WCO: Meta-Analysis Defends Bone Benefit for Vitamin D with Calcium

June 6, 2006

TORONTO ? The concept of calcium and vitamin D supplementation for prevention of osteoporosis, relegated recently to the realm of unfounded notion, got a spirited defense here.

TORONTO, June 6 ? The concept of calcium and vitamin D supplementation for prevention of osteoporosis, relegated recently to the realm of unfounded notion, got a spirited defense here.

The combination is "very effective, but you have to give it to the right people and in the right dose," Steven Boonen, M.D., Ph.D., of Leuven University in Belgium said at the World Congress on Osteoporosis here.

Dr. Boonen presented results of a meta-analysis of major randomized placebo-controlled trials that analyzed the effects of vitamin D alone or in combination with calcium. The meta-analysis found that in patients getting 800 units of vitamin D and more than 1,000 mg of calcium a day, there was a 21% reduction in risk of fracture compared to placebo.

The meta-analysis included the RECORD study, published last year in The Lancet, and data from the Women's Health Initiative, published earlier this year in the New England Journal of Medicine. Both the latter studies found no benefit to adding calcium to vitamin D to prevent fractures in menopausal women.

But Dr. Boonen said their methods were flawed, leading to an incorrect conclusion.

For one thing, he said, neither study had enough statistical power to find an effect. For instance, he said, the RECORD trial, looking at hip fractures, had 2,649 participants and only 93 events. By contrast, Dr. Boonen said, he and his colleagues had a patient pool of 16,978 individuals and 812 fractures.

Also, he said, both studies were community-based, meaning that many of their participants were actually getting enough calcium and vitamin D without taking supplements. By including such healthy women, he said, "you dilute the treatment effect."

"It doesn't make sense to give calcium and vitamin D if there's no insufficiency," he said.

And finally, he noted, in both trials, compliance was on the order of 40% and 50%. When the researchers analyzed those who actually took their supplements, he said, "they did see an effect."

Dr. Boonen and colleagues actually presented two analyses. In one, they looked at randomized clinical trials comparing vitamin D alone to placebo and found no effect. The odds ratio was actually slightly in favor of placebo at 1.10, but the 95% confidence interval ranged from 0.89 to 1.36.

On the other hand, they found that when combined with calcium vitamin D had a significant benefit in reducing fracture. The odds ratio was 0.79, with a 95% confidence interval from 0.64 to 0.97. The number needed to treat to prevent one fracture was 132.

A subsidiary analysis showed that low doses of vitamin D-below 800 units a day-had no effect, he said.

For clinicians, "the point of (the study) is that you should always give both," said endocrinologist B. Lawrence Riggs, M.D., of the Mayo Clinic in Rochester, Minn., who chaired the session in which Dr. Boonen's research was presented.

"Some people believe that vitamin D is enough but vitamin D exerts its effect on bone predominantly by increasing absorption of calcium," Dr. Riggs said in an interview. "If you don't have enough calcium, it's not effective."

Dr. Boonen told reporters after his presentation that clinicians need to pay attention to four factors. They must prescribe a combination of calcium and vitamin D, the doses must be high enough, the patients must be in need of the supplements, and finally they must actually take their medication.