Tumor-induced osteomalacia

Abstract

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.

Keywords: Fibroblast growth factor 23; Molecular mechanism; Oncogenic osteomalacia; Treatment; Tumor-induced osteomalacia.

Fig. 1

Mechanism of tumor-induced osteomalacia. FGF-23, fibroblast growth factor 23; MEPE, matrix extracellular phosphoglycoprotein.

Fig. 2

Flow chart of tumor-induced osteomalacia diagnosis and treatment. TIO, tumor-induced osteomalacia; TMP/GFR, tubular maximum phosphate reabsorption per glomerular filtration rate; PTH, parathyroid hormone; SPECT, single photon emission computed tomography; PET/CT, positron emission tomography/computed tomography; MRI, magnetic resonance imaging; CT, computed tomography.