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Effect of Clodronate Treatment on Risk of Fracture: A Systematic Review and Meta-analysis

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Abstract

A systematic review and a meta-analysis of data of literature were performed to evaluate the efficacy of clodronate in the reduction of risk of fractures in patients with osteoporosis or tumour diseases. A systematic review was conducted to identify original articles, reviews, and any other literature report suitable for the purposes of the meta-analysis, limited to prospective randomized trials that included a placebo or an untreated control arm. The search has identified 18 trials, 13 of which in patients with cancer diseases (breast cancer and multiple myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in elderly women living in community. A placebo control arm was used in 13 trials. Treatment and follow-up duration ranged from 3 months to 5 years. The meta-analysis showed that treatment with clodronate was associated with a reduction of the probability of new fractures compared with controls (OR = 0.572, 95 % CI 0.465–0.704 for new vertebral fractures; OR = 0.668, 95 % CI 0.494–0.905 for new non-vertebral fractures; and OR = 0.744, 95 % CI 0.635–0.873 for new overall fractures in those articles where vertebral and non-vertebral new fractures were not considered separately). Similar findings were observed in the separate analysis in patients with cancer forms or osteoporosis. The results of the meta-analysis have demonstrated that clodronate is effective in reducing the risk of vertebral, non-vertebral, and overall fractures in patients with skeletal fragility.

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Acknowledgments

The authors thank Dr. Luca Cavalieri (Chiesi Farmaceutici, Parma, Italy) for the conception of the meta-analysis, Dr. Thomas Zwingers (CROS NT, Verona, Italy) for the statistical planning and analysis, and Dr. Luca Cantini (Medical Writer) for the manuscript preparation. Statistical analysis was funded by Chiesi Farmaceutici S.p.A., Italy.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. Only one study was previous performed by B. Frediani (already published Frediani et al. [38]) and all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Rheumatology Department, Osteoporosis and Osteoarticular Instrumental Diagnosis Centre, University of Siena, Siena, Italy

    B. Frediani

  2. Medical Affairs DFI Department, Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43100, Parma, Italy

    E. Baraldi & G. Cremonesi

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  1. B. Frediani
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  2. E. Baraldi
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Correspondence to E. Baraldi.

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Frediani B. has been a scientific advisor or consultant to Abiogen, Amgen, Chiesi, Lilly, MSD, Servier, Stroder. Baraldi E. and Cremonesi G. is an employee of Chiesi Farmaceutici S.p.A.

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Frediani, B., Baraldi, E. & Cremonesi, G. Effect of Clodronate Treatment on Risk of Fracture: A Systematic Review and Meta-analysis. Calcif Tissue Int 95, 295–307 (2014). https://doi.org/10.1007/s00223-014-9903-2

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