Endocrinology and Metabolism

Review Articles

Mineral, Bone & Muscle
Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease: Yosuke Nakagawa, Hirotaka Komaba; Endocrinol Metab. 2024;39(3):407-415. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1978

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Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

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Endocrine disorders linked to chronic kidney disease: Mechanisms and clinical implications
Marcio J Concepción-Zavaleta, Jenyfer M Fuentes-Mendoza, Elida P López-Ramírez, Jesús A Martínez-García, Luis A Concepción-Urteaga, José Paz-Ibarra
World Journal of Nephrology.2026;[Epub] CrossRef
Diabetes progression and its association with fracture risk in type 2 diabetes
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Pre-Parathyroidectomy PTH as an Integrated Biomarker of Glandular Remodeling and Skeletal Turnover in Secondary Hyperparathyroidism
Min-Tser Liao, Chia-Chao Wu, Yi-Chou Hou, Kuo-Wang Tsai, Li-Jane Shih, Kuo-Cheng Lu, Chien-Lin Lu
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Allopurinol has no effect on calcitriol or other CKD-MBD biomarkers: a randomized double-blind study
Tiago E Costa, Julia C Lauar, Mariana L R Innecchi, Luiza Karla R P Araujo, Venceslau A Coelho, Luciene M dos Reis, Rosa M A Moysés, Rosilene M Elias
Journal of the Endocrine Society.2026;[Epub] CrossRef
Combination therapy with nutritional vitamin D and calcimimetics in secondary hyperparathyroidism: a mechanism-based approach to restoring PTH regulation
Chien-Lin Lu, Yi-Chou Hou, Chia-Chao Wu, Te-Chao Fang, Cai-Mei Zheng, Kuo-Cheng Lu
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O.I. Nishkumai, O.B. Iaremenko, V.E. Kondratiuk, Mike K.S. Chan, M.B. Dzhus, I.V. Rudenko, A.B. Bezrodnyi
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Association Between Serum Parathyroid Hormone Levels and Femoral Bone Mineral Density in Patients with Chronic Kidney Disease Stage 3
Laura Montaño-Azor, Petra Cantón Guerrero, María Ángeles Jiménez Sánchez, María José Jiménez Moral, Raquel María García-Sáez, María Encarnación Rodríguez-Ortiz, Mariano Rodríguez, Victoria Pendón-Ruiz de Mier, Esperanza Romero-Rodríguez
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Gene expression and hormonal signaling in osteoporosis: from molecular mechanisms to clinical breakthroughs
Gurinderdeep Singh, Ronald Darwin, Krishna Chandra Panda, Shaikh Amir Afzal, Shashwat Katiyar, Ram C. Dhakar, Sangeetha Mani
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Amira Hassan Elsaid Dohuim, Medhat Abd El Megeid Ghazy, Nahla Abdel Aziz Nosair, Amr Khalifa Hussien
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Hanine AlArab, Anna Zenno, Melinda Pierce
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Serum Calcium as a Determinant of Fibroblast Growth Factor 23 Levels in Patients With Primary Hyperparathyroidism and Graves’ Disease
Hiroyuki Yamashita, Yusuke Mori, Yasuo Imanishi, Hisakazu Shindo, Daisuke Tatsushima, Seigo Tachibana, Takashi Fukuda, Hiroshi Takahashi, Yuji Nagayama, Shinya Satoh
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Bin Xu, Rui Ma, Yuqiang Wu, Chi Liu, Xiangrong Song
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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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Abstract PDF PubReader ePub

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

Surgical management strategies and clinical outcomes of cutaneous skeletal hypophosphatemia syndrome: a case series
Yi Qiao, Jin Dai, Ting Zhuang, Yicong Liu, Xiuzhi Ren
Frontiers in Pediatrics.2026;[Epub] CrossRef
Adefovir dipivoxil-induced hypophosphatemic osteomalacia and osteoporosis: a case report and literature review
Wenshu Yu, Chunxia Deng, Shangyu Chen, Hui Jiang, Jiaqin Jiang
Frontiers in Endocrinology.2026;[Epub] CrossRef
Oral manifestations of X-linked hypophosphatemic rickets: diagnostic and therapeutic strategies from the perspective of systemic homeostatic imbalance
Yunfan Cai, Yue Feng, Baize Zhang, Jingrui Kang, Ling Li, Xiang Li, Zhiting Li, Shengquan Cheng, Xin Sun, Yujiang Chen, Tao Ye, Li’an Wu, Kaiyan Wang, Lina Niu
Oral Science and Homeostatic Medicine.2026;[Epub] CrossRef
Hypophosphatemic osteomalacia caused by diffuse tenosynovial giant cell tumor misdiagnosed as spondyloarthritis: a case report
Yazhen Su, Xingxing Zhao, Ruihong Hou, Dan Ma, Ke Xu, Liyun Zhang
Frontiers in Endocrinology.2026;[Epub] CrossRef
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
X-linked hypophosphatemia and tumor-induced osteomalacia: a narrative review and expert opinion on the diagnostic and therapeutic challenges in the era of burosumab
Maria Luisa Brandi, Cristina Eller Vainicher, Danilo Fintini, Andrea Giusti, Andrea Magnolato, Salvatore Minisola, Sandro Giannini
Orphanet Journal of Rare Diseases.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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