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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2865
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 6 2374-2377
Copyright © 2007 by The Endocrine Society

BRIEF REPORT

Determination of the Elimination Half-Life of Fibroblast Growth Factor-23

Azarmindokht Khosravi1, Carolee M. Cutler1, Marilyn H. Kelly, Richard Chang, Richard E. Royal, Richard M. Sherry, Felasfa M. Wodajo, Neal S. Fedarko and Michael T. Collins

Skeletal Clinical Studies Unit (A.K., C.M.C., M.H.K., M.T.C.), Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research; Department of Radiology (R.C.), Mark O. Hatfield Clinical Center; and Surgery Branch (R.E.R., R.M.S.), National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; Department of Orthopedics and Pediatrics (F.M.W.), Georgetown University, Washington, D.C.; and Division of Geriatric Medicine and Gerontology (N.S.F.), Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224

Address all correspondence and requests for reprints to: Michael T. Collins, M.D., Chief, Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 228 MSC 4320, Bethesda, Maryland 20892-4320. E-mail: mc247k{at}nih.gov.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disease caused by mesenchymal tumors that secrete fibroblast growth factor-23 (FGF-23), a newly-described vitamin D and phosphate-regulating hormone. Surgical removal of the tumor, the ectopic source of circulating FGF-23, offers the opportunity to determine the elimination half-life of FGF-23.

Objective: The aim of the study was to determine the elimination half-life of FGF-23.

Patients/Methods: The tumors were removed from three patients with TIO, and serum samples were taken every 30 min for up to 72 h after the operation. FGF-23 was measured by both a C-terminal/intact assay and an intact assay, and the elimination half-life was determined by one phase exponential decay methodology.

Setting: The Mark O. Hatfield Clinical Research Center of the National Institutes of Health, a tertiary referral clinical research center, was the setting for the study.

Results: The elimination life of FGF-23 as determined by C-terminal/intact and intact assays was 46 ± 12 and 58 ± 34 min, respectively.

Conclusions: The plasma half-life of serum FGF-23 is in the range of 46–58 min.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
TUMOR-INDUCED OSTEOMALACIA (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia, renal phosphate wasting, osteomalacia, and inappropriately low 1,25(OH)2-vitamin D3 (1,25-D). It is often associated with progressive bone pain, muscle weakness, fatigue, nonhealing and recurrent fractures, as well as secondary hyperparathyroidism (1, 2, 3). TIO is caused by phosphaturic mesenchymal tumors (PMTs) of mixed connective tissue type that ectopically secrete molecules known as "phosphatonins" (4, 5, 6). To date, fibroblast growth factor-23 (FGF-23) appears to be the most clinically significant phosphatonin in TIO (7, 8, 9).

FGF-23 has emerged as an important regulator of both phosphate and vitamin D metabolism. The primary physiological source of FGF-23 appears to be bone cells (10, 11, 12, 13). FGF-23 inhibits both phosphate reabsorption and 1-{alpha} hydroxylation of 25-hydroxyvitamin D3 at the proximal renal tubule (14, 15, 16, 17, 18, 19, 20, 21). Much remains to be learned about FGF-23, including its physiological regulation and serum half-life. An earlier report determined the half-life of FGF-23 to be 21.5 min (22). We determined the biological half-life of FGF-23 in three patients with TIO by measuring serum FGF-23 for up to 3 d after surgical removal of PMTs and analyzed the data by one phase exponential decay methodology.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patients

Patient 1 was a 57-yr-old man who developed bone pain and weakness 2 yr before diagnosis. Initially, when multiple areas of increased tracer uptake were seen on bone scan, a diagnosis of multiple myeloma was entertained. However, laboratory studies were consistent with TIO and showed low serum phosphorus, ratio of tubular reabsorption rate for phosphorus to the glomerular filtration rate (TmP/GFR), and 1,25-D. PTH was slightly elevated (Table 1Go). Functional studies [whole body sestamibi, octreotide, and positron emission tomography (PET) scans] showed increased uptake in the left groin (anterior medial thigh). Anatomical studies [computed tomography (CT) and magnetic resonance imaging (MRI) scans] identified a nodular soft tissue lesion in the left femoral triangle. The lesion was excised, and serum FGF-23 was measured every 30 min for the first 120 min and then less frequently for 2 d after the operation. The tumor was characterized as an angiolipoma with additional features consistent with a PMT. The patient’s serum phosphorus and FGF-23 levels have remained in the normal range since the tumor was removed.


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  		TABLE 1. Biochemical parameters

 
Patient 2 was a 38-yr-old man who had 5 yr of symptoms including bilateral foot pain and ankle swelling, bone pain, mostly in his back and ribs, fractures with minimal trauma, and proximal muscle weakness. Laboratory studies showed low serum phosphorus and TmP/GFR, with an inappropriately low-normal serum 1,25-D. Serum PTH was high-normal, and alkaline phosphatase was elevated (Table 1Go). Bone scan revealed multiple areas of increased activity. Whole body sestamibi scan was negative, PET/CT scan and octreoscan revealed intense increased uptake in the head of the left fibula, suspicious for tumor. MRI showed a 1.7-cm lesion in the head of the left fibula, abutting the supermedial cortex of the fibular head and occupying about one third of the marrow space. The tumor was removed surgically, and pathology of the excised tumor revealed a spindle cell neoplasm with features of a PMT. As in patient 1, serum FGF-23 was measured 30 min for the first 120 min, and then less frequently for 3 d after the operation. Serum phosphorus returned to normal by postoperative d 5. The patient’s serum phosphorus and FGF-23 levels have remained in the normal range since the tumor was removed.

Patient 3 was a 47-yr-old man who presented 5 yr earlier with a progressive illness that included bone pain, weakness, and multiple fractures. On x-ray he was found to have multiple rib fractures, and bone scan revealed numerous fractures throughout the skeleton. Serum phosphorus, TmP/GFR, and 1,25-D were low (Table 1Go). Renal function and serum 25 (OH) vitamin D levels were normal, and PTH was mildly elevated. A suggestive, but atypical lesion was localized to the fat pad of the heel of the left foot with a combination of 111In-penetreotide octreotide scan, PET/CT scan, and MRI. The fact that this site was the likely source of FGF-23 was confirmed by selective venous catheterization of the left leg and the demonstration of a gradient in the FGF-23 concentrations between the proximal and distal lower extremity. The FGF-23 concentrations in a peripheral vein and multiple proximal veins in the lower extremity were 428–578 relative units (RU)/ml, whereas the concentration in the low superficial femoral vein was 1201 RU/ml.

The left heel lesion was removed, and serial serum FGF-23 concentrations (intact and C-terminal protein) were measured every 30 min for the first 120 min, and then less frequently after that, for 2 d after the operation. Histology of the tumor was consistent with a PMT and demonstrated spindle cells, clusters of osteoclast-like giant cells, foci of poorly formed cartilaginous metaplasia, and a multifocal appearance with a few hemangiopericytoma-like vessels. The patient’s serum phosphorus and FGF-23 levels have remained in the normal range since the tumor was removed in January 2005.

All three patients had normal renal and hepatic function.

Methods

TmP/GFR was calculated by the method of Bijvoet et al. (23). FGF-23 was measured by two assays: one that detects both C-terminal and intact FGF-23 (C-terminal/intact, Immutopics, Inc., San Clemente, CA) and intact ELISA assay (Kainos Laboratories, Inc., Tokyo, Japan), according to the manufacturers’ specifications. Plasma samples were taken just before tumor removal, every 30 min for the first 120 min, and periodically for up to 3 d postoperatively. The elimination half-life (t1/2) of FGF-23 was calculated by a method fitting the data to a one phase exponential decay equation (Prism 4; GraphPad Software, San Diego, CA), using the following equation: N = N0e–(0.693/thalf)t + plateau, where N is the FGF-23 concentration at a given time point, N0 is the initial FGF-23 concentration, and the plateau is the final steady-state FGF-23 concentration.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
There was a rapid decline in the serum concentration of FGF-23 upon tumor removal (Fig. 1Go). The calculated elimination half-life of FGF-23 for the three patients, as calculated from the C-terminal/intact assay measurements, was: 34 ± 2 (1 SD), 47 ± 9, and 58 ± 3 min (Fig. 1Go), for a mean half-life of 46 ± 12 min. The half-life, as calculated by the intact assay was: 27 ± 1, 94 ± 12, and 52 ± 5 min (Fig. 1Go), for a mean half-life of 58 ± 34 min. After the initial precipitous drop in FGF-23, there was a sustained plateau level of 52, 153, and 123 RU/ml (mean, 109 ± 52), in patients 1, 2, and 3, respectively, when FGF-23 was measured by the C-terminus assay. In the intact assay, the plateau level approached the detection limit of the assay.


Figure 1
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  		FIG. 1. Elimination half-life of FGF-23. FGF-23 was measured by the C-terminal/intact assay (A–C), and intact assay (D–F). The values for patient 1 (A and D), patient 2 (B and E), and patient 3 (C and F) are shown. FGF-23 was measured at the time points indicated after tumor removal. Calculated half-life (t1/2) for each patient by each assay is inset in each panel. Combined values for the half-life for the three patients as determined by the C-terminal/intact assay was 46 ± 12 min, and by the intact assay 58 ± 34 min.

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
By performing serial measurement of plasma FGF-23 after tumor removal and using a one phase exponential decay method, we calculated the elimination half-life of FGF-23 to be between 46 and 58 min. Because the elimination half-life of the hormone after tumor removal has been found to be very similar to the biological half-life in other endocrine tumors, this result probably reflects the biological half-life of FGF-23 (24). However, it is possible that the elimination half-life of tumoral FGF-23 may not be the same as that of biologically normal FGF-23 produced by osteogenic cells, which have been shown to be the physiological source of FGF-23. FGF-23 is most likely glycosylated under normal physiological conditions (25), and tumors sometimes function using nonphysiological posttranslational modification machinery (26). Thus, given the fact that glycosylation may play a role in secretion, and/or metabolism and elimination (27), it is possible that the half-life reported here may only reflect what occurs in the case of tumors. Furthermore, many PMTs also produced PHEX (phosphate regulating gene with homology to endopeptidases on the X-chromosome) (28). PHEX, which is the protein mutated in X-linked hypophosphatemia, plays an as yet undefined role in phosphate metabolism, and it is possible that tumoral PHEX could play a role in the FGF-23 degradation in this disease.

The half-life we determined in these patients by this method was significantly greater than that found by Takeuchi et al. (21.5 vs. 46–57 min; Ref. 22). This is likely due the different methods used to calculate the half-life. Takeuchi et al. (22) used a semilog transformation on serum from three time points. When the data were fit to both semilog transformation and single phase exponential decay models, the data fit the latter better. It is likely that the calculation of the half-life by this model and using more time points represents the biological half-life of FGF-23. However, some of the variation in the half-life seen in these three patients may simply reflect individual variation in FGF-23 clearance. It is interesting to note, however, that in all three patients there was a sustained level of C-terminal FGF-23 beyond 72 h after tumor removal. This could reflect a very long half-life for the removal of the C-terminal fragment from the serum, as has been suggested to be the case in postrenal transplantation hypophosphatemia (29), sustained secretion of C-terminal fragment by some other tissue(s), or a source of FGF-23 from another biological compartment (cerebrospinal fluid, for example). Differential secretion of C-terminal and intact molecule FGF-23 has been shown to occur in tissues (cells) lacking polypeptide GalNAc-transferase T3, a glycosylase involved in FGF-23 metabolism (27). It would not have been useful to measure serum C-terminal FGF-23 values beyond 72 h in an effort to determine the elimination half-life of C-terminal FGF-23, because physiological production of FGF-23 resumes 2–5 d after tumor removal.

In summary, measurement of the disappearance of FGF-23 from the circulation after surgical excision of FGF-23-producing tumors indicates that the elimination half-life, and thus circulating half-life of FGF-23, is between 46 and 58 min.


   Footnotes
 
{smtexp}This study was supported by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research, Intramural Research Program, National Institutes of Health, Department of Health and Human Services.

Author Disclosure Summary: The authors have nothing to disclose.

First Published Online March 20, 2007

1 A.K. and C.M.C. contributed equally to the work. Back

Abbreviations: CT, Computed tomography; 1,25-D, 1,25(OH)2-vitamin D3; FGF, fibroblast growth factor; MRI, magnetic resonance imaging; PET, positron emission tomography; PHEX, phosphate regulating gene with homology to endopeptidases on the X-chromosome; PMT, phosphaturic mesenchymal tumor; RU, relative units; TIO, tumor-induced osteomalacia; TmP/GFR, ratio of tubular reabsorption rate for phosphorus to the glomerular filtration rate.

Received December 27, 2006.

Accepted March 13, 2007.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Cai Q, Hodgson SF, Kao PC, Lennon VA, Klee GG, Zinsmiester AR, Kumar R 1994 Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia. N Engl J Med 330:1645–1649[Free Full Text]
  2. Shane E, Parisien M, Henderson JE, Dempster DW, Feldman F, Hardy MA, Tohme JF, Karaplis AC, Clemens TL 1997 Tumor-induced osteomalacia: clinical and basic studies. J Bone Miner Res 12:1502–1511[CrossRef][Medline]
  3. Jan de Beur SM 2005 Tumor-induced osteomalacia. JAMA 294:1260–1267[Abstract/Free Full Text]
  4. Kumar R 2000 Tumor-induced osteomalacia and the regulation of phosphate homeostasis. Bone 27:333–338[Medline]
  5. Drezner MK 2001 Tumor-induced osteomalacia. Rev Endocr Metab Disord 2:175–186[CrossRef][Medline]
  6. Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, Econs MJ, Inwards CY, Jan de Beur SM, Mentzel T, Montgomery E, Michal M, Miettinen M, Mills SE, Reith JD, O’Connell JX, Rosenberg AE, Rubin BP, Sweet DE, Vinh TN, Wold LE, Wehrli BM, White KE, Zaino RJ, Weiss SW 2004 Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 28:1–30[CrossRef][Medline]
  7. White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, Lorenz-Depiereux B, Miyauchi A, Yang IM, Ljunggren O, Meitinger T, Strom TM, Juppner H, Econs MJ 2001 The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. J Clin Endocrinol Metab 86:497–500[Abstract/Free Full Text]
  8. Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H 2003 Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663[Abstract/Free Full Text]
  9. Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, Fukumoto S 2002 Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957–4960[Abstract/Free Full Text]
  10. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P 2003 FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683–692[CrossRef][Medline]
  11. Mirams M, Robinson BG, Mason RS, Nelson AE 2004 Bone as a source of FGF23: regulation by phosphate? Bone 35:1192–1199[Medline]
  12. Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, Juppner H, Lanske B 2004 Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 23:421–432[CrossRef][Medline]
  13. Sitara D, Razzaque MS, St-Arnaud R, Huang W, Taguchi T, Erben RG, Lanske B 2006 Genetic ablation of vitamin D activation pathway reverses biochemical and skeletal anomalies in Fgf-23-null animals. Am J Pathol 169:2161–2170[Abstract/Free Full Text]
  14. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T 2001 Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98:6500–6505[Abstract/Free Full Text]
  15. Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N 2003 Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1{alpha},25-dihydroxyvitamin D3 production. J Biol Chem 278:2206–2211[Abstract/Free Full Text]
  16. Bai X, Miao D, Li J, Goltzman D, Karaplis AC 2004 Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Endocrinology 145:5269–5279[Abstract/Free Full Text]
  17. Saito H, Maeda A, Ohtomo SI, Hirata M, Kusano K, Kato S, Ogata E, Segawa H, Miyamoto KI, Fukushima N 2005 Circulating FGF-23 is regulated by 1{alpha},25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem 280:2543–2549[Abstract/Free Full Text]
  18. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T 2004 FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435[CrossRef][Medline]
  19. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T 2004 Targeted ablation of Ffg23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568[CrossRef][Medline]
  20. Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, Juppner H, Wolf M 2005 Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16:2205–2215[Abstract/Free Full Text]
  21. Collins MT, Lindsay JR, Jain A, Kelly MH, Cutler CM, Weinstein LS, Liu J, Fedarko NS, Winer KK 2005 Fibroblast growth factor-23 is regulated by 1{alpha},25-dihydroxyvitamin D. J Bone Miner Res 20:1944–1950[CrossRef][Medline]
  22. Takeuchi Y, Suzuki H, Ogura S, Imai R, Yamazaki Y, Yamashita T, Miyamoto Y, Okazaki H, Nakamura K, Nakahara K, Fukumoto S, Fujita T 2004 Venous sampling for fibroblast growth factor-23 confirms preoperative diagnosis of tumor-induced osteomalacia. J Clin Endocrinol Metab 89:3979–3982[Abstract/Free Full Text]
  23. Bijvoet OL, Morgan DB, Fourman P 1969 The assessment of phosphate reabsorption. Clin Chim Acta 26:15–24[CrossRef][Medline]
  24. Maier GW, Kreis ME, Renn W, Pereira PL, Haring HU, Becker HD 1998 Parathyroid hormone after adenectomy for primary hyperparathyroidism. A study of peptide hormone elimination kinetics in humans. J Clin Endocrinol Metab 83:3852–3856[Abstract/Free Full Text]
  25. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E 2004 Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 36:579–581[CrossRef][Medline]
  26. Dennis JW, Granovsky M, Warren CE 1999 Protein glycosylation in development and disease. Bioessays 21:412–421[CrossRef][Medline]
  27. Kato K, Jeanneau C, Tarp MA, Benet-Pages A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H 2006 Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. J Biol Chem 281:18370–18377[Abstract/Free Full Text]
  28. De Beur SM, Finnegan RB, Vassiliadis J, Cook B, Barberio D, Estes S, Manavalan P, Petroziello J, Madden SL, Cho JY, Kumar R, Levine MA, Schiavi SC 2002 Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res 17:1102–1110[CrossRef][Medline]
  29. Bhan I, Shah A, Holmes J, Isakova T, Gutierrez O, Burnett SA, Juppner H, Wolf M 2006 Post-transplant hypophosphatemia: tertiary ‘hyper-phosphatoninism’? Kidney Int 70:1486–1494[CrossRef][Medline]



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