1. 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

2. 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

3. 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

4. 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.

5. 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 /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
Papapoulos S et al, J Bone Miner Res 2012;27:694
DOST00156-AUS

7. Zol and Men Boonen 1066

8. 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

9. Morphometric Vertebral Fractures by Treatment15
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

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

11. 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
mths

12. OC8 QCT and Finite Element Analysis Spine and Hip 2

13. Oral Recombinant Calcitonin