Skip to main content

Advertisement

Log in

Bone management in hematologic stem cell transplant recipients

Osteoporosis International Aims and scope Submit manuscript

Abstract

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture.

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

Access this article

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

References

  1. McClune BL, Majhail NS (2013) Osteoporosis after stem cell transplantation. Curr Osteoporos Rep 11:305–310

    Article  PubMed  Google Scholar 

  2. Takayanagi H (2015) SnapShot: osteoimmunology. Cell Metab 21(502):e501

    Google Scholar 

  3. Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, San Martin J, Dansey R (2012) Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401–419

    Article  CAS  PubMed  Google Scholar 

  4. Raggatt LJ, Partridge NC (2010) Cellular and molecular mechanisms of bone remodeling. J Biol Chem 285:25103–25108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ria R, Scarponi AM, Falzetti F et al (2007) Loss of bone mineral density and secondary hyperparathyroidism are complications of autologous stem cell transplantation. Leuk Lymphoma 48:923–930

    Article  CAS  PubMed  Google Scholar 

  6. Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transplant 9:215–233

    Article  CAS  PubMed  Google Scholar 

  7. Joseph RW, Alousi A, Konda B et al (2011) High incidence of vitamin D deficiency in patients undergoing allogeneic stem cell transplantation. Am J Hematol 86:954–956

    Article  CAS  PubMed  Google Scholar 

  8. Hadji P, Ziller M, Maskow C, Albert U, Kalder M (2009) The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer. Eur J Cancer 45:3205–3212

    Article  CAS  PubMed  Google Scholar 

  9. Rizzoli R, Biver E (2015) Glucocorticoid-induced osteoporosis: who to treat with what agent? Nat Rev Rheumatol 11:98–109

    Article  CAS  PubMed  Google Scholar 

  10. Schimmer AD, Quatermain M, Imrie K, Ali V, McCrae J, Stewart AK, Crump M, Derzko C, Keating A (1998) Ovarian function after autologous bone marrow transplantation. J Clin Oncol 16:2359–2363

    Article  CAS  PubMed  Google Scholar 

  11. Serio B, Pezzullo L, Fontana R et al (2013) Accelerated bone mass senescence after hematopoietic stem cell transplantation. Transl Med UniSa 5:7–13

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Takamatsu Y, Simmons PJ, Moore RJ, Morris HA, To LB, Levesque JP (1998) Osteoclast-mediated bone resorption is stimulated during short-term administration of granulocyte colony-stimulating factor but is not responsible for hematopoietic progenitor cell mobilization. Blood 92:3465–3473

    Article  CAS  PubMed  Google Scholar 

  13. Philibert D, Desmeules S, Filion A, Poirier M, Agharazii M (2008) Incidence and severity of early electrolyte abnormalities following autologous haematopoietic stem cell transplantation. Nephrol Dial Transplant 23:359–363

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Schulte C, Beelen DW, Schaefer UW, Mann K (2000) Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study. Osteoporos Int 11:344–353

    Article  CAS  PubMed  Google Scholar 

  17. Bhatia S (2011) Long-term health impacts of hematopoietic stem cell transplantation inform recommendations for follow-up. Expert Rev Hematol 4:437–452 quiz 453–434

    Article  PubMed  PubMed Central  Google Scholar 

  18. Anandi P, Jain NA, Tian X, Wu CO, Pophali PA, Koklanaris E, Ito S, Savani BN, Barrett J, Battiwalla M (2016) Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors. Bone Marrow Transplant 51:1101–1106

    Article  CAS  PubMed  Google Scholar 

  19. Ebeling PR (2013) Transplantation osteoporosis. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism 8th Edition:495–507

    Chapter  Google Scholar 

  20. Buchs N, Helg C, Collao C, Chapuis B, Slosman D, Bonjour JP, Rizzoli R (2001) Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss. Osteoporos Int 12:880–886

    Article  CAS  PubMed  Google Scholar 

  21. Ebeling PR (2005) Bone disease after bone marrow transplantation bone disease of organ transplantation. In: Compston J, Shane E (eds) , vol 19. Elsevier, Academic Press chap, London, pp 339–352

    Chapter  Google Scholar 

  22. Pawlowska M, Yang Q, Hamata B, Kendler DL, Broady R (2016) Early changes in bone mineral density and trabecular bone score following allogeneic stem cell transplant. Bone Marrow Transplant 51:738–740

    Article  CAS  PubMed  Google Scholar 

  23. Lee WY, Baek KH, Rhee EJ, Tae HJ, Oh KW, Kang MI, Lee KW, Kim SW, Kim CC, Oh ES (2004) Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation. Bone Marrow Transplant 34:89–94

    Article  CAS  PubMed  Google Scholar 

  24. Gandhi MK, Lekamwasam S, Inman I et al (2003) 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 121:462–468

    Article  PubMed  Google Scholar 

  25. Champlin RE (2003) Selection of autologous or allogeneic transplantation. In: Kufe DW, Pollock RE, Weichselbaum RR et al (eds) Holland-Frei cancer medicine, 6th edn. BC Decker, Hamilton (ON)

    Google Scholar 

  26. Bagcchi S (2015) Stem-cell transplantation increases fracture risk. Lancet Oncol 16:e201

    Article  PubMed  Google Scholar 

  27. Pundole XN, Barbo AG, Lin H, Champlin RE, Lu H (2015) Increased incidence of fractures in recipients of hematopoietic stem-cell transplantation. J Clin Oncol 33:1364–1370

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pundole X, Cheema HI, Petitto GS, Lopez-Olivo MA, Suarez-Almazor ME, Lu H (2017) Prevention and treatment of bone loss and fractures in patients undergoing a hematopoietic stem cell transplant: a systematic review and meta-analysis. Bone Marrow Transplant 52:663–670

    Article  CAS  PubMed  Google Scholar 

  29. Lin JN, Chen HJ, Yang CH, Lai CH, Lin HH, Chang CS, Liang JA (2017) Risk of osteoporosis and pathologic fractures in cancer patients who underwent hematopoietic stem cell transplantation: a nationwide retrospective cohort study. Oncotarget 8:34811–34819

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  31. Berenson JR, Lichtenstein A, Porter L et al (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma Myeloma Aredia Study Group. N Engl J Med 334:488–493

    Article  CAS  PubMed  Google Scholar 

  32. Raje N, Terpos E, Willenbacher W et al (2018) Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 19:370–381

    Article  CAS  PubMed  Google Scholar 

  33. Pacifici R (2010) The immune system and bone. Arch Biochem Biophys 503:41–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Weitzmann MN, Pacifici R (2005) Role of the immune system in postmenopausal bone loss. Curr Osteoporos Rep 3:92–97

    Article  PubMed  Google Scholar 

  35. Nakashima T, Hayashi M, Takayanagi H (2012) New insights into osteoclastogenic signaling mechanisms. Trends Endocrinol Metab 23:582–590

    Article  CAS  PubMed  Google Scholar 

  36. Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–1508

    Article  CAS  PubMed  Google Scholar 

  37. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055

    Article  CAS  PubMed  Google Scholar 

  38. Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S (1999) Interleukin-1beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone 25:255–259

    Article  CAS  PubMed  Google Scholar 

  39. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106:1481–1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fuller K, Murphy C, Kirstein B, Fox SW, Chambers TJ (2002) TNFalpha potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology 143:1108–1118

    Article  CAS  PubMed  Google Scholar 

  41. Kobayashi K, Takahashi N, Jimi E et al (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191:275–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nanes MS (2003) Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene 321:1–15

    Article  CAS  PubMed  Google Scholar 

  43. Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y (2004) IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 15:49–60

    Article  PubMed  CAS  Google Scholar 

  44. Ross FP (2003) Interleukin 7 and estrogen-induced bone loss. Trends Endocrinol Metab 14:147–149

    Article  PubMed  CAS  Google Scholar 

  45. Takayanagi H, Ogasawara K, Hida S et al (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408:600–605

    Article  CAS  PubMed  Google Scholar 

  46. Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X, Weitzmann MN, Pacifici R (2007) IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest 117:122–132

    Article  CAS  PubMed  Google Scholar 

  47. Quinn JM, Sims NA, Saleh H, Mirosa D, Thompson K, Bouralexis S, Walker EC, Martin TJ, Gillespie MT (2008) IL-23 inhibits osteoclastogenesis indirectly through lymphocytes and is required for the maintenance of bone mass in mice. J Immunol 181:5720–5729

    Article  CAS  PubMed  Google Scholar 

  48. Quach JM, Askmyr M, Jovic T, Baker EK, Walsh NC, Harrison SJ, Neeson P, Ritchie D, Ebeling PR, Purton LE (2015) Myelosuppressive therapies significantly increase pro-inflammatory cytokines and directly cause bone loss. J Bone Miner Res 30:886–897

    Article  CAS  PubMed  Google Scholar 

  49. Yao S, Sucheston LE, Smiley SL, Davis W, Conroy JM, Nowak NJ, Ambrosone CB, McCarthy PL Jr, Hahn T (2011) Common genetic variants are associated with accelerated bone mineral density loss after hematopoietic cell transplantation. PLoS One 6:e25940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gao L, Zhang Y, Hu B et al (2016) Phase II multicenter, randomized, double-blind controlled study of efficacy and safety of umbilical cord-derived mesenchymal stromal cells in the prophylaxis of chronic graft-versus-host disease after HLA-haploidentical stem-cell transplantation. J Clin Oncol 34:2843–2850

    Article  CAS  PubMed  Google Scholar 

  51. Sui B, Hu C, Zhang X, Zhao P, He T, Zhou C, Qiu X, Chen N, Zhao X, Jin Y (2016) Allogeneic mesenchymal stem cell therapy promotes osteoblastogenesis and prevents glucocorticoid-induced osteoporosis. Stem Cells Transl Med 5:1238–1246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Phetfong J, Sanvoranart T, Nartprayut K, Nimsanor N, Seenprachawong K, Prachayasittikul V, Supokawej A (2016) Osteoporosis: the current status of mesenchymal stem cell-based therapy. Cell Mol Biol Lett 21:12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Stern JM, Sullivan KM, Ott SM, Seidel K, Fink JC, Longton G, Sherrard DJ (2001) Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study. Biol Blood Marrow Transplant 7:257–264

    Article  CAS  PubMed  Google Scholar 

  54. Tauchmanova L, Selleri C, Esposito M, Di Somma C, Orio F Jr, Bifulco G, Palomba S, Lombardi G, Rotoli B, Colao A (2003) Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies. Osteoporos Int 14:1013–1019

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. Banfi A, Podesta M, Fazzuoli L, Sertoli MR, Venturini M, Santini G, Cancedda R, Quarto R (2001) High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors: a mechanism for post-bone marrow transplantation osteopenia. Cancer 92:2419–2428

    Article  CAS  PubMed  Google Scholar 

  57. Roodman GD (1997) Mechanisms of bone lesions in multiple myeloma and lymphoma. Cancer 80:1557–1563

    Article  CAS  PubMed  Google Scholar 

  58. Hameed A, Brady JJ, Dowling P, Clynes M, O’Gorman P (2014) Bone disease in multiple myeloma: pathophysiology and management. Cancer Growth Metastasis 7:33–42

    Article  PubMed  PubMed Central  Google Scholar 

  59. Manolagas SC, O’Brien CA, Almeida M (2013) The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 9:699–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chatterjee R, Kottaridis PD (2002) Treatment of gonadal damage in recipients of allogeneic or autologous transplantation for haematological malignancies. Bone Marrow Transplant 30:629–635

    Article  CAS  PubMed  Google Scholar 

  61. Socie G, Stone JV, Wingard JR et al (1999) Long-term survival and late deaths after allogeneic bone marrow transplantation. N Engl J Med 341:14–21

    Article  Google Scholar 

  62. Tauchmanova L, Selleri C, Rosa GD, Pagano L, Orio F, Lombardi G, Rotoli B, Colao A (2002) High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 95:1076–1084

    Article  PubMed  Google Scholar 

  63. Ferrara JL, Levine JE (2006) Graft-versus-host disease in the 21st century: new perspectives on an old problem. Semin Hematol 43:1–2

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  66. Lai CC, Chen WS, Chang DM, Tsao YP, Wu TH, Chou CT, Tsai CY (2015) Increased serum fibroblast growth factor-23 and decreased bone turnover in patients with systemic lupus erythematosus under treatment with cyclosporine and steroid but not steroid only. Osteoporos Int 26:601–610

    Article  CAS  PubMed  Google Scholar 

  67. Pfeilschifter J, Diel IJ (2000) Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol 18:1570–1593

    Article  CAS  PubMed  Google Scholar 

  68. Hui SK, Khalil A, Zhang Y, Coghill K, Le C, Dusenbery K, Froelich J, Yee D, Downs L (2010) Longitudinal assessment of bone loss from diagnostic computed tomography scans in gynecologic cancer patients treated with chemotherapy and radiation. Am J Obstet Gynecol 203(353):e351–e357

    Google Scholar 

  69. Higham CE, Faithfull S (2015) Bone health and pelvic radiotherapy. Clin Oncol (R Coll Radiol) 27:668–678

    Article  CAS  Google Scholar 

  70. May KP, West SG, McDermott MT, Huffer WE (1994) The effect of low-dose methotrexate on bone metabolism and histomorphometry in rats. Arthritis Rheum 37:201–206

    Article  CAS  PubMed  Google Scholar 

  71. Rehman MU, Tahir M, Ali F, Qamar W, Lateef A, Khan R, Quaiyoom A, Oday OH, Sultana S (2012) Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. Mol Cell Biochem 365:119–127

    Article  CAS  PubMed  Google Scholar 

  72. Le Meignen M, Auquier P, Barlogis V et al (2011) Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities. Blood 118:1481–1489

    Article  PubMed  CAS  Google Scholar 

  73. McClune BL, Polgreen LE, Burmeister LA, Blaes AH, Mulrooney DA, Burns LJ, Majhail NS (2011) Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients. Bone Marrow Transplant 46:1–9

    Article  CAS  PubMed  Google Scholar 

  74. Horwitz ME (2011) Reduced intensity versus myeloablative allogeneic stem cell transplantation for the treatment of acute myeloid leukemia, myelodysplastic syndrome and acute lymphoid leukemia. Curr Opin Oncol 23:197–202

    Article  PubMed  Google Scholar 

  75. Kwee TC, de Klerk JM, Nievelstein RA (2011) Imaging of bone marrow involvement in lymphoma: state of the art and future directions. ScientificWorldJournal 11:391–402

    Article  PubMed  PubMed Central  Google Scholar 

  76. Daldrup-Link HE, Henning T, Link TM (2007) MR imaging of therapy-induced changes of bone marrow. Eur Radiol 17:743–761

    Article  PubMed  Google Scholar 

  77. Park JM, Jung HA, Kim DW, Lee JW, Kim CC, Hahn ST (2001) Magnetic resonance imaging of the bone marrow after bone marrow transplantation or immunosuppressive therapy in aplastic anemia. J Korean Med Sci 16:725–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Patriarca F, Carobolante F, Zamagni E et al (2015) The role of positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in the evaluation of patients with multiple myeloma undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant 21:1068–1073

    Article  PubMed  Google Scholar 

  79. Rizzo JD, Wingard JR, Tichelli A, Lee SJ, Van Lint MT, Burns LJ, Davies SM, Ferrara JL, Socie G (2006) Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT). Bone Marrow Transplant 37:249–261

    Article  CAS  PubMed  Google Scholar 

  80. Majhail NS, Rizzo JD, Lee SJ et al (2012) Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant 18:348–371

    Article  PubMed  Google Scholar 

  81. Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM, International Society for Clinical Densitometry (2014) Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 17:225–242

  82. Johnell O, Kanis JA, Oden A et al (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20:1185–1194

    Article  PubMed  Google Scholar 

  83. Kanis JA, Johnell O, Oden A, De Laet C, Jonsson B, Dawson A (2002) Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies. Bone 30:251–258

    Article  CAS  PubMed  Google Scholar 

  84. Pundole X, Murphy WA, Ebede CC et al (2018) Fracture risk prediction using FRAX in patients following hematopoietic stem cell transplantation. Arch Osteoporos 13:38

    Article  PubMed  Google Scholar 

  85. Clowes JA, Eastell R (2000) The role of bone turnover markers and risk factors in the assessment of osteoporosis and fracture risk. Baillieres Best Pract Res Clin Endocrinol Metab 14:213–232

    Article  CAS  PubMed  Google Scholar 

  86. Vasikaran SD (2009) Should serial assessment of bone turnover markers be included in fracture risk calculation in elderly women? Nat Clin Pract Endocrinol Metab 5:12–13

    Article  PubMed  Google Scholar 

  87. Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420

    Article  CAS  PubMed  Google Scholar 

  88. Sproat L, Bolwell B, Rybicki L, Dean R, Sobecks R, Pohlman B, Andresen S, Sweetenham J, Copelan E, Kalaycio M (2011) Vitamin D level after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant 17:1079–1083

    Article  CAS  PubMed  Google Scholar 

  89. Urbain P, Ihorst G, Biesalski HK, Bertz H (2012) Course of serum 25-hydroxyvitamin D(3) status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation. Ann Hematol 91:759–766

    Article  CAS  PubMed  Google Scholar 

  90. Glotzbecker B, Ho VT, Aldridge J, Kim HT, Horowitz G, Ritz J, Soiffer R, Avigan D, Rosenblatt J (2013) Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD. Bone Marrow Transplant 48:593–597

    Article  CAS  PubMed  Google Scholar 

  91. Valimaki MJ, Kinnunen K, Volin L, Tahtela R, Loyttyniemi E, Laitinen K, Makela P, Keto P, Ruutu T (1999) A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. Bone Marrow Transplant 23:355–361

    Article  CAS  PubMed  Google Scholar 

  92. Frisk P, Arvidson J, Ljunggren O, Gustafsson J (2012) Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D. Bone Marrow Transplant 47:657–662

    Article  CAS  PubMed  Google Scholar 

  93. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  PubMed  Google Scholar 

  94. Sunyecz JA (2008) The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 4:827–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, Valimaki MJ (2005) 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 90:3877–3885

    Article  CAS  PubMed  Google Scholar 

  97. Tauchmanova L, De Simone G, Musella T, Orio F, Ricci P, Nappi C, Lombardi G, Colao A, Rotoli B, Selleri C (2006) Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation. Bone Marrow Transplant 37:81–88

    Article  CAS  PubMed  Google Scholar 

  98. Grigg AP, Shuttleworth P, Reynolds J, Schwarer AP, Szer J, Bradstock K, Hui C, Herrmann R, Ebeling PR (2006) Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 91:3835–3843

    Article  CAS  PubMed  Google Scholar 

  99. Hari P, DeFor TE, Vesole DH, Bredeson CN, Burns LJ (2013) Intermittent zoledronic acid prevents bone loss in adults after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 19:1361–1367

    Article  CAS  PubMed  Google Scholar 

  100. Grigg A, Butcher B, Khodr B, Bajel A, Hertzberg M, Patil S, D’Souza AB, Ganly P, Ebeling P, Wong E (2017) An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial. Bone Marrow Transplant 52:1288–1293

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  103. Body JJ, Bergmann P, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Reginster JY, Rozenberg S, Kaufman JM (2007) Management of cancer treatment-induced bone loss in early breast and prostate cancer -- a consensus paper of the Belgian Bone Club. Osteoporos Int 18:1439–1450

    Article  CAS  PubMed  Google Scholar 

  104. Body JJ (2005) Bisphosphonates in oncology: focus on clinical experience with pamidronate. Am J Cancer 4:293–305

    Article  CAS  Google Scholar 

  105. Saad F, Brown JE, Van Poznak C et al (2012) Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 23:1341–1347

    Article  CAS  PubMed  Google Scholar 

  106. Khan AA, Morrison A, Hanley DA et al (2015) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30:3–23

    Article  PubMed  Google Scholar 

  107. de Villiers TJ, Hall JE, Pinkerton JV, Perez SC, Rees M, Yang C, Pierroz DD (2016) Revised global consensus statement on menopausal hormone therapy. Maturitas 91:153–155

    Article  PubMed  Google Scholar 

  108. Body JJ, Bergmann P, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, Rozenberg S, Reginster JY (2010) Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club. Osteoporos Int 21:1657–1680

    Article  PubMed  PubMed Central  Google Scholar 

  109. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  CAS  PubMed  Google Scholar 

  110. Body JJ (2012) Denosumab for the management of bone disease in patients with solid tumors. Expert Rev Anticancer Ther 12:307–322

    Article  CAS  PubMed  Google Scholar 

  111. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) 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 96:972–980

    Article  CAS  PubMed  Google Scholar 

  112. Pundole X, Partow K, Lu H (2014) Denosumab increases bone mineral density in a young osteoporotic woman on dialysis after allogeneic stem cell transplantation for hematologic malignancy. IBMS BoneKEy:11

  113. Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, Dalsky GP, Marcus R (2007) Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 357:2028–2039

    Article  CAS  PubMed  Google Scholar 

  114. Lekamwasam S, Adachi JD, Agnusdei D et al (2012) A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 23:2257–2276

    Article  CAS  PubMed  Google Scholar 

  115. Gertz MA, Dingli D (2014) How we manage autologous stem cell transplantation for patients with multiple myeloma. Blood 124:882–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Moreau P, San Miguel J, Sonneveld P et al (2017) Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv52–iv61

    Article  CAS  PubMed  Google Scholar 

  117. Hautmann AH, Elad S, Lawitschka A et al (2011) Metabolic bone diseases in patients after allogeneic hematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease. Transpl Int 24:867–879

    Article  PubMed  Google Scholar 

  118. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine S (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930

    Article  CAS  PubMed  Google Scholar 

  119. Rizzoli R, Body JJ, Brandi ML et al (2013) Cancer-associated bone disease. Osteoporos Int 24:2929–2953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Gnant M, Pfeiler G, Dubsky PC et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386:433–443

    Article  CAS  PubMed  Google Scholar 

  121. Hadji P, Kyvernitakis I, Kann PH et al (2016) GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab. Osteoporos Int 27:2967–2978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF (2018) Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol 6:445–454

    Article  CAS  PubMed  Google Scholar 

  123. Mucowski SJ, Mack WJ, Shoupe D, Kono N, Paulson R, Hodis HN (2014) Effect of prior oophorectomy on changes in bone mineral density and carotid artery intima-media thickness in postmenopausal women. Fertil Steril 101:1117–1122

    Article  PubMed  PubMed Central  Google Scholar 

  124. Castelo-Branco C, Pons F, Martinez de Osaba MJ, Garrido J, Fortuny A (1996) Menstrual history as a determinant of current bone density in young hirsute women. Metabolism 45:515–518

    Article  CAS  PubMed  Google Scholar 

  125. Boonen S, Sellmeyer DE, Lippuner K, Orlov-Morozov A, Abrams K, Mesenbrink P, Eriksen EF, Miller PD (2008) Renal safety of annual zoledronic acid infusions in osteoporotic postmenopausal women. Kidney Int 74:641–648

    Article  CAS  PubMed  Google Scholar 

  126. Miller PD (2011) The kidney and bisphosphonates. Bone 49:77–81

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to D. L. Kendler.

Ethics declarations

Conflicts of interest

P Hadji received honoraria, travel grants, and scientific research grants from Amgen, Eli Lilly, MSD, Novartis, Pfizer, Procter & Gamble, and Roche. D Kendler received honoraria, speakers bureau, and/or research grants from Amgen, Eli Lilly, MSD, Pfizer, Astrazenica, and Astellas. T de Villiers has acted as a consultant or speaker for the following companies: Abbott, Amgen, Aspen, MSD, Pfizer. R Rizzoli received fees for consultancy or lectures from Danone, EffRx, Nestlé, ObsEva, and Radius Health. PR Ebeling received research grants, honoraria, and/or speakers’ fees from Amgen, Eli Lilly, Novartis, and Gilead. J Cannata-Andia received honoraria and scientific research grants from Amgen, Shire, and VIFOR/Fresenius. JJ Body, ML Brandi, MJ Cannata-Ortiz, A El Magrahoui, G Guglielmi, and DD Pierroz have no conflict of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kendler, D., Body, J., Brandi, M. et al. Bone management in hematologic stem cell transplant recipients. Osteoporos Int 29, 2597–2610 (2018). https://doi.org/10.1007/s00198-018-4669-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-018-4669-4

Keywords

Navigation