Tumour induced osteomalacia: a diagnostic challenge and its implications in orthopaedic surgery


  • Shivkumar Santpure Department of Orthopedics, Santpure Hospital, Aurangabad, Maharashtra, India
  • Ansari Muqtadeer Abdul Aziz Department of Orthopedics, Government Medical College and Hospital, Aurangabad, Maharashtra, India
  • Gagandeep Mahi Department of Orthopedics, Government Medical College and Hospital, Aurangabad, Maharashtra, India
  • Lokesh Kumar Yogi Department of Orthopedics, Government Medical College and Hospital, Aurangabad, Maharashtra, India




TIO, FGF-23, Osteomalacia


Tumor-induced osteomalacia (TIO) is a paraneoplastic phenomenon which encompasses a wide array of clinical features ranging from musculoskeletal pain to pathological fractures. An excess of fibroblast growth factor 23 (FGF23) is produced which is a parahormone with its target receptors in proximal convoluted tubules of glomeruli. This results in decreased blood phosphate levels and decreased hydroxylation of 25-OH vitamin-D, ultimately leading to osteomalacia. Compliance with medical treatment is unsatisfactory and tedious owing to repeated dosing schedules and overwhelming side effects. Surgical excision of the lesion is the only suitable treatment.


Liu S, Quarles LD. How fibroblast growth factor 23 works. J Am Society Nephrology. 2007;18:1637-47.

Alonso G, Varsavsky M. Tumour-induced osteomalacia: an emergent paraneoplastic syndrome. Endocrinology Nutricion. 2016;63:181-6.

Weidner N. Review and update: oncogenic osteomalacia rickets. Ultra-structural Pathology. 1991;15:317-33.

Perwad F, Portale AA. Vitamin D metabolism in the kidney: regulation by phosphorus and fibroblast growth factor 23. Molecular Cellular Endocrinology. 2011;347:17-24.

Pal R, Bhadada SK, Singhare A, Bhansali A, Kamalanathan S, Chadha M, et al. Tumor-induced osteomalacia: experience from three tertiary care centers in India. Endocr Connect. 2019;8(3):266-76.

Jung GH, Kim JD, Cho Y, Chung SH, Lee JH, Sohn KR. A 9 months old phosphate uric mesenchymal tumor mimicking the intractable rickets. J Pediatr Orthop B. 2010;19:127-32.

ADHR Consortium. Autosomal dominant hypo-phosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26(3):345-8.

White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, et al. The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. J Clin Endocrinol Metab. 2001;86(2):497-500.

Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res Off J Am Soc Bone Miner Res. 2004;19(3):429-35.

Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):53-77.

Hannan FM, Athanasou NA, Teh J, Gibbons CLMH, Shine B, Thakker RV. Oncogenic hypo-phosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1. Eur J Endocrinol Eur Fed Endocr Soc. 2008;158 (2):265-71.

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF-23. Nature. 2006;444(7120):770-4.

Hu FK, Yuan F, Jiang CY, Lv DW, Mao BB, Zhang Q, et al. Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphate uric mesenchymal tumor mixed with connective tissue variants and review of the literature. Chin J Cancer. 2011;30(11):794-804.

Mark B, Gridley D, Lal S, Geetha R, Feiz I. Phosphat uric mesenchymal tumor of the brain without tumor-induced osteomalacia in an 8 years old girl: case report. J Neurosurg Pediatr. 2016;17:573-7.

Uramoto N, Furukawa M, Yoshizaki T. Malignant phosphate uric mesenchymal tumor, mixed connective tissue variant of the tongue. Auris Nasus Larynx. 2009;36(1):104-5.

Ledford CK, Zelenski NA, Cardona DM, Brigman BE, Eward WC. The phosphate uric mesenchymal tumor: why is definitive diagnosis and curative surgery often delayed. Clin Orthop. 2013;471(11):3618-25.

Beur JSM. Tumor-induced osteomalacia. JAMA. 2005;294(10):1260-7.

Hautmann AH, Schroeder J, Wild P, Hautmann MG, Huber E, Hoffstetter P, et al. Tumor-induced osteomalacia: increased level of FGF-23 in a patient with a phosphate uric mesenchymal tumor at the tibia expressing periostin. Case Rep Endocrinol. 2014;2014:729387.

Agrawal K, Bhadada S, Mittal BR, Shukla J, Sood A, Bhattacharya A, et al. Comparison of 18F-FDG and 68Ga Dotatate PET/CT in localization of tumor causing oncogenic osteomalacia. Clin Nucl Med. 2015;40(1):6-10.

Hesse E, Rosenthal H, Bastian L. Radiofrequency ablation of a tumor causing oncogenic osteomalacia. N Engl J Med. 2007;357 (4):422-4.

Khosravi A, Cutler CM, Kelly MH, Chang R, Royal RE, Sherry RM, et al. Determination of the elimination half-life of fibroblast growth factor-23. J Clin Endocrinol Metab. 2007;92(6):2374-7.

Folpe AL, Smith FJC, Billings SD, Bisceglia M, Bertoni F, Cho JY, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 2004;28 (1):1-30.

Ogura E, Kageyama K, Fukumoto S, Yagihashi N, Fukuda Y, Kikuchi T, et al. Development of tumor-induced osteomalacia in a subcutaneous tumor. World J Surg Oncology. 2016;14:4.

Prader A, Illig R, Uehlinger E, Stalder G. Rickets following bone tumor. Helvetica Paediatrica Acta. 1959;14:554-65.

Seufert J, Ebert K, Muller J, Eulert J, Hendrich C, Werner E, et al. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med. 2001;345(26):1883-8.

Andreopoulou P, Millo C, Reynolds J, Kelly M, Brillante B, Wodajo FM, et al. Multimodality Diagnosis and Treatment of Tumor Induced Osteomalacia. Endocrine Reviews. 2010;31(1):OR08-6S49.

Deep NL, Cain RB, McCullough AE, Hoxworth JM, Lal D. Sino nasal phosphate uric mesenchymal tumor: case report and systematic review. Allergy Rhinol Provid RI. 2014;5(3):1627.

Aono Y, Yamazaki Y, Yasutake J, Kawata T, Hasegawa H, Urakawa I, et al. Therapeutic effects of anti-FGF23 antibodies in hypo-phosphatemi crickets/osteomalacia. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;24 (11):1879-88.