title: Tumor-induced osteomalacia.
abstract: Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed.
authors.affiliation: Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Chong
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
mesh_terms: D000465:Algorithms; D000818:Animals; D003937:Diagnosis, Differential; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy; D009372:Neoplasms, Connective Tissue / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D010018:Osteomalacia / Q000175:diagnosis / Q000209:etiology / Q000473:pathology / Q000628:therapy; D010257:Paraneoplastic Syndromes; D010710:Phosphates / Q000378:metabolism / Q000502:physiology
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23