{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:59:13Z","timestamp":1788580753972,"version":"build-2803163510"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["ZIADE000649"],"award-info":[{"award-number":["ZIADE000649"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tumor\u2010induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by ectopic production of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMTs). Acting on renal tubule cells, excess FGF23 decreases phosphate reabsorption and 1,25\u2010dihydroxy\u2010vitamin D (1,25D) production, leading to hypophosphatemia, impaired bone mineralization, pain, and fractures. Fibronectin 1\u2010fibroblast growth factor receptor 1 (FN1\u2010FGFR1) gene fusions have been identified as possible drivers in up to 40% of resected PMTs. Based on the presumptive role of FGFR1 signaling by chimeric FN1\u2010FGFR1 proteins, the effectiveness of infigratinib, a FGFR1\u20103 tyrosine kinase inhibitor, was studied in an open\u2010label, single\u2010center, phase 2 trial. The primary endpoint was persistent normalization of blood phosphate and FGF23 after discontinuation. Four adults with TIO (two nonlocalized, two nonresectable PMTs) were treated with daily infigratinib for up to 24\u2009weeks. All patients had a favorable biochemical response that included reduction in intact FGF23, and normalization of blood phosphate and 1,25D. However, these effects disappeared after drug discontinuation with biochemistries returning to baseline; no patients entered biochemical remission. In the two patients with identifiable tumors, 68Gallium (68Ga)\u2010DOTATATE and 18Fluoride (18F)\u2010Fluorodeoxyglucose (FDG) PET\/CT\u00a0scans showed a decrease in PMT activity without change in tumor size. Patients experienced mild to moderate, treatment\u2010related, dose\u2010limiting adverse events (AEs), but no serious AEs. Three patients had dose interruptions due to AEs; one patient continued on a low dose for the entire 24\u2009weeks and one patient stopped therapy at 17\u2009weeks due to an AE. The study closed early due to a failure to meet the primary endpoint and a higher\u2010than\u2010expected incidence of ocular AEs. Infigratinib treatment lowered FGF23, increased blood phosphate, and suppressed PMT activity, confirming the role of FGFR signaling in PMT pathogenesis. However, treatment\u2010related AEs at efficacy doses and disease persistence on discontinuation support restricting the use of infigratinib to patients with life\u2010limiting metastatic PMTs. \u00a9 2022 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10661","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T03:48:35Z","timestamp":1654832915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Infigratinib Reduces Fibroblast Growth Factor 23 (\n                    <scp>FGF23)<\/scp>\n                    and Increases Blood Phosphate in\n                    <scp>Tumor\u2010Induced<\/scp>\n                    Osteomalacia"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-3284","authenticated-orcid":false,"given":"Iris R.","family":"Hartley","sequence":"first","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-5299","authenticated-orcid":false,"given":"Kelly L.","family":"Roszko","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobai","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Epidemiology, Clinical Center, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Pozo","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Streit","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaydira","family":"del Rivero","sequence":"additional","affiliation":[{"name":"National Cancer Institute, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Teresa","family":"Magone","sequence":"additional","affiliation":[{"name":"Ophthalmology Consult Services Section National Eye Institute (NEI)  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaele R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department, Clinical Center, National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roo","family":"Vold","sequence":"additional","affiliation":[{"name":"QED Therapeutics  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl L.","family":"Dambkowski","sequence":"additional","affiliation":[{"name":"QED Therapeutics  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-7644","authenticated-orcid":false,"given":"Michael T.","family":"Collins","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3491","authenticated-orcid":false,"given":"Rachel I.","family":"Gafni","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2019.07.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"Folpe AL Fanburg\u2010Smith JC Billings SD et al. Most osteomalacia\u2010associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature.Am J Surg Pathol.2004;28(1):1\u201030.","DOI":"10.1097\/00000478-200401000-00001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00691-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.44"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3219"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10178"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2528"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4184"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4233"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcpc1104567"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-19-0341"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.137"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4465"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.5009"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103164"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.2048"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0229"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.08.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2020399"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)93112-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.08.026"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0416-4"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712361105"},{"key":"e_1_2_9_25_1","unstructured":"QED Therapeutics Inc.Truseltiq (infigratinib) [package insert]. U.S. Food and Drug Administration website.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214622s000lbl.pdf. Accessed June 18 2022."}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10661","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm4.10661","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm4.10661","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:57:21Z","timestamp":1710410241000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/7478966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/jbm4.10661"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10661","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JBM4.10661\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10661\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10661\/v1\/review2","asserted-by":"object"}]},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"assertion":[{"value":"2022-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10661"}}