma levels of inorganic pyrophosphate in children using the ATP sulfurylase method. J Clin Endocrinol Metab. 2022;107:109\u201318.","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Current Osteoporosis Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-023-00814-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11914-023-00814-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-023-00814-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T10:32:27Z","timestamp":1729852347000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11914-023-00814-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":119,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["814"],"URL":"https:\/\/doi.org\/10.1007\/s11914-023-00814-6","relation":{},"ISSN":["1544-1873","1544-2241"],"issn-type":[{"value":"1544-1873","type":"print"},{"value":"1544-2241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]},"assertion":[{"value":"3 July 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"D. T. B. is an inventor listed on patents owned by Yale University for therapeutics treating <i>ENPP1<\/i> deficiency, and is an equity holder and receives research and consulting support from Inozyme Pharma, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}]}}