{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:44:32Z","timestamp":1793472272983,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K09018"],"award-info":[{"award-number":["JP18K09018"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Excess fibroblast growth factor 23 (FGF23), a mature osteocyte-derived phosphaturic hormone, causes chronic hypophosphatemic osteomalacia in adults. This rare condition was recently reported in 2 alcoholic patients, with marked improvement upon cessation of alcohol consumption, suggesting a link between alcohol and FGF23-related hypophosphatemia within the highly limited cases. This study aimed to investigate whether the source of excess FGF23 in alcohol-induced FGF23-related hypophosphatemic osteomalacia is the bone or the other organs. To achieve this goal, an immunohistochemical approach for the bone obtained from a patient was employed. Initial attempts at quantifying FGF23 in the bone using conventional immunohistochemistry (IHC) faced issues in quantifiability and sensitivity for low FGF23 expression levels. Therefore, next-generation IHC with phosphor-integrated dots (PIDs) was applied, which enabled the quantification of FGF23 expression in the bone across a broad range. Preliminary analyses using IHC with PIDs on normal bone samples (n\u2009=\u200912) provided a reference level (154.5 PID particles per cell). IHC with PIDs quantified suppressed physiological FGF23 expression in the bone samples from 3 patients with tumor-induced osteomalacia, where FGF23 is oversecreted from a tumor (13.6 PID particles per cell). Subsequently, bone samples obtained from a 70-yr-old male with alcohol-induced FGF23-related hypophosphatemic osteomalacia were analyzed, showing a higher number of PID particles per cell (199.4 PID particles per cell) than the reference level. This study suggests that orthotopic, bone-derived FGF23 is implicated in alcohol-induced FGF23-related hypophosphatemic osteomalacia. Furthermore, the study also demonstrated that highly sensitive IHC with PIDs could aid in the differential diagnosis of FGF23-related hypophosphatemia of unknown origin. Specifically, a bone sample with a low number of PID particles per cell indicates an excess ectopic secretion of FGF23; a bone sample with a normal to high number of PID particles per cell indicates an excess orthotopic secretion of FGF23.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf010","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T19:00:19Z","timestamp":1737054019000},"source":"Crossref","is-referenced-by-count":3,"title":["Excess fibroblast growth factor 23 in alcoholic osteomalacia is derived from the bone"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5450-2247","authenticated-orcid":false,"given":"Naoko","family":"Hidaka","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]},{"name":"Osteoporosis Center, The University of Tokyo Hospital , Tokyo 113-8655 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University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]},{"name":"Osteoporosis Center, The University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Osteoporosis Center, The University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]},{"name":"Department of Orthopedic Surgery, The University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Sensory and Motor System Medicine, Surgical Sciences, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ushiku","sequence":"additional","affiliation":[{"name":"Department of 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