scholarly journals Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children

2014 ◽  
Vol 3 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Vickie Braithwaite ◽  
Kerry S Jones ◽  
Shima Assar ◽  
Inez Schoenmakers ◽  
Ann Prentice
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Local Community ◽  
Iron Status ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Normal Range ◽  
Hydroxyvitamin D ◽  
Fgf23 Concentration ◽  
History Of

Elevated C-terminal fibroblast growth factor 23 (C-FGF23) concentrations have been reported in Gambian children with and without putative Ca-deficiency rickets. The aims of this study were to investigate whether i) elevated C-FGF23 concentrations in Gambian children persist long term; ii) they are associated with higher intact FGF23 concentrations (I-FGF23), poor iron status and shorter 25-hydroxyvitamin D half-life (25OHD-t1/2); and iii) the persistence and predictors of elevated FGF23 concentrations differ between children with and without a history of rickets. Children (8–16 years, n=64) with a history of rickets and a C-FGF23 concentration >125 RU/ml (bone deformity (BD), n=20) and local community children with a previously measured elevated C-FGF23 concentration (LC+, n=20) or a previously measured C-FGF23 concentration within the normal range (LC−, n=24) participated. BD children had no remaining signs of bone deformities. C-FGF23 concentration had normalised in BD children, but remained elevated in LC+ children. All the children had I-FGF23 concentration within the normal range, but I-FGF23 concentration was higher and iron status poorer in LC+ children. 1,25-dihydroxyvitamin D was the strongest negative predictor of I-FGF23 concentration (R2=18%; P=0.0006) and soluble transferrin receptor was the strongest positive predictor of C-FGF23 concentration (R2=33%; P≤0.0001). C-FGF23 and I-FGF23 concentrations were poorly correlated with each other (R2=5.3%; P=0.07). 25OHD-t1/2 was shorter in BD children than in LC− children (mean (s.d.): 24.5 (6.1) and 31.5 (11.5) days respectively; P=0.05). This study demonstrated that elevated C-FGF23 concentrations normalised over time in Gambian children with a history of rickets but not in local children, suggesting a different aetiology; that children with resolved rickets had a shorter 25OHD-t1/2, suggesting a long-standing increased expenditure of 25OHD, and that iron deficiency is a predictor of elevated C-FGF23 concentrations in both groups of Gambian children.

scholarly journals Iron status and fibroblast growth factor-23 in Gambian children

Bone ◽  
2012 ◽  
Vol 50 (6) ◽  
pp. 1351-1356 ◽  
Author(s):  
Vickie Braithwaite ◽  
Landing M.A. Jarjou ◽  
Gail R. Goldberg ◽  
Ann Prentice
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iron Status ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

scholarly journals Quantitative ELISA-Like Immunohistochemistry of Fibroblast Growth Factor 23 in Diagnosis of Tumor-Induced Osteomalacia and Clinical Characteristics of the Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fangke Hu ◽  
Chengying Jiang ◽  
Qiang Zhang ◽  
Huaiyin Shi ◽  
Lixin Wei ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Clinical Features ◽  
Fibroblast Growth Factor 23 ◽  
The Body ◽  
Fibroblast Growth ◽  
Mesenchymal Tumors ◽  
History Of ◽  
Paraneoplastic Disorder ◽  
Formalin Fixed

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder and fibroblast growth factor 23 (FGF23) plays a key role in its pathogenesis. This study was conducted to describe a novel FGF23 detecting procedure and describe clinical features of the disease. Fourteen TIO cases were retrieved and FGF23 expression was measured by quantitative ELISA-like immunohistochemistry using formalin-fixed and paraffin-embedded tissues. As summarized from 14 TIO cases, clinical features of TIO were long-standing history of osteomalacia, hypophosphatemia, and urinary phosphate wasting. The associated tumors were mostly benign phosphaturic mesenchymal tumors mixed connective tissue variant (PMTMCT) which could be located anywhere on the body, and most of them could be localized by conventional examinations and octreotide scanning. By quantitative ELISA-like immunohistochemistry, all the 14 TIO cases had high FGF23 expression (median 0.69, 25%–75% interquartile 0.57–1.10, compared with 26 non-TIO tumors of median 0.07, 25%–75% interquartile 0.05–0.11,p<0.001). The quantitative ELISA-like immunohistochemistry was a feasible and reproducible procedure to detect the high FGF23 expression in formalin-fixed and paraffin-embedded biopsies or specimens. Since TIO was often delay-diagnosed or misdiagnosed, clinicians and pathologists should be aware of TIO and PMTMCT, respectively.

scholarly journals Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

2018 ◽  
Vol 29 (10) ◽  
pp. 2583-2592 ◽  
Author(s):  
Cassianne Robinson-Cohen ◽  
Traci M. Bartz ◽  
Dongbing Lai ◽  
T. Alp Ikizler ◽  
Munro Peacock ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Genetic Variants ◽  
Fibroblast Growth Factor 23 ◽  
Phosphate Transport ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Genome Wide ◽  
Fgf23 Concentration

BackgroundFibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.MethodsWe performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m2 to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log–transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.ResultsWe discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0×10−24), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.ConclusionsCommon genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Tarah Fatani ◽  
Asma Binjab ◽  
Hope Weiler ◽  
Atul Sharma ◽  
Celia Rodd
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Gestational Age ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Hydroxyvitamin D ◽  
Liquid Chromatography Tandem Mass ◽  
Appropriate For Gestational Age ◽  
High Concentrations ◽  
A Prospective Study

AbstractTo explore the temporal evolution of 25-hydroxyvitamin D [25(OH)D], its epimer, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and minerals in healthy appropriate-for-gestational-age preterms.A prospective study was undertaken in infants born at 28–32 weeks with monitoring at 1, 3, 5 weeks and term.Morning plasma and urine calcium; phosphorus; creatinine; PTH, C-terminal and intact FGF23 (iFGF23) and liquid chromatography-tandem mass spectrometry measurements of 25(OH)D were undertaken. Analyses included regression models.Some 11 infants (5 males) were recruited at a median gestational age of 31.2 weeks (interquartile range: 28.1–31.8). Standard chemistries were normal. No infant was vitamin D deficient; 58% achieved 50 nmol/L with a median intake of 540 IU/day. High concentrations of C-3 epimer were detected. iFGF23 and C-terminal concentrations were persistently elevated (double and ten times adult norms, respectively). Tubular resorption of phosphorus was normal (88%±8%).Most infants achieved acceptable 25(OH)D

Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population?

2015 ◽  
Vol 48 (6) ◽  
pp. 431-436 ◽  
Author(s):  
Maria Bożentowicz-Wikarek ◽  
Piotr Kocełak ◽  
Aleksander Owczarek ◽  
Magdalena Olszanecka-Glinianowicz ◽  
Małgorzata Mossakowska ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Elderly Population ◽  
Iron Status ◽  
Fibroblast Growth Factor 23 ◽  
The Elderly ◽  
Fibroblast Growth ◽  
The Relationship

Fibroblast growth factor 23 production in bone is directly regulated by 1α,25-dihydroxyvitamin D, but not PTH

2010 ◽  
Vol 299 (5) ◽  
pp. F1212-F1217 ◽  
Author(s):  
Fumie Saji ◽  
Takashi Shigematsu ◽  
Toshifumi Sakaguchi ◽  
Masaki Ohya ◽  
Hikari Orita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Renal Insufficiency ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Dihydroxyvitamin D ◽  
Fgf23 Concentration ◽  
Group A

Fibroblast growth factor 23 (FGF23), which is primarily produced by osteocytes in bone, regulates renal phosphate excretion and 1α,25-dihydroxyvitamin D [1,25(OH)2D3] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating serum FGF23, but the direct effect on circulating FGF23 levels in renal insufficiency is still unclear. To identify the major regulator of FGF23 synthesis in renal insufficiency, we compared the effect of parathyroid hormone (PTH) and 1,25(OH)2D3 on FGF23 synthesis in the calvariae of normal rats with that of uremic rats in vitro. 1,25(OH)2D3 treatment significantly increased the FGF23 concentration in the medium from both groups, but the degree of increase in the uremic group was markedly higher than in the control group. A significant increase in FGF23 mRNA expression occurred as early as 4 h after treatment and reached the maximum within 8 h in the uremic group, whereas in the normal group a significant increase in FGF23 mRNA expression was observed only at 8 h. In addition, the expression of vitamin D receptor (VDR) mRNA in the calvariae of uremic rats was markedly higher than in normal rats. However, in neither group did PTH treatment affect the medium FGF23 concentration or the FGF23 mRNA levels. These results suggest that FGF23 synthesis in bone is regulated by 1,25(OH)2D3 directly, not by PTH, and that increased VDR mRNA expression induced the relatively swift and strong response in the uremic group.

scholarly journals Glucocorticoids dexamethasone and prednisolone suppress fibroblast growth factor 23 (FGF23)

2021 ◽  
Author(s):  
Martina Feger ◽  
Franz Ewendt ◽  
Jörg Strotmann ◽  
Holger Schäffler ◽  
Daniela Kempe-Teufel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iron Status ◽  
Fibroblast Growth Factor 23 ◽  
List Type ◽  
Fibroblast Growth ◽  
Active Vitamin ◽  
Active Vitamin D

Abstract Fibroblast growth factor 23 (FGF23) is a hormone mainly secreted by bone cells. Its most prominent effects are the regulation of renal phosphate reabsorption and calcitriol (active vitamin D, 1,25(OH)2D3) formation, effects dependent on its co-receptor αKlotho. Besides these actions, further paracrine and endocrine effects exist. The production of FGF23 is regulated by 1,25(OH)2D3, parathyroid hormone, dietary phosphate intake, iron status, as well as inflammation. Glucocorticoids are hormones with anti-inflammatory properties and are, therefore, widely used for acute and chronic inflammatory diseases, autoimmune disorders, and malignancies. The present study explored whether glucocorticoids influence the production of FGF23 in vitro as well as in mice. Fgf23 transcription was analyzed by semi-quantitative real-time PCR. Serum concentrations of FGF23 and 1,25(OH)2D3 were measured by ELISA. Urinary phosphate and Ca2+ excretion were determined in metabolic cages. As a result, in UMR106 rat osteoblast-like cells and in MC3T3-E1 cells, both, dexamethasone and prednisolone, downregulated Fgf23 transcription and FGF23 protein synthesis. Dexamethasone increased Dmp1 and Phex (encoding FGF23-regulating genes) as well as Nfkbia (encoding NFκB inhibitor IκBα) transcription in UMR106 cells. In mice, a single injection of dexamethasone or prednisolone was followed by a significant decrease of serum C-terminal and intact FGF23 concentration and bone Fgf23 mRNA expression within 12 h. These effects were paralleled by increased renal phosphate excretion and enhanced 1,25(OH)2D3 formation. We conclude that a single glucocorticoid treatment strongly downregulates the FGF23 plasma concentration. Key messages Glucocorticoids dexamethasone and prednisolone suppress the formation of bone-derived hormone fibroblast growth factor 23 (FGF23) in vitro. The effect is accompanied by an upregulation of Dmp1, Phex, and IκBα, negative regulators of FGF23, in UMR106 osteoblast-like cells. Glucocorticoid receptor antagonist RU-486 attenuates the effect of dexamethasone on FGF23, Dmp1, and Phex. In mice, a single glucocorticoid dose suppresses FGF23 and enhances 1,25(OH)2D3 (active vitamin D).

scholarly journals Tumour-induced Osteomalacia Secondary to a Sarcoma

2016 ◽  
Vol 12 (2) ◽  
pp. 104 ◽  
Author(s):  
Karla Victoria Rodriguez-Velver ◽  
◽  
◽  
◽  
◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Rare Case ◽  
Bone Fractures ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Biochemical Characteristics ◽  
History Of ◽  
Benign Tumours

Tumour-induced osteomalacia (TIO), is a rare paraneoplasatic syndrome found in >95% of benign tumours that secrete fibroblast growth factor 23 - a phosphaturic circulating hormone. A rare case of a TIO secondary to a sarcoma, in a 21-year old man with history of bone fractures and distinctive physical and biochemical characteristics is presented and discussed.

Sign in / Sign up

Export Citation Format

Share Document