To the Editor: We believe that Tang and Nordin1 misunderstood the findings of our recent study of calcium supplementation.2

We disagree with their claim that the increase in the number of women with self- or family-reported myocardial infarction, stroke or sudden death became non-significant after adjustment for covariables. They correctly noted that the increased number of women experiencing the composite endpoint of cardiovascular events (after adjudication of events and inclusion of unreported events from hospital records) was not statistically significant. However, the increased event rate for this composite endpoint with calcium was statistically significant (rate ratio, 1.43; 95% CI, 1.01–2.04; P = 0.043). Thus, in our study, the number of women needed to treat with calcium for 5 years to cause one cardiovascular event was 29, and the corresponding number to prevent one fracture was 50.2

Tang and Nordin then meta-analysed data from five studies of calcium and vitamin D supplementation to conclude that calcium supplementation does not increase mortality.1 We disagree.

For one of the studies, they classified a subgroup of participants who received annual vitamin D but no calcium supplements as having received “calcium supplementation”.3 Further, for the RECORD (Randomised Evaluation of Calcium Or vitamin D) study, they compared the number of deaths between people receiving and not receiving vitamin D (16.5% v 17.4%) rather than between those receiving and not receiving calcium (17.7% v 16.2%).4 The trend for increased deaths with calcium supplementation in RECORD was greater when analysis was restricted to those treated with calcium monotherapy (18.5%) and placebo (16.3%).

As our study was of calcium monotherapy, the results of Tang and Nordin’s meta-analysis are of questionable relevance to our findings. In addition, ours was a 5-year study, and the differences in vascular events between the groups only emerged after 2 years.2 Only one study in Tang and Nordin’s meta-analysis had an average follow-up duration of more than 25 months.4

Further, there is evidence from other studies of trends towards vascular events occurring more frequently in people who take calcium monotherapy.2,5,6 In three out of four studies that reported mortality, there were trends towards increased death rates in people receiving calcium.2,4-6 As we concluded,2 these data are not definitive, but flag cardiac health as an area of concern in relation to calcium use.

Finally, we did not suggest that calcium supplementation should not be given to older women. However, in view of the evidence that any fracture risk reduction with calcium is small (< 10%),7,8 and the suggestions that calcium supplementation might increase the risk of hip fractures9-11 and vascular events, it seems reasonable and timely to reassess the role of calcium supplementation.

In reply: In Table 5 of Bolland and colleagues’ study, the P value after allowing for covariables was 0.08,1 which is not significant. This was without including smoking, which would undoubtedly have reduced the significance further as there were more smokers in the calcium group.

Based on Bolland and colleagues’ suggestion, we reanalysed the data by removing the group receiving vitamin D but no calcium supplements in the NoNOF (Nottingham Neck of Femur) study,2 and using data for those treated with calcium monotherapy (18.5%) compared to placebo (16.3%) in the RECORD (Randomised Evaluation of Calcium Or vitamin D) study.3 The reanalysis still failed to show any evidence of an increase in mortality (relative risk, 1.05; 95% CI, 0.88–1.26; P = 0.56).