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A decrease in serum 1,25(OH)2D after elective hip replacement and during bone healing is associated with changes in serum iron and plasma FGF23

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Abstract

Objective

Although calcitriol is essential for bone healing, its serum concentrations are low after hip surgery, and they continue to decline during bone healing. This study aimed to test the hypothesis of an association of changes in calcitriol production with the status of fibroblast growth factor 23 (FGF23) and iron deficiency after elective hip replacement for coxarthrosis.

Methods

In this prospective study, we measured the biomarkers of 17 patients undergoing elective hip replacement on admission, on the first day after surgery, and at the regular check-up after 48 ± 8 days. The serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, transferrin, ferritin, parathyroid hormone, intact plasma FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) were determined.

Results

In our patients who underwent elective hip replacement, significant correlations existed between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron.

Conclusions

The production of calcitriol is compromised after elective hip replacement surgery, leading to reduced levels of active vitamin D in the serum. Significant correlations between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron on the first day as well as 7 weeks after surgery could inspire future studies to determine whether and how calcitriol deficiency should be corrected, especially in fracture cases.

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References

  1. Kanis JA, Johnell O, Oden A et al (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang N, Chen Y, Ji J et al (2020) The relationship between serum vitamin D and fracture risk in the elderly: a meta-analysis. J Orthop Surg Res 15:81

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lips P, Netelenbos JC, Jongen MJM et al (1982) Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metab Bone Dis Rel Res 4:85–93

    Article  CAS  Google Scholar 

  4. Meller Y, Kestenbaum RS, Shany S et al (1985) Parathormone, calcitonin, and vitamin D metabolites during normal fracture healing in geriatric patients. Clin Orthop Relat Res 199:272–279

    Article  Google Scholar 

  5. Yu-Yahiro JA, Michael RH, Dubin NH et al (2001) Serum and urine markers of bone metabolism during the year after hip fracture. J Am Geriatr Soc 49:877–883

    Article  CAS  PubMed  Google Scholar 

  6. Briggs AD, Kuan V, Greiller CL et al (2013) Longitudinal study of vitamin D metabolites after long bone fracture. J Bone Miner Res 28:1301–1307

    Article  CAS  PubMed  Google Scholar 

  7. Blomberg Jensen M, Husted H, Bjerrum PJ et al (2018) Compromised activation of vitamin D after elective surgery: a prospective pilot study. JBMR Plus 2:281–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zura R, Xiong Z, Einhorn T et al (2016) Epidemiology of fracture nonunion in 18 human bones. JAMA Surg 151:e162775

    Article  PubMed  Google Scholar 

  9. Sim DS, Tay K, Howe TS et al (2021) Preoperative severe vitamin D deficiency is a significant independent risk factor for poorer functional outcome and quality of life 6 months after surgery for fragility hip fractures. Osteoporos Int 32:2217–2224

    Article  CAS  PubMed  Google Scholar 

  10. Bouillon R, Carmeliet G, Verlinden L et al (2008) Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 29:726–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fu L, Tang T, Miao Y et al (2009) Effect of 1,25-dihydroxy vitamin D3 on fracture healing and bone remodeling in ovariectomized rat femora. Bone 44:893–898

    Article  CAS  PubMed  Google Scholar 

  12. Lips P (2007) Relative value of 25(OH)D and 1,25(OH)2D measurements. J Bone Miner Res 22:1668–1671

    Article  CAS  PubMed  Google Scholar 

  13. Meller Y, Shainkin-Kestenbaum R, Shany S et al (1984) Parathyroid hormone, calcitonin, and vitamin D metabolites during normal fracture healing in humans. A preliminary report. Clin Orthop Relat Res 183:238–245

    Article  CAS  Google Scholar 

  14. Lidor C, Dekel S, Edelstein S (1987) The metabolism of vitamin D3 during fracture healing in chicks. Endocrinology 120:389–393

    Article  CAS  PubMed  Google Scholar 

  15. Alkalay D, Shany S, Dekel S (1989) Serum and bone vitamin D metabolites in elective patients and patients after fracture. J Bone Jt Surg Br 71:85–87

    Article  CAS  Google Scholar 

  16. Kato A, Bishop JE, Norman AW (1998) Evidence for a 1 alpha,25-dihydroxyvitamin D3 receptor/binding protein in a membrane fraction isolated from a chick tibial fracture-healing callus. Biochem Biophys Res Commun 244:724–727

    Article  CAS  PubMed  Google Scholar 

  17. Tauber C, Noff D, Noff M et al (1990) Blood levels of active metabolites of vitamin D3 in fracture repair in humans. A preliminary report. Arch Orthop Trauma Surg 109:265–267

    Article  CAS  PubMed  Google Scholar 

  18. Jingushi S, Iwaki A, Higuchi O et al (1998) Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing. Endocrinology 139:1467–1473

    Article  CAS  PubMed  Google Scholar 

  19. St-Arnaud R, Naja RP (2011) Vitamin D metabolism, cartilage and bone fracture repair. Mol Cell Endocrinol 347:48–54

    Article  CAS  PubMed  Google Scholar 

  20. Yoshiko Y, Wang H, Minamizaki T et al (2007) Mineralized tissue cells are a principal source of FGF23. Bone 40:1565–1573

    Article  CAS  PubMed  Google Scholar 

  21. Goebel S, Lienau J, Rammoser U et al (2009) FGF23 is a putative marker for bone healing and regeneration. J Orthop Res 27:1141–1146

    Article  CAS  PubMed  Google Scholar 

  22. Verstuyf A, Carmeliet G, Bouillon R et al (2010) Vitamin D: a pleiotropic hormone. Kidney Int 78:140–145

    Article  CAS  PubMed  Google Scholar 

  23. Quarles LD (2012) Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol 8:276–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bosworth C, de Boer IH (2013) Impaired vitamin D metabolism in CKD. Semin Nephrol 33:158–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vaculik J, Wenchich L, Bobelyak M et al (2021) Decrease in serum calcitriol (but not free 25-hydroxyvitamin D) concentration in hip fracture healing. J Endocrinol Invest 44:1847–1855

    Article  CAS  PubMed  Google Scholar 

  26. Rupp T, Butscheidt S, Vettorazzi E et al (2019) High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis. Osteoporos Int 30:1655–1662

    Article  CAS  PubMed  Google Scholar 

  27. David V, Martin A, Isakova T et al (2016) Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 89:135–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hanudel MR, Chua K, Rappaport M et al (2016) Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice. Am J Physiol Renal Physiol 311:F1369–F1377

    Article  PubMed  PubMed Central  Google Scholar 

  29. Edmonston D, Wolf M (2020) FGF23 at the crossroads of phosphate, iron economy and erythropoiesis. Nat Rev Nephrol 16:7–19

    Article  CAS  PubMed  Google Scholar 

  30. Farrow EG, Yu X, Summers LJ et al (2011) Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A 108:E1146-1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hannemann A, Nauck M, Volzke H et al (2021) Interactions of anemia, FGF-23, and bone in healthy adults-results from the study of health in pomerania (SHIP). J Clin Endocrinol Metab 106:e288–e299

    Article  PubMed  Google Scholar 

  32. Imel EA, Peacock M, Gray AK et al (2011) Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab 96:3541–3549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Katsumata S, Katsumata-Tsuboi R, Uehara M et al (2009) Severe iron deficiency decreases both bone formation and bone resorption in rats. J Nutr 139:238–243

    Article  CAS  PubMed  Google Scholar 

  34. Braithwaite V, Prentice AM, Doherty C et al (2012) FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study. Int J Pediatr Endocrinol 2012:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Braithwaite V, Jarjou LM, Goldberg GR et al (2012) Iron status and fibroblast growth factor-23 in Gambian children. Bone 50:1351–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Braithwaite V, Jones KS, Assar S et al (2014) Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children. Endocr Connect 3:1–10

    Article  PubMed  CAS  Google Scholar 

  37. Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  38. Pasquali M, Tartaglione L, Rotondi S et al (2015) Calcitriol/calcifediol ratio: an indicator of vitamin D hydroxylation efficiency? BBA clinical 3:251–256

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wolf M, Koch TA, Bregman DB (2013) Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res 28:1793–1803

    Article  CAS  PubMed  Google Scholar 

  40. Lewerin C, Ljunggren O, Nilsson-Ehle H et al (2017) Low serum iron is associated with high serum intact FGF23 in elderly men: the Swedish MrOS study. Bone 98:1–8

    Article  CAS  PubMed  Google Scholar 

  41. Bozentowicz-Wikarek M, Kocelak P, Owczarek A et al (2015) Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population? Clin Biochem 48:431–436

    Article  CAS  PubMed  Google Scholar 

  42. Ratsma DMA, Zillikens MC, van der Eerden BCJ (2021) Upstream regulators of fibroblast growth factor 23. Front Endocrinol 12:45

    Article  Google Scholar 

  43. Sim JJ, Lac PT, Liu IL et al (2010) Vitamin D deficiency and anemia: a cross-sectional study. Ann Hematol 89:447–452

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Alena Adamová, Ludmila Hauptvoglová and Tereza Malá and for their excellent technical assistance in this project, and Xiao Svec for proofreading the manuscript.

Funding

This investigation was supported by the project for conceptual development of research organization 00023728 (Institute of Rheumatology, Prague, Czech Republic).

Author information

Authors and Affiliations

  1. Orthopedic Department, Bulovka Hospital, Prague, Czech Republic

    J. Vaculik & M. Bobelyak

  2. Institute of Rheumatology, Prague, Czech Republic

    L. Wenchich, K. Pavelka & J. J. Stepan

  3. Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic

    K. Pavelka & J. J. Stepan

  4. Third Faculty of Medicine, Charles University, Prague, Czech Republic

    J. Vaculik & M. Bobelyak

  5. Orthopedic Department, First Faculty of Medicine, Charles University, Prague, Czech Republic

    J. Vaculik

Authors
  1. J. Vaculik
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  2. L. Wenchich
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  3. M. Bobelyak
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  4. K. Pavelka
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Contributions

All authors participated in drafting or revising this manuscript. All authors had access to the data, and have read and accepted the final version of the manuscript for submission. All authors take responsibility for the integrity of the data and the accuracy of the data analysis. JV and MB performed clinical assessment, followed-up with patients, and interpreted the data. LW. contributed to biochemical determination and data analysis. KP performed critical revisions of the manuscript. JJS designed this study, performed data analysis and prepared the manuscript.

Corresponding author

Correspondence to J. J. Stepan.

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Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study.

Ethical approval

All procedures performed in the present study involving humans were in accordance with the institutional research committee and with the principles of the Declaration of Helsinki. The study was approved by the Institutional Review Board of the Bulovka Hospital, Prague, Czech Republic.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Vaculik, J., Wenchich, L., Bobelyak, M. et al. A decrease in serum 1,25(OH)2D after elective hip replacement and during bone healing is associated with changes in serum iron and plasma FGF23. J Endocrinol Invest 45, 1039–1044 (2022). https://doi.org/10.1007/s40618-022-01746-1

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  • DOI: https://doi.org/10.1007/s40618-022-01746-1

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