Tumor-Induced Osteomalacia

Calcif Tissue Int. 2021 Jan;108(1):128-142. doi: 10.1007/s00223-020-00691-6. Epub 2020 Jun 5.


Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral production of fibroblast growth factor 23 (FGF23). The hallmark biochemical features include hypophosphatemia due to renal phosphate wasting, inappropriately normal or frankly low 1,25-dihydroxy-vitamin D, and inappropriately normal or elevated FGF23. TIO is caused by typically small, slow growing, benign phosphaturic mesenchymal tumors (PMTs) that are located almost anywhere in the body from the skull to the feet, in soft tissue or bone. The recent identification of fusion genes in a significant subset of PMTs has provided important insights into PMT tumorigenesis. Although management of this disease may seem straightforward, considering that complete resection of the tumor leads to its cure, locating these often-tiny tumors is frequently a challenge. For this purpose, a stepwise, systematic approach is required. It starts with thorough medical history and physical examination, followed by functional imaging, and confirmation of identified lesions by anatomical imaging. If the tumor resection is not possible, medical therapy with phosphate and active vitamin D is indicated. Novel therapeutic approaches include image-guided tumor ablation and medical treatment with the anti-FGF23 antibody burosumab or the pan-FGFR tyrosine kinase inhibitor, BGJ398/infigratinib. Great progress has been made in the diagnosis and treatment of TIO, and more is likely to come, turning this challenging, debilitating disease into a gratifying cure for patients and their providers.

Keywords: FGF23; Hypophosphatemia; Tumor-induced osteomalacia.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / genetics
  • Humans
  • Hypophosphatemia*
  • Neoplasms, Connective Tissue* / complications
  • Osteomalacia* / etiology
  • Paraneoplastic Syndromes* / etiology
  • Phenylurea Compounds / therapeutic use
  • Phosphates
  • Pyrimidines / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • FGF23 protein, human
  • Phenylurea Compounds
  • Phosphates
  • Pyrimidines
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • infigratinib
  • burosumab

Supplementary concepts

  • Oncogenic osteomalacia