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Tumor-Induced Osteomalacia

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Abstract

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.

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Authors and Affiliations

  1. Endocrinology Department, School of Medicine, Pontificia Universidad Católica de Chile, Av. Diagonal Paraguay 362, Cuarto piso, Santiago, Chile

    Pablo Florenzano & Macarena Jimenez

  2. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Iris R. Hartley

  3. Skeletal Disorders and Mineral Homeostasis Section, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    Iris R. Hartley, Kelly Roszko, Rachel I. Gafni & Michael T. Collins

  4. Skeletal Disorders and Mineral Homeostasis Section, NIDCR, NIH, 30 Convent Drive, Building 30, Room 228, MSC 4320, Bethesda, MD, 20892-4320, USA

    Michael T. Collins

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  1. Pablo Florenzano
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The NIDCR receives financial support from QED Pharma to study BGJ398 in tumor-induced osteomalacia. The Pontificia Universidad Católica de Chile (PF, MJ) receives research support from Ultragenyx Pharmaceutical, Inc. for research related to hypophosphatemic rickets. Work in the Laboratories of IH, KR, RG, MC is supported by the Intramural Research Program of the NIH, NIDCR.

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Florenzano, P., Hartley, I.R., Jimenez, M. et al. Tumor-Induced Osteomalacia. Calcif Tissue Int 108, 128–142 (2021). https://doi.org/10.1007/s00223-020-00691-6

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