, 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. TsartsalisEmail author
  • George I. Lambrou
  • Dimitrios Tsartsalis
  • Christos Savvidis
  • Maria Karantza
  • Evangelos Terpos
  • Christina Kanaka-Gantenbein
  • George P. Chrousos
  • Antonis Kattamis


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.


Osteoporosis Bone mineral density Bisphosphonates β-thalassemia Zolendronic acid 


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)


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Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Athanasios N. Tsartsalis
    • 1
    Email author
  • 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

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