1 2 Anti - reabsorptive agents in women with osteoporosis : determining 3 statistical equivalence according to evidence - based methods 4

8 Abstract 9 Background In the present study, we undertook an 10 equivalence analysis on the effectiveness of the main anti11 reabsorptive agents indicated for women with osteoporosis. 12 Methods Our methodology was a combination of meta13 analysis (both pair-wise meta-analysis and network meta14 analysis) and equivalence testing. The end-point was the 15 incidence on new vertebral fractures. The anti-reabsorptive 16 agents examined included alendronate, zolendronate, 17 ibandronate, risedronate, and denosumab. 18 Results Our analysis involved nine randomized trials. 19 Ten head-to-head indirect comparisons were examined 20 through network meta-analysis and the respective values of 21 RR were estimated. The 95 % confidence intervals for RR 22 remained within the interval of a relative ±40 % variation 23 for all comparisons that involved alendronate, risedronate, 24 ibandronate, and denosumab. In contrast, the comparisons 25 involving zolendronate satisfied a post hoc margin up to 26 ±67 %. 27 Conclusion Our results confirm that most of these anti28 reabsorptive drugs (namely, alendronate, risedronate, 29 ibandronate, and denosumab) are equivalent according to 30 reasonable equivalence margins. 1