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Besides reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, FGF-23 inhibits the renal 1\u03b1-hydroxylase and stimulates the 24-hydroxylase, and it appears to reduce parathyroid hormone (PTH) secretion in short-term studies. FGF-23 synthesis and secretion by osteocytes and osteoblasts is upregulated through 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and through an increased dietary phosphate intake. FGF-23 levels are elevated or inappropriately normal in patients with tumor-induced osteomalacia and several inherited hypophosphatemic disorders, but the most significant increases are found in patients with chronic kidney disease (CKD). During the early stages of CKD, increased FGF-23 production enhances urinary phosphate excretion and thus prevents the development of hyperphosphatemia, reduces the circulating levels of 1,25(OH)2D3, and therefore contributes to the development of secondary hyperparathyroidism. In patients with end-stage renal disease (ESRD), FGF-23 levels can be extremely high and were shown to be predictors of bone mineralization, left ventricular hypertrophy, vascular calcification, and mortality. It remains to be determined, however, whether FGF-23 represents simply a sensitive biomarker of an abnormal phosphate homeostasis or has, independent of serum phosphate levels, potentially negative \u201coff-target\u201d effects. Nonetheless, reducing the production and\/or the biologic activity of FGF-23 may be an important therapeutic goal for this patient population. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.170","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T14:53:18Z","timestamp":1278427998000},"page":"2091-2097","source":"Crossref","is-referenced-by-count":142,"title":["FGF-23: More than a regulator of renal phosphate handling?"],"prefix":"10.1093","volume":"25","author":[{"given":"Harald","family":"J\u00fcppner","sequence":"first","affiliation":[{"name":"Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Wolf","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro B.","family":"Salusky","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,6,30]]},"reference":[{"key":"2024020320101064100_bib1","first-page":"920","volume-title":"Endocrinology","author":"Potts","year":"1996"},{"key":"2024020320101064100_bib2","volume-title":"Endocrinology","author":"Gardella","year":"2010","edition":"5th ed"},{"key":"2024020320101064100_bib3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/B978-012286551-0\/50009-9","volume-title":"Pediatric Bone: Biology and Diseases","author":"St-Arnaud","year":"2003"},{"key":"2024020320101064100_bib4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1210\/er.2005-0019","article-title":"The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23","volume":"27","author":"White","year":"2006","journal-title":"Endocr Rev."},{"key":"2024020320101064100_bib5","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1172\/JCI36479","article-title":"Endocrine functions of bone in mineral metabolism regulation","volume":"118","author":"Quarles","year":"2008","journal-title":"J Clin Invest."},{"key":"2024020320101064100_bib6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1097\/MNH.0b013e3282fd6e5b","article-title":"PHEX, FGF23, DMP1 and beyond","volume":"17","author":"Strom","year":"2008","journal-title":"Curr Opin Nephrol Hypertens."},{"key":"2024020320101064100_bib7","volume-title":"The Kidney","author":"J\u00fcppner","year":"2008"},{"key":"2024020320101064100_bib8","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"White KE, Evans WE, O\u00b4Riordan JLH, Speer MC, Econs MJ, Lorenz-Depiereux B, Grabowski M, Meittinger T, Strom TM. 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