Vert Non-Vert Hip ** ** Zoledronic Acid3 Zoledronic Acid4 Denosumab5 Avoid direct comparisons of efficacy as treatments are not tested in comparator trials RIS 5 (VERT-NA) RIS 5 (VERT-MN) RIS 2.5/5 (Hip Study) Strontium ranelate (SOTI)1 ** (TROPOS)2 ** Subgroup/post hoc analysis Zoledronic Acid3 Zoledronic Acid4 ** ALN 5/10 (FIT1) ALN 5/10 (FIT2) Denosumab5 Adapted from: Martin and Seeman. Clin Sci 2007; 112:77 Meunier et al. NEJM 2004; 50:459 Reginster et al. JCEM 2005; 90: 816 Black et al. NEJM 2007; 356:1809 Lyles et al. NEJM 2007; 357:1799 Cummings et al. NEJM 2009; 361:756 Neer et al. NEJM 2001; 344:1434 RLX 60 (MORE) RLX 120 (MORE) *IBAN 2.5 *IBAN inter Teriparatide 20µg6 *PTH 1-84 Calcitriol Calcitonin Calcium Vitamin D 0.2 0.6 1.0 0.2 0.6 1.0 0.2 0.6 1.0 *Not available in Australia

Phase II Extension: 8 years Denosumab (abstract) Placebo –6 –4 –2 2 4 6 8 72 12 24 36 48 % Change (LSM + 95% CI) 6.8% Parent Study Extension Study All on Denosumab 60 mg Q6M Total Hip BMD Denosumab Denosumab Denosumab Placebo N = 124 N = 23 N = 87 N = 12 Month 96 –4 4 8 12 16 96 72 24 36 48 16.5% % Change (LSM + 95% CI) Lumbar Spine BMD Denosumab Denosumab Denosumab Placebo N = 124 N = 22 N = 88 N = 12 Placebo McClung MR et al. Abstract and Oral Presentation, ASBMR Annual Meeting. San Diego, USA 2011

Change in Cortical Porosity % Porosity Change at 12 months % Porosity Change at 12 months Placebo ALN DMAb Placebo ALN DMAb 60 10 40 5 20 –5 –20 –10 –40 5 10 15 0.2 0.4 0.6 0.8 PTH change (3-month AUC) Deciles of PTH AUC (adjusted for baseline CTX) Scatter plot, regression lines and 95% confidence regions Errors bars represent 95% CIs

Alternative therapies given in: Stopping Denosumab FREEDOM - Time to first osteoporotic fracture during the off-treatment period (abstract/poster, post hoc) Alternative therapies given in: 42% - Placebo 27% - Denosumab Subjects at risk, N Placebo Denosumab 470 327 227 154 148 108 51 57 2 1 N = number of subjects at risk. Error bars represent 95% confidence intervals. Adapted from: Brown JP et al. J Bone Miner Res 26(Suppl 1):FR0446 and poster at ASBMR 2011, San Diego.

Vert Fx (%/yr) Non-Vert Fx (%/yr) FREEDOM Study EXTENSION Study 1.4% EXTENSION Study 0.0 2.2% 0.9% 3.1% 0.7% 1.1% 0.5 1.0 1.5 2.0 2.5 3.0 4.0 3.5 FREEDOM Study Yrs 1 2 3 4/5* *Annualized rate Vert Fx (%/yr) Placebo Denosumab Denosumab 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 3.1% 2.7% 2.3% 2.6% 2.0% 1.9% 1.2% 1.1% Non-Vert Fx (%/yr) N = number of subjects in the primary efficacy analysis set who were still on study at the beginning of each period Source: Figure 03-2.1.5 Papapoulos S et al, J Bone Miner Res 2012;27:694 DOST00156-AUS

Zol and Men Boonen 1066

1.4% % Change FNeck BMD Serum PINP (ng/mL) 2 4 6 8 1 3 5 Yrs +3.1% Start of extension trial 2 4 6 8 1 3 5 Yrs +3.1% +4.5% 1.4% p<.0007 Z6 Z3P3 Change (%) % Change FNeck BMD 20 40 60 1 2 3 4 5 6 Yrs Z6 Z3P3 Start of extension trial Serum PINP (ng/mL) Table 5-6 8

Morphometric Vertebral Fractures by Treatment 15 RR=0.48 95%CI (0.3,0.9) P=0.03 PBO 10.9% 10 6.2% (30/486) % Patients 52% reduction ZOL 3.3% 5 3.0% (14/469) Z3P3 Z6 Core study (Year 0-3) Extension study (Year 3-6) Clinical vertebral fractures (n=11): NS

Odanacatib and shallow resorption pits Leung et al Bone 2011;49:623

Odanacatib 5 years LS BMD 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0 - 2.0 50/50/50 mg 50/placebo/placebo 0 12 24 36 48 60 mths

OC8 QCT and Finite Element Analysis Spine and Hip 2

Oral Recombinant Calcitonin