Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Therapy Insight: orthopedic complications after solid organ transplantation in childhood

Nature Clinical Practice Nephrology volume 3, pages 96–105 (2007)Cite this article

Abstract

Several factors, such as immobilization, metabolic bone disease and immunosuppressive drugs, can compromise the quality of bone in children who have undergone solid organ transplantation. In contrast to adults, decreased bone mineral density has been reported in only a small proportion of pediatric transplant patients, and the relationship between low bone mineral density and fracture risk has not been established in children. Nevertheless, fractures, scoliosis, and joint and spinal degeneration are common in patients who received solid organ grafts as children. Avascular bone necrosis occurs infrequently in this patient population. Future studies should evaluate the effects of the underlying disease, transplantation and immunosuppression on the metabolism of bone and cartilage. On the basis of our own clinical experience and literature review, the growing spine of children who have received transplants should be continuously evaluated, and follow-up of bone mineral density is indicated. By contrast, routine MRI of the joints seems unnecessary.

Key Points

  • Compared with the normal population, the risk of fractures after solid organ transplantation is much increased in childhood

  • Scoliosis, vertebral fractures and back pain are common in pediatric transplant recipients

  • Correction of spinal deformity has reasonable outcomes in pediatric transplant recipients; there are no data on brace treatment in this population

  • The risk of avascular necrosis of joints is markedly reduced with newer immunosuppressive medications, and routine MRI of the hip joints seems unnecessary

  • Study of bone metabolic disorders and fracture prevention using pharmacological agents in pediatric transplant recipients is urgently needed

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Multiple thoracic vertebral compression fractures in a 13-year-old boy 6 months after cardiac transplantation for Fanconi syndrome.
Figure 2: Successful surgical correction of scoliosis following pediatric heart transplantation.
Figure 3: Back pain and disk degeneration following pediatric renal transplantation.
Figure 4: Avascular bone necrosis and repair following pediatric liver transplantation.

Similar content being viewed by others

References

  1. Elmstedt E (1982) Spontaneous fractures in the renal graft recipient: a discriminant analysis of 144 cases. Clin Orthop 162: 195–201

    Google Scholar 

  2. Ramsey-Goldman R et al. (1999) Increased risk of fracture in patients receiving solid organ transplants. J Bone Miner Res 14: 456–463

    Article  CAS  Google Scholar 

  3. Leidig-Bruckner G et al. (2001) Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet 357: 342–347

    Article  CAS  Google Scholar 

  4. O'Shaughnessy EA et al. (2002) Risk factors for fractures in kidney transplantation. Transplantation 74: 362–366

    Article  Google Scholar 

  5. Lindsay R (2004) Bone loss after cardiac transplantation. N Engl J Med 350: 751–754

    Article  CAS  Google Scholar 

  6. Danzig LA et al. (1976) Avascular necrosis of the femoral head following cardiac transplantation: report of a case. Clin Orthop Relat Res 117: 217–220

    Google Scholar 

  7. Burton DS et al. (1978) Total hip arthroplasty in the cardiac transplant patient. Clin Orthop Relat Res 130: 186–190

    Google Scholar 

  8. Bradbury G et al. (1994) Avascular necrosis of bone after cardiac transplantation. J Bone Joint Surg Am 76: 1385–1388

    Article  CAS  Google Scholar 

  9. Lieberman JR et al. (2000) Symptomatic osteonecrosis of the hip after orthotopic liver transplantation. J Arthroplasty 15: 767–771

    Article  CAS  Google Scholar 

  10. Horiuchi H et al. (2004) Osteonecrosis of the femoral head in Japanese adults after liver transplantation: a preliminary report. J Orthop Sci 9: 119–121

    Article  Google Scholar 

  11. Inoue S et al. (2003) Risk factors for nontraumatic osteonecrosis of the femoral head after renal transplantation. J Orthop Sci 8: 751–756

    Article  Google Scholar 

  12. Lopez-Ben R et al. (2004) Incidence of hip osteonecrosis among renal transplantation recipients: a prospective study. Clin Radiol 59: 431–438

    Article  CAS  Google Scholar 

  13. Asano T et al. (2004) Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation 27: 220–225

    Article  Google Scholar 

  14. Metselaar HJ et al. (1985) Incidence of osteonecrosis after renal transplantation. Acta Orthop Scand 56: 413–415

    Article  CAS  Google Scholar 

  15. Hill SA et al. (1995) Bone fractures in children undergoing orthotopic liver transplantation. Pediatr Radiol 25 (Suppl 1): S112–S117

    PubMed  Google Scholar 

  16. Ruderman RJ et al. (1979) Orthopedic complications of renal transplantation in children. Transplant Proc 11: 104–106

    CAS  PubMed  Google Scholar 

  17. Dunn HK and Aiona MD (1982) Spinal instrumentation and fusion for idiopathic scoliosis in a renal transplant patient: a case report. Spine 7: 177–179

    Article  CAS  Google Scholar 

  18. Ceroni D et al. (2001) Corrective surgery for idiopathic scoliosis after heart transplantation. Eur Spine J 10: 454–457

    Article  CAS  Google Scholar 

  19. Compston J (2003) The skeletal effects of liver transplantation in children. Liver Transplant 9: 371–372

    Article  Google Scholar 

  20. Okajima H et al. (2003) Long-term effects of liver transplantation on bone mineral density in children with end-stage liver disease: a 2-year prospective study. Liver Transpl 9: 360–364

    Article  Google Scholar 

  21. Daniels MW et al. (2003) Bone mineral density in pediatric transplant recipients. Transplantation 76: 673–678

    Article  Google Scholar 

  22. Guthery SL et al. (2003) Bone mineral density in long-term survivors following pediatric liver transplantation. Liver Transpl 9: 365–370

    Article  Google Scholar 

  23. Saland JM (2004) Osseous complications of pediatric transplantation. Pediatr Transpl 8: 400–415

    Article  Google Scholar 

  24. Leonard MB (2005) Assessment of bone mass following renal transplantation in children. Pediatr Nephrol 20: 360–367

    Article  Google Scholar 

  25. Helenius I et al. (2006) Incidence and predictors of fractures after solid organ transplantation: a five-year prospective, population based study. J Bone Miner Res 21: 380–387

    Article  Google Scholar 

  26. Helenius I et al. (2006) Scoliosis after solid organ transplantation in children and adolescents. Am J Transpl 6: 324–330

    Article  CAS  Google Scholar 

  27. Uittenbogaart CH et al. (1978) Aseptic necrosis after renal transplantation in children. Am J Dis Child 132: 765–767

    CAS  PubMed  Google Scholar 

  28. Stern PJ and Watts HG (1979) Osteonecrosis after renal transplantation. J Bone Joint Surg Am 61: 851–856

    Article  CAS  Google Scholar 

  29. Beals RK et al. (2002) Avascular necrosis of the femoral head following heart transplant in a child. Pediatr Transplant 6: 423–426

    Article  Google Scholar 

  30. Chung SM (1976) The arterial supply of the developing proximal end of the human femur. J Bone Joint Surg Am 58: 961–970

    Article  CAS  Google Scholar 

  31. Trueta J (1957) The normal vascular anatomy of the human femoral head during growth. J Bone Joint Surg Br 39: 358–394

    Article  Google Scholar 

  32. Ogden JA (1974) Changing patterns of proximal femoral vascularity. J Bone Joint Surg Am 56: 941–950

    Article  CAS  Google Scholar 

  33. NIH Consensus development panel on osteoporosis prevention, diagnosis, and therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285: 785–795

  34. Sochette EB and Mäkitie O (2005) Osteoporosis in chronically ill children. Ann Med 37: 286–294

    Article  Google Scholar 

  35. Feber J et al. (1994) Bone mineral density after renal transplantation in children. J Pediatr 125: 870–875

    Article  CAS  Google Scholar 

  36. Canalis E (1996) Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 81: 3441–3447

    CAS  PubMed  Google Scholar 

  37. Canalis E (1998) Inhibitory actions of glucocorticoids on skeletal growth: is insulin-like growth factor I to blame? Endocrinology 139: 3041–3042

    Article  CAS  Google Scholar 

  38. Compston JE (1995) Bone mineral density: BMC, BMD or corrected BMD? Bone 16: 5–7

    Article  CAS  Google Scholar 

  39. Klaus G et al. (1998) Weight-/height-related bone mineral density is not reduced after renal transplantation. Ped Nephrol 12: 343–348

    Article  CAS  Google Scholar 

  40. Wren TA et al. (2005) Bone densitometry in pediatric populations: discrepancies in the diagnosis of osteoporosis by DXA and CT. J Pediatr 146: 776–779

    Article  Google Scholar 

  41. Leonard MB and Bachrach LK (2001) Assessment of bone mineralization following renal transplantation in children: limitations of DXA and the confounding effects of delayed growth and development. Am J Transplant 1: 193–196

    Article  CAS  Google Scholar 

  42. Bartosh SM et al. (2003) Long-term outcomes in pediatric renal transplant recipients who survive into adulthood. Transplantation 76: 1195–1200

    Article  Google Scholar 

  43. Shane E et al. (2004) Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. N Engl J Med 350: 767–776

    Article  CAS  Google Scholar 

  44. Grotz W et al. (2001) Effect of ibandronate on bone loss and renal function after kidney transplantation. J Am Soc Nephrol 12: 1530–1537

    CAS  PubMed  Google Scholar 

  45. Whyte MP et al. (2003) Bisphosphonate-induced osteopetrosis. N Engl J Med 349: 457–463

    Article  CAS  Google Scholar 

  46. Brumsen C et al. (1997) Long-term effects of bisphosphonates on the growing skeleton: studies of young patients with severe osteoporosis. Medicine 76: 266–283

    Article  CAS  Google Scholar 

  47. Marini JC (2003) Do bisphosphonates make children's bones better or brittle? N Engl J Med 349: 423–426

    Article  Google Scholar 

  48. Peltonen J et al. (2006) Surgical correction of spinal deformities after solid organ transplantation in childhood. Eur Spine J 15: 1230–1238

    Article  Google Scholar 

  49. Helenius I et al. (2006) Spine after solid organ transplantation in childhood: a clinical, radiographic, and an MRI analysis of 40 patients. Spine 31: 2130–2136

    Article  Google Scholar 

  50. Nissinen M et al. (1993) Trunk asymmetry and screening for scoliosis: a longitudinal cohort study of pubertal schoolchildren. Acta Pediatr 82: 77–82

    Article  CAS  Google Scholar 

  51. Beals RK et al. (1972) Heart disease and idiopathic scoliosis. Clin Orthop 89: 112–116

    Article  CAS  Google Scholar 

  52. Beneux J et al. (1976) Scoliosis and congenital cardiopathies [French]. Rev Chir Orthop Reparatrice Appar Mot 62: 781–792

    CAS  PubMed  Google Scholar 

  53. Coran DL et al. (1999) Spinal fusion in patients with congenital heart disease: predictors of outcome. Clin Orthop 364: 99–107

    Article  Google Scholar 

  54. Reckles LN et al. (1975) The association of scoliosis and congenital heart defects. J Bone Joint Surg Am 57: 449–455

    Article  CAS  Google Scholar 

  55. Ruiz-Iban MA et al. (2005) Scoliosis after median sternotomy in children with congenital heart disease. Spine 30: E214–E218

    Article  Google Scholar 

  56. Primiano FP et al. (1983) Early echocardiographic and pulmonary function findings in idiopathic scoliosis. J Ped Orthop 3: 475–481

    Article  Google Scholar 

  57. Gazioglu K et al. (1968) Pulmonary function in idiopathic scoliosis. J Bone Joint Surg Am 50: 1391–1399

    Article  Google Scholar 

  58. Remes V et al. (2002) Lung function in diastrophic dysplasia. Pediatr Pulmonol 33: 277–282

    Article  Google Scholar 

  59. Westgate HD and Moe JH (1969) Pulmonary function in kyphoscoliosis before and after correction by the Harrington instrumentation method. J Bone Joint Surg Am 51: 935–946

    Article  Google Scholar 

  60. Kerttula LI et al. (2000) Post-traumatic findings of the spine after earlier vertebral fracture in young patients: clinical and MRI study. Spine 25: 1104–1108

    Article  CAS  Google Scholar 

  61. Helenius I et al. (2006) Avascular bone necrosis of the hip joint after solid organ transplantation in childhood: a clinical and MRI analysis. Transplantation 81: 1621–1627

    Article  Google Scholar 

  62. Arlet J (1992) Nontraumatic avascular necrosis of the femoral head. Clin Orthop 277: 12–21

    Google Scholar 

  63. Heimann WG and Freiberger RH (1960) Avascular necrosis of the femoral and humeral heads after high dosage corticosteroid therapy. N Engl J Med 263: 672–675

    Article  CAS  Google Scholar 

  64. Ferrari P et al. (2002) Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation 27: 1147–1152

    Article  Google Scholar 

  65. Li X et al. (2005) Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporosis Int 16: 101–108

    Article  Google Scholar 

  66. Calder JD et al. (2004) Apoptosis—a significant cause of bone cell death in osteonecrosis of the femoral head. J Bone Joint Surg Br 86: 1209–1213

    Article  CAS  Google Scholar 

  67. Kim SY et al. (2005) Vascularized compared with non-vascularized fibular grafts for large osteonecrotic lesions of the femoral head. J Bone Joint Surg Am 87: 2012–2018

    Article  Google Scholar 

  68. Churchill MA and Spencer JD (1991) End-stage avascular necrosis of bone in renal transplant patients: the natural history. J Bone Joint Surg Br 73: 618–620

    Article  CAS  Google Scholar 

  69. Kim YH et al. (2003) Contemporary total hip arthroplasty with and without cement in patients with osteonecrosis of the femoral head. J Bone and Joint Surg Am 83: 675–681

    Article  Google Scholar 

  70. Goffin E et al. (1993) Epiphyseal impaction as a cause of severe osteoarticular pain of lower limbs after renal transplantation. Kidney Int 44: 98–101

    Article  CAS  Google Scholar 

  71. Stevens JM et al. (1995) Post-renal transplant distal limb pain: an under-recognized complication of transplantation distinct from avascular necrosis of bone? Transplantation 60: 305–309

    Article  CAS  Google Scholar 

  72. Waller S et al. (2006) Bone mineral density in children with chronic renal failure. Pediatr Nephrol [doi: 10.1007/s00467-006-0292-2]

    Article  Google Scholar 

  73. Boucek M et al. (2002) The registry of international society for heart and lung transplantation: sixth official pediatric report 2003. J Heart Lung Transpl 22: 636–652

    Article  Google Scholar 

  74. Vidhun J and Sarwal R (2005) Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol 20: 418–426

    Article  Google Scholar 

  75. Seikku P et al. (2006) Methylprednisolone exposure in pediatric renal transplant patients. Am J Transpl 6: 1451–1458

    Article  CAS  Google Scholar 

  76. MacKelvie K et al. (2001) A school-based exercise intervention augments bone mineral accrual in early pubertal girls. J Pediatr 139: 501–508

    Article  CAS  Google Scholar 

  77. El-Husseini A et al. (2004) Treatment of osteopenia and osteoporosis in renal transplant children and adolescents. Pediatr Transplant 8: 357–361

    Article  Google Scholar 

  78. Sellers E et al. (1998) The use of pamidronate in three children with renal disease. Pediatr Nephrol 12: 778–781

    Article  CAS  Google Scholar 

  79. Lai KU et al. (2005) The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 87: 2155–2159

    Article  Google Scholar 

  80. Pritchett JW (2001) Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop 386: 173–178

    Article  Google Scholar 

Download references

Acknowledgements

This study was financially supported by Helsinki University Central Hospital, the Päivikki and Sakari Sohlberg Foundation, the Foundation for Pediatric Research, the Paulo Foundation, and the Academy of Finland.

Author information

Authors and Affiliations

  1. I Helenius is Consultant Orthopedic Spine Surgeon, H Jalanko is Chief Pediatric Nephrologist, S Salminen is Consultant Pediatric Orthopedic Surgeon, H Sairanen is Chief Pediatric Cardiac and Transplantation Surgeon, C Holmberg is Chief Pediatrician, and J Peltonen is Chief Pediatric Orthopedic Surgeon, all at the Hospital for Children and Adolescents, Helsinki University Central Hospital, and V Remes is Consultant Orthopedic Surgeon at the Surgical Hospital, Helsinki University Central Hospital, Helsinki, Finland.,

    Ilkka Helenius, Hannu Jalanko, Ville Remes, Sari Salminen, Heikki Sairanen, Christer Holmberg & Jari Peltonen

Authors
  1. Ilkka Helenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hannu Jalanko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ville Remes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sari Salminen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heikki Sairanen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christer Holmberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jari Peltonen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilkka Helenius.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Helenius, I., Jalanko, H., Remes, V. et al. Therapy Insight: orthopedic complications after solid organ transplantation in childhood. Nat Rev Nephrol 3, 96–105 (2007). https://doi.org/10.1038/ncpneph0384

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneph0384

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing