"They Must Actually Take Their Medication"

A new report indicates that treatment with calcium and vitamin D might actually reduce the incidence of hip fractures.  This appears to contradict some other studies that were reported widely in the popular media.  

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 new report was a meta-analysis, meaning that the authors pooled the results of several studies.  As seen in Wikipedia:

In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. The first meta-analysis was performed by Karl Pearson in 1904, in an attempt to overcome the problem of reduced statistical power in studies with small sample sizes; analyzing the results from a group of studies can allow more accurate data analysis.

To give an idea of why the meta-analysis might be more valid than the other studies, the authors point out:

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.

I'm not sophisticated enough with statistics to be able to give an opinion of the validity of this particular analysis, and the report I am citing here has not yet been subjected to peer review.  Therefore, the results are to be considered to be preliminary.  

What is interesting is the list of reasons given, for why the meta-analysis gives results that are different than the previously-reported studies.  It turns out that the positive effect is seen only in those patients who actually had a deficiency of either calcium or vitamin D.  If the patient's regular diet provides enough of those nutrients, there is no effect from supplements.   Some patients in the studies did not take doses that were high enough.  Some did not take both the calcium and the vitamin D.  Also, the prior reports included in the analysis patients who did not actually take the supplements at all:

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.

It seems kind of obvious to say that the patients actually have to take the supplements in order to see an effect, but in daily practice, noncompliance turns out to be a common problem.  Sometimes the factors that seem too obvious to even consider, are the ones that turn out to be important.