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 1-α-hydroxylation of 25-hydroxyvitamin D leading to hypophosphatemia and low levels of 1,25 dihydroxy vitamin D. A step-wise approach utilizing functional imaging (FDG-PET and octreotide scintigraphy) followed by anatomical imaging (CT and/or MRI), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be found, medical treatment with phosphate supplements and active vitamin D (calcitriol or alfacalcidiol) 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.