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

Abstract

UNLABELLED:

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 1alpha,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.

• Authors: 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
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 20 Issue 11 Pg. 1944-50 (Nov 2005) ISSN: 0884-0431 [Print] United States
• PMID: 16234967 (Publication Type: Case Reports, Journal Article)

Chemical References

• FGF23 protein, human
• Teriparatide
• Phosphorus
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Calcitriol
• Calcium

Topics

• Adult
• Calcitriol (blood, pharmacology, therapeutic use)
• Calcium (blood)
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood, metabolism)
• Fibrous Dysplasia, Polyostotic (blood, therapy)
• Humans
• Hypoparathyroidism (blood, drug therapy)
• Middle Aged
• Phosphorus (blood, urine)
• Pseudohypoparathyroidism (blood, drug therapy)
• Teriparatide (pharmacology, therapeutic use)