{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:40:30Z","timestamp":1783431630328,"version":"3.54.6"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bone"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.bone.2025.117698","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T20:55:07Z","timestamp":1761857707000},"page":"117698","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Autosomal recessive hypophosphatemic rickets type 2 (ARHR2): Is phosphate supplementation safe?"],"prefix":"10.1016","volume":"202","author":[{"given":"Martin","family":"Munteanu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rutsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Nitschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kornak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Kiewert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Spiekermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"H\u00f6ppner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Grasemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0005","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41436-020-00983-0","article-title":"Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI)","volume":"23","author":"Ferreira","year":"2021","journal-title":"Genet. Med."},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0010","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1172\/JCI117370","article-title":"Expression of the murine plasma cell nucleotide pyrophosphohydrolase PC-1 is shared by human liver, bone, and cartilage cells. Regulation of PC-1 expression in osteosarcoma cells by transforming growth factor-beta","volume":"94","author":"Huang","year":"1994","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.bone.2025.117698_bb0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0003-9861(84)90356-4","article-title":"Can biological calcification occur in the presence of pyrophosphate?","volume":"231","author":"Meyer","year":"1984","journal-title":"Arch. Biochem. Biophys."},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0020","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s11302-022-09867-1","article-title":"Role of the extracellular ATP\/pyrophosphate metabolism cycle in vascular calcification","volume":"19","author":"Villa-Bellosta","year":"2023","journal-title":"Purinergic Signal"},{"key":"10.1016\/j.bone.2025.117698_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2021.116111","article-title":"Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) due to ENPP1-deficiency","volume":"153","author":"H\u00f6ppner","year":"2021","journal-title":"Bone"},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0030","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1161\/CIRCGENETICS.108.797704","article-title":"Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy","volume":"1","author":"Rutsch","year":"2008","journal-title":"Circ. Cardiovasc. Genet."},{"issue":"10","key":"10.1016\/j.bone.2025.117698_bb0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0163-5","article-title":"ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP","volume":"50","author":"Nitschke","year":"2018","journal-title":"Exp. Mol. Med."},{"issue":"13","key":"10.1016\/j.bone.2025.117698_bb0040","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.3390\/cells13131128","article-title":"Inhibition of vascular smooth muscle cell proliferation by ENPP1: the role of CD73 and the adenosine signaling axis","volume":"13","author":"Tchernychev","year":"2024","journal-title":"Cells"},{"issue":"3","key":"10.1016\/j.bone.2025.117698_bb0045","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s11914-020-00577-4","article-title":"Generalized arterial calcification of infancy: new insights, controversies, and approach to management","volume":"18","author":"Boyce","year":"2020","journal-title":"Curr. Osteoporos. Rep."},{"issue":"5","key":"10.1016\/j.bone.2025.117698_bb0050","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2350\/07-06-0297.1","article-title":"Idiopathic infantile arterial calcification: the spectrum of clinical presentations","volume":"11","author":"Chong","year":"2008","journal-title":"Pediatr. Dev. Pathol."},{"key":"10.1016\/j.bone.2025.117698_bb0055","doi-asserted-by":"crossref","DOI":"10.1111\/cen.15028","article-title":"Natural history of ENPP1 deficiency: nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2","author":"Dursun","year":"2024","journal-title":"Clin. Endocrinol."},{"issue":"11","key":"10.1016\/j.bone.2025.117698_bb0060","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1002\/jbmr.4418","article-title":"Ectopic calcification and hypophosphatemic rickets: natural history of ENPP1 and ABCC6 deficiencies","volume":"36","author":"Ferreira","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2025.117698_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115656","article-title":"Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization","volume":"142","author":"Maulding","year":"2021","journal-title":"Bone"},{"issue":"1","key":"10.1016\/j.bone.2025.117698_bb0070","doi-asserted-by":"crossref","DOI":"10.1146\/annurev-pathmechdis-051222-121126","article-title":"ENPP1 in blood and bone: skeletal and soft tissue diseases induced by ENPP1 deficiency","volume":"19","author":"Ferreira","year":"2024","journal-title":"Annu. Rev. Pathol.: Mech. Dis."},{"issue":"5","key":"10.1016\/j.bone.2025.117698_bb0075","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/ajmg.a.37574","article-title":"Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification","volume":"170","author":"Ferreira","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"issue":"4","key":"10.1016\/j.bone.2025.117698_bb0080","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/ng1221","article-title":"Mutations in ENPP1 are associated with \u201cidiopathic\u201d infantile arterial calcification","volume":"34","author":"Rutsch","year":"2003","journal-title":"Nat. Genet."},{"issue":"4","key":"10.1016\/j.bone.2025.117698_bb0085","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/jbmr.3938","article-title":"Clinical and biochemical phenotypes in a family with ENPP1 mutations","volume":"35","author":"Kotwal","year":"2020","journal-title":"J. Bone Miner. Res."},{"issue":"3","key":"10.1016\/j.bone.2025.117698_bb0090","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/jbmr.3911","article-title":"Human heterozygous ENPP1 deficiency is associated with early onset osteoporosis, a phenotype recapitulated in a mouse model of Enpp1 deficiency","volume":"35","author":"Oheim","year":"2020","journal-title":"J. Bone Miner. Res."},{"issue":"10","key":"10.1016\/j.bone.2025.117698_bb0095","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1038\/s41436-021-01228-4","article-title":"Correspondence on \u201cProspective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI)\u201d by Ferreira et al","volume":"23","author":"Stern","year":"2021","journal-title":"Genet. Med."},{"issue":"3","key":"10.1016\/j.bone.2025.117698_bb0100","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/tropej\/46.3.132","article-title":"Radiographic scoring method for the assessment of the severity of nutritional rickets","volume":"46","author":"Thacher","year":"2000","journal-title":"J. Trop. Pediatr."},{"key":"10.1016\/j.bone.2025.117698_bb0105","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bone.2019.02.010","article-title":"Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: utility of the radiographic rickets severity score","volume":"122","author":"Thacher","year":"2019","journal-title":"Bone"},{"issue":"11","key":"10.1016\/j.bone.2025.117698_bb0110","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1093\/ndt\/gfab331","article-title":"Tubular phosphate handling: references from child to adulthood in the era of standardized serum creatinine","volume":"37","author":"Derain Dubourg","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"issue":"9","key":"10.1016\/j.bone.2025.117698_bb0115","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1007\/s00467-010-1544-8","article-title":"Pediatric reference intervals for random urine calcium, phosphorus and total protein","volume":"25","author":"Slev","year":"2010","journal-title":"Pediatr. Nephrol."},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0120","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":"Levy-Litan","year":"2010","journal-title":"Am. J. Hum. Genet."},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0125","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2010.01.006","article-title":"Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets","volume":"86","author":"Lorenz-Depiereux","year":"2010","journal-title":"Am. J. Hum. Genet."},{"issue":"4","key":"10.1016\/j.bone.2025.117698_bb0130","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.bone.2011.06.029","article-title":"A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene","volume":"49","author":"Saito","year":"2011","journal-title":"Bone"},{"issue":"10","key":"10.1016\/j.bone.2025.117698_bb0135","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/rheumatology\/kes089","article-title":"Novel compound heterozygous mutations in ENPP1 cause hypophosphataemic rickets with anterior spinal ligament ossification","volume":"51","author":"Mehta","year":"2012","journal-title":"Rheumatology"},{"issue":"7\u20138","key":"10.1016\/j.bone.2025.117698_bb0140","article-title":"Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1","volume":"28","author":"Steichen-Gersdorf","year":"2015","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"10.1016\/j.bone.2025.117698_bb0145","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bone.2015.05.040","article-title":"Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets","volume":"79","author":"Capelli","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.bone.2025.117698_bb0150","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.911672","article-title":"Case report and review of literature: autosomal recessive hypophosphatemic rickets type 2 caused by a pathogenic variant in ENPP1 gene","volume":"13","author":"Choe","year":"2022","journal-title":"Front. Endocrinol."},{"issue":"5","key":"10.1016\/j.bone.2025.117698_bb0155","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/jbmr.4254","article-title":"Response of the <scp>ENPP1<\/scp> -deficient skeletal phenotype to Oral phosphate supplementation and\/or enzyme replacement therapy: comparative studies in humans and mice","volume":"36","author":"Ferreira","year":"2021","journal-title":"J. Bone Miner. Res."},{"issue":"10189","key":"10.1016\/j.bone.2025.117698_bb0160","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":"10.1016\/j.bone.2025.117698_bb0165","doi-asserted-by":"crossref","DOI":"10.1007\/s40620-023-01884-6","article-title":"The use of burosumab to treat autosomal-recessive hypophosphatemic rickets type 2: rationale and a first clinical experience","author":"Parolin","year":"2024","journal-title":"J. Nephrol."},{"issue":"3","key":"10.1016\/j.bone.2025.117698_bb0170","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0022-3476(78)80427-2","article-title":"Idiopathic infantile arterial calcification in siblings: radiologic diagnosis and successful treatment","volume":"92","author":"Meradji","year":"1978","journal-title":"J. Pediatr."},{"issue":"8","key":"10.1016\/j.bone.2025.117698_bb0175","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1002\/jbmr.4315","article-title":"<scp>INZ-701<\/scp> prevents ectopic tissue calcification and restores bone architecture and growth in <scp>ENPP1<\/scp> -deficient mice","volume":"36","author":"Cheng","year":"2021","journal-title":"J. Bone Miner. Res."},{"issue":"1","key":"10.1016\/j.bone.2025.117698_bb0180","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10006","article-title":"ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy","volume":"6","author":"Albright","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bone.2025.117698_bb0185","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.035691","article-title":"ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy (GACI)","author":"Khan","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.bone.2025.117698_bb0190","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.012765","article-title":"Mutant Enpp1asj mice as a model for generalized arterial calcification of infancy","author":"Li","year":"2013","journal-title":"Dis. Model. Mech."},{"issue":"11","key":"10.1016\/j.bone.2025.117698_bb0195","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.15252\/emmm.201707532","article-title":"Oral administration of pyrophosphate inhibits connective tissue calcification","volume":"9","author":"Dedinszki","year":"2017","journal-title":"EMBO Mol. Med."},{"issue":"5","key":"10.1016\/j.bone.2025.117698_bb0200","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1161\/CIRCRESAHA.111.247965","article-title":"Genetics in arterial calcification","volume":"109","author":"Rutsch","year":"2011","journal-title":"Circ. Res."},{"issue":"4","key":"10.1016\/j.bone.2025.117698_bb0205","doi-asserted-by":"crossref","first-page":"4S27","DOI":"10.1016\/S0929-693X(24)00154-4","article-title":"Autosomal recessive hypophosphatemic rickets type 2 due to ENPP1 deficiency (ARHR2)","volume":"31","author":"Edouard","year":"2024","journal-title":"Arch. Pediatr."},{"issue":"8","key":"10.1016\/j.bone.2025.117698_bb0210","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.4103\/njcp.njcp_2046_21","article-title":"Comparative analysis of fibroblast growth Factor-23 as a correlate of cardiovascular disease among individuals with chronic kidney disease, hypertensives, and healthy controls","volume":"25","author":"Abiola","year":"2022","journal-title":"Niger. J. Clin. Pract."},{"issue":"2","key":"10.1016\/j.bone.2025.117698_bb0215","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0002-9440(10)63996-X","article-title":"PC-1 Nucleoside Triphosphate Pyrophosphohydrolase Deficiency in Idiopathic Infantile Arterial Calcification","volume":"158","author":"Rutsch","year":"2001","journal-title":"Am. J. Pathol."}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328225003102?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328225003102?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:25:01Z","timestamp":1780557901000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S8756328225003102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":43,"alternative-id":["S8756328225003102"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2025.117698","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Autosomal recessive hypophosphatemic rickets type 2 (ARHR2): Is phosphate supplementation safe?","name":"articletitle","label":"Article Title"},{"value":"Bone","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bone.2025.117698","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117698"}}