1. Chapter 84 Chapter 84 Strontium Ranelate in the Prevention of Osteoporotic Fractures Copyright © 2013 Elsevier Inc. All rights reserved.

2. FIGURE 84.1 Plot showing 1-, 3-, and 5-year vertebral and nonvertebral fracture risk results from SOTI and TROPOS comparing strontium ranelate and placebo. * Post hoc analysis in a subgroup of women at high risk of fractures (age ≥ 74 years with a T-score ≤ –2.4). PEP, primary end point; SEP, secondary end point; SOTI, Spinal Osteoporosis Therapeutic Intervention; TROPOS, TReatment Of Peripheral Osteoporosis. Source: modified from Marie et al. (2011) [1]. 2

3. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 84.2 Long-term incidence of fracture with strontium ranelate: 10-year results. Cumulative incidence of new vertebral fracture (A), new nonvertebral fracture (B), and new osteoporotic fracture (C) in the 10-year population between 0 and 5 years of treatment with strontium ranelate and between 6 and 10 years of treatment with strontium ranelate (gray bars) and in the FRAX ® -matched placebo group of TROPOS between 0 and 5 years (white bars). NS, nonsignificant; TROPOS, TReatment Of Peripheral Osteoporosis. Source: modified from Reginster etal. (2012) [16]. 3

4. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 84.3 Finite element analysis results comparing strontium ranelate and alendronate in a Segmented failure load and trabecular and cortical stress model (relative change from baseline ± standard deviation (SD)). p values between groups are for multiple comparisons (Bonferroni criterion); *p < 0.05; **p < 0.01; *** p < 0.005 versus baseline. Source: Rizzoli etal. (2011) [30]. 4

5. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 84.4 Effect of strontium ranelate on bone strength following proximal tibia implant insertion in rats. The X-ray image (A) depicts an implant in rat proximal tibia, while the bar chart (B) shows the effects of strontium ranelate (625mg/kg 5/7 days) and control on pull-out strength (N) of a titanium implant inserted in proximal tibia. Values are mean ± standard error of the mean (SEM). *p < 0.05 compared to control. Source: modified from Maimoun etal. (2010) [67]. 5