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Pediatric Transplants

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D

Bone Marrow Transplantation volume 47, pages 657–662 (2012)Cite this article

Abstract

We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <−1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (⩽37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

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References

  1. Banfi A, Bianchi G, Galotto M, Cancedda R, Quarto R . Bone marrow stromal damage after chemo/radiotherapy: occurrence, consequences and possibilities of treatment. Leuk Lymphoma 2001; 42: 863–870.

    Article  CAS  PubMed  Google Scholar 

  2. Brennan BM, Shalet SM . Endocrine late effects after bone marrow transplant. Br J Haematol 2002; 118: 58–66.

    Article  PubMed  Google Scholar 

  3. Baird K, Cooke K, Schultz KR . Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am 2010; 57: 297–322.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Taskinen M, Saarinen-Pihkala UM, Hovi L, Vettenranta K, Makitie O . Bone health in children and adolescents after allogeneic stem cell transplantation: high prevalence of vertebral compression fractures. Cancer 2007; 110: 442–451.

    Article  PubMed  Google Scholar 

  6. Meacham LR, Gurney JG, Mertens AC, Ness KK, Sklar CA, Robison LL et al. Body mass index in long-term adult survivors of childhood cancer: a report of the Childhood Cancer Survivor Study. Cancer 2005; 103: 1730–1739.

    Article  PubMed  Google Scholar 

  7. Chow EJ, Simmons JH, Roth CL, Baker KS, Hoffmeister PA, Sanders JE et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 2010; 16: 1674–1681.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kananen K, Volin L, Tahtela R, Laitinen K, Ruutu T, Valimaki MJ . Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 2002; 29: 33–39.

    Article  CAS  PubMed  Google Scholar 

  9. Faulhaber GA, Premaor MO, Moser Filho HL, Silla LM, Furlanetto TW . Low bone mineral density is associated with insulin resistance in bone marrow transplant subjects. Bone Marrow Transplant 2009; 43: 953–957.

    Article  CAS  PubMed  Google Scholar 

  10. Duncan CN, Vrooman L, Apfelbaum EM, Whitley K, Bechard L, Lehmann LE . 25-hydroxy vitamin D deficiency following pediatric hematopoietic stem cell transplant. Biol Blood Marrow Transplant 2011; 17: 749–753.

    Article  CAS  PubMed  Google Scholar 

  11. Nysom K, Holm K, Michaelsen KF, Hertz H, Jacobsen N, Muller J et al. Bone mass after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant 2000; 25: 191–196.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. 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  PubMed  Google Scholar 

  14. Taskinen M, Kananen K, Valimaki M, Loyttyniemi E, Hovi L, Saarinen-Pihkala U et al. Risk factors for reduced areal bone mineral density in young adults with stem cell transplantation in childhood. Pediatr Transplant 2006; 10: 90–97.

    Article  CAS  PubMed  Google Scholar 

  15. Gustafsson G, Kreuger A, Clausen N, Garwicz S, Kristinsson J, Lie SO et al. Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Acta Paediatr 1998; 87: 1151–1161.

    Article  CAS  PubMed  Google Scholar 

  16. Lonnerholm G, Simonsson B, Arvidson J, Bengtsson M, Carlson K, Hagberg H et al. Autologous bone marrow transplantation in children with acute lymphoblastic leukemia. Acta Paediatr 1992; 81: 1017–1022.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Karlberg P, Taranger J, Engstrom I, Karlberg J, Landstrom T, Lichtenstein H et al. I. physical growth from birth to 16 years and longitudinal outcome of the study during the same age period. Acta Paediatr Scand Suppl 1976; 258: 7–76.

    Article  Google Scholar 

  19. Frisk P, Rössner SM, Norgren S, Arvidson J, Gustafsson J . Glucose metabolism and body composition in young adults treated with TBI during childhood. Bone Marrow Transplant (e-pub ahead of print 13 December 2010; doi:10.1038/bmt2010.307).

  20. 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  PubMed  Google Scholar 

  21. Marshall D, Johnell O, Wedel H . Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312: 1254–1259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jarfelt M, Fors H, Lannering B, Bjarnason R . Bone mineral density and bone turnover in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol 2006; 154: 303–309.

    Article  CAS  PubMed  Google Scholar 

  23. Mauras N, Pescovitz OH, Allada V, Messig M, Wajnrajch MP, Lippe B . Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: a phase III multicenter, double-blind, randomized two-year trial. J Clin Endocrinol Metab 2005; 90: 3946–3955.

    Article  CAS  PubMed  Google Scholar 

  24. Valimaki VV, Alfthan H, Lehmuskallio E, Loyttyniemi E, Sahi T, Stenman UH et al. Vitamin D status as a determinant of peak bone mass in young Finnish men. J Clin Endocrinol Metab 2004; 89: 76–80.

    Article  PubMed  Google Scholar 

  25. Holick MF . Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 2009; 19: 73–78.

    Article  PubMed  Google Scholar 

  26. Holick MF . Vitamin D deficiency. N Engl J Med 2007; 357: 266–281.

    Article  CAS  PubMed  Google Scholar 

  27. Arekat MR, And G, Lemke S, Moses AM . Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. J Clin Densitom 2002; 5: 267–271.

    Article  PubMed  Google Scholar 

  28. Cohen A, Rovelli A, Bakker B, Uderzo C, van Lint MT, Esperou H et al. Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT. Blood 1999; 93: 4109–4115.

    CAS  PubMed  Google Scholar 

  29. Ribom EL, Ljunggren O, Mallmin H . Use of a Swedish T-score reference population for women causes a two-fold increase in the amount of postmenopausal Swedish patients that fulfill the WHO criteria for osteoporosis. J Clin Densitom 2008; 11: 404–411.

    Article  PubMed  Google Scholar 

  30. Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP et al. Proximal femur bone mineral levels of US adults. Osteoporos Int 1995; 5: 389–409.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Bishop N, Braillon P, Burnham J, Cimaz R, Davies J, Fewtrell M et al. Dual-energy X-ray aborptiometry 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  PubMed  Google Scholar 

  33. 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  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden

    P Frisk, J Arvidson & J Gustafsson

  2. Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    Ö Ljunggren

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  1. P Frisk
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  2. J Arvidson
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  4. J Gustafsson
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Correspondence to P Frisk.

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Jan Gustafsson has received consulting fees from Ipsen and lecture fees from NovoNordisk. Jan Gustafsson holds stock options in Pfizer.

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Frisk, P., Arvidson, J., Ljunggren, Ö. et al. Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D. Bone Marrow Transplant 47, 657–662 (2012). https://doi.org/10.1038/bmt.2011.147

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