Skip to main content

Advertisement

SpringerLink
Log in

The Transplant Recipient and Issues in Bone Metabolism

  • Original Paper
  • Published:
Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Changes in mineral metabolism parameters and the skeleton are commonly seen in kidney transplant recipients, especially in the first 6 months post-transplant. They include correction of complications of end-stage kidney disease, such as hypocalcemia, hyperphosphatemia and secondary hyperparathyroidism—although the latter itself may not resolve fully or may develop de novo with time. Hypercalcemia and hypophosphatemia may occur due to imbalance of their respective regulatory hormones or effects of immunosuppressive medications. Bone formation tends to decrease, and although significant loss of bone mineral density is common, the association of these changes with the significantly increased fracture risk is not well established. Therapeutic approaches have included the use of calcium, vitamin D compounds, bisphosphonates, or calcimimetics which have positively impacted bone mineral density; however, limited data are available in regard to fracture prevention. Thus, studies assessing hard clinical outcomes are urgently needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

PTH:

Parathyroid hormone

BMD:

Bone mineral density

VDR:

Vitamin D receptor

References

  1. (OPTN). OPaTN. National Data, Kidney Graft/Patient Survival. OPTN Web site. Accessed August 6, 2011.

  2. Nikkel LE, Hollenbeak CS, Fox EJ, Uemura T, Ghahramani N. Risk of fractures after renal transplantation in the United States. Transplantation. 2009;87(12):1846–51.

    Google Scholar 

  3. Vautour LM, Melton LJ 3rd, Clarke BL, Achenbach SJ, Oberg AL, McCarthy JT. Long-term fracture risk following renal transplantation: a population-based study. Osteoporos Int. 2004;15(2):160–7.

    Article  PubMed  Google Scholar 

  4. Uhlig K, Berns JS, Kestenbaum B, Kumar R, Leonard MB, Martin KJ, et al. KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD-MBD). Am J Kidney Dis. 2010;55(5):773–99.

    Article  PubMed  Google Scholar 

  5. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2006;69(11):1945–53.

    Article  PubMed  CAS  Google Scholar 

  6. Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson KB. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003;64(6):2272–9.

    Article  PubMed  CAS  Google Scholar 

  7. Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005;16(7):2205–15.

    Google Scholar 

  8. Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79(12):1370–8.

    Article  PubMed  CAS  Google Scholar 

  9. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. 2001;12(10):2131–8.

    PubMed  CAS  Google Scholar 

  10. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005;16(2):520–8.

    Article  PubMed  CAS  Google Scholar 

  11. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the dialysis outcomes and practice patterns study (DOPPS). Am J Kidney Dis. 2008;52(3):519–30.

    Article  PubMed  CAS  Google Scholar 

  12. Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359(6):584–92.

    Google Scholar 

  13. Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305(23):2432–9.

    Google Scholar 

  14. Sprague SM, Belozeroff V, Danese MD, Martin LP, Olgaard K. Abnormal bone and mineral metabolism in kidney transplant patients—a review. Am J Nephrol. 2008;28(2):246–53.

    Article  PubMed  CAS  Google Scholar 

  15. Mikuls TR, Julian BA, Bartolucci A, Saag KG. Bone mineral density changes within six months of renal transplantation. Transplantation. 2003;75(1):49–54.

    Google Scholar 

  16. Marcen R, Caballero C, Pascual J, Teruel JL, Tenorio M, Ocana J, et al. Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study. Transplantation. 2006;81(6):826–31.

    Google Scholar 

  17. Ball AM, Gillen DL, Sherrard D, Weiss NS, Emerson SS, Seliger SL, et al. Risk of hip fracture among dialysis and renal transplant recipients. JAMA. 2002;288(23):3014–8.

    Google Scholar 

  18. Weisinger JR, Carlini RG, Rojas E, Bellorin-Font E. Bone disease after renal transplantation. Clin J Am Soc Nephrol. 2006;1(6):1300–13.

    Article  PubMed  CAS  Google Scholar 

  19. Epstein S. Post-transplantation bone disease: the role of immunosuppressive agents and the skeleton. J Bone Miner Res. 1996;11(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  20. Josephson MA, Schumm LP, Chiu MY, Marshall C, Thistlethwaite JR, Sprague SM. Calcium and calcitriol prophylaxis attenuates posttransplant bone loss. Transplantation. 2004;78(8):1233–6.

    Google Scholar 

  21. Cueto-Manzano AM, Konel S, Hutchison AJ, Crowley V, France MW, Freemont AJ, et al. Bone loss in long-term renal transplantation: histopathology and densitometry analysis. Kidney Int. 1999;55(5):2021–9.

    Article  PubMed  CAS  Google Scholar 

  22. Ozel L, Ata P, Ozel MS, Toros AB, Kara M, Unal E, et al. Risk factors for osteoporosis after renal transplantation and effect of vitamin D receptor Bsm I polymorphism. Transplant Proc. 2011;43(3):858–62.

    Article  PubMed  CAS  Google Scholar 

  23. Torres A, Garcia S, Gomez A, Gonzalez A, Barrios Y, Concepcion MT, et al. Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation. Kidney Int. 2004;65(2):705–12.

    Article  PubMed  CAS  Google Scholar 

  24. Egbuna OI, Taylor JG, Bushinsky DA, Zand MS. Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure. Clin Transplant. 2007;21(4):558–66.

    Google Scholar 

  25. Green J, Debby H, Lederer E, Levi M, Zajicek HK, Bick T. Evidence for a PTH-independent humoral mechanism in post-transplant hypophosphatemia and phosphaturia. Kidney Int. 2001;60(3):1182–96.

    Article  PubMed  CAS  Google Scholar 

  26. Schwarz C, Bohmig GA, Steininger R, Mayer G, Oberbauer R. Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression. Nephrol Dial Transplant. 2001;16(2):378–82.

    Article  PubMed  CAS  Google Scholar 

  27. Ghanekar H, Welch BJ, Moe OW, Sakhaee K. Post-renal transplantation hypophosphatemia: a review and novel insights. Curr Opin Nephrol Hypertens. 2006;15(2):97–104.

    Article  PubMed  CAS  Google Scholar 

  28. Economidou D, Dovas S, Papagianni A, Pateinakis P, Memmos D. FGF-23 levels before and after renal transplantation. J Transplant. 2009;2009:379082.

    PubMed  Google Scholar 

  29. Bhan I, Shah A, Holmes J, Isakova T, Gutierrez O, Burnett SM, et al. Post-transplant hypophosphatemia: tertiary ‘Hyper-Phosphatoninism’? Kidney Int. 2006;70(8):1486–94.

    Article  PubMed  CAS  Google Scholar 

  30. Seeherunvong W, Wolf M. Tertiary excess of fibroblast growth factor 23 and hypophosphatemia following kidney transplantation. Pediatr Transplant. 2011;15(1):37–46.

    Article  PubMed  Google Scholar 

  31. Wolf M, Molnar MZ, Amaral AP, Czira ME, Rudas A, Ujszaszi A, et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol. 2011;22(5):956–66.

    Article  PubMed  CAS  Google Scholar 

  32. Wesseling-Perry K, Tsai EW, Ettenger RB, Juppner H, Salusky IB. Mineral abnormalities and long-term graft function in pediatric renal transplant recipients: a role for FGF-23? Nephrol Dial Transplant. 2011.

  33. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009(113):S1–S130.

  34. Monier-Faugere MC, Mawad H, Qi Q, Friedler RM, Malluche HH. High prevalence of low bone turnover and occurrence of osteomalacia after kidney transplantation. J Am Soc Nephrol. 2000;11(6):1093–9.

    PubMed  CAS  Google Scholar 

  35. Rojas E, Carlini RG, Clesca P, Arminio A, Suniaga O, De Elguezabal K, et al. The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling. Kidney Int. 2003;63(5):1915–23.

    Article  PubMed  Google Scholar 

  36. Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med. 1991;325(8):544–50.

    Google Scholar 

  37. Conley E, Muth B, Samaniego M, Lotfi M, Voss B, Armbrust M, et al. Bisphosphonates and bone fractures in long-term kidney transplant recipients. Transplantation. 2008;86(2):231–7.

    Google Scholar 

  38. Durieux S, Mercadal L, Orcel P, Dao H, Rioux C, Bernard M, et al. Bone mineral density and fracture prevalence in long-term kidney graft recipients. Transplantation. 2002;74(4):496–500.

    Google Scholar 

  39. Akaberi S, Simonsen O, Lindergard B, Nyberg G. Can DXA predict fractures in renal transplant patients? Am J Transplant. 2008;8(12):2647–51.

    Article  PubMed  CAS  Google Scholar 

  40. Leonard MB. A structural approach to skeletal fragility in chronic kidney disease. Semin Nephrol. 2009;29(2):133–43.

    Article  PubMed  Google Scholar 

  41. Nickolas TL, Stein E, Cohen A, Thomas V, Staron RB, McMahon DJ, et al. Bone mass and microarchitecture in CKD patients with fracture. J Am Soc Nephrol. 2010;21(8):1371–80.

    Article  PubMed  Google Scholar 

  42. Bacchetta J, Boutroy S, Vilayphiou N, Juillard L, Guebre-Egziabher F, Rognant N, et al. Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease. J Bone Miner Res. 2010;25(4):849–57.

    PubMed  Google Scholar 

  43. Edwards BJ DA, Tsai J. Elevated incidence of Fractures in Solid Organ Transplant Recipients on glucocorticoid-sparing immuno-suppressive regimens. J Osteopor. 2011;in press.

  44. Pascual J, Zamora J, Galeano C, Royuela A, Quereda C. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2009(1):CD005632.

  45. Grotz W, Nagel C, Poeschel D, Cybulla M, Petersen KG, Uhl M, et al. Effect of ibandronate on bone loss and renal function after kidney transplantation. J Am Soc Nephrol. 2001;12(7):1530–7.

    Google Scholar 

  46. Copley JB, Germain M, Stern L, Pankewycz O, Katznelson S, Shah T, et al. Evaluation of cinacalcet HCl treatment after kidney transplantation. Transplant Proc. 2010;42(7):2503–8.

    Article  PubMed  CAS  Google Scholar 

  47. Borchhardt KA, Diarra D, Sulzbacher I, Benesch T, Haas M, Sunder-Plassmann G. Cinacalcet decreases bone formation rate in hypercalcemic hyperparathyroidism after kidney transplantation. Am J Nephrol. 2010;31(6):482–9.

    Article  PubMed  Google Scholar 

  48. Cejka D, Benesch T, Krestan C, Roschger P, Klaushofer K, Pietschmann P, et al. Effect of teriparatide on early bone loss after kidney transplantation. Am J Transplant. 2008;8(9):1864–70.

    Article  PubMed  CAS  Google Scholar 

  49. De Sevaux RG, Hoitsma AJ, Corstens FH, Wetzels JF. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol. 2002;13(6):1608–14.

    Article  PubMed  Google Scholar 

  50. Jeffery JR, Leslie WD, Karpinski ME, Nickerson PW, Rush DN. Prevalence and treatment of decreased bone density in renal transplant recipients: a randomized prospective trial of calcitriol versus alendronate. Transplantation. 2003;76(10):1498–502.

    Google Scholar 

  51. Cueto-Manzano AM, Konel S, Freemont AJ, Adams JE, Mawer B, Gokal R, et al. Effect of 1, 25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation. Am J Kidney Dis. 2000;35(2):227–36.

    Article  PubMed  CAS  Google Scholar 

  52. Mainra R, Elder GJ. Individualized therapy to prevent bone mineral density loss after kidney and kidney-pancreas transplantation. Clin J Am Soc Nephrol. 2010;5(1):117–24.

    Article  PubMed  Google Scholar 

  53. Abediazar S, Nakhjavani MR. Effect of alendronate on early bone loss of renal transplant recipients. Transplant Proc. 2011;43(2):565–7.

    Article  PubMed  CAS  Google Scholar 

  54. Coco M, Glicklich D, Faugere MC, Burris L, Bognar I, Durkin P, et al. Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate. J Am Soc Nephrol. 2003;14(10):2669–76.

    Article  PubMed  CAS  Google Scholar 

  55. Lan G, Peng L, Xie X, Peng F, Wang Y, Yu S. Alendronate is effective to treat bone loss in renal transplantation recipients. Transplant Proc. 2008;40(10):3496–8.

    Article  PubMed  CAS  Google Scholar 

  56. Serra AL, Schwarz AA, Wick FH, Marti HP, Wuthrich RP. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20(7):1315–9.

    Google Scholar 

  57. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20(7):1311–4.

    Google Scholar 

  58. Leca N, Laftavi M, Gundroo A, Kohli R, Min I, Karam J, et al. Early and severe hyperparathyroidism associated with hypercalcemia after renal transplant treated with cinacalcet. Am J Transplant. 2006;6(10):2391–5.

    Article  PubMed  CAS  Google Scholar 

  59. Szwarc I, Argiles A, Garrigue V, Delmas S, Chong G, Deleuze S, et al. Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism. Transplantation. 2006;82(5):675–80.

    Google Scholar 

  60. Apostolou T, Kollia K, Damianou L, Kaitsioti H, Kotsiev V, Dracopoulos S, et al. Hypercalcemia due to resistant hyperparathyroidism in renal transplant patients treated with the calcimimetic agent cinacalcet. Transplant Proc. 2006;38(10):3514–6.

    Article  PubMed  CAS  Google Scholar 

  61. El-Amm JM, Doshi MD, Singh A, Migdal S, Morawski K, Sternbauer D, et al. Preliminary experience with cinacalcet use in persistent secondary hyperparathyroidism after kidney transplantation. Transplantation. 2007;83(5):546–9.

    Google Scholar 

  62. Srinivas TR, Schold JD, Womer KL, Kaplan B, Howard RJ, Bucci CM, et al. Improvement in hypercalcemia with cinacalcet after kidney transplantation. Clin J Am Soc Nephrol. 2006;1(2):323–6.

    Article  PubMed  CAS  Google Scholar 

  63. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2007;22(8):2362–5.

    Article  PubMed  CAS  Google Scholar 

  64. Serra AL, Savoca R, Huber AR, Hepp U, Delsignore A, Hersberger M, et al. Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Nephrol Dial Transplant. 2007;22(2):577–83.

    Article  PubMed  CAS  Google Scholar 

  65. Peng LW, Logan JL, James SH, Scott KM, Lien YH. Cinacalcet-associated graft dysfunction and nephrocalcinosis in a kidney transplant recipient. Am J Med. 2007;120(9):e7–9.

    Article  PubMed  Google Scholar 

  66. Borchhardt KA, Heinzl H, Mayerwoger E, Horl WH, Haas M, Sunder-Plassmann G. Cinacalcet increases calcium excretion in hypercalcemic hyperparathyroidism after kidney transplantation. Transplantation. 2008;86(7):919–24.

    Google Scholar 

  67. Schwarz A, Merkel S, Leitolf H, Haller H. The effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism. Transplantation. 2011;91(5):560–5.

    Google Scholar 

  68. Henschkowski J, Bischoff-Ferrari HA, Wuthrich RP, Serra AL. Renal function in patients treated with cinacalcet for persistent hyperparathyroidism after kidney transplantation. Kidney Blood Press Res. 2011;34(2):97–103.

    Article  PubMed  CAS  Google Scholar 

  69. Bergua C, Torregrosa JV, Cofan F, Oppenheimer F. Cinacalcet for the treatment of hypercalcemia in renal transplanted patients with secondary hyperparathyroidism. Transplant Proc. 2007;39(7):2254–5.

    Article  PubMed  CAS  Google Scholar 

  70. Cho ME, Duan Z, Chamberlain CE, Reynolds JC, Ring MS, Mannon RB. Cinacalcet improves bone density in post-kidney transplant hyperparathyroidism. Transplant Proc. 2010;42(9):3554–8.

    Article  PubMed  CAS  Google Scholar 

  71. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344(19):1434–41.

    Google Scholar 

  72. Mahajan A, Narayanan M, Jaffers G, Concepcion L. Hypoparathyroidism associated with severe mineral bone disease postrenal transplantation, treated successfully with recombinant PTH. Hemodial Int. 2009;13(4):547–50.

    Article  PubMed  Google Scholar 

  73. Nogueira EL, Costa AC, Santana A, Guerra JO, Silva S, Mil-Homens C, et al. Teriparatide efficacy in the treatment of severe hypocalcemia after kidney transplantation in parathyroidectomized patients: a series of five case reports. Transplantation. 2011;92(3):316–20.

    Google Scholar 

  74. Cancela AL, Oliveira RB, Graciolli FG, dos Reis LM, Barreto F, Barreto DV, et al. Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate binder, calcitriol and calcium concentration in the dialysate. Nephron Clin Pract. 2011;117(1):c74–82.

    Article  PubMed  CAS  Google Scholar 

  75. Wesseling-Perry K, Pereira RC, Sahney S, Gales B, Wang HJ, Elashoff R, et al. Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism. Kidney Int. 2011;79(1):112–9.

    Article  PubMed  CAS  Google Scholar 

  76. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.

    Google Scholar 

  77. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80.

    Article  PubMed  CAS  Google Scholar 

  78. Stoch SA, Zajic S, Stone J, Miller DL, Van Dyck K, Gutierrez MJ, et al. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther. 2009;86(2):175–82.

    Article  PubMed  CAS  Google Scholar 

  79. Jamal SA, Ljunggren O, Stehman-Breen C, Cummings SR, McClung MR, Goemaere S, et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011;26(8):1829–35.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Rd, Farr8 Renal Unit, Boston, MA, 02215, USA

    Marta Christov

  2. Division of Nephrology and Hypertension, North Shore University Health System, Evanston Hospital and University of Chicago School of Medicine, 2650 North Ridge Avenue, Evanston, IL, 60201, USA

    Stuart M. Sprague

Authors
  1. Marta Christov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stuart M. Sprague
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marta Christov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Christov, M., Sprague, S.M. The Transplant Recipient and Issues in Bone Metabolism. Clinic Rev Bone Miner Metab 10, 209–218 (2012). https://doi.org/10.1007/s12018-011-9118-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12018-011-9118-2

Keywords

Search

Navigation