Fibroblast growth factor-23 is regulated by 1α,25-dihydroxyvitamin D

Michael T. Collins, John R. Lindsay, Alka Jain, Marilyn H. Kelly, Carolee M. Cutler, Lee S. Weinstein, Jie Liu, Neal S. Fedarko, Karen K. Winer

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Abstract

Serum FGF-23 regulation was studied in patients with hypoparathyroidism or pseudohypoparathyroidism treated with calcitriol. Serum FGF-23 levels changed in parallel in response to changes in serum 1,25-D, suggesting that FGF-23 may be regulated by 1,25-D. In addition, the phosphaturic effect of FGF-23 may be diminished in the absence of PTH action on the kidney. Introduction: Fibroblast growth factor (FGF)-23 is a recently described hormone that has been shown to be involved in the regulation of phosphate and vitamin D metabolism. The physiologic role of FGF-23 in mineral metabolism and how serum FGF-23 levels are regulated have yet to be elucidated. Three patients with mineral metabolism defects that allowed for the investigation of the regulation of FGF-23 were studied. Materials and Methods: Patient 1 had postsurgical hypoparathyroidism and Munchausen's syndrome and consumed a pharmacologic dose of calcitriol. Patient 2 had postsurgical hypoparathyroidism and fibrous dysplasia of bone. She was treated with increasing doses of calcitriol followed by synthetic PTH(1-34). Patient 3 had pseudohypoparathyroidism type 1B and tertiary hyperparathyroidism. She underwent parathyroidectomy, which was followed by the development of hungry bone syndrome and hypocalcemia, requiring treatment with calcitriol. Serum FGF-23 and serum and urine levels of mineral metabolites were measured in all three patients. Results: Patient 1 had an acute and marked increase in serum FGF-23 (70 to 670 RU/ml; normal range, 18-108 RU/ml) within 24 h in response to high-dose calcitriol administration. Patient 2 showed stepwise increases in serum FGF-23 from 117 to 824 RU/ml in response to increasing serum levels of 1α,25-dihydroxyvitamin D (1,25-D). Finally, before parathyroidectomy, while hypercalcemic, euphosphatemic, with low levels of 1,25-D (10 pg/ml; normal range, 22-67 pg/ml), and with very high serum PTH (863.7 pg/ml; normal range, 6.0-40.0 pg/ml), patient 3 had high serum FGF-23 levels (217 RU/ml). After surgery, while hypocalcemic, euphosphatemic, and with high serum levels of serum 1,25-D (140 pg/ml), FGF-23 levels were higher than preoperative levels (305 RU/ml). It seemed that the phosphaturic effect of FGF-23 was diminished in the absence of PTH or a PTH effect. Conclusions: Serum FGF-23 may be regulated by serum 1,25-D, and its phosphaturic effect may be less in the absence of PTH.

Original languageEnglish (US)
Pages (from-to)1944-1950
Number of pages7
JournalJournal of Bone and Mineral Research
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2005

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Keywords

  • 1α-hydroxylase
  • Fibroblast growth factor-23
  • Fibrous dysplasia
  • Hypoparathyroidism
  • McCune-Albright syndrome
  • Phosphate
  • Phosphaturia
  • Phosphorus
  • Pseudohypoparathyroidism
  • Vitamin D

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Collins, M. T., Lindsay, J. R., Jain, A., Kelly, M. H., Cutler, C. M., Weinstein, L. S., Liu, J., Fedarko, N. S., & Winer, K. K. (2005). Fibroblast growth factor-23 is regulated by 1α,25-dihydroxyvitamin D. Journal of Bone and Mineral Research, 20(11), 1944-1950. https://doi.org/10.1359/JBMR.050718