1. Chapter 80 Chapter 80 Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis Copyright © 2013 Elsevier Inc. All rights reserved.

2. FIGURE 80.1 The chemical structure of bisphosphonates (BP). Source: from Russell et al. (2008), with permission. 2

3. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 80.2 Side-chain differences determine the effect of bisphosphonates. ALN: alendronate; FPPS: Farnesyl pyrophosphate synthetase; ISA: ibandronate; RIS: risedronate; ZOL: zoledronic acid. 3

4. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 80.3 Cumulative incidence of clinical vertebral fractures after long-term treatment with alendronate. ALN: Alendronate; ARR: Absolute risk ratio; FIT: Fracture intervention trial; PLB: Placebo; RRR: Relative risk ratio. Source: data obtained from Black et al. (2006) [46], used with permission. 4

5. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 80.4 Cumulative incidence of morphometric vertebral fractures after long-term treatment with zoledronic acid (ZOL). CI: Confidence interval; PBO: Placebo; Z3P3: Initial 3 years of ZOL then placebo; Z6: 6 years of ZOL. Source: data obtained from Black et al. (2012) [86], used with permission. 5

6. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 80.5 X-rays showing an impending femoral shaft fracture (A) and a representative atypical diaphyseal femoral fracture (B) with thickened cortices and a beak or spike. Source: radiographs courtesy of Drs Joseph Lane and Aasis Unnanuntana, Hospital for Special Surgery, New York, N.Y. From Watts and Diab (2010), with permission [157]. 6