Abstract
Bone loss is recognized as worsening the quality of life in long-term survivors of Allo-SCT. This study evaluated the risk factors associated with bone loss and the role of zoledronic acid in preventing bone loss in allogeneic recipients. Fifty-three patients who underwent HLA-matched Allo-SCT were evaluated for their bone mineral density (BMD) in the lumbar spine and femoral neck at regular intervals. Zoledronic acid (4 mg) was given i.v. to 18 patients (ZA patients) at 2 months after SCT and then every 3 months until 2 years. Grade 2–4 acute GVHD was associated with bone loss (odds ratio (OR)=4.90, 95% confidence interval (CI)=1.41–16.99; P=0.012) at 1 year after SCT, whereas extensive chronic GVHD and steroid use were both unfavorable prognostic factors (OR=9.00 and 7.22, 95% CI=1.52–53.40 and 1.44–36.22; P=0.016, respectively) in terms of osteopenia/osteoporosis at 2 years after transplantation. The use of zoledronic acid significantly prevented bone loss in the femoral neck as well as the spine (OR=0.18, 95% CI=0.05–0.69, P=0.012). Therefore, BMD measurements and the use of zoledronic acid are recommended in cases of GVHD or long-term steroid use after Allo-SCT to prevent bone loss and threatening skeletal events.
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
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.
Valimaki MJ, Kinnunen K, Volin L, Tahtela R, Loyttyniemi 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.
Stern JM, Sullivan KM, Ott SM, Seidel K, Fink JC, Longton G et al. Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study. Biol Blood Marrow Transplant 2001; 7: 257–264.
Tauchmanova L, Serio B, Del Puente A, Risitano AM, Esposito A, De Rosa G et al. Long-lasting bone damage detected by dual-energy X-ray absorptiometry, phalangeal osteosonogrammetry, and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2002; 87: 5058–5065.
Schimmer AD, Minden MD, Keating A . Osteoporosis after blood and marrow transplantation: clinical aspects. Biol Blood Marrow Transplant 2000; 6: 175–181.
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.
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, Sohn SK, Kim JG, Cho YY, Moon JH, Shin HJ et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplant 2007; 40: 541–547.
Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.
Lee KH, Choi SJ, Lee JH, Lee JS, Kim WK, Lee KB et al. Prognostic factors identifiable at the time of onset of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Haematologica 2005; 90: 939–948.
Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.
Kanis JA, Seeman E, Johnell O, Rizzoli R, Delmas P . The perspective of the International Osteoporosis Foundation on the official positions of the International Society for Clinical Densitometry. Osteoporos Int 2005; 16: 456–459, discussion 579–80.
Banfi A, Podesta M, Fazzuoli L, Sertoli MR, Venturini M, Santini G et al. High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors: a mechanism for post-bone marrow transplantation osteopenia. Cancer 2001; 92: 2419–2428.
Marcus R, Wong M, Heath III H, Stock JL . Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Endocr Rev 2002; 23: 16–37.
Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002; 87: 3609–3617.
Delmas PD . Treatment of postmenopausal osteoporosis. Lancet 2002; 359: 2018–2026.
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, 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.
Neville-Webbe HL, Evans CA, Coleman RE, Holen I . Mechanisms of the synergistic interaction between the bisphosphonate zoledronic acid and the chemotherapy agent paclitaxel in breast cancer cells in vitro. Tumour Biol 2006; 27: 92–103.
Hershman DL, McMahon DJ, Crew KD, Cremers S, Irani D, Cucchiara G et al. Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 2008; 26: 4739–4745.
Mundy GR, Yoneda T, Hiraga T . Preclinical studies with zoledronic acid and other bisphosphonates: impact on the bone microenvironment. Semin Oncol 2001; 28 (2 Suppl 6): 35–44.
Croucher PI, De Hendrik R, Perry MJ, Hijzen A, Shipman CM, Lippitt J et al. Zoledronic acid treatment of 5T2 MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 2003; 18: 482–492.
Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M . Stimulation of gamma delta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000; 96: 384–392.
Gober HJ, Kistowska M, Angman L, Jeno P, Mori L, De Libero G . Human T cell receptor gamma delta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med 2003; 197: 163–168.
Tassone P, Forciniti S, Galea E, Morrone G, Turco MC, Martinelli V et al. Growth inhibition and synergistic induction of apoptosis by zoledronate and dexamethasone in human myeloma cell lines. Leukemia 2000; 14: 841–844.
Jagdev SP, Coleman RE, Shipman CM, Rostami HA, Croucher PI . The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer 2001; 84: 1126–1134.
Kuroda J, Kimura S, Segawa H, Kobayashi Y, Yoshikawa T, Urasaki Y et al. The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate. Blood 2003; 102: 2229–2235.
Kimura S, Kuroda J, Segawa H, Sato K, Nogawa M, Yuasa T et al. Antiproliferative efficacy of the third-generation bisphosphonate, zoledronic acid, combined with other anticancer drugs in leukemic cell lines. Int J Hematol 2004; 79: 37–43.
Fiegl M, Juergens M, Hiddemann W, Braess J . Cytotoxic activity of the third-generation bisphosphonate zoledronic acid in acute myeloid leukemia. Leuk Res 2007; 31: 531–539.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chae, Y., Kim, J., Moon, J. et al. Pilot study on the use of zoledronic acid to prevent bone loss in allo-SCT recipients. Bone Marrow Transplant 44, 35–41 (2009). https://doi.org/10.1038/bmt.2008.414
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.414
Keywords
This article is cited by
-
Bone turnover markers as an aid to monitor osteoporosis following allogeneic hematopoietic stem cell transplantation
Annals of Hematology (2020)
-
Bone management in hematologic stem cell transplant recipients
Osteoporosis International (2018)
-
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 Transplantation (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 Transplantation (2017)
-
Ibandronate for the prevention of bone loss after allogeneic stem cell transplantation for hematologic malignancies: a randomized-controlled trial
BoneKEy Reports (2016)