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New Therapies for Hypophosphatemia-Related to FGF23 Excess

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Abstract

FGF23 is a hormone produced by osteocytes in response to an elevation in the concentration of extracellular phosphate. Excess production of FGF23 by bone cells, or rarely by tumors, is the hormonal basis for several musculoskeletal syndromes characterized by hypophosphatemia due to renal phosphate wasting. FGF23-dependent chronic hypophosphatemia causes rickets and osteomalacia, as well as other skeletal complications. Genetic disorders of FGF23-mediated hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), fibrous dysplasia of bone, McCune-Albright syndrome, and epidermal nevus syndrome (ENS), also known as cutaneous skeletal hypophosphatemia syndrome (CSHS). The principle acquired form of FGF23-mediated hypophosphatemia is tumor-induced osteomalacia (TIO). This review summarizes current knowledge about the pathophysiology and clinical presentation of the most common FGF23-mediated conditions, with a focus on new treatment modalities. For many decades, calcitriol and phosphate supplements were the mainstay of therapy. Recently, burosumab, a monoclonal blocking antibody to FGF23, has been approved for treatment of XLH in children and adults, and an active comparator trial in children has shown good efficacy and safety for this drug. The remainder of FGF23-mediated hypophosphatemic disorders continue to be treated with phosphate and calcitriol, although ongoing trials with burosumab for treatment of tumor-induced osteomalacia show early promise. Burosumab may be an effective treatment for the remainder of FGF23-mediated disorders, but clinical trials to support that possibility are at present not available.

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Fig. 1
Fig. 2

Adapted from Imel, E.A. et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open label, phase 3 trial. Lancet (London, England) 393: 2416–2427 (2019)

Fig. 3

Adapted from Insogna, K.L. et al. A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. Journal of Bone and Mineral Research 33:1383–1393 (2018)

Fig. 4

Adapted from Portale, A.A. et al. Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. Calcified Tissue International 105: 271–284 (2019)

Fig. 5

Adapted from Insogna, K.L., et al., Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X-Linked Hypophosphatemia: A Phase 3, Single-Arm, International Trial. J Bone Miner Res, 2019. 34(12): p. 2183–2191

Fig. 6

Adapted from Wolf, M. & White, K.E. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Current Opinion in Nephrology and Hypertension 23: 411–419 (2014)

Fig. 7

Adapted from Florenzano, P., R.I. Gafni, and M.T. Collins, Tumor-induced osteomalacia. Bone Reports, 2017. 7: p. 90–97

Fig. 8

Adapted from El-Maouche, D., et al., (68)Ga-DOTATATE for Tumor Localization in Tumor-Induced Osteomalacia. The Journal of Clinical Endocrinology and Metabolism, 2016. 101(10): p. 3575–3581

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References

  1. Chong WH et al (2011) Tumor-induced osteomalacia. Endocr Relat Cancer 18(3):R53–R77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Minisola S et al (2017) Tumour-induced osteomalacia. Nature reviews Disease primers 3:17044–17044

    Article  PubMed  Google Scholar 

  3. Glorieux FH et al (1980) Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. N Engl J Med 303(18):1023–1031

    Article  CAS  PubMed  Google Scholar 

  4. Carpenter TO et al (2018) Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med 378(21):1987–1998

    Article  CAS  PubMed  Google Scholar 

  5. Imel EA et al (2019) Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet 393(10189):2416–2427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Imel EA et al (2015) Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. The Journal of clinical endocrinology and metabolism 100(7):2565–2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Insogna KL et al (2018) A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. J Bone Miner Res 33(8):1383–1393

    Article  CAS  PubMed  Google Scholar 

  8. Insogna KL et al (2019) Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X-Linked Hypophosphatemia: A Phase 3, Single-Arm. International Trial J Bone Miner Res 34(12):2183–2191

    Article  CAS  PubMed  Google Scholar 

  9. Portale AA et al (2019) Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. Calcif Tissue Int 105(3):271–284

    Article  CAS  PubMed  Google Scholar 

  10. Ruppe MD et al (2016) Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia. Bone reports 5:158–162

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jan de Beur, S., et al., Burosumab improves the biochemical, skeletal, and clinical symptoms of tumor-induced osteomalacia (TIO) syndrome, in World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. 2019: Paris, France.

  12. Bhattacharyya N et al (2012) Fibroblast growth factor 23: state of the field and future directions. Trends Endocrinol Metab 23(12):610–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tagliabracci VS et al (2014) Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. Proc Natl Acad Sci U S A 111(15):5520–5525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Erben RG (2016) Update on FGF23 and Klotho signaling. Mol Cell Endocrinol 432:56–65

    Article  CAS  PubMed  Google Scholar 

  15. Andrukhova O et al (2012) FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 51(3):621–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shimada T et al (2004) Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113(4):561–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Albright F, Butler AM, Bloomberg E (1937) RICKETS RESISTANT TO VITAMIN D THERAPY. Am J Dis Child 54(3):529–547

    Google Scholar 

  18. Eicher EM et al (1976) Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci U S A 73(12):4667–4671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Morgan JM et al (1974) Renal transplantation in hypophosphatemia with vitamin D-resistant rickets. Arch Intern Med 134(3):549–552

    Article  CAS  PubMed  Google Scholar 

  20. Meyer RA Jr, Meyer MH, Gray RW (1989) Parabiosis suggests a humoral factor is involved in X-linked hypophosphatemia in mice. J Bone Miner Res 4(4):493–500

    Article  PubMed  Google Scholar 

  21. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets (1995) The HYP Consortium. Nat Genet 11(2):130–136

    Article  Google Scholar 

  22. White KE, Evans WE (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26(3):345–348

    Article  CAS  Google Scholar 

  23. Shimada T et al (2001) Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 98(11):6500–6505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jonsson KB et al (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348(17):1656–1663

    Article  CAS  PubMed  Google Scholar 

  25. Yamazaki Y et al (2002) Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87(11):4957–4960

    Article  CAS  PubMed  Google Scholar 

  26. Addison WN et al (2010) Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage. J Bone Miner Res 25(4):695–705

    CAS  PubMed  Google Scholar 

  27. Barros NM et al (2013) Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. J Bone Miner Res 28(3):688–699

    Article  CAS  PubMed  Google Scholar 

  28. David V et al (2011) ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate. Am J Physiol Renal Physiol 300(3):F783–F791

    Article  CAS  PubMed  Google Scholar 

  29. Beck-Nielsen SS et al (2009) Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol 160(3):491–497

    Article  CAS  PubMed  Google Scholar 

  30. Rafaelsen S et al (2016) Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol 174(2):125–136

    Article  CAS  PubMed  Google Scholar 

  31. Ruppe, M.D., X-Linked Hypophosphatemia, in GeneReviews (Internet), M.P. Adam, et al., Editors. 1993, University of Washington, Seattle; 1993–2019.: Seattle (WA).

  32. Rothenbuhler A et al (2019) High Incidence of Cranial Synostosis and Chiari I Malformation in Children With X-Linked Hypophosphatemic Rickets (XLHR). J Bone Miner Res 34(3):490–496

    Article  CAS  PubMed  Google Scholar 

  33. Turan S et al (2010) Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia. Bone 46(2):402–409

    Article  CAS  PubMed  Google Scholar 

  34. Pesta DH et al (2016) Hypophosphatemia promotes lower rates of muscle ATP synthesis. Faseb j 30(10):3378–3387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Connor J et al (2015) Conventional Therapy in Adults With X-Linked Hypophosphatemia: Effects on Enthesopathy and Dental Disease. J Clin Endocrinol Metab 100(10):3625–3632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liang G et al (2009) Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice. Calcif Tissue Int 85(3):235–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hirao Y et al (2016) Extensive ossification of the paraspinal ligaments in a patient with vitamin D-resistant rickets: Case report with literature review. Int J Surg Case Rep 27:125–128

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shiba M et al (2015) Cervical ossification of posterior longitudinal ligament in x-linked hypophosphatemic rickets revealing homogeneously increased vertebral bone density. Asian Spine J 9(1):106–109

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chesher D et al (2018) Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis 41(5):865–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fishman G et al (2004) Hearing impairment in familial X-linked hypophosphatemic rickets. Eur J Pediatr 163(10):622–623

    PubMed  Google Scholar 

  41. Carpenter TO et al (2011) A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res 26(7):1381–1388

    Article  PubMed  Google Scholar 

  42. Carpenter TO et al (1994) Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia. J Clin Endocrinol Metab 78(6):1378–1383

    CAS  PubMed  Google Scholar 

  43. Baroncelli GI et al (2001) Effect of growth hormone treatment on final height, phosphate metabolism, and bone mineral density in children with X-linked hypophosphatemic rickets. J Pediatr 138(2):236–243

    Article  CAS  PubMed  Google Scholar 

  44. Haffner D et al (2004) Effects of growth hormone treatment on body proportions and final height among small children with X-linked hypophosphatemic rickets. Pediatrics 113(6):e593–e596

    Article  PubMed  Google Scholar 

  45. Zivicnjak M et al (2011) Three-year growth hormone treatment in short children with X-linked hypophosphatemic rickets: effects on linear growth and body disproportion. J Clin Endocrinol Metab 96(12):E2097–E2105

    Article  CAS  PubMed  Google Scholar 

  46. Alon U, Chan JC (1985) Effects of hydrochlorothiazide and amiloride in renal hypophosphatemic rickets. Pediatrics 75(4):754–763

    CAS  PubMed  Google Scholar 

  47. Seikaly MG, Baum M (2001) Thiazide diuretics arrest the progression of nephrocalcinosis in children with X-linked hypophosphatemia. Pediatrics 108(1):E6

    Article  CAS  PubMed  Google Scholar 

  48. Carpenter TO et al (1996) 24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets–a clinical research center study. J Clin Endocrinol Metab 81(6):2381–2388

    CAS  PubMed  Google Scholar 

  49. Sullivan W et al (1992) A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 75(3):879–885

    CAS  PubMed  Google Scholar 

  50. Carpenter TO et al (2014) Effect of paricalcitol on circulating parathyroid hormone in X-linked hypophosphatemia: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 99(9):3103–3111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Imel EA et al (2015) Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab 100(7):2565–2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ruppe MD et al (2016) Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia. Bone Rep 5:158–162

    Article  PubMed  PubMed Central  Google Scholar 

  53. Benet-Pages A et al (2004) FGF23 is processed by proprotein convertases but not by PHEX. Bone 35(2):455–462

    Article  CAS  PubMed  Google Scholar 

  54. Econs MJ, McEnery PT (1997) Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder. J Clin Endocrinol Metab 82(2):674–681

    Article  CAS  PubMed  Google Scholar 

  55. Wolf M, White KE (2014) Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens 23(4):411–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Imel, E.A., et al., Oral Iron Replacement Normalizes Fibroblast Growth Factor 23 in Iron-Deficient Patients With Autosomal Dominant Hypophosphatemic Rickets. J Bone Miner Res, 2019.

  57. Steichen-Gersdorf E et al (2015) Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1. J Pediatr Endocrinol Metab 28(7–8):967–970

    CAS  PubMed  Google Scholar 

  58. Feng JQ et al (2006) Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 38(11):1310–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ichikawa S et al (2017) A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice. Endocrinology 158(3):470–476

    Article  CAS  PubMed  Google Scholar 

  60. Folpe AL et al (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):1–30

    Article  PubMed  Google Scholar 

  61. Carpenter TO et al (2005) Fibroblast growth factor 7: an inhibitor of phosphate transport derived from oncogenic osteomalacia-causing tumors. J Clin Endocrinol Metab 90(2):1012–1020

    Article  CAS  PubMed  Google Scholar 

  62. De Beur SM et al (2002) Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res 17(6):1102–1110

    Article  PubMed  Google Scholar 

  63. Florenzano P, Gafni RI, Collins MT (2017) Tumor-induced osteomalacia Bone reports 7:90–97

    Article  PubMed  Google Scholar 

  64. Nakahama H et al (1995) Prostate cancer-induced oncogenic hypophosphatemic osteomalacia. Urol Int 55(1):38–40

    Article  CAS  PubMed  Google Scholar 

  65. Narvaez J et al (2005) Acquired hypophosphatemic osteomalacia associated with multiple myeloma. Joint Bone Spine 72(5):424–426

    Article  PubMed  Google Scholar 

  66. Sanders, L., The young woman was a healthy and avid runner. Now she could barely walk. Why?, in The New York Times. 2018: New York, NY. p. 20.

  67. Jan De Beur S et al (2019) OR13–1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome. Journal of the Endocrine Society 2019:2019. https://doi.org/10.1210/js.2019-OR13-1

    Article  Google Scholar 

  68. Lee JC et al (2015) Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour. J Pathol 235(4):539–545

    Article  CAS  PubMed  Google Scholar 

  69. El-Maouche D et al (2016) (68)Ga-DOTATATE for Tumor Localization in Tumor-Induced Osteomalacia. The Journal of clinical endocrinology and metabolism 101(10):3575–3581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jan de Beur SM et al (2002) Localisation of mesenchymal tumours by somatostatin receptor imaging. Lancet 359(9308):761–763

    Article  CAS  PubMed  Google Scholar 

  71. Hesse E et al (2007) Oncogenic osteomalacia: exact tumor localization by co-registration of positron emission and computed tomography. J Bone Miner Res 22(1):158–162

    Article  CAS  PubMed  Google Scholar 

  72. Hesse E, Rosenthal H, Bastian L (2007) Radiofrequency ablation of a tumor causing oncogenic osteomalacia. N Engl J Med 357(4):422–424

    Article  CAS  PubMed  Google Scholar 

  73. Wild D et al (2005) 68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur J Nucl Med Mol Imaging 32(6):724

    Article  PubMed  Google Scholar 

  74. Zhang J et al (2015) 68Ga DOTATATE PET/CT is an Accurate Imaging Modality in the Detection of Culprit Tumors Causing Osteomalacia. Clin Nucl Med 40(8):642–646

    Article  PubMed  Google Scholar 

  75. Bhavani N et al (2016) Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced osteomalacia. Clin Endocrinol 84(1):134–140

    Article  CAS  Google Scholar 

  76. Rayamajhi SJ et al (2019) Tumor-induced osteomalacia - Current imaging modalities and a systematic approach for tumor localization. Clin Imaging 56:114–123

    Article  PubMed  Google Scholar 

  77. Maybody M et al (2016) Ga-68 DOTATOC PET/CT-Guided Biopsy and Cryoablation with Autoradiography of Biopsy Specimen for Treatment of Tumor-Induced Osteomalacia. Cardiovasc Intervent Radiol 39(9):1352–1357

    Article  PubMed  PubMed Central  Google Scholar 

  78. Basu S, Fargose P (2016) 177Lu-DOTATATE PRRT in Recurrent Skull-Base Phosphaturic Mesenchymal Tumor Causing Osteomalacia: A Potential Application of PRRT Beyond Neuroendocrine Tumors. Journal of nuclear medicine technology 44(4):248–250

    Article  PubMed  Google Scholar 

  79. Chong WH et al (2011) The importance of whole body imaging in tumor-induced osteomalacia. The Journal of clinical endocrinology and metabolism 96(12):3599–3600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Collins, M.T., et al., Striking Response of Tumor-Induced Osteomalacia to the FGFR Inhibitor NVP-BGJ398. J Bone Miner Res, 2015. 28(Supplement 1): p. Available at https://www.asbmr.org/education/AbstractDetail?aid=c5464be6-d873-49f3-bb71-719e2198867e. Accessed January 8, 2020.

  81. Baia LC et al (2015) Phosphate and FGF-23 homeostasis after kidney transplantation. Nat Rev Nephrol 11(11):656–666

    Article  CAS  PubMed  Google Scholar 

  82. Okada M et al (1982) 2 cases of nonspecific multiple ulcers of the small intestine associated with osteomalacia caused by long-term intravenous administration of saccharated ferric oxide. Nihon Naika Gakkai Zasshi 71(11):1566–1572

    Article  CAS  PubMed  Google Scholar 

  83. Okada M et al (1983) Hypophosphatemia induced by intravenous administration of Saccharated iron oxide. Klin Wochenschr 61(2):99–102

    Article  CAS  PubMed  Google Scholar 

  84. Sato K et al (1997) Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin D production in renal tubules. Bone 21(1):57–64

    Article  CAS  PubMed  Google Scholar 

  85. Sato K, Shiraki M (1998) Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J 45(4):431–439

    Article  CAS  PubMed  Google Scholar 

  86. Schouten BJ et al (2009) Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem 46(Pt 2):167–169

    Article  PubMed  Google Scholar 

  87. Yamamoto S et al (2012) Fibroblast growth factor 23-related osteomalacia caused by the prolonged administration of saccharated ferric oxide. Intern Med 51(17):2375–2378

    Article  PubMed  Google Scholar 

  88. Imamura K (1984) Effects of intravenous administration of iron preparations on the metabolism of phosphorus Comparative study on 3 iron preparations. Fukuoka Igaku Zasshi 75(6):316–326

    CAS  PubMed  Google Scholar 

  89. Schaefer B et al (2016) Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk. PLoS ONE 11(12):e0167146

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Felsenfeld AJ et al (1986) Hypophosphatemia in long-term renal transplant recipients: effects on bone histology and 1,25-dihydroxycholecalciferol. Miner Electrolyte Metab 12(5–6):333–341

    CAS  PubMed  Google Scholar 

  91. Levi M (2001) Post-transplant hypophosphatemia. Kidney Int 59(6):2377–2387

    Article  CAS  PubMed  Google Scholar 

  92. Moorhead JF et al (1974) Hypophosphataemic osteomalacia after cadaveric renal transplantation. Lancet 1(7860):694–697

    Article  CAS  PubMed  Google Scholar 

  93. Rosenbaum RW et al (1981) Decreased phosphate reabsorption after renal transplantation: Evidence for a mechanism independent of calcium and parathyroid hormone. Kidney Int 19(4):568–578

    Article  CAS  PubMed  Google Scholar 

  94. Evenepoel P et al (2007) Tertiary 'hyperphosphatoninism' accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant 7(5):1193–1200

    Article  CAS  PubMed  Google Scholar 

  95. Cianciolo G, Cozzolino M (2016) FGF23 in kidney transplant: the strange case of Doctor Jekyll and Mister Hyde. Clin Kidney J 9(5):665–668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Alshayeb HM, Josephson MA, Sprague SM (2013) CKD-mineral and bone disorder management in kidney transplant recipients. Am J Kidney Dis 61(2):310–325

    Article  CAS  PubMed  Google Scholar 

  97. Cianciolo G et al (2016) Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy. Am J Nephrol 43(6):397–407

    Article  CAS  PubMed  Google Scholar 

  98. Nafidi O et al (2009) Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia. Ann Surg 249(5):824–827

    Article  PubMed  Google Scholar 

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  1. Department of Medicine Section of Endocrinology, Yale School of Medicine, PO Box 802080, New Haven, CT, 06520, USA

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Athonvarangkul, D., Insogna, K.L. New Therapies for Hypophosphatemia-Related to FGF23 Excess. Calcif Tissue Int 108, 143–157 (2021). https://doi.org/10.1007/s00223-020-00705-3

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