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Bone Abstracts (2014) 3 LB3 | DOI: 10.1530/boneabs.3.LB3

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Meta-analysis of randomised trials shows limited evidence to support the use of bisphosphonates for fracture prevention in osteogenesis imperfecta

Jannie Hald2, Bente Langdahl2, Evangelos Evangelou3 & Stuart Ralston1

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1University of Edinburgh, Edinburgh, UK; 2University of Aarhus, Aarhus, Denmark; 3University of Ioannina, Ioaninna, Greece.


Osteogenesis imperfecta refers to a group of inherited disorders characterised by increased bone fragility, low bone mass and fragility fractures. Most patients carry mutations in the genes that encode type I collagen or other proteins involved in its post-translational modification. Bisphosphonates are widely used in the treatment of osteogenesis imperfecta but clinical trials have been powered to detect effects on BMD rather than fracture. In order to gain better understanding of the effects of bisphosphonates on fracture in OI we conducted a meta-analysis of randomised placebo controlled trials in which fracture data had been reported. Relative risks (RR) and 95% CI were calculated under fixed and random effects models and heterogeneity assessed by the I2 statistic We identified six eligible studies which had included 424 subjects with 721 patient-years of follow-up. Most had Sillence type I OI (59.9%) followed by type IV (22.1%) and type III (14.6%). In 3.3% of cases the type was unknown. The bisphosphonates used were oral risedronate, oral alendronate, oral olpadronate and intravenous pamidronate. Only one study was conducted in adults with OI. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (RR 0.83, 95% CI (0.69–1.00), P=0.052) with no heterogeneity between studies (I2=0). Total fracture numbers were reduced by bisphosphonate treatment (RR 0.71 (0.52–0.97) P=0.031, but with considerable heterogeneity (I2=39%). This was explained by one study in which a substantial effect on fracture numbers was driven by a small number of placebo-treated patients who suffered multiple fractures. When this study was excluded, bisphosphonates had no effect on fracture number (RR 0.79 (0.62–1.02), P=0.07, I2=0%). We conclude that there is limited evidence to support the use of bisphosphonates for fracture prevention in OI and that further adequately powered trials with a fracture endpoint are urgently needed.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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