Extra Calcium for Women Takes Some Clinical Knocks

By Gina Kolata

A large, seven-year study of healthy women over the age of 50 found no broad benefit from calcium and vitamin D supplements in preventing broken bones, despite widespread endorsement by doctors for the supplements.

The study, whose results were being reported Thursday in the New England Journal of Medicine, also found no evidence that the supplements prevented colorectal cancer, and it found an increased risk of kidney stones.

The study’s leaders said there were hints of benefits for some subgroups in the study. But the supplements’ only positive effect in the overall study population 36,282 normal, healthy women ages 50 to 79 was a 1 percent increase in bone density at the hip.

The $18 million study was part of the Women’s Health Initiative, a U.S. government project that, last week, reported findings that low-fat diets do not protect against breast or colorectal cancer or heart disease. A few years ago, the initiative’s study on hormone treatment after menopause showed it had more health risks than benefits.

In every case, the Women’s Health Initiative was testing hypotheses that arose from studies that observed populations and correlated certain health practices with medical outcomes. But such observational studies, statisticians agree, can yield misleading information because a group that happens to follow certain health advice may differ in unknown ways from groups that did not. Those drawbacks are alleviated in a clinical trial, like those of the Women’s Health Initiative, which randomly assigned women to a preventive strategy, like hormones or diet or supplements, or not, and looked for definite results a fractured bone, a case of cancer, a heart attack.

In this case, the participants were randomly assigned to take 1,000 milligrams of calcium and 400 international units of vitamin D a day, or to take placebos, and were followed for seven years. Researchers looked for effects on bone density, fractures and colorectal cancer.

The lack of an effect on colorectal cancer over the seven-year period was so clear that it has aroused little debate. But the effect on bones is another story. Osteoporosis specialists said the study will probably put a dent in the widespread medical practice of recommending that all women take calcium and vitamin D supplements starting at menopause if not sooner, as a sort of insurance policy against osteoporosis. But beyond that there is no agreement on what, if anything, healthy women should do.

The study’s investigators emphasized encouraging hints and biological plausibility in the data. When they looked only at adherent women, or those who took 80 percent of their pills, the supplements reduced hip fractures by 29 percent. The annual rate of hip fractures in adherent women taking the supplements was 10 per 10,000 as compared to 14 per 10,000 in adherent women taking placebos.

In a separate subgroup analysis of all women in the study over 60, the investigators saw a 21 percent reduction in hip fractures in the group taking the supplements. The rate was 19 per 10,000 in women over 60 taking the supplements, compared with 24 per 10,000 in women over 60 taking placebos. But such subgroup analyses are questioned by many statisticians, who point out that there always will be subgroups in a large study showing one effect or another, simply by chance. Some subgroups, as happened in this study, will show a positive effect and others, as in this study, will show a negative effect, but those effects often are nothing more than random fluctuations in the data. David Freedman, a statistician at the University of California, Berkeley, who has written books on clinical trial design and analysis, said women who take their pills as directed year in and year out are known to be different from ordinary women, so it is a mistake to generalize from them to the entire population.

Jacques Rossouw, a project officer for the study, explained the limitations. “These are secondary analyses and are exploratory to some extent,” he said.

Nonetheless, said Elizabeth Nabel, the study’s director, the subgroup data and the increase in hip bone density do indicate the value of adequate calcium and vitamin D. “Based on all the results, women particularly those over 60 should consider taking calcium and vitamin D for bone health,” she said.

Others were not so sure.

Ethel Siris, president of the National Osteoporosis Foundation, said the new study had made her question the advice given by many doctors that all women take calcium supplements regardless of what is in their diet. “We didn’t think it hurt, which is why doctors routinely gave it,” she explained.

The new study, she said, shows it can hurt to take the supplements among the women taking them there were an 5 additional cases of kidney stones per 10,000 women per year. So, Siris said, her suggestion is that doctors only urge the supplements upon women who are not getting enough calcium 1,200 to 1,500 milligrams a day from their diets.

“Enough is enough,” Siris said. “Too much of a good thing isn’t a good thing.”