Endocrinology and Metabolism

Review Article

Mineral, Bone & Muscle
Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia: Nobuaki Ito, Naoko Hidaka, Hajime Kato; Endocrinol Metab. 2024;39(2):255-261. Published online March 11, 2024; DOI: https://doi.org/10.3803/EnM.2023.1908

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Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.

Citations

Citations to this article as recorded by

Paraneoplastic endocrine syndromes: a contemporary overview
Juan Eduardo Quiroz-Aldave, Jacsel Suarez-Rojas, Elman Rolando Gamarra-Osorio, Katia Rivera-Fabián, María Del Carmen Durand-Vásquez, Luis Alberto Concepción-Urteaga, José Paz-Ibarra, Marcio José Concepción-Zavaleta
Expert Review of Endocrinology & Metabolism.2025; 20(1): 51. CrossRef
Excess fibroblast growth factor 23 in alcoholic osteomalacia is derived from the bone
Naoko Hidaka, Yuko Oyama, Minae Koga, Naoki Kondo, Yoichi Yasunaga, Taketoshi Shimakura, Noriaki Yamamoto, Hideaki E Takahashi, Yoichi Iwafuchi, So Watanabe, Soichiro Kimura, Yoshitomo Hoshino, Hajime Kato, Yuka Kinoshita, Hiroshi Kobayashi, Takeyuki Tana
JBMR Plus.2025;[Epub] CrossRef
Acquired hypophosphatemic osteomalacia: case series from a Peruvian referral center (1999–2023)
José Paz-Ibarra, Sofía Sáenz-Bustamante, Manuel Inostroza-Fernández, Paola Sifuentes Hermenegildo, Liliana Ancajima Lescano, Marcio Concepción-Zavaleta, Alejandro Román-González, Alfredo Adolfo Reza-Albarrán
Archives of Osteoporosis.2024;[Epub] CrossRef

Case Report

A Case of Tumor-induced Osteomalacia with Elevated Fibroblast Growth Factor-23.: Hae Sung Kim, Hyun Seung Jung, Hee Jung Kim, Sung Yeon Kim, Sang Wan Kim, Chan Soo Shin, Chong Jai Kim, Seong Yeon Kim; J Korean Endocr Soc. 2007;22(2):142-148. Published online April 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.2.142

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Abstract PDF

Tumor-induced osteomalacia (TIO), a paraneoplastic disease, is characterized by hypophosphatemia, and caused by renal phosphate wasting inappropriately, normal or decreased 1, 25(OH)2D3 production, and defective calcification of cartilage and bone. Because the removal of the responsible tumor normalizes phosphate metabolism, unidentified humoral phosphaturic factors (phosphatonin) are believed to be responsible for this syndrome. These factors include fibroblast growth factor (FGF)-23, secreted frizzled-related protein-4 and matrix extracellular phosphoglycoprotein. However, no case of TIO producing FGF-23 has been clearly reported in Korea. Herein, a case of TIO producing FGF-23 in a 45-year-old woman is reported. The patient presented with a large tumor on her buttock, with severe bone and muscle pain. A histological examination of the tumor revealed a mixed connective tissue tumor, consisting of deposition of calcified materials and surrounding primitive spindle cells, with prominent vascularity. Whether FGF-23 is a secreted factor, as well as its levels of expression in tumors were investigated. An immunohistochemical study showed the tumor cells to be FGF-23 positive. Furthermore, the levels of serum FGF-23 were extremely high and an RT-PCR analysis, using total RNA from the tumor, revealed the abundant expression of FGF-23 mRNA. After removal of the tumor, all the biochemical and hormonal abnormalities disappeared, with marked symptomatic improvement.

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