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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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.
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.
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.
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.
Cummings SR, Bates D, Black DM . Clinical use of bone densitometry: scientific review. JAMA 2002; 288: 1889–1897.
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.
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.
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.
Weilbaecher KN . Mechanisms of osteoporosis after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2000; 6: 165–174.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Schulte CM, Beelen DW . Bone loss following hematopoietic stem cell transplantation: a long-term follow-up. Blood 2004; 103: 3635–3643.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Woo SB, Hellstein JW, Kalmar JR . Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006; 144: 753–761.
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.
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.
McDonough AK, Curtis JR, Saag KG . The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 2008; 20: 131–137.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Daniels MW, Wilson DM, Paguntalan HG, Hoffman AR, Bachrach LK . Bone mineral density in pediatric transplant recipients. Transplantation 2003; 76: 673–678.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Ebeling PR . Approach to the patient with transplantation-related bone loss. J Clin Endocrinol Metab 2009; 94: 1483–1490.
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.
Author information
Authors and Affiliations
Corresponding author
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
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2010.198
Keywords
This article is cited by
-
Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk
Calcified Tissue International (2024)
-
Fracture risk and assessment in adults with cancer
Osteoporosis International (2023)
-
To D or not to D: vitamin D in hematopoietic cell transplantation
Bone Marrow Transplantation (2020)
-
Predictors of impaired bone health in long-term survivors after allogeneic stem cell transplantation
Bone Marrow Transplantation (2019)
-
Minimizing Disability from Graft-Versus-Host Disease
Current Physical Medicine and Rehabilitation Reports (2018)