Tumor-induced osteomalacia is an acquired paraneoplastic disease of the bone that occurs due to oversecretion of the phosphaturic hormone FGF23 by a functioning tumor. Clinical features are similar to other causes of osteomalacia such as bone pains, bone deformities, and bone weakness. The underlying causative tumor is usually asymptomatic. Laboratory hallmarks are hypophosphatemia, phosphaturia, and low 1,25 dihydroxy vitamin D. The causative tumor must be located by a combination of physical examination and functional and anatomical imaging tests. Cure is possible and prognosis is favorable when the causative tumor is completely excised. When surgery is not possible or carries significant postoperative morbidity, a variety of pharmacologic agents and tumor-directed therapies can be employed.
KeywordsTumor-induced osteomalacia Oncogenic osteomalacia Paraneoplastic syndrome Phosphatonin Fibroblast growth factor 23
1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid octreotate
1,4,7,10-Tetraazacyclododecane-N,N,N,N-tetraacetic-acid-D-Phe1 -Tyr3 –octreotide
Fibroblast growth factor
Matrix extracellular phosphoglycoprotein
Magnetic resonance imaging
Positron emission tomography
Phosphaturic mesenchymal tumor
Phosphaturic mesenchymal tumor, mixed connective tissue variant
Secreted frizzled-related protein 4
Single photon emission computed tomography
Tubular maximum reabsorption of phosphate corrected for glomerular filtration rate
Tubular phosphate reabsorption
- 6.Basu S, Fargose P. 177Lu-DOTATATE PRRT as promising new treatment approach in recurrent skull base phosphaturic mesenchymal tumor causing paraneoplastic oncogenic osteomalacia: a potential therapeutic application of PRRT beyond NET. J Nucl Med Technol. First published online September 15. 2016; https://doi.org/10.2967/jnmt.116.177873.CrossRefGoogle Scholar
- 8.Carpenter TO, Miller PD, Weber TJ, Peacock M, Ruppe MD, Insogna K, Osei S, Luca D, Skrinar A, San Martin J, Jan de Beur S. Effects of KRN23, an ant-FGF23 antibody on patients with tumor-induced osteomalacia and epidermal nevus syndrome: results from an ongoing phase 2 study. 2016. http://www.ultragenyx.com/file.cfm/22/docs/Carpenter_2016_ASBMR_Oral_TIO_Final.pdf. Accessed 8 Jan 2017.
- 12.Elderman JH, Wabbijn M, de Jongh F. Hypophosphataemia due to FGF-23 producing B cell non-Hodgkin’s lymphoma. BMJ Case Rep. 2016; https://doi.org/10.1136/bcr-2015-213954.
- 15.Fukumoto S. Anti-fibroblast growth factor 23 antibody therapy. Curr Opin Nephrol Hypertens. 2014a;23(4):346–51. https://doi.org/10.1097/01.mnh.0000447012.98357.da.CrossRefPubMedGoogle Scholar
- 20.Haeusler G, Freilinger M, Dominkus M, Egerbacher M, Amann G, Kolb A, et al. Tumor-induced hypophosphatemic rickets in an adolescent boy—clinical presentation, diagnosis, and histological findings in growth plate and muscle tissue. J Clin Endocrinol Metab. 2010;95(10):4511–7. https://doi.org/10.1210/jc.2010-0543.CrossRefPubMedGoogle Scholar
- 25.Hu F, Jiang C, Zhang Q, Shi H, Wei L, Wang Y, et al. Quantitative ELISA-like immunohistochemistry of fibroblast growth factor 23 in diagnosis of tumor-induced osteomalacia and clinical characteristics of the disease. Dis Markers. 2016:3176978. https://doi.org/10.1155/2016/3176978.CrossRefGoogle Scholar
- 27.Jain AS, Shelley S, Muthukrishnan I, Kalal S, Amalachandran J, Chandran S. Diagnostic importance of contrast enhanced F-fluorodeoxyglucose positron emission computed tomography in patients with tumor induced osteomalacia: our experience. Indian J Nucl Med. 2016;31(1):14–9. https://doi.org/10.4103/0972-3919.172344.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Jing H, Li F, Zhong D, Zhuang H. 99mTc-HYNIC-TOC (99mTc-Hydrazinonicotinyl-Tyr3-Octreotide) scintigraphy identifying two separate causative tumors in a patient with tumor-induced osteomalacia (TIO). Clin Nucl Med. 2013;38(8):664–7. https://doi.org/10.1097/RLU.0b013e3182996293.CrossRefPubMedGoogle Scholar
- 40.Ratanasuwan T, Chetsurakarn S, Ongphiphadhanakul B, Damrongkitchaiporn S. A case report of tumor-induced osteomalacia: eight year followed-up. J Med Assoc Thail. 2008;91(12):1900–3.Google Scholar
- 43.Sandoval MAS, Palermo MA, Carrillo R, Bundoc R, Carnate JM, Galsim R. Successful treatment of tumour-induced osteomalacia after resection of an oral peripheral ossifying fibroma. BMJ Case Rep. 2017; https://doi.org/10.1136/bcr-2016-218637.
- 51.Wang X, Mu Y. Emphasis should be placed on the diagnosis and therapy of tumor induced osteomalacia. Chin Med J. 2011;124(2):163–5. https://doi.org/10.3760/cma.j.issn.0366-6999.2011.02.001.CrossRefPubMedGoogle Scholar
- 54.Yavropoulou MP, Gerothanasi N, Frydas A, Triantafyllou E, Poulios C, Hytiroglou P, et al. Tumor-induced osteomalacia due to a recurrent mesenchymal tumor overexpressing several growth factor receptors. Endocrinol Diab Metab Case Rep. 2015; https://doi.org/10.1530/EDM-15-0025.
- 56.Zhang X, Yu Z, Tonghua L, Yao B, Zhaohuan L. Mesenchymoma associated with vitamin D-resistant hypophosphatemic osteomalacia: case report and review of literature. Chin Med J. 1980;93(6):391–9.Google Scholar