Vitamin D With Calcium May Reduce Mortality in Elderly

Janis C. Kelly

June 22, 2012

June 22, 2012 — Increasing intake of vitamin D and calcium reduces fracture risk in older patients and may also reduce overall mortality, Lars Rejnmark, PhD, from Aarhus University Hospital in Denmark, and colleagues report in an article published online May 17 and in the August print issue of the Journal of Clinical Endocrinology and Metabolism. The pooled analysis of 70,528 patients from 8 major vitamin D trials showed that vitamin D with calcium reduced mortality in the elderly, but vitamin D alone did not.

"This is the largest study ever performed on effects of calcium and vitamin D on mortality," Dr. Rejnmark said in a news release. "Our results showed reduced mortality in elderly patients using vitamin D supplements in combination with calcium, but these results were not found in patients on vitamin D alone."

Mark Bolland, MBChB, from the Bone and Joint Research Group, Department of Medicine, University of Auckland, New Zealand, reviewed the study for Medscape Medical News.

In an email, Dr. Bolland, who was not involved in the analysis, said, "The authors have put a very large amount of effort into performing an individual patient data meta-analysis of vitamin D ± calcium on mortality. For vitamin D used alone, the results agree with most previous analyses and show that vitamin D supplementation by itself did not impact on mortality. Similar past analyses have shown that vitamin D alone does not prevent fractures or falls. The trials have usually been carried out in community-dwelling individuals, and I think the current evidence is quite strong that for these people, routine vitamin D supplements are not indicated. Ongoing large trials are looking at whether vitamin D supplements might alter other outcomes like cardiovascular events, cancer, and infections, and the results of those trials might change that advice (or might also add further weight to the existing data and recommendations)."

The patient data set was 86.8% women, with a median age of 70 years (interquartile range, 62 - 77 years). Over the course of 3 years, using the pooled data from 24 randomized controlled trials and assessing individual patient data from 8 trials that assessed at least 1000 patients per study, death was reduced by 9% in those treated with vitamin D with calcium. More specifically, "[v]itamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88 - 0.99]," the authors write. "However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84 - 0.98)." Because they adjusted for incident fractures, the authors conclude that the reduced mortality was not a result of fewer fractures but represents a beneficial effect beyond the reduced fracture risk.

The number needed to treat with vitamin D plus calcium for 3 years to prevent 1 death was 151.

The possibility that increased calcium might increase myocardial infarction risk (with or without vitamin D) has been raised by 2 meta-analyses performed by Dr. Bolland's group. However, Dr. Bolland said, "For coadministered calcium and vitamin D, the results [of the Rejnmark analysis] are more difficult to interpret. The authors chose to include a cluster-randomized trial in their analyses...that had a very large influence on the results because the benefits of calcium and vitamin D in that trial were much greater than any other trial.

"In a cluster-randomized trial with only a few clusters, there is much greater potential for confounding because individual participants are not randomized. In the Larsen trial, there were a number of important differences between people assigned to calcium and vitamin D and those not, and it seems likely that these differences (and/or differences between the clusters) contributed to the effects observed," Dr. Bolland continued.

"In the current paper, when the authors removed the Larsen trial from their analyses, the effect of calcium and vitamin D on mortality was not statistically significant. To me, the results rule out a significant increase in mortality with calcium and vitamin D, but when the Larsen trial results are removed, the results are consistent with no effect of calcium and vitamin D on mortality, and do not exclude or confirm the possibility of small benefits," he concluded.

"Some studies have suggested calcium (with or without vitamin D) supplements can have adverse effects on cardiovascular health," Dr. Rejnmark said in the release. "Although our study does not rule out such effects, we found that calcium with vitamin D supplementation to elderly participants is overall not harmful to survival, and may have beneficial effects on general health."

Dr. Bolland pointed out that, in contrast to the suggestions of Dr. Rejnmark and colleagues from their findings, recent Institute of Medicine guidelines stress that "more is not necessarily better" with regard to vitamin D and calcium and that the US Preventive Services Task Force has recommended against calcium and vitamin D supplements for healthy postmenopausal women living in the community.

"These suggest that in the future less emphasis will be placed on calcium and vitamin D for older patients than has happened in the past," Dr. Bolland said.

The study was supported by Furst Medisinsk Laboratorium and Nycomed; the work of several authors was supported by noncommercial funding from the National Health and Medical Research Council, Australia; Australian Commonwealth Department of Health and Ageing; Danish Council for Independent Research in Medical Sciences; the United Kingdom Medical Research Council; the Chief Scientists Office of the Scottish Medical Health Directorates; the Danish Osteoporosis Association; the Municipality of the City of Randers; and Randers Central Hospital. Dr. Rejnmark has received speakers' fees from Bristol-Myers Squibb and Eli Lilly. Other coauthors have served on advisory boards for Shire Pharmaceuticals; received speakers' fees from Shire Pharmaceuticals, Straken Pharmaceuticals, Servier, Amgen, GSK, Eli Lilly, or MSD; received consultancy fees from Nycomed, Shire, and Prostrakan (all of whom market calcium and vitamin D supplements), Amgen, or Novartis; or received research grants from Roche and Amgen. Dr. Bolland has disclosed no relevant financial relationships.

J Clin Endocrinol Metabol. Published online May 17, 2012. Abstract