Bolland et al did not control for vitamin D concentrations during their study but said only that the women with serum 25-hydroxyvitamin D concentrations below 25 nmol/l were excluded.1 This implies that serum concentrations of vitamin D were not monitored during the study. This is important because, according to the results of the Framingham offspring study, low serum concentrations of vitamin D are strictly associated with an increase in vascular risk2 and may impair calcium absorption.2
Two important confounding factors are not controlled for—consumption of non-steroidal anti-inflammatory drugs and analgesics and previous hormone replacement therapy. These two potent confounders may completely reverse the results and also interact with each other on cardiovascular risk.3 4 5
To consider the self reported events separately from those unreported but taken from the national database of hospital admissions is surprising. When self reported and unreported events are considered together the differences between calcium and placebo group no longer reach significance. This is the study result: the analysis of self reported events alone looks like window dressing.
Competing interests: None declared.
References
- 1.Bolland MJ, Barber PS, Doughty RN, Mason B, Horne A, Ames R, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008;336:262-6. (2 February.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008. doi 10.1161/circulationaha.107.706127 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.García Rodríguez LA, Egan K, FitzGerald GA. Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? PLoS Med 2007;4(5):e157 10.1371/journal.pmed.0040157 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) programme: a randomised comparison. Lancet 2006;368:1771-81. [DOI] [PubMed] [Google Scholar]
- 5.Bresalier RS, Sandler RS, Quan H, JA, Oxenius B, Horgan K. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005;352:1092-102. [DOI] [PubMed] [Google Scholar]