Advertisement

Hormones

, Volume 17, Issue 2, pp 153–166 | Cite as

The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis

  • Athanasios N. Tsartsalis
  • George I. Lambrou
  • Dimitrios Tsartsalis
  • Christos Savvidis
  • Maria Karantza
  • Evangelos Terpos
  • Christina Kanaka-Gantenbein
  • George P. Chrousos
  • Antonis Kattamis
Review

Abstract

Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedges’s g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I2 statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm2). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.

Keywords

Osteoporosis Bone mineral density Bisphosphonates β-thalassemia Zolendronic acid 

Notes

Authors’ contributions

ANT: Data collection, review of the literature, primary reviewer, statistical analysis, drafted the manuscript, GIL: Review of the literature, secondary reviewer, statistical analysis, meta-analysis, drafted the manuscript, DT: Statistical analysis, CS: Data collection, review of the literature, third reviewer, MK: Review of the literature, ET: Review of the literature, CK: Review of the literature, critical reading, GPC: Review of the literature, critical reading, proof-edited the manuscript, gave final permission for submission, AT: Critical reading.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This study does not contain any original human or animal study performed by the authors.

Informed consent

Not applicable

Supplementary material

42000_2018_19_MOESM1_ESM.xlsx (3 mb)
ESM 1 (XLSX 3021 kb)

References

  1. 1.
    Otrock ZK, Azar ST, Shamseddeen WA et al (2006) Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis: results of a phase II clinical trial. Ann Hematol 85(9):605–609CrossRefPubMedGoogle Scholar
  2. 2.
    Musallam KM, Taher AT, Rachmilewitz EA (2012) Beta-thalassemia intermedia: a clinical perspective. Cold Spring Harb Perspect Med 2(7):a013482CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Schnedl WJ, Schenk M, Lackner S, Holasek SJ, Mangge H (2017) Beta-thalassemia minor, carbohydrate malabsorption and histamine intolerance. J Community Hosp Intern Med Perspect 7(4):227–229CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Coley TB (1925) Series of cases of sp lenomegaly in children with anemia and peculiar bone changes. Trans Am Pediat Soc 47:29Google Scholar
  5. 5.
    Vogiatzi MG, Macklin EA, Fung EB et al (2009) Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res Off J Am Soc Bone Miner Res 24(3):543–557CrossRefGoogle Scholar
  6. 6.
    Terpos E, Voskaridou E (2010) Treatment options for thalassemia patients with osteoporosis. Ann N Y Acad Sci 1202:237–243CrossRefPubMedGoogle Scholar
  7. 7.
    Carmina E, Di Fede G, Napoli N et al (2004) Hypogonadism and hormone replacement therapy on bone mass of adult women with thalassemia major. Calcif Tissue Int 74(1):68–71CrossRefPubMedGoogle Scholar
  8. 8.
    Hatori M, Sparkman J, Teixeira CC et al (1995) Effects of deferoximine on chondrocyte alkaline phosphatase activity: proxidant role of deferoximine in thalassemia. Calcif Tissue Int 57(3):229–236CrossRefPubMedGoogle Scholar
  9. 9.
    Lasco A, Morabito N, Gaudio A et al (2001) Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major. Osteoporos Int 12(7):570–575CrossRefPubMedGoogle Scholar
  10. 10.
    Voskaridou E, Terpos E (2005) Osteoprotegerin to soluble receptor activator of nuclear factor kappa-B ligand ratio is reduced in patients with thalassaemia-related osteoporosis who receive vitamin D3. Eur J Haematol 74(4):359–361CrossRefPubMedGoogle Scholar
  11. 11.
    Anapliotou ML, Kastanias IT, Psara P et al (1995) The contribution of hypogonadism to the development of osteoporosis in thalassaemia major: new therapeutic approaches. Clin Endocrinol 42(3):279–287CrossRefGoogle Scholar
  12. 12.
    Morabito N, Lasco A, Gaudio A et al (2002) Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporos Int 13(8):644–649CrossRefPubMedGoogle Scholar
  13. 13.
    Lindsay R (1993) Prevention and treatment of osteoporosis. Lancet 341(8848):801–805CrossRefPubMedGoogle Scholar
  14. 14.
    Papapoulos SE (2011) Use of bisphosphonates in the management of postmenopausal osteoporosis. Ann N Y Acad Sci 1218:15–32CrossRefPubMedGoogle Scholar
  15. 15.
    Higgins JP, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dragioti E, Dimoliatis I, Evangelou E (2015) Disclosure of researcher allegiance in meta-analyses and randomised controlled trials of psychotherapy: a systematic appraisal. BMJ Open 5(6):e007206CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Dragioti E, Dimoliatis I, Fountoulakis KN, Evangelou E (2015) A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy. Ann General Psychiatry 14:25CrossRefGoogle Scholar
  18. 18.
    Forni GL, Perrotta S, Giusti A et al (2012) Neridronate improves bone mineral density and reduces back pain in beta-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study. Br J Haematol 158(2):274–282CrossRefPubMedGoogle Scholar
  19. 19.
    Gilfillan CP, Strauss BJ, Rodda CP et al (2006) A randomized, double-blind, placebo-controlled trial of intravenous zoledronic acid in the treatment of thalassemia-associated osteopenia. Calcif Tissue Int 79(3):138–144CrossRefPubMedGoogle Scholar
  20. 20.
    Pennisi P, Pizzarelli G, Spina M, Riccobene S, Fiore CE (2003) Quantitative ultrasound of bone and clodronate effects in thalassemia-induced osteoporosis. J Bone Miner Metab 21(6):402–408CrossRefPubMedGoogle Scholar
  21. 21.
    Skordis N, Ioannou YS, Kyriakou A et al (2008) Effect of bisphosphonate treatment on bone mineral density in patients with thalassaemia major. Pediatr Endocrinol Rev 6(Suppl 1):144–148PubMedGoogle Scholar
  22. 22.
    Voskaridou E, Anagnostopoulos A, Konstantopoulos K et al (2006) Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial. Haematologica 91(9):1193–1202PubMedGoogle Scholar
  23. 23.
    Voskaridou E, Christoulas D, Antoniadou L, Terpos E (2008) Continuous increase in erythropoietic activity despite the improvement in bone mineral density by zoledronic acid in patients with thalassemia intermedia-induced osteoporosis. Acta Haematol 119(1):40–44CrossRefPubMedGoogle Scholar
  24. 24.
    Voskaridou E, Christoulas D, Konstantinidou M et al (2008) Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long-term follow-up of a randomized, placebo-controlled trial. Haematologica 93(10):1588–1590CrossRefPubMedGoogle Scholar
  25. 25.
    Voskaridou E, Christoulas D, Xirakia C et al (2009) Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration. Haematologica 94(5):725–728CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Perifanis V, Vyzantiadis T, Tziomalos K et al (2007) Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia. Ann Hematol 86(1):23–30CrossRefPubMedGoogle Scholar
  27. 27.
    Voskaridou E, Terpos E, Spina G et al (2003) Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassaemia. Br J Haematol 123(4):730–737CrossRefPubMedGoogle Scholar
  28. 28.
    Leung TF, Chu Y, Lee V et al (2009) Long-term effects of pamidronate in thalassemic patients with severe bone mineral density deficits. Hemoglobin 33(5):361–369CrossRefPubMedGoogle Scholar
  29. 29.
    Chatterjee R, Shah FT, Davis BA et al (2012) Prospective study of histomorphometry, biochemical bone markers and bone densitometric response to pamidronate in beta-thalassaemia presenting with osteopenia-osteoporosis syndrome. Br J Haematol 159(4):462–471CrossRefPubMedGoogle Scholar
  30. 30.
    Perifanis V, Vyzantiadis T, Vakalopoulou S et al (2004) Treatment of beta-thalassaemia-associated osteoporosis with zoledronic acid. Br J Haematol 125(1):91–92 author reply 3-4CrossRefPubMedGoogle Scholar
  31. 31.
    Basha NK, Shetty B, Shenoy UV (2014) Prevalence of hypoparathyroidism (HPT) in Beta thalassemia major. J Clin Diagn Res 8(2):24–26Google Scholar
  32. 32.
    Byun JH, Jang S, Lee S et al (2017) The efficacy of bisphosphonates for prevention of osteoporotic fracture: an update meta-analysis. J Bone Metab 24(1):37–49CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Dede AD, Trovas G, Chronopoulos E et al (2016) Thalassemia-associated osteoporosis: a systematic review on treatment and brief overview of the disease. Osteoporos Int 27(12):3409–3425CrossRefPubMedGoogle Scholar
  34. 34.
    Brown JE, Ellis SP, Lester JE et al (2007) Prolonged efficacy of a single dose of the bisphosphonate zoledronic acid. Clin Cancer Res 13(18 Pt 1):5406–5410CrossRefPubMedGoogle Scholar
  35. 35.
    Bhardwaj A, Swe KM, Sinha NK, Osunkwo I (2016) Treatment for osteoporosis in people with ss-thalassaemia. Cochrane Database Syst Rev 3:CD010429PubMedGoogle Scholar
  36. 36.
    Shamshirsaz AA, Bekheirnia MR, Kamgar M et al (2003) Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocr Disord 3(1):4CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Voskaridou E, Kyrtsonis MC, Terpos E et al (2001) Bone resorption is increased in young adults with thalassaemia major. Br J Haematol 112(1):36–41CrossRefPubMedGoogle Scholar
  38. 38.
    Reid IR, Brown JP, Burckhardt P et al (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346(9):653–661CrossRefPubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Athanasios N. Tsartsalis
    • 1
  • George I. Lambrou
    • 2
    • 3
    • 4
  • Dimitrios Tsartsalis
    • 5
  • Christos Savvidis
    • 6
  • Maria Karantza
    • 2
  • Evangelos Terpos
    • 7
  • Christina Kanaka-Gantenbein
    • 3
  • George P. Chrousos
    • 2
    • 3
    • 4
  • Antonis Kattamis
    • 4
  1. 1.Department of Endocrinology Diabetes and MetabolismNaval Hospital of AthensAthensGreece
  2. 2.First Department of Pediatrics, Choremeio Research LaboratoryNational and Kapodistrian University of AthensAthensGreece
  3. 3.Division of Endocrinology Diabetes and Metabolism, First Department of PediatricsNational and Kapodistrian University of AthensAthensGreece
  4. 4.Hematology/Oncology Unit, First Department of PediatricsNational and Kapodistrian University of AthensAthensGreece
  5. 5.Department of Clinical PhysiologyLinköping UniversityLinköpingSweden
  6. 6.Department of Endocrinology and Metabolism “Hippocration” General HospitalAthensGreece
  7. 7.Department of Clinical Therapeutics, Medical School, “Alexandra” General HospitalNational and Kapodistrian University of AthensAthensGreece

Personalised recommendations