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
  • Published:

Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients

Abstract

Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6–12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving 5 mg of prednisone equivalent daily for >3 months) can be screened earlier (for example, 3–6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Huma Z, Boulad F, Black P, Heller G, Sklar C . Growth in children after bone marrow transplantation for acute leukemia. Blood 1995; 86: 819–824.

    CAS  PubMed  Google Scholar 

  2. Kanis JA . Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group Osteoporos Int 1994; 4: 368–381.

    Article  CAS  Google Scholar 

  3. Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, El-Hajj Fuleihan G, Kutilek S et al. Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 2008; 11: 43–58.

    Article  Google Scholar 

  4. Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom 2008; 11: 6–21.

    Article  Google Scholar 

  5. Cummings SR, Bates D, Black DM . Clinical use of bone densitometry: scientific review. JAMA 2002; 288: 1889–1897.

    Article  Google Scholar 

  6. Wainwright SA, Marshall LM, Ensrud KE, Cauley JA, Black DM, Hillier TA et al. Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 2005; 90: 2787–2793.

    Article  CAS  Google Scholar 

  7. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 2004; 34: 195–202.

    Article  CAS  Google Scholar 

  8. Rizzo JD, Wingard JR, Tichelli A, Lee SJ, Van Lint MT, Burns LJ et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2006; 12: 138–151.

    Article  Google Scholar 

  9. Weilbaecher KN . Mechanisms of osteoporosis after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2000; 6: 165–174.

    Article  CAS  Google Scholar 

  10. Hamdy NA . Targeting the RANK/RANKL/OPG signaling pathway: a novel approach in the management of osteoporosis. Curr Opin Investig Drugs 2007; 8: 299–303.

    CAS  PubMed  Google Scholar 

  11. Petryk A, Bergemann TL, Polga KM, Ulrich KJ, Raatz SK, Brown DM et al. Prospective study of changes in bone mineral density and turnover in children after hematopoietic cell transplantation. J Clin Endocrinol Metab 2006; 91: 899–905.

    Article  CAS  Google Scholar 

  12. Castelo-Branco C, Rovira M, Pons F, Durán M, Sierra J, Vives A et al. The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation. Maturitas 1996; 23: 307–312.

    Article  CAS  Google Scholar 

  13. Massenkeil G, Fiene C, Rosen O, Michael R, Reisinger W, Arnold R . Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis. Leukemia 2001; 15: 1701–1705.

    Article  CAS  Google Scholar 

  14. Tauchmanova L, De Simone G, Musella T, Orio F, Ricci P, Nappi C et al. Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 37: 81–88.

    Article  CAS  Google Scholar 

  15. Tauchmanova L, Selleri C, Esposito M, Di Somma C, Orio Jr F, Bifulco G et al. Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies. Osteoporos Int 2003; 14: 1013–1019.

    Article  CAS  Google Scholar 

  16. Valimaki MJ, Kinnunen K, Volin L, Tähtelä R, Löyttyniemi E, Laitinen K et al. A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. Bone Marrow Transplant 1999; 23: 355–361.

    Article  CAS  Google Scholar 

  17. Yao S, Smiley SL, West K, Lamonica D, Battiwalla M, McCarthy Jr PL et al. Accelerated bone mineral density loss occurs with similar incidence and severity, but with different risk factors, after autologous vs allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2010; 16: 1130–1137.

    Article  CAS  Google Scholar 

  18. Tauchmanova L, Colao A, Lombardi G, Rotoli B, Selleri C . Bone loss and its management in long-term survivors from allogeneic stem cell transplantation. J Clin Endocrinol Metab 2007; 92: 4536–4545.

    Article  CAS  Google Scholar 

  19. Grigg AP, Shuttleworth P, Reynolds J, Schwarer AP, Szer J, Bradstock K et al. Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2006; 91: 3835–3843.

    Article  CAS  Google Scholar 

  20. Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, Valimaki MJ . Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate. J Clin Endocrinol Metab 2005; 90: 3877–3885.

    Article  CAS  Google Scholar 

  21. Chae YS, Kim JG, Moon JH, Kim SN, Lee SJ, Kim YJ et al. Pilot study on the use of zoledronic acid to prevent bone loss in allo-SCT recipients. Bone Marrow Transplant 2009; 44: 35–41.

    Article  CAS  Google Scholar 

  22. D’Souza AB, Grigg AP, Szer J, Ebeling PR . Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantation. Intern Med J 2006; 36: 600–603.

    Article  Google Scholar 

  23. Schulte CM, Beelen DW . Bone loss following hematopoietic stem cell transplantation: a long-term follow-up. Blood 2004; 103: 3635–3643.

    Article  CAS  Google Scholar 

  24. Tauchmanova L, Ricci P, Serio B, Lombardi G, Colao A, Rotoli B et al. Short-term zoledronic acid treatment increases bone mineral density and marrow clonogenic fibroblast progenitors after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2005; 90: 627–634.

    Article  CAS  Google Scholar 

  25. Savani BN, Donohue T, Kozanas E, Shenoy A, Singh AK, Childs RW et al. Increased risk of bone loss without fracture risk in long-term survivors after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 517–520.

    Article  Google Scholar 

  26. Ebeling PR, Thomas DM, Erbas B, Hopper JL, Szer J, Grigg AP . Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation. J Bone Miner Res 1999; 14: 342–350.

    Article  CAS  Google Scholar 

  27. Gandhi MK, Lekamwasam S, Inman I, Kaptoge S, Sizer L, Love S et al. Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study. Br J Haematol 2003; 121: 462–468.

    Article  Google Scholar 

  28. Ria R, Scarponi AM, Falzetti F, Ballanti S, Di Ianni M, Sportoletti P et al. Loss of bone mineral density and secondary hyperparathyroidism are complications of autologous stem cell transplantation. Leuk Lymphoma 2007; 48: 923–930.

    Article  CAS  Google Scholar 

  29. Schimmer AD, Mah K, Bordeleau L, Cheung A, Ali V, Falconer M et al. Decreased bone mineral density is common after autologous blood or marrow transplantation. Bone Marrow Transplant 2001; 28: 387–391.

    Article  CAS  Google Scholar 

  30. Keilholz U, Max R, Scheibenbogen C, Wuster C, Korbling M, Haas R . Endocrine function and bone metabolism 5 years after autologous bone marrow/blood-derived progenitor cell transplantation. Cancer 1997; 79: 1617–1622.

    Article  CAS  Google Scholar 

  31. Kashyap A, Kandeel F, Yamauchi D, Palmer JM, Niland JC, Molina A et al. Effects of allogeneic bone marrow transplantation on recipient bone mineral density: a prospective study. Biol Blood Marrow Transplant 2000; 6: 344–351.

    Article  CAS  Google Scholar 

  32. Buchs N, Helg C, Collao C, Chapuis B, Slosman D, Bonjour JP et al. Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss. Osteoporos Int 2001; 12: 880–886.

    Article  CAS  Google Scholar 

  33. MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008; 148: 197–213.

    Article  Google Scholar 

  34. Qaseem A, Snow V, Shekelle P, Hopkins Jr R, Forciea MA, Owens DK . Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2008; 149: 404–415.

    Article  Google Scholar 

  35. Woo SB, Hellstein JW, Kalmar JR . Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006; 144: 753–761.

    Article  CAS  Google Scholar 

  36. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001; 44: 1496–1503.

  37. Homik J, Cranney A, Shea B, Tugwell P, Wells G, Adachi R et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev 2000 Art. No. CD001347.

  38. McDonough AK, Curtis JR, Saag KG . The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 2008; 20: 131–137.

    Article  Google Scholar 

  39. De Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, Van Staa TP . Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum 2007; 56: 208–214.

    Article  CAS  Google Scholar 

  40. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B et al. Assessment of fracture risk. Osteoporos Int 2005; 16: 581–589.

    Article  Google Scholar 

  41. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B . Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001; 12: 989–995.

    Article  CAS  Google Scholar 

  42. Saag KG, Shane E, Boonen S, Marín F, Donley DW, Taylor KA et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007; 357: 2028–2039.

    Article  CAS  Google Scholar 

  43. Ross PD, Davis JW, Epstein RS, Wasnich RD . Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 1991; 114: 919–923.

    Article  CAS  Google Scholar 

  44. Kelly KM, Thornton JC, Hughes D, Osunkwo I, Weiner M, Wang J et al. Total body bone measurements: a cross-sectional study in children with acute lymphoblastic leukemia during and following completion of therapy. Pediatr Blood Cancer 2009; 52: 33–38.

    Article  Google Scholar 

  45. Arikoski P, Komulainen J, Riikonen P, Parviainen M, Jurvelin JS, Voutilainen R et al. Impaired development of bone mineral density during chemotherapy: a prospective analysis of 46 children newly diagnosed with cancer. J Bone Miner Res 1999; 14: 2002–2009.

    Article  CAS  Google Scholar 

  46. Arikoski P, Komulainen J, Riikonen P, Jurvelin JS, Voutilainen R, Kroger H . Reduced bone density at completion of chemotherapy for a malignancy. Arch Dis Child 1999; 80: 143–148.

    Article  CAS  Google Scholar 

  47. Klopfenstein KJ, Clayton J, Rosselet R, Kerlin B, Termuhlen A, Gross T . Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplant. Pediatr Blood Cancer 2009; 53: 675–677.

    Article  Google Scholar 

  48. Bhatia S, Ramsay NK, Weisdorf D, Griffiths H, Robison LL . Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies. Bone Marrow Transplant 1998; 22: 87–90.

    Article  CAS  Google Scholar 

  49. Nysom K, Holm K, Michaelsen KF, Hertz H, Muller J, Molgaard C . Bone mass after treatment of malignant lymphoma in childhood. Med Pediatr Oncol 2001; 37: 518–524.

    Article  CAS  Google Scholar 

  50. Daniels MW, Wilson DM, Paguntalan HG, Hoffman AR, Bachrach LK . Bone mineral density in pediatric transplant recipients. Transplantation 2003; 76: 673–678.

    Article  Google Scholar 

  51. Leung TF, Hung EC, Lam CW, Li CK, Chu Y, Chik KW et al. Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation. Bone Marrow Transplant 2005; 36: 331–336.

    Article  CAS  Google Scholar 

  52. Kaste SC, Shidler TJ, Tong X, Srivastava DK, Rochester R, Hudson MM et al. Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone marrow transplantation. Bone Marrow Transplant 2004; 33: 435–441.

    Article  CAS  Google Scholar 

  53. Prentice A, Parsons TJ, Cole TJ . Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 1994; 60: 837–842.

    Article  CAS  Google Scholar 

  54. Leonard MB, Shults J, Elliott DM, Stallings VA, Zemel BS . Interpretation of whole body dual energy X-ray absorptiometry measures in children: comparison with peripheral quantitative computed tomography. Bone 2004; 34: 1044–1052.

    Article  Google Scholar 

  55. Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI . Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr 1999; 135: 182–188.

    Article  CAS  Google Scholar 

  56. Bachrach LK . Dual energy X-ray absorptiometry (DEXA) measurements of bone density and body composition: promise and pitfalls. J Pediatr Endocrinol Metab 2000; 13 (Suppl 2): 983–988.

    PubMed  Google Scholar 

  57. Frisk P, Arvidson J, Gustafsson J, Lönnerholm G . Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia. Bone Marrow Transplant 2004; 33: 205–210.

    Article  CAS  Google Scholar 

  58. Bakker B, Oostdijk W, Bresters D, Walenkamp MJ, Vossen JM, Wit JM . Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplant 2004; 33: 1049–1056.

    Article  CAS  Google Scholar 

  59. Bakker B, Massa GG, Oostdijk W, Van Weel-Sipman MH, Vossen JM, Wit JM . Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur J Pediatr 2000; 159: 31–37.

    Article  CAS  Google Scholar 

  60. Bishop N, Braillon P, Burnham J, Cimaz R, Davies J, Fewtrell M et al. Dual-energy X-ray absorptiometry assessment in children and adolescents with diseases that may affect the skeleton: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 2008; 11: 29–42.

    Article  Google Scholar 

  61. Carpenter PA, Hoffmeister P, Chesnut III CH, Storer B, Charuhas PM, Woolfrey AE et al. Bisphosphonate therapy for reduced bone mineral density in children with chronic graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 683–690.

    Article  CAS  Google Scholar 

  62. Wasilewski-Masker K, Kaste SC, Hudson MM, Esiashvili N, Mattano LA, Meacham LR . Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics 2008; 121: e705–e713.

    Article  Google Scholar 

  63. Children's Oncology Group. Long-term followup guidelines for survivors of childhood, adolescent and young adult cancers: Bone health (Version 3.0—10/08). http://www.survivorshipguidelines.org (accessed 15 April 2010).

  64. Ebeling PR . Approach to the patient with transplantation-related bone loss. J Clin Endocrinol Metab 2009; 94: 1483–1490.

    Article  CAS  Google Scholar 

  65. Subbiah V, Madsen VS, Raymond AK, Benjamin RS, Ludwig JA . Of mice and men: divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int 2010; 21: 1041–1045.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N S Majhail.

Ethics declarations

Competing interests

Linda J Burns has received research funding from Novartis Pharmaceuticals for a clinical trial of zoledronic acid in hematopoietic cell transplant recipients. The remaining authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McClune, B., Polgreen, L., Burmeister, L. et al. Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients. Bone Marrow Transplant 46, 1–9 (2011). https://doi.org/10.1038/bmt.2010.198

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.198

Keywords

This article is cited by

Search

Quick links