Performance evaluation of the new chemiluminescent intact FGF23 assay relative to the existing assay system

Katô, Hajime; Hidaka, Naoko; Koga, Minoru; Ogawa, Noriyuki; Takahashi, Shichihiro; Miyazaki, Hiromi; Nangaku, Masaomi; Makita, Noriko; Ito, Nobuaki

doi:10.1007/s00774-021-01258-7

Cited by 17 publications

(26 citation statements)

References 31 publications

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“…Patients with histopathological confirmation of PMT who underwent surgery were categorized as having “definite TIO.” Patients with acquired hypophosphatemic osteomalacia with FGF23 >30 pg/mL measured by the Kainos FGF23 assay (Kainos, Tokyo, Japan) or the Determinar CL FGF23 assay (Minaris Medical, Tokyo, Japan) without histopathological confirmation were categorized as “clinically diagnosed TIO,” after excluding intravenous iron preparation‐induced FGF23‐related hypophosphatemic osteomalacia. ( 4,20‐22 )…”

Section: Methodsmentioning

confidence: 99%

Clinical Challenges in Diagnosis, Tumor Localization and Treatment of Tumor-Induced Osteomalacia: Outcome of a Retrospective Surveillance

Hidaka

Koga

Kimura

et al. 2020

Journal of Bone and Mineral Research

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Tumor-induced osteomalacia (TIO) is an acquired fibroblast growth factor 23 (FGF23)-related hypophosphatemic osteomalacia caused by phosphaturic mesenchymal tumors (PMTs) developed in the bone or soft tissue. Diagnostic delay should be addressed, and ideal techniques to localize PMTs and efficient treatment options should be explored to improve the outcomes of this rare disease. To clarify the detailed clinical course and outcomes of TIO patients, retrospective questionnaire surveys were conducted among physicians from the Japanese Society for Bone and Mineral Research (JSBMR) and the Japan Endocrine Society (JES). The primary survey collected the number of TIO patients between January 2007 and December 2018. The secondary survey aimed to obtain the detailed characteristics, laboratory data, and outcomes. Eighty-eight patients (52 males, mean: 52 years old) were included, and 24 patients were clinically diagnosed with TIO without localized PMTs. The median duration from the onset to detection of high FGF23 levels was 3.4 years, with 77 patients being initially misdiagnosed. Among the methods used to detect small, localized PMTs (≤10 mm), fluorine-18-fluorodeoxyglucose-positron emission tomography/ computed tomography and somatostatin receptor scintigraphy were less sensitive than somatostatin receptor positron emission tomography/computed tomography (SRPET/CT). Systemic venous sampling (SVS) of FGF23 was performed in 53 patients; among them, SVS was considered useful for detecting localized PMTs in 45 patients with diverse tumor sizes. Finally, 45 patients achieved biochemical remission by surgery, 39 patients continued pharmaceutical treatment, including burosumab (11 patients), and four patients died. These results encouraged us to further increase the awareness of TIO and to improve the accessibility of SRPET/CT and SVS. Further evidence about the efficacy of new pharmaceutical treatments is awaited.

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Section: Methodsmentioning

confidence: 99%

Clinical Challenges in Diagnosis, Tumor Localization and Treatment of Tumor-Induced Osteomalacia: Outcome of a Retrospective Surveillance

Hidaka

Koga

Kimura

et al. 2020

Journal of Bone and Mineral Research

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“…Using this method, the reference range of FGF23 is 16.1 to 49.3 pg/mL with cut‐off values for FGF23‐related hypophosphatemia of 30 pg/mL. ( 20,21 )…”

Section: Methodsmentioning

confidence: 99%

“…Using this method, the reference range of FGF23 is 16.1 to 49.3 pg/mL with cut-off values for FGF23-related hypophosphatemia of 30 pg/mL. (20,21) Measurement of plasma PP i Plasma was collected from participants to measure the plasma PP i concentrations. After plasma isolation, samples were filtered through a 30 kDa membrane (PALL, Port Washington, NY, USA) via centrifugation to remove platelets and frozen at À80 C within 1 hour of blood collection for single use.…”

Section: Measurement Of Intact Fgf23mentioning

confidence: 99%

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

Katô

Ansh

Lester

et al. 2020

Journal of Bone and Mineral Research

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Homozygous ENPP1 mutations are associated with autosomal recessive hypophosphatemic rickets type 2 (ARHR2), severe ossification of the spinal ligaments, and generalized arterial calcification of infancy type 1. There are a limited number of reports on phenotypes associated with heterozygous ENPP1 mutations. Here, we report a series of three probands and their families with heterozygous and compound heterozygous ENPP1 mutations. The first case (case 1) was a 47-year-old male, diagnosed with early-onset osteoporosis and low-normal serum phosphate levels, which invoked suspicion for hypophosphatemic rickets. The second and third cases were 77-and 54-year-old females who both presented with severe spinal ligament ossification and the presumptive diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). Upon workup, fibroblast growth factor 23 (FGF23) was noted to be relatively high in case 2 and serum phosphorous was low-normal in case 3, and the diagnoses of X-linked hypophosphatemic rickets (XLH) and ARHR2 were considered. Genetic testing for genes related to congenital hypophosphatemic rickets was therefore performed, revealing heterozygous ENPP1 variants in cases 1 and 2 (case 1, c.536A>G, p.Asn179Ser; case 2, c.1352A>G, p.Tyr451Cys) and compound heterozygous ENPP1 variants in case 3 constituting the same variants present in cases 1 and 2 (c.536A>G, p.Asn179Ser and c.1352A>G, p.Tyr451Cys). Several in silico tools predicted the two variants to be pathogeneic, a finding confirmed by in vitro biochemical analysis demonstrating that the p.Asn179Ser and p.Tyr451Cys ENPP1 variants possessed a catalytic velocity of 45% and 30% compared with that of wildtype ENPP1, respectively. Both variants were therefore categorized as pathogenic loss-of-function mutations. Our findings suggest that ENPP1 mutational status should be evaluated in patients presenting with the diagnosis of idiopathic DISH, ossification of the posterior longitudinal ligament (OPLL), and early-onset osteoporosis.

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“…A previous study proposed a serum level of intact FGF23 of 30 pg/mL or higher in the presence of chronic hypophosphatemia for the diagnosis of FGF23-related hypophosphatemia [91]. In 2019, the measurement of serum levels of intact FGF23 by a chemiluminescent enzyme immunoassay to diagnose FGF23-related hypophosphatemia was covered by the national health insurance system in Japan [92]. Genetic testing is also useful for confirming the diagnosis of hereditary hypophosphatemic rickets/osteomalacia, such as XLH; however, it is not yet covered by the national health insurance system in Japan.…”

Section: Fgf23-related Hyperphosphatemic and Hypophosphatemic Disordersmentioning

confidence: 99%

Advances in understanding of phosphate homeostasis and related disorders

Michigami

2022

Endocr J

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Inorganic phosphate (Pi) in the mammalian body is balanced by its influx and efflux through the intestines, kidneys, bones, and soft tissues, at which several sodium/Pi co-transporters mediate its active transport. Pi homeostasis is achieved through the complex counter-regulatory feedback balance between fibroblast growth factor 23 (FGF23), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), and parathyroid hormone. FGF23, which is mainly produced by osteocytes in bone, plays a central role in Pi homeostasis and exerts its effects by binding to the FGF receptor (FGFR) and αKlotho in distant target organs. In the kidneys, the main target, FGF23 promotes the excretion of Pi and suppresses the production of 1,25(OH) 2 D. Deficient and excess FGF23 result in hyperphosphatemia and hypophosphatemia, respectively. FGF23-related hypophosphatemic rickets/osteomalacia include tumor-induced osteomalacia and various genetic diseases, such as X-linked hypophosphatemic rickets. Coverage by the national health insurance system in Japan for the measurement of FGF23 and the approval of burosumab, an FGF23-neutralizing antibody, have had a significant impact on the diagnosis and treatment of FGF23-related hypophosphatemic rickets/osteomalacia. Some of the molecules responsible for genetic hypophosphatemic rickets/osteomalacia are highly expressed in osteocytes and function as local regulators of FGF23 production. A number of systemic factors also regulate FGF23 levels. Although the mechanisms responsible for Pi sensing in mammals have not yet been elucidated in detail, recent studies have suggested the involvement of FGFR1. The further clarification of the mechanisms by which osteocytes detect Pi levels and regulate FGF23 production will lead to the development of better strategies to treat hyperphosphatemic and hypophosphatemic conditions.

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Performance evaluation of the new chemiluminescent intact FGF23 assay relative to the existing assay system

Cited by 17 publications

References 31 publications

Clinical Challenges in Diagnosis, Tumor Localization and Treatment of Tumor-Induced Osteomalacia: Outcome of a Retrospective Surveillance

Clinical Challenges in Diagnosis, Tumor Localization and Treatment of Tumor-Induced Osteomalacia: Outcome of a Retrospective Surveillance

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

Advances in understanding of phosphate homeostasis and related disorders

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