Tumor-induced osteomalacia (TIO) is a rare paraneoplastic form of renal
phosphate wasting that results in severe hypophosphatemia, a defect in vitamin
D metabolism, and osteomalacia. This debilitating disorder is illustrated
by the clinical presentation of a 55-year-old woman with progressive fatigue,
weakness, and muscle and bone pain with fractures. After a protracted clinical
course and extensive laboratory evaluation, tumor-induced osteomalacia was
identified as the basis of her clinical presentation. In this article, the
distinctive clinical characteristics of this syndrome, the advances in diagnosis
of TIO, and new insights into the pathophysiology of this disorder are discussed.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
A, Octreotide scan demonstrating small mesenchymal tumor in the head
of the humerus (arrowhead). B, Hemangiopericytoma with numerous pericytes
and vascular channels (hematoxylin and eosin stain). Original magnification
×100. C, Bone biopsy with Goldner stain. Excessive osteoid or unmineralized
bone matrix composed mainly of collagen stains pink. Mineralized bone stains
blue. Normal bone usually has a very thin, barely visible layer of osteoid.
The presence of excessive osteoid is indicative of osteomalacia. This bone
biopsy demonstrates severe osteomalacia. Original magnification ×20.
In tumor-induced osteomalacia, fibroblast growth factor 23 (FGF-23)
and other phosphatonins ectopically produced by a mesenchymal tumor lead to
excess circulating FGF-23 levels. In autosomal dominant hypophosphatemic rickets,
FGF-23 excess results from mutations in the FGF-23 gene
that render the protein resistant to cleavage and inactivation. In X-linked
hypophosphatemia, the mechanism of FGF-23 excess is more speculative; mutations
in the PHEX endopeptidase (presumably located on
osteoblasts or osteocytes), are thought to either directly or indirectly result
in FGF-23 excess by interfering with processing and inactivation of FGF-23.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 47
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.