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

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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.

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Notes

  1. QBP Q value of Cochran’s heterogeneity statistic in samples treated with BP, QPlacebo Q value of Cochran’s heterogeneity statistic in samples received placebo, df degrees of freedom, I2 percentage of total variation across studies

  2. See footnote 1

  3. In all studies, patients and controls received calcium and vitamin D supplementation. Also, in the studies under consideration, only in the study of Morabito et al. (2002) were three patients mentioned with hypoparathyroidism. In the other studies, there was no mention of the presence of hypoparathyroidism in the patient cohort. This is indeed an important aspect, since in the case of parathyroid dysfunction, calcium and vitamin D supplementation is mandatory [31]. Basha NK, Shetty B, Shenoy UV, 2014 Prevalence of Hypoparathyroidism (HPT) in Beta Thalassemia Major. Journal of clinical and diagnostic research: JCDR 8(2): 24–6.

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Authors and Affiliations

  1. Department of Endocrinology Diabetes and Metabolism, Naval Hospital of Athens, Dinokratous 70, 11521, Athens, Greece

    Athanasios N. Tsartsalis

  2. First Department of Pediatrics, Choremeio Research Laboratory, National and Kapodistrian University of Athens, Thivon & Levadeias, Goudi, 11527, Athens, Greece

    George I. Lambrou, Maria Karantza & George P. Chrousos

  3. Division of Endocrinology Diabetes and Metabolism, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias, Goudi, 11527, Athens, Greece

    George I. Lambrou, Christina Kanaka-Gantenbein & George P. Chrousos

  4. Hematology/Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias, Goudi, 11527, Athens, Greece

    George I. Lambrou, George P. Chrousos & Antonis Kattamis

  5. Department of Clinical Physiology, Linköping University, Linköping, SE-58183, Linköping, Sweden

    Dimitrios Tsartsalis

  6. Department of Endocrinology and Metabolism “Hippocration” General Hospital, Vasilissis Sofias 114, 11527, Athens, Greece

    Christos Savvidis

  7. Department of Clinical Therapeutics, Medical School, “Alexandra” General Hospital, National and Kapodistrian University of Athens, Lourou, 11527, Athens, Greece

    Evangelos Terpos

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  1. Athanasios N. Tsartsalis
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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.

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Correspondence to Athanasios N. Tsartsalis.

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

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Tsartsalis, A.N., Lambrou, G.I., Tsartsalis, D. et al. The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis. Hormones 17, 153–166 (2018). https://doi.org/10.1007/s42000-018-0019-3

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