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Oncogenic osteomalacia illustrating the effect of fibroblast growth factor 23 on phosphate homeostasis.

Westerberg PA, Linde T, Vanderschueren D, Billen J, Jans I, Ljunggren Ö - Clin Kidney J (2012)

Bottom Line: In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol.Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal.The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

ABSTRACT
In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol. A patient suffering from OOM is described. Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal. The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

No MeSH data available.


Related in: MedlinePlus

Mechanisms of increased FGF23. Hypophosphataemia due to increased FGF23 may be due to paraneoplastic synthesis by mesenchymal tumours, genetic defects affecting the FGF23 synthesis and possibly phosphate sensing in bone cells or a mutation in FGF23 itself rendering it resistant against enzymatic degradation. FGF23 signals via FGF receptors in conjunction with its co-receptor klotho in the kidney downregulating phosphate transporters and decreasing calcitriol synthesis. Mutated or knocked out klotho in animals causes hyperphosphataemia and increased calcitriol, despite high FGF23. A mutation in gene coding for NaPi-IIc causes renal phosphate wasting with a compensatory increase in calcitriol and hypercalciuria due to increased intestinal calcium absorption. Abbreviations: PHEX, phosphate-regulating gene with homology to endopeptidases on the X chromosome; DMP, dentin matrix protein; ENPP, ectonucleotide pyrophosphatase/phosphodiesterase; FE-Pi, fractional excretion of phosphate; ↓ means decreased expression or function; ↑ means increased concetration or function.
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fig2: Mechanisms of increased FGF23. Hypophosphataemia due to increased FGF23 may be due to paraneoplastic synthesis by mesenchymal tumours, genetic defects affecting the FGF23 synthesis and possibly phosphate sensing in bone cells or a mutation in FGF23 itself rendering it resistant against enzymatic degradation. FGF23 signals via FGF receptors in conjunction with its co-receptor klotho in the kidney downregulating phosphate transporters and decreasing calcitriol synthesis. Mutated or knocked out klotho in animals causes hyperphosphataemia and increased calcitriol, despite high FGF23. A mutation in gene coding for NaPi-IIc causes renal phosphate wasting with a compensatory increase in calcitriol and hypercalciuria due to increased intestinal calcium absorption. Abbreviations: PHEX, phosphate-regulating gene with homology to endopeptidases on the X chromosome; DMP, dentin matrix protein; ENPP, ectonucleotide pyrophosphatase/phosphodiesterase; FE-Pi, fractional excretion of phosphate; ↓ means decreased expression or function; ↑ means increased concetration or function.

Mentions: Increased FGF23 may be due to a mutation in the FGF23 gene, making it resistant against enzymatic degradation as in autosomal dominant hypophosphataemic rickets [9]. Mutations in the PHEX, DMP1 or ENPP1 genes, respectively, induce a defect in the normal regulation of FGF23 synthesis in osteocytes by unknown mechanisms. These mutations all give rise to hereditary rickets, see Table 2 and [10]. The recessive disorder hereditary hypophosphataemic rickets with hypercalciuria on the other hand is due to mutations in the SLC34A3 gene, causing decreased activity of the tubular sodium phosphate co-transporter NaPi-IIc [11]. The condition is associated with increased calcitriol and hypercalciuria and a decrease in serum FGF23. Mutations in SLC34A1 resulting in a decrease in NaPi-IIa cause nephrolithiasis, osteoporosis and mild hypophosphataemia [12] (see Figure 2). Acquired chronic hypophosphataemia may be due to general or selective proximal tubular damage or Fanconi syndrome, caused by light chains associated with monoclonal gammopathies or other tubular toxins. FGF23 is normal or decreased in chronic hypophosphataemic disorders not caused by FGF23 excess [13]. The patient in this case had an acquired form of phosphate wasting, the FGF23 level was increased and there were no other features of general tubular dysfunction.


Oncogenic osteomalacia illustrating the effect of fibroblast growth factor 23 on phosphate homeostasis.

Westerberg PA, Linde T, Vanderschueren D, Billen J, Jans I, Ljunggren Ö - Clin Kidney J (2012)

Mechanisms of increased FGF23. Hypophosphataemia due to increased FGF23 may be due to paraneoplastic synthesis by mesenchymal tumours, genetic defects affecting the FGF23 synthesis and possibly phosphate sensing in bone cells or a mutation in FGF23 itself rendering it resistant against enzymatic degradation. FGF23 signals via FGF receptors in conjunction with its co-receptor klotho in the kidney downregulating phosphate transporters and decreasing calcitriol synthesis. Mutated or knocked out klotho in animals causes hyperphosphataemia and increased calcitriol, despite high FGF23. A mutation in gene coding for NaPi-IIc causes renal phosphate wasting with a compensatory increase in calcitriol and hypercalciuria due to increased intestinal calcium absorption. Abbreviations: PHEX, phosphate-regulating gene with homology to endopeptidases on the X chromosome; DMP, dentin matrix protein; ENPP, ectonucleotide pyrophosphatase/phosphodiesterase; FE-Pi, fractional excretion of phosphate; ↓ means decreased expression or function; ↑ means increased concetration or function.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400509&req=5

fig2: Mechanisms of increased FGF23. Hypophosphataemia due to increased FGF23 may be due to paraneoplastic synthesis by mesenchymal tumours, genetic defects affecting the FGF23 synthesis and possibly phosphate sensing in bone cells or a mutation in FGF23 itself rendering it resistant against enzymatic degradation. FGF23 signals via FGF receptors in conjunction with its co-receptor klotho in the kidney downregulating phosphate transporters and decreasing calcitriol synthesis. Mutated or knocked out klotho in animals causes hyperphosphataemia and increased calcitriol, despite high FGF23. A mutation in gene coding for NaPi-IIc causes renal phosphate wasting with a compensatory increase in calcitriol and hypercalciuria due to increased intestinal calcium absorption. Abbreviations: PHEX, phosphate-regulating gene with homology to endopeptidases on the X chromosome; DMP, dentin matrix protein; ENPP, ectonucleotide pyrophosphatase/phosphodiesterase; FE-Pi, fractional excretion of phosphate; ↓ means decreased expression or function; ↑ means increased concetration or function.
Mentions: Increased FGF23 may be due to a mutation in the FGF23 gene, making it resistant against enzymatic degradation as in autosomal dominant hypophosphataemic rickets [9]. Mutations in the PHEX, DMP1 or ENPP1 genes, respectively, induce a defect in the normal regulation of FGF23 synthesis in osteocytes by unknown mechanisms. These mutations all give rise to hereditary rickets, see Table 2 and [10]. The recessive disorder hereditary hypophosphataemic rickets with hypercalciuria on the other hand is due to mutations in the SLC34A3 gene, causing decreased activity of the tubular sodium phosphate co-transporter NaPi-IIc [11]. The condition is associated with increased calcitriol and hypercalciuria and a decrease in serum FGF23. Mutations in SLC34A1 resulting in a decrease in NaPi-IIa cause nephrolithiasis, osteoporosis and mild hypophosphataemia [12] (see Figure 2). Acquired chronic hypophosphataemia may be due to general or selective proximal tubular damage or Fanconi syndrome, caused by light chains associated with monoclonal gammopathies or other tubular toxins. FGF23 is normal or decreased in chronic hypophosphataemic disorders not caused by FGF23 excess [13]. The patient in this case had an acquired form of phosphate wasting, the FGF23 level was increased and there were no other features of general tubular dysfunction.

Bottom Line: In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol.Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal.The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

ABSTRACT
In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol. A patient suffering from OOM is described. Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal. The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

No MeSH data available.


Related in: MedlinePlus