{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:45:06Z","timestamp":1790073906108,"version":"4.0.1"},"reference-count":211,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.<\/jats:p>","DOI":"10.3390\/genes13101880","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T21:11:51Z","timestamp":1666041111000},"page":"1880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-6180","authenticated-orcid":false,"given":"Nipith","family":"Charoenngam","sequence":"first","affiliation":[{"name":"Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"},{"name":"Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA 02138, USA"},{"name":"Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryan","family":"Nasr","sequence":"additional","affiliation":[{"name":"Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2847-4737","authenticated-orcid":false,"given":"Arash","family":"Shirvani","sequence":"additional","affiliation":[{"name":"Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6023-9062","authenticated-orcid":false,"given":"Michael F.","family":"Holick","sequence":"additional","affiliation":[{"name":"Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","unstructured":"El Sayed, S.A., Nezwek, T.A., and Varacallo, M. (2022). Physiology, Bone. StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Florencio-Silva, R., Sasso, G.R.d.S., Sasso-Cerri, E., Sim\u00f5es, M.J., and Cerri, P.S. (2015). Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/421746"},{"key":"ref_3","first-page":"73","article-title":"Regulation of Bone Metabolism","volume":"5","author":"Shahi","year":"2017","journal-title":"Rep. Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"758","DOI":"10.4158\/EP12141.RA","article-title":"Bone as an endocrine organ","volume":"18","author":"Guntur","year":"2012","journal-title":"Endocr. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1210\/jc.2017-01127","article-title":"Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group","volume":"102","author":"Wu","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrendo.2013.137","article-title":"Osteopetrosis: Genetics, treatment and new insights into osteoclast function","volume":"9","author":"Sobacchi","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1750-1172-4-5","article-title":"Osteopetrosis","volume":"4","author":"Stark","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11914-018-0415-2","article-title":"Genetics of Osteopetrosis","volume":"16","author":"Palagano","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fendo.2019.00085","article-title":"One Disease, Many Genes: Implications for the Treatment of Osteopetroses","volume":"10","author":"Penna","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s004670050354","article-title":"Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: Pathogenesis of impaired acidification","volume":"11","author":"Nagai","year":"1997","journal-title":"Pediatr. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1542\/peds.109.6.e97","article-title":"Osteopetrosis, Lymphedema, Anhidrotic Ectodermal Dysplasia, and Immunodeficiency in a Boy and Incontinentia Pigmenti in His Mother","volume":"109","author":"Corradini","year":"2002","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/8756-3282(91)90030-M","article-title":"Morphologic features of bone in human osteopetrosis","volume":"12","author":"Helfrich","year":"1991","journal-title":"Bone"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/MOP.0000000000000914","article-title":"Diagnosis and management of pediatric metabolic bone diseases associated with skeletal fragility","volume":"32","author":"Charoenngam","year":"2020","journal-title":"Curr. Opin Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e929","DOI":"10.1097\/MD.0000000000000929","article-title":"99Tcm-MDP Imaging of Osteopetrosis: Case Report","volume":"94","author":"Zheng","year":"2015","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/pch\/11.1.37","article-title":"When bone becomes marble: Head and neck manifestations of osteopetrosis","volume":"11","author":"Hamdan","year":"2006","journal-title":"Paediatr. Child Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1365-2990.2003.00474.x","article-title":"Neurological aspects of osteopetrosis","volume":"29","author":"Steward","year":"2003","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e248","DOI":"10.1038\/mtna.2015.21","article-title":"Effective Small Interfering RNA Therapy to Treat CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2","volume":"4","author":"Capulli","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_18","first-page":"2149","article-title":"Camurati-Engelmann disease","volume":"73","author":"Kinoshita","year":"2015","journal-title":"Nihon Rinsho"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/ajmg.a.20671","article-title":"TGFB1 mutations in four new families with Camurati-Engelmann disease: Confirmation of independently arising LAP-domain-specific mutations","volume":"127","author":"Kinoshita","year":"2004","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s00223-019-00532-1","article-title":"Camurati\u2013Engelmann Disease","volume":"104","author":"Boudin","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/jmg.9.1.73","article-title":"Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature","volume":"9","author":"Sparkes","year":"1972","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.2005.033522","article-title":"Camurati-Engelmann disease: Review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment","volume":"43","author":"Janssens","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1542\/peds.75.2.321","article-title":"Progressive diaphyseal dysplasia: Evaluation of corticosteroid therapy","volume":"75","author":"Naveh","year":"1985","journal-title":"Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.aace.2021.08.002","article-title":"Losartan as a Steroid-Sparing Adjunct in a Patient With Features of Refractory Camurati-Engelmann Disease","volume":"8","author":"Agarwal","year":"2022","journal-title":"AACE Clin. Case Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4103\/ijnm.IJNM_44_19","article-title":"Camurati-Engelmann disease with good treatment response to Losartan","volume":"34","author":"Abdulla","year":"2019","journal-title":"Indian J. Nucl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a022301","DOI":"10.1101\/cshperspect.a022301","article-title":"Targeting TGF-\u03b2 Signaling for Therapeutic Gain","volume":"9","author":"Akhurst","year":"2017","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/JOE-20-0285","article-title":"Looking for new anabolic treatment from rare diseases of bone formation","volume":"248","author":"Rossi","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s00223-019-00543-y","article-title":"Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis","volume":"104","author":"Wordsworth","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s11914-017-0375-y","article-title":"Melorheostosis: A Rare Sclerosing Bone Dysplasia","volume":"15","author":"Kotwal","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00223-007-9043-z","article-title":"A Novel LEMD3 Mutation Common to Patients with Osteopoikilosis With and Without Melorheostosis","volume":"81","author":"Couto","year":"2007","journal-title":"Calcif. Tissue Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s41467-018-03720-z","article-title":"Somatic activating mutations in MAP2K1 cause melorheostosis","volume":"9","author":"Kang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00223-019-00565-6","article-title":"Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series","volume":"105","author":"Gnoli","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1097\/PAS.0000000000001310","article-title":"Melorheostosis: A Clinical, Pathologic, and Radiologic Case Series","volume":"43","author":"Fick","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1053\/j.jfas.2009.08.004","article-title":"Melorheostosis: A Literature Review and Case Report with Surgical Considerations","volume":"49","author":"Gagliardi","year":"2010","journal-title":"J. Foot Ankle Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.crad.2010.02.004","article-title":"Classical and unusual imaging appearances of melorheostosis","volume":"65","author":"Suresh","year":"2010","journal-title":"Clin. Radiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1148\/127.2.439","article-title":"99mTc-Pyrophosphate Bone Imaging in Osteopoikilosis, Osteopathia Striata, and Melorheostosis","volume":"127","author":"Whyte","year":"1978","journal-title":"Radiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e257","DOI":"10.4158\/ACCR-2020-0169","article-title":"Pyknodysostosis (Osteopetrosis Acro-Osteolytica)","volume":"6","author":"Schmidt","year":"2020","journal-title":"AACE Clin. Case Rep."},{"key":"ref_38","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). Pycnodysostosis. GeneReviews((R)), University of Washington."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1210\/jc.2003-031055","article-title":"Decreased Bone Turnover and Deterioration of Bone Structure in Two Cases of Pycnodysostosis","volume":"89","author":"Valenta","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5624\/isd.2011.41.4.177","article-title":"Pyknodysostosis: Report of a rare case with review of literature","volume":"41","author":"Ramaiah","year":"2011","journal-title":"Imaging Sci. Dent."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.aace.2021.02.006","article-title":"Pycnodysostosis: A Growth Hormone Responsive Skeletal Dysplasia","volume":"7","author":"Thalange","year":"2021","journal-title":"AACE Clin. Case Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1053\/meta.2001.24924","article-title":"Pycnodysostosis: Clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy","volume":"50","author":"Soliman","year":"2001","journal-title":"Metab.\u2014Clin. Exp."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1002\/ajmg.a.36557","article-title":"Upper airway surgery of obstructive sleep apnea in pycnodysostosis: Case report and literature review","volume":"164","author":"Testani","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1597\/12-233","article-title":"Challenges in the Orthodontic Treatment of a Patient with Pycnodysostosis","volume":"51","author":"Aguena","year":"2014","journal-title":"Cleft Palate-Craniofacial J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nm.2388","article-title":"Lrp5 functions in bone to regulate bone mass","volume":"17","author":"Cui","year":"2011","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa013444","article-title":"High Bone Density Due to a Mutation in LDL-Receptor\u2013Related Protein 5","volume":"346","author":"Boyden","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/jbmr.2706","article-title":"Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases","volume":"31","author":"Gregson","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1359\/JBMR.050303","article-title":"An Autosomal Dominant High Bone Mass Phenotype in Association With Craniosynostosis in an Extended Family Is Caused by an LRP5 Missense Mutation","volume":"20","author":"Kwee","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bone.2019.05.003","article-title":"New explanation for autosomal dominant high bone mass: Mutation of low-density lipoprotein receptor-related protein 6","volume":"127","author":"Whyte","year":"2019","journal-title":"Bone"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115550","DOI":"10.1016\/j.bone.2020.115550","article-title":"High bone mass from mutation of low-density lipoprotein receptor-related protein 6 (LRP6)","volume":"141","author":"Brance","year":"2020","journal-title":"Bone"},{"key":"ref_51","first-page":"874","article-title":"A Case of Unusual Bone Development","volume":"13","author":"Pyle","year":"1931","journal-title":"JBJS"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Houschyar, K.S., Tapking, C., Borrelli, M.R., Popp, D., Duscher, D., Maan, Z.N., Chelliah, M.P., Li, J., Harati, K., and Wallner, C. (2019). Wnt Pathway in Bone Repair and Regeneration\u2014What Do We Know So Far. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00170"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/jmg.24.6.321","article-title":"Pyle disease (metaphyseal dysplasia)","volume":"24","author":"Beighton","year":"1987","journal-title":"J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/ajmg.a.32253","article-title":"The Erlenmeyer flask bone deformity in the skeletal dysplasias","volume":"149","author":"Faden","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.radcr.2016.10.003","article-title":"Pyle disease (metaphyseal dysplasia) presenting in two adult sisters","volume":"11","author":"Soares","year":"2016","journal-title":"Radiol. Case Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/jbmr.1794","article-title":"Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers","volume":"28","author":"Hamdy","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jbspin.2015.10.013","article-title":"Van Buchem\u2019s Disease","volume":"83","author":"Nassar","year":"2016","journal-title":"Jt. Bone Spine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1086\/301721","article-title":"Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21","volume":"62","author":"Balemans","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.metabol.2017.10.005","article-title":"Genetics of Sost\/SOST in sclerosteosis and van Buchem disease animal models","volume":"80","author":"Sebastian","year":"2018","journal-title":"Metabolism"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1002\/jbmr.474","article-title":"Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover","volume":"26","author":"Hamdy","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/hmg\/10.5.537","article-title":"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)","volume":"10","author":"Balemans","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.bone.2012.10.009","article-title":"Novel SOST gene mutation in a sclerosteosis patient and her parents","volume":"52","author":"Bhadada","year":"2013","journal-title":"Bone"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/jbmr.2782","article-title":"A Novel Domain-Specific Mutation in a Sclerosteosis Patient Suggests a Role of LRP4 as an Anchor for Sclerostin in Human Bone","volume":"31","author":"Fijalkowski","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/bdr2.1676","article-title":"A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2","volume":"112","author":"Jamsheer","year":"2020","journal-title":"Birth Defects Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.7326\/0003-4819-84-4-393","article-title":"The Clinical Features of Sclerosteosis","volume":"84","author":"Beighton","year":"1976","journal-title":"Ann. Intern. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1399-0004.1984.tb00481.x","article-title":"The syndromic status of sclerosteosis and van Buchem disease","volume":"25","author":"Beighton","year":"1984","journal-title":"Clin. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.metabol.2017.10.007","article-title":"Juvenile Paget disease","volume":"80","author":"Polyzos","year":"2018","journal-title":"Metab.\u2014Clin. Exp."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jbspin.2005.05.009","article-title":"Genetics of Paget\u2019s disease of bone","volume":"73","author":"Michou","year":"2006","journal-title":"Jt. Bone Spine"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"(2002). Osteoprotegerin Deficiency and Juvenile Paget\u2019s Disease. N. Engl. J. Med., 347, 1622\u20131623.","DOI":"10.1056\/NEJM200211143472015"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/archophthalmol.2010.76","article-title":"Ocular Manifestations of Juvenile Paget Disease","volume":"128","author":"Kerr","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bone.2014.07.034","article-title":"Novel homozygous mutations in the osteoprotegerin gene TNFRSF11B in two unrelated patients with juvenile Paget\u2019s disease","volume":"68","author":"Naot","year":"2014","journal-title":"Bone"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"269","DOI":"10.11138\/ccmbm\/2017.14.2.269","article-title":"Periostin and sclerostin levels in juvenile Paget\u2019s disease","volume":"14","author":"Polyzos","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1007\/s00774-010-0198-8","article-title":"Profound hypocalcemia following effective response to zoledronic acid treatment in a patient with juvenile Paget\u2019s disease","volume":"28","author":"Polyzos","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s002470050708","article-title":"Calcitonin treatment in osteoectasia with hyperphosphatasia (juvenile Paget\u2019s disease): Radiographic changes after treatment","volume":"29","author":"Mercimek","year":"1999","journal-title":"Pediatr. Radiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1210\/jc.2013-3762","article-title":"Denosumab Treatment for Juvenile Paget\u2019s Disease: Results From Two Adult Patients With Osteoprotegerin Deficiency (\u201cBalkan\u201d Mutation in the TNFRSF11B Gene)","volume":"99","author":"Polyzos","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1056\/NEJMoa050893","article-title":"Recombinant Osteoprotegerin for Juvenile Paget\u2019s Disease","volume":"353","author":"Cundy","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1093\/qjmed\/hcu075","article-title":"Paget\u2019s disease of bone","volume":"107","author":"Tan","year":"2014","journal-title":"QJM Int. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"23","DOI":"10.31128\/AJGP-10-20-5690","article-title":"Paget\u2019s disease of bone: A clinical update","volume":"50","author":"Cook","year":"2021","journal-title":"Aust. J. Gen. Pract."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/00003086-198704000-00014","article-title":"Pathogenesis of Paget\u2019s disease based on viral etiology","volume":"217","author":"Mirra","year":"1987","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S8756-3282(00)00278-7","article-title":"Familial Paget\u2019s disease of bone: Patterns of inheritance and frequency of linkage to chromosome 18q","volume":"26","author":"Hocking","year":"2000","journal-title":"Bone"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s12018-016-9226-0","article-title":"Clinical and Genetic Advances in Paget\u2019s Disease of Bone: A Review","volume":"15","author":"Alonso","year":"2017","journal-title":"Clin. Rev. Bone Miner. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/jbmr.542","article-title":"A nonsynonymous TNFRSF11A variation increases NF\u03baB activity and the severity of Paget\u2019s disease","volume":"27","author":"Gianfrancesco","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11914-021-00676-w","article-title":"Genetic Determinants of Paget\u2019s Disease of Bone","volume":"19","author":"Makaram","year":"2021","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1359\/jbmr.070333","article-title":"Identification of Sex-Specific Associations Between Polymorphisms of the Osteoprotegerin Gene, TNFRSF11B, and Paget\u2019s Disease of Bone","volume":"22","author":"Beyens","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11882-021-01001-2","article-title":"Paget\u2019s Disease of Bone: Osteoimmunology and Osteoclast Pathology","volume":"21","author":"Rabjohns","year":"2021","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s10354-016-0517-3","article-title":"Imaging of Paget\u2019s disease of bone","volume":"167","author":"Winn","year":"2017","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1359\/jbmr.061001","article-title":"Long-Term Control of Bone Turnover in Paget\u2019s Disease With Zoledronic Acid and Risedronate","volume":"22","author":"Hosking","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s00223-016-0150-6","article-title":"Treatment of Paget\u2019s Disease of Bone with Denosumab: Case Report and Literature Review","volume":"99","author":"Reid","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1359\/jbmr.090707","article-title":"Osteopathia striata with cranial sclerosis owing to WTX gene defect","volume":"25","author":"Perdu","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1399-0004.2012.01905.x","article-title":"Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus","volume":"83","author":"Holman","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.a.30107","article-title":"Osteopathia striata with cranial sclerosis: Clinical, radiological, and bone histological findings in an adolescent girl","volume":"129","author":"Ward","year":"2004","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_92","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). Osteopathia Striata with Cranial Sclerosis. GeneReviews((R)), University of Washington."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"100194","DOI":"10.1016\/j.omsc.2020.100194","article-title":"Orthognathic surgery in a patient with osteopathia striata combined with cranial sclerosis: A case report","volume":"6","author":"Sultana","year":"2020","journal-title":"Oral Maxillofac. Surg. Cases"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s40618-015-0419-z","article-title":"Identification of a novel LEMD3 Y871X mutation in a three-generation family with osteopoikilosis and review of the literature","volume":"39","author":"Zhang","year":"2016","journal-title":"J. Endocrinol. Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s10067-011-1916-x","article-title":"Osteopoikilosis: What does the rheumatologist must know about it?","volume":"31","author":"Woyciechowsky","year":"2012","journal-title":"Clin. Rheumatol."},{"key":"ref_96","first-page":"84","article-title":"Plasma cell myeloma with unusual presentations","volume":"6","author":"Krishnappa","year":"2013","journal-title":"J. Orthop. Traumatol. Rehabil."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00296-010-1664-2","article-title":"A rare benign disorder mimicking metastasis on radiographic examination: A case report of osteopoikilosis","volume":"31","author":"Ozdemirel","year":"2011","journal-title":"Rheumatol. Int."},{"key":"ref_98","first-page":"93","article-title":"Osteopoikilosis: A major diagnostic problem solved by bone scintigraphy","volume":"31","author":"Tuncel","year":"2012","journal-title":"Rev. Espa\u00f1ola Med. Nucl. Imagen Mol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s11845-010-0595-y","article-title":"Osteopoikilosis","volume":"179","author":"Ellanti","year":"2010","journal-title":"Ir. J. Med. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s00198-019-04921-y","article-title":"Hypophosphatasia: Canadian update on diagnosis and management","volume":"30","author":"Khan","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Mornet, E. (2007). Hypophosphatasia. Orphanet J. Rare Dis., 2.","DOI":"10.1186\/1750-1172-2-40"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/jbmr.3075","article-title":"Hypophosphatasia: Enzyme Replacement Therapy Brings New Opportunities and New Challenges","volume":"32","author":"Whyte","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.14","article-title":"Hypophosphatasia\u2014Aetiology, nosology, pathogenesis, diagnosis and treatment","volume":"12","author":"Whyte","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.metabol.2017.08.013","article-title":"Hypophosphatasia","volume":"82","author":"Mornet","year":"2018","journal-title":"Metab. \u2014Clin. Exp."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00296-008-0710-9","article-title":"How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or chronic inflammatory joint diseases?","volume":"29","author":"Beck","year":"2009","journal-title":"Rheumatol. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/088307380201700314","article-title":"Pyridoxine-Dependent Seizures Associated With Hypophosphatasia in a Newborn","volume":"17","author":"Mugnol","year":"2002","journal-title":"J. Child Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"732621","DOI":"10.3389\/fgene.2021.732621","article-title":"Case Report: Variations in the ALPL Gene in Chinese Patients With Hypophosphatasia","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","article-title":"Alkaline Phosphatase and Hypophosphatasia","volume":"98","author":"Whyte","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/BF01800216","article-title":"Increased plasma pyridoxal-5\u2032-phosphate levels before and after pyridoxine loading in carriers of perinatal\/infantile hypophosphatasia","volume":"13","author":"Chodirker","year":"1990","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_110","first-page":"230","article-title":"Hypophosphatasia: Clinical manifestation and burden of disease in adult patients","volume":"14","author":"Conti","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab. Off. J. Ital. Soc. Osteoporos. Miner. Metab. Skelet. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/0002-9343(57)90124-9","article-title":"Hypophosphatasia","volume":"22","author":"Fraser","year":"1957","journal-title":"Am. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bone.2017.02.011","article-title":"Hypophosphatasia: An overview For 2017","volume":"102","author":"Whyte","year":"2017","journal-title":"Bone"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bone.2016.08.019","article-title":"Hypophosphatasia: Natural history study of 101 affected children investigated at one research center","volume":"93","author":"Whyte","year":"2016","journal-title":"Bone"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.2147\/DDDT.S154922","article-title":"Profile of asfotase alfa in the treatment of hypophosphatasia: Design, development, and place in therapy","volume":"12","author":"Bowden","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1056\/NEJMoa1106173","article-title":"Enzyme-replacement therapy in life-threatening hypophosphatasia","volume":"366","author":"Whyte","year":"2012","journal-title":"New Engl. J. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11926-018-0778-5","article-title":"Hypophosphatasia: From Diagnosis to Treatment","volume":"20","author":"Simon","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.bone.2007.01.020","article-title":"Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene","volume":"40","author":"Haberlandt","year":"2007","journal-title":"Bone"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13023-019-1014-8","article-title":"FGF23 and its role in X-linked hypophosphatemia-related morbidity","volume":"14","author":"Mughal","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.2215\/CJN.02680310","article-title":"Reciprocal Control of 1,25-Dihydroxyvitamin D and FGF23 Formation Involving the FGF23\/Klotho System","volume":"5","author":"Friedlander","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1507\/endocrj.EJ15-0275","article-title":"Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: Prevalence, biochemical data and treatment","volume":"62","author":"Endo","year":"2015","journal-title":"Endocr. J."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1530\/EJE-08-0818","article-title":"Incidence and prevalence of nutritional and hereditary rickets in southern Denmark","volume":"160","author":"Gram","year":"2009","journal-title":"Eur. J. Endocrinol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1530\/EJE-15-0515","article-title":"Hereditary hypophosphatemia in Norway: A retrospective population-based study of genotypes, phenotypes, and treatment complications","volume":"174","author":"Rafaelsen","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_123","first-page":"3615","article-title":"Mutational Analysis of PHEX Gene in X-Linked Hypophosphatemia1","volume":"83","author":"Dixon","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23","volume":"26","author":"White","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ajhg.2010.01.010","article-title":"Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene","volume":"86","author":"Hershkovitz","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bone.2008.10.040","article-title":"Molecular analysis of DMP1 mutants causing autosomal recessive hypophosphatemic rickets","volume":"44","author":"Farrow","year":"2009","journal-title":"Bone"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/jbmr.340","article-title":"A clinician\u2019s guide to X-linked hypophosphatemia","volume":"26","author":"Carpenter","year":"2011","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1007\/s11999-008-0547-2","article-title":"Deformity correction in children with hereditary hypophosphatemic rickets","volume":"466","author":"Petje","year":"2008","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/EC-13-0103","article-title":"Therapeutic management of hypophosphatemic rickets from infancy to adulthood","volume":"3","author":"Linglart","year":"2014","journal-title":"Endocr. Connect."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41581-019-0152-5","article-title":"Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia","volume":"15","author":"Haffner","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/MED.0b013e328358be97","article-title":"Hypophosphatemic rickets","volume":"19","author":"Baroncelli","year":"2012","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_132","first-page":"326","article-title":"Pharmaceutical Approval Update","volume":"43","author":"Choy","year":"2018","journal-title":"P T A Peer-Rev. J. Formul. Manag."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1056\/NEJMoa1714641","article-title":"Burosumab Therapy in Children with X-Linked Hypophosphatemia","volume":"378","author":"Carpenter","year":"2018","journal-title":"New Engl. J. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1016\/S0140-6736(19)30654-3","article-title":"Burosumab versus conventional therapy in children with X-linked hypophosphataemia: A randomised, active-controlled, open-label, phase 3 trial","volume":"393","author":"Imel","year":"2019","journal-title":"Lancet"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1210\/jc.2003-030036","article-title":"Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets","volume":"88","author":"Doria","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00467-011-2046-z","article-title":"Growth in PHEX-associated X-linked hypophosphatemic rickets: The importance of early treatment","volume":"27","author":"Quinlan","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4161\/derm.24494","article-title":"Sunlight and Vitamin D: A global perspective for health","volume":"5","author":"Wacker","year":"2013","journal-title":"Dermatoendocrinol"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jcot.2019.07.004","article-title":"Vitamin D for skeletal and non-skeletal health: What we should know","volume":"10","author":"Charoenngam","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1172\/JCI29449","article-title":"Resurrection of vitamin D deficiency and rickets","volume":"116","author":"Holick","year":"2006","journal-title":"J. Clin. Invest."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3389\/fped.2020.00315","article-title":"Diagnosis and Management of Vitamin D Dependent Rickets","volume":"8","author":"Levine","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1073\/pnas.1031395100","article-title":"Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: A cause of vitamin D resistance","volume":"100","author":"Chen","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1172\/JCI98680","article-title":"CYP3A4 mutation causes vitamin D-dependent rickets type 3","volume":"128","author":"Roizen","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1172\/JCI112483","article-title":"Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D","volume":"77","author":"Balsan","year":"1986","journal-title":"J. Clin. Investig."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/0002-9343(81)90338-7","article-title":"Axial osteomalacia: Clinical, laboratory and genetic investigation of an affected mother and son","volume":"71","author":"Whyte","year":"1981","journal-title":"Am. J. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/art.1780210619","article-title":"Atypical axial osteomalacia. report of four cases with two having features of ankylosing spondylitis","volume":"21","author":"Nelson","year":"1978","journal-title":"Arthritis Rheum."},{"key":"ref_147","first-page":"23","article-title":"The Molecular and Genetic Basis of Fibroblast Growth Factor Receptor 3 Disorders: The Achondroplasia Family of Skeletal Dysplasias, Muenke Craniosynostosis, and Crouzon Syndrome with Acanthosis Nigricans","volume":"21","author":"Vajo","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_148","first-page":"291","article-title":"Achondroplasia: Development, pathogenesis, and therapy","volume":"246","author":"Ornitz","year":"2017","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-018-0972-6","article-title":"Achondroplasia: A comprehensive clinical review","volume":"14","author":"Pauli","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/ng0395-321","article-title":"Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3","volume":"9","author":"Tavormina","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_151","first-page":"39","article-title":"Thanatophoric dysplasia type I","volume":"42","author":"Chang","year":"2001","journal-title":"Acta Paediatr. Taiwan"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Yolanda, N., Yulianto, F., Arina, S., and Edwin, J. (2019). A full-term infant with type II thanatophoric dysplasia. Case Rep. Perinat. Med., 8.","DOI":"10.1515\/crpm-2018-0035"},{"key":"ref_153","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). Hypochondroplasia. GeneReviews((R)), University of Washington."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature13775","article-title":"Statin treatment rescues FGFR3 skeletal dysplasia phenotypes","volume":"513","author":"Yamashita","year":"2014","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1073\/pnas.97.2.668","article-title":"The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate","volume":"97","author":"McCormick","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.matbio.2017.12.011","article-title":"The pathogenic roles of heparan sulfate deficiency in hereditary multiple exostoses","volume":"71\u201372","author":"Pacifici","year":"2018","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_157","first-page":"110","article-title":"Hereditary Multiple Exostoses: A review of clinical appearance and metabolic pattern","volume":"13","author":"Beltrami","year":"2016","journal-title":"Clin. Cases Miner. Bone Metab. Off. J. Ital. Soc. Osteoporos. Miner. Metab. Skelet. Dis."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"8062","DOI":"10.4076\/1757-1626-2-8062","article-title":"Fracture of an osteochondroma treated successfully with total excision: Two case reports","volume":"2","author":"Kose","year":"2009","journal-title":"Cases J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.diii.2014.11.013","article-title":"Spontaneous healing of an osteochondroma fracture","volume":"96","author":"Errani","year":"2015","journal-title":"Diagn. Interv. Imaging"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2484\/rcr.v3i3.99","article-title":"Non-Traumatic Fracture of an Osteochondroma Mimicking Malignant Degeneration in an Adult with Hereditary Multiple Exostoses","volume":"3","author":"Robbins","year":"2015","journal-title":"Radiol. Case Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e50208","DOI":"10.7554\/eLife.50208","article-title":"Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt\/\u03b2-Catenin","volume":"8","author":"Deng","year":"2019","journal-title":"eLife"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/21678707.2018.1483232","article-title":"Hereditary multiple exostoses: Are there new plausible treatment strategies?","volume":"6","author":"Pacifici","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Abdullah, N.R.A., Jason, W.L.C., and Nasruddin, A.B. (2017). Pachydermoperiostosis: A rare mimicker of acromegaly. Endocrinol. Diabetes Metab. Case Rep., 2017.","DOI":"10.1530\/EDM-17-0029"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e232238","DOI":"10.1136\/bcr-2019-232238","article-title":"Touraine-Solente-Gole syndrome","volume":"12","author":"Mittal","year":"2019","journal-title":"BMJ Case Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jpra.2019.04.004","article-title":"Touraine\u2013Solente\u2013Gole syndrome: Clinical manifestation with bilateral true eyelid ptosis","volume":"21","author":"Akaranuchat","year":"2019","journal-title":"JPRAS Open"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13256-018-1961-z","article-title":"Pachydermoperiostosis (Touraine-Solente-Gole syndrome): A case report","volume":"13","author":"Joshi","year":"2019","journal-title":"J. Med. Case Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"E923","DOI":"10.1210\/jc.2012-3568","article-title":"Mutations in the SLCO2A1 Gene and Primary Hypertrophic Osteoarthropathy: A Clinical and Biochemical Characterization","volume":"98","author":"Zhang","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"102217","DOI":"10.1016\/j.scr.2021.102217","article-title":"Establishment of a novel human iPSC line (SDQLCHi032-A) derived from a patient with primary hypertrophic osteoarthropathy caused by HPGD homozygous mutation","volume":"52","author":"Li","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/ng.153","article-title":"Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy","volume":"40","author":"Uppal","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e8865","DOI":"10.1097\/MD.0000000000008865","article-title":"Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: Two case reports","volume":"96","author":"Zhang","year":"2017","journal-title":"Medicine"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0140-6736(56)91186-2","article-title":"Reversal of pulmonary hypertrophic osteoarthropathy by vagotomy","volume":"267","author":"Flayell","year":"1956","journal-title":"Lancet"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"e563","DOI":"10.1097\/SCS.0000000000001149","article-title":"Pachydermoperiostosis: Aesthetic Treatment of Prematurely Aging Face With Facelift and Botulinum Toxin A","volume":"25","author":"Bingol","year":"2014","journal-title":"J. Craniofacial Surg."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1086\/497706","article-title":"Clinical and molecular findings in osteoporosis-pseudoglioma syndrome","volume":"77","author":"Ai","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.tjo.2015.04.002","article-title":"Complex genetics of familial exudative vitreoretinopathy and related pediatric retinal detachments","volume":"5","author":"Kondo","year":"2015","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Chen, J., Stahl, A., Krah, N.M., Seaward, M.R., Joyal, J.-S., Juan, A.M., Hatton, C.J., Aderman, C.M., Dennison, R.J., and Willett, K.L. (2012). Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030203"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1086\/383202","article-title":"Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q","volume":"74","author":"Toomes","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1136\/bjo.85.9.1139","article-title":"Bilateral retinal detachments at birth: The osteoporosis pseudoglioma syndrome","volume":"85","author":"Wilson","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"334","DOI":"10.4103\/jpn.JPN_107_20","article-title":"Osteoporosis Pseudoglioma Syndrome","volume":"15","author":"Gowda","year":"2020","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.bone.2008.04.020","article-title":"Osteoporosis-pseudoglioma syndrome: Description of 9 new cases and beneficial response to bisphosphonates","volume":"43","author":"Streeten","year":"2008","journal-title":"Bone"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/24725625.2018.1454573","article-title":"Efficacy of denosumab therapy for osteoporosis-pseudoglioma syndrome with osteoporosis: A case report","volume":"3","author":"Miyazawa","year":"2019","journal-title":"Mod. Rheumatol. Case Rep."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"e121031","DOI":"10.5812\/ijem-121031","article-title":"Clinical Response to Treatment with Teriparatide in an Adolescent with Osteoporosis-Pseudoglioma Syndrome (OPPG): A Case Report","volume":"20","author":"Homaei","year":"2022","journal-title":"Int. J. Endocrinol. Metab."},{"key":"ref_182","doi-asserted-by":"crossref","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":"ref_183","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1097\/GIM.0b013e3181a1ff7b","article-title":"Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition","volume":"11","author":"Basel","year":"2009","journal-title":"Genet. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.metabol.2017.06.001","article-title":"Osteogenesis imperfecta\u2014A clinical update","volume":"80","author":"Tournis","year":"2018","journal-title":"Metab.\u2014Clin. Exp."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1002\/jbmr.4011","article-title":"Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta","volume":"35","author":"Dubail","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1530\/EJE-14-0017","article-title":"THERAPY OF ENDOCRINE DISEASE: Treatment of osteogenesis imperfecta in adults","volume":"171","author":"Lindahl","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_187","unstructured":"Subramanian, S., and Viswanathan, V.K. (2022). Osteogenesis Imperfecta. StatPearls, StatPearls Publishing."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11914-016-0299-y","article-title":"Advances in the Classification and Treatment of Osteogenesis Imperfecta","volume":"14","author":"Thomas","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/jbmr.2567","article-title":"Intravenous Bisphosphonate Therapy of Young Children With Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years","volume":"30","author":"Palomo","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_191","first-page":"e1","article-title":"Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta","volume":"4","author":"Hennedige","year":"2014","journal-title":"J. Oral Maxillofac. Res."},{"key":"ref_192","first-page":"24","article-title":"Safety and efficacy of denosumab in children with osteogenesis imperfect--a first prospective trial","volume":"16","author":"Franklin","year":"2016","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"115333","DOI":"10.1016\/j.bone.2020.115333","article-title":"Increased fracture rate in children and adolescents with Marfan syndrome","volume":"135","author":"Mora","year":"2020","journal-title":"Bone"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/rheumatology\/39.3.307","article-title":"Bone mineral density in adults with Marfan syndrome","volume":"39","author":"Carter","year":"2000","journal-title":"Rheumatology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.chiabu.2019.03.008","article-title":"Fracture incidence in Ehlers-Danlos syndrome\u2014A population-based case-control study","volume":"91","author":"Rolfes","year":"2019","journal-title":"Child Abus. Negl."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00198-019-05269-z","article-title":"Higher fracture prevalence and smaller bone size in patients with hEDS\/HSD\u2014A prospective cohort study","volume":"31","author":"Banica","year":"2020","journal-title":"Osteoporos. Int."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1002\/ajmg.a.36029","article-title":"Increased fracture risk and low bone mineral density in patients with loeys\u2013dietz syndrome","volume":"161","author":"Tan","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers\u2013Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. J. Med. Genet. Part C: Semin. Med. Genet."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1136\/jmg.37.1.9","article-title":"The molecular genetics of Marfan syndrome and related microfibrillopathies","volume":"37","author":"Robinson","year":"2000","journal-title":"J. Med. Genet."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/ng1392","article-title":"Heterozygous TGFBR2 mutations in Marfan syndrome","volume":"36","author":"Mizuguchi","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_201","first-page":"576","article-title":"Loeys-Dietz syndrome: A primer for diagnosis and management","volume":"16","author":"MacCarrick","year":"2014","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"e625","DOI":"10.1212\/NXG.0000000000000625","article-title":"Novel Mutation of the TGF-\u03b2 3 Protein (Loeys-Dietz Type 5) Associated With Aortic and Carotid Dissections","volume":"7","author":"Hussein","year":"2021","journal-title":"Neurol. Genet."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O","article-title":"Ehlers-Danlos syndromes: Revised nosology, Villefranche, 1997","volume":"77","author":"Beighton","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"ref_204","first-page":"137","article-title":"Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome","volume":"8","author":"Bannas","year":"2015","journal-title":"Appl. Clin. Genet."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1007\/s001980070104","article-title":"Bone Density in Ehlers-Danlos Syndrome","volume":"11","author":"Carbone","year":"2000","journal-title":"Osteoporos. Int."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1136\/ard.57.10.630","article-title":"Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry","volume":"57","author":"Dolan","year":"1998","journal-title":"Ann. Rheum. Dis."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.jbspin.2006.01.026","article-title":"Bone mineral density in Marfan syndrome. A large case-control study","volume":"73","author":"Moura","year":"2006","journal-title":"Jt. Bone Spine"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e1279768","DOI":"10.1080\/19381980.2017.1279768","article-title":"Multiple fractures in infants who have Ehlers-Danlos\/hypermobility syndrome and or vitamin D deficiency: A case series of 72 infants whose parents were accused of child abuse and neglect","volume":"9","author":"Holick","year":"2017","journal-title":"Dermato-Endocrinology"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Holick, M.F., Shirvani, A., and Charoenngam, N. (2021). Fetal Fractures in an Infant with Maternal Ehlers-Danlos Syndrome, CCDC134 Pathogenic Mutation and a Negative Genetic Test for Osteogenesis Imperfecta. Children, 8.","DOI":"10.3390\/children8060512"},{"key":"ref_210","unstructured":"(2022, April 06). OSTEOGENESIS IMPERFECTA, TYPE XXII.; OI22. Available online: https:\/\/www.omim.org\/entry\/619795."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41588-018-0302-x","article-title":"An atlas of genetic influences on osteoporosis in humans and mice","volume":"51","author":"Morris","year":"2019","journal-title":"Nat. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:35Z","timestamp":1760144135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":211,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["genes13101880"],"URL":"https:\/\/doi.org\/10.3390\/genes13101880","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}