Skip to main content

Advertisement

SpringerLink
Log in

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia

  • Clinical Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of β-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than −1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3–15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5–12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5–12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7–6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in β-thalassaemia-associated osteopenia.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. Voskaridou E, Terpos E (2004) New insights into the pathophysiology and management of osteoporosis in patients with beta thalassemia. Br J Haematol 127:127–139

    Article  PubMed  CAS  Google Scholar 

  2. Jensen CE, Tuck SM, Old J, Morris RW, Yardumian A, De Sanctis V, Hoffbrand AV, Wonke B (1997) Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassemia. Eur J Haematol 59:76–81

    Article  PubMed  CAS  Google Scholar 

  3. Chapman RW, Hussain MA, Gorman A, Laulicht M, Politis D, Flynn DM, Sherlock S, Hoffbrand AV (1982) Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassemia major and iron overload. J Clin Pathol 35:487–91

    PubMed  CAS  Google Scholar 

  4. Bekheirnia MR, Abdollah Shamshirsaz A, Kamgar M, Bouzari N, Erfanzadeh G, Pourzahedgilani N, Tabatabaie SM, Abdollah Shamshirsaz A, Kimiagar M, Ezzati F, Larijani B (2004) Serum zinc and its relation to bone mineral density in beta-thalassemic adolescents. Biol Trace Elem Res 97:215–224

    Article  PubMed  CAS  Google Scholar 

  5. Lasco A, Morabito N, Gaudio A, Buemi M, Wasniewska M, Frisina N (2001) Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major. Osteoporos Int 12:570–575

    Article  PubMed  CAS  Google Scholar 

  6. Rogers MJ (2004) From molds and macrophages to mevalonate: a decade of progress in understanding the molecular mode of action of bisphosphonates. Calcif Tissue Int 75:451–461

    Article  PubMed  CAS  Google Scholar 

  7. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661

    Article  PubMed  CAS  Google Scholar 

  8. Aydinok Y, Erermis S, Bukosoglu N, Yilmaz D, Solak V (2005) Psychosocial implications of Thalassemia Major. Pediatr Int 47:84–89

    Article  PubMed  Google Scholar 

  9. Vichinsky EP (1998) The morbidity of bone disease in thalassemia. Ann N Y Acad Sci 850:344–348

    Article  PubMed  CAS  Google Scholar 

  10. Anapliotou ML, Kastanias IT, Psara P, Evangelou EA, Liparaki M, Dimitriou P (1995) The contribution of hypogonadism to the development of osteoporosis in thalassemia major: new therapeutic approaches. Clin Endocrinol 42:279–287

    CAS  Google Scholar 

  11. Carmina E, Di Fede G, Napoli N, Renda G, Vitale G, Lo Pinto C, Bruno D, Malizia R, Rini GB (2004) Hypogonadism and hormone replacement therapy on bone mass of adult women with thalassemia major. Calcif Tissue Int 74:68–71

    Article  PubMed  CAS  Google Scholar 

  12. Lasco A, Morabito N, Gaudio A, Crisafulli A, Meo A, Denuzzo G, Frisina N (2002) Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis. J Endocrinol Invest 25:338–344

    PubMed  CAS  Google Scholar 

  13. Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P, Choubtum L, Sriphrapradang A, Domrongkitchaiporn S, Sirisriro R, Rajatanavin R (2003) Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. J Clin Endocrinol Metab 88:3966–3972

    Article  PubMed  CAS  Google Scholar 

  14. Chan YL, Pang LM, Chik KW, Cheng JC, Li CK (2002) Patterns of bone diseases in transfusion-dependent homozygous thalassemia major: predominance of osteoporosis and desferrioxamine-induced bone dysplasia. Pediatr Radiol 32:492–497

    Article  PubMed  Google Scholar 

  15. Voskaridou E, Kyrtsonis MC, Terpos E, Skordili M, Theodoropoulos I, Bergele A, Diamanti E, Kalovidouris A, Loutradi A, Loukopoulos D (2001) Bone resorption is increased in young adults with thalassemia major. Br J Haematol 112:36–41

    Article  PubMed  CAS  Google Scholar 

  16. Morabito N, Gaudio A, Lasco A, Atteritano M, Pizzoleo MA, Cincotta M, La Rosa M, Guarino R, Meo A, Frisina N (2004) Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. J Bone Miner Res 19:722–727

    Article  PubMed  CAS  Google Scholar 

  17. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91

    Article  PubMed  CAS  Google Scholar 

  18. Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR; Fracture Intervention Trial (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124

    Article  PubMed  CAS  Google Scholar 

  19. Morabito N, Lasco A, Gaudio A, Crisafulli A, Di Pietro C, Meo A, Frisina N (2002) Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporos Int 13:644–649

    Article  PubMed  CAS  Google Scholar 

  20. Voskaridou E, Terpos E, Spina G, Palermos J, Rahemtulla A, Loutradi A, Loukopoulos D (2003) Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassemia. Br J Haematol 123:730–737

    Article  PubMed  CAS  Google Scholar 

  21. Perifanis V, Vyzantiadis T, Vakalopoulou S, Tziomalos K, Garypidou V, Athanassiou-Metaxa M, Harsoulis F (2004) Treatment of beta-thalassemia-associated osteoporosis with zoledronic acid [letter]. Br J Haematol 125:91–92

    Article  PubMed  Google Scholar 

  22. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein M, Coleman RE, Reitsma DJ, Seaman JJ, Chen BL, Ambros Y (2001) Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 7:377–387

    PubMed  CAS  Google Scholar 

  23. Gilfillan CP, Psihogios V, Strauss BJ, Bowden DK, Rodda CP (1999) Bone mineral density in homozygous β-thalassemia: relationship to anthropometry and gonadal status. Abstract and oral presentation. ANZBMS Annual Scientific Meeting, Cairns, Australia; Aug 14–18

  24. Vogiatzi MG, Autio KA, Mait JE, Schneider R, Lesser M, Giardina PJ (2005) Low bone mineral density in adolescents with β-thalassemia. Ann N Y Acad Sci 1054:462–466

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by a research grant from Novartis Pharmaceuticals. The authors thank the following study coordinators for their assistance: Karen Parisienne (Monash Medical Centre) and Tegan Sturrock and Fiona Rennison (Royal Prince Alfred Hospital). The authors also thank the staff of the thalassemia treatment units and chemical pathology departments at both institutions for their support.

Author information

Authors and Affiliations

  1. Department of Medicine, Frankston Hospital, P.O. Box 52, Frankston, Victoria, 3199, Australia

    C. P. Gilfillan

  2. Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, 3168, Australia

    B. J. S. Strauss

  3. Department of Biochemistry and Molecular Biology, Monash Medical Centre, 246 Clayton Road, Clayton, 3168, Australia

    C. P. Rodda

  4. Department of Pathology and Medical Therapy Unit, Monash Medical Centre, 246 Clayton Road, Clayton, 3168, Australia

    D. K. Bowden

  5. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia

    A.-M. Kean, M. Obaid & B. A. Crawford

  6. Faculty of Medicine, University of Sydney, Sydney, Australia

    B. A. Crawford

Authors
  1. C. P. Gilfillan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. J. S. Strauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. P. Rodda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. K. Bowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A.-M. Kean
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Obaid
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. A. Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. P. Gilfillan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gilfillan, C.P., Strauss, B.J.S., Rodda, C.P. et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia. Calcif Tissue Int 79, 138–144 (2006). https://doi.org/10.1007/s00223-006-0314-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-006-0314-x

Keywords

Search

Navigation