1. Calcium/Vitamin D-related CV Events Based on Poster 1163 “Risk of Cardiovascular Events with Calcium/Vitamin D – a Re-Analysis of the Women’s Health Initiative” Mark Bolland, Andrew Grey, Gregory Gamble, Ian Reid Monday, October 18, 2010 ASBMR 2010 Toronto, Ontario

2. Background A consistent pattern of increased myocardial infarction (MI) risk from calcium supplementation vs. placebo was demonstrated in a meta-analysis of 11,900 subjects (Bolland et al. IOF 2010, Abstract OC25) Reid et al. re-analyzed the interaction between BMI and the calcium/vitamin D intervention in the Women’s Health Initiative (WHI) As part of the WHI, postmenopausal women received 1 g calcium plus 400 IU vitamin D or placebo and were followed for 7 years At baseline, 54% (20,000) of the cohort were already taking personal calcium supplements and approximately 16,000 women were not

3. For non-obese women (BMI<30 kg/m 2 ) randomized to calcium/vitamin D, there was a significant increased risk for: – A revascularization procedure (28%) – Total MI, coronary heart disease, death and revascularization (24%)

4. Results In women not taking personal calcium supplements at baseline, a significant increase in MI and combined stroke/MI was observed In women taking personal calcium supplements at baseline, there was no evidence of altered cardiovascular disease (CVD) events The addition of vitamin D therefore did not abrogate the effect of calcium on CVD end points except in obese women

5. Other Studies on Calcium/Vitamin D and Vascular Events In a meta-analysis of 3 such studies, the HR was similar to that identified in the WHI where the combination of calcium/vitamin D increased the risk of MI by 21% and stroke by 20% Given the similarity of the CVD risk between calcium alone and calcium + vitamin D, it is reasonable to hypothesize that the addition of vitamin D to calcium does not make a substantive difference to CVD risk

6. Meta-analysis of Calcium ± Vitamin D Effect on Stroke Based on the meta-analysis, a 15% increase in the combination of MI and stroke is associated with calcium supplementation with or without vitamin D

7. Summary According to these data, if 1000 people were treated with calcium for 5 years (± Vitamin D), this would result in an estimated increase of: MIs = 4x Stroke = 4x Deaths = 2x At the same time, 3 fractures would be prevented. Findings suggest that reassessment of the role of calcium supplementation ± vitamin D in osteoporosis prevention and treatment is warranted