Calcium deficiency reduces circulating levels of FGF23.

Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia.

[1]  V. Shalhoub,et al.  Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. , 2011, Kidney international.

[2]  B. Meijers,et al.  Targeting FGF23 and phosphorus in CKD, do not forget calcium. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  G. Åkerström,et al.  Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. , 2010, Kidney international.

[4]  J. Silver,et al.  PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. , 2010, American journal of physiology. Renal physiology.

[5]  J. Muñoz-Castañeda,et al.  FGF23 fails to inhibit uremic parathyroid glands. , 2010, Journal of the American Society of Nephrology : JASN.

[6]  M. Wolf,et al.  Recent advances in the rapidly evolving field of fibroblast growth factor 23 in chronic kidney disease , 2010, Current opinion in nephrology and hypertension.

[7]  M. Fukagawa,et al.  FGF23-parathyroid interaction: implications in chronic kidney disease. , 2010, Kidney international.

[8]  J. Silver,et al.  Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. , 2010, Kidney international.

[9]  R. Kitazawa,et al.  Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. , 2010, Kidney international.

[10]  T. Akizawa,et al.  Involvement of Alpha-Klotho and Fibroblast Growth Factor Receptor in the Development of Secondary Hyperparathyroidism , 2010, American Journal of Nephrology.

[11]  M. Mohammadi,et al.  The parathyroid is a target organ for FGF23 in rats. , 2007, The Journal of clinical investigation.

[12]  G. Åkerström,et al.  Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. , 2007, The Journal of endocrinology.

[13]  D. Kuypers,et al.  Tertiary ‘Hyperphosphatoninism’ Accentuates Hypophosphatemia and Suppresses Calcitriol Levels in Renal Transplant Recipients , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  Jason R. Stubbs,et al.  Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. , 2006, Journal of the American Society of Nephrology : JASN.

[15]  M. Inaba,et al.  Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism. , 2006, European journal of endocrinology.

[16]  T. Shimada,et al.  Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. , 2005, American journal of physiology. Renal physiology.

[17]  M. Inaba,et al.  FGF-23 in patients with end-stage renal disease on hemodialysis. , 2004, Kidney international.

[18]  Y. Takeuchi,et al.  Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. , 2004, The Journal of clinical investigation.

[19]  Y. Takeuchi,et al.  FGF‐23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  F. Llach,et al.  Aluminum administration in the Rat separately affects the osteoblast and Bone mineralization , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  E. Eisenberg.  EFFECTS OF SERUM CALCIUM LEVEL AND PARATHYROID EXTRACTS ON PHOSPHATE AND CALCIUM EXCRETION IN HYPOPARATHYROID PATIENTS. , 1965, The Journal of clinical investigation.

[22]  H. Sulkowitch,et al.  A COMPARISON OF THE EFFECTS OF A.T. 10 (DIHYDROTACHYSTEROL) AND VITAMIN D ON CALCIUM AND PHOSPHORUS METABOLISM IN HYPOPARATHYROIDISM. , 1938, The Journal of clinical investigation.

[23]  A. Marble,et al.  STUDIES ON THE MODE OF ACTION OF IRRADIATED ERGOSTEROL: IV. in Hypoparathyroidism. , 1932, The Journal of clinical investigation.