University at Buffalo - The State University of New York

Published: February 16, 2006

By LOIS BAKER
Contributing Editor

Daily calcium and vitamin D supplements do not lower the risk of colorectal cancer in postmenopausal women as previous studies had suggested, results of the national Women's Health Initiative (WHI) clinical trial have shown.

Jean Wactawski-Wende is first author on the colorectal cancer study and co-author on the hip fracture study.
PHOTO: DOUGLAS LEVERE

The supplements provided a modest benefit in preserving bone mass and preventing hip fractures, particularly in older women, but had no effect on other types of fractures.

The findings appear in two reports in the current (Feb. 16, 2006) issue of the New England Journal of Medicine.

Jean Wactawski-Wende, associate professor of social and preventive medicine in the School of Public Health and Health Professions, is first author on the colorectal cancer study and a co-author on the hip fracture study.

"There has been a public perception that calcium and vitamin D supplements can prevent colorectal cancer and observational studies have suggested that those who have higher intakes have less disease," said Wactawski-Wende. "Unfortunately, this long-term clinical trial, in which some of the women were followed for more than nine years, does not support this assumption.

"Results of the effect of calcium and vitamin D supplementation on bone fractures showed a significant positive effect on bone density, as well as a non-significant 12 percent decrease in risk of hip fractures overall," she said.

"Further analyses showed that the group who took most of the recommended supplements over the course of the trial had a 29 percent reduction in risk of hip fracture, and women over age 60 had a 21 percent reduction in risk of hip fracture.

"Overall, the most important message to women from these studies," said Wactawski-Wende, "is that all women should have an adequate intake of calcium and vitamin D to preserve their bone density. For women over 60, this may be especially important. Although women should consider taking calcium and vitamin D supplements along with adequate dietary intake to protect their bones, they should not expect these supplements to provide protection against colorectal cancer."

A total of 36,282 postmenopausal women, including 963 from Western New York, took part in the WHI calcium/vitamin D trial. Half were assigned randomly to receive 1,000 mg of calcium carbonate combined with 400 International Units of vitamin D3 daily, while the other half took matching placebos. Participants were followed for 6-10 years.

Colorectal cancer is the third most common cancer in U.S. women and the third leading cause of cancer deaths in women, according to the American Cancer Society. Observational studies had suggested that both higher intakes of calcium, as well as vitamin D intake, may decrease the risk of colorectal cancer, although there was little clinical trial data available.

Results of the colon-cancer analysis showed that over an average of seven years, a total of 322 women in the study were diagnosed with invasive colorectal cancer. There was no statistically significant difference between the supplement and comparison groups in the number of colorectal cancer cases—13 colorectal cancer cases per 10,000 person-years in the supplement group and 12 per 10,000 person-years in the placebo group—or in the characteristics or severity of tumors.

There also was no difference between groups in the number of polyps reported by the participants. When the investigators analyzed only the data obtained from participants who had the best compliance in taking their study pills, there was still no benefit seen from calcium/vitamin D supplementation on colorectal cancer. The supplements were generally well tolerated; however, participants in the supplement group had a higher risk of developing kidney stones.

To determine if baseline vitamin D level might have some effect on the outcome, researchers measured blood levels of vitamin D in a subgroup of participants at the start of the study. The effect of the intervention on colorectal cancer did not differ by baseline blood levels of vitamin D.

In assessing the colon cancer findings, Wactawski-Wende noted that participants already had relatively high personal intakes of both calcium and vitamin D at the start of the study—about twice the national average. These initial high levels may have prevented the intervention supplements from affecting colon-cancer rates further, she said. However, even when looking at those participants with the lowest personal intakes of calcium, the findings on colorectal cancer did not change.

Wactawski-Wende also noted that the average follow-up of seven years may not have been long enough to find an effect. "Colorectal cancer is thought to take 10-20 years to develop. Although we saw no evidence of a trend toward protection in the later years of follow-up, we'll continue to follow these women for five more years, which may allow us to identify any later effects of the intervention."

Overall, there were fewer deaths in the supplement group than in the placebo group—744 compared to 807—hinting that calcium and vitamin D supplements may have a positive effect on mortality, said Wactawski-Wende. Analyses that will take a closer look at mortality are planned.

Results of the effect of calcium and vitamin D supplementation on hip fractures supported conventional wisdom that these supplements can help keep bones strong. The fracture analyses showed that 374 women had hip fractures, for a rate of 14 per 10,000 women per year in the supplement group, compared to 16 per 10,000 per year in the placebo group.

Osteoporosis, a skeletal disorder characterized by weakened bones leading to an increased risk of fracture, is a major cause of disability, loss of independence and death, according to the National Institutes of Health. It contributes to an estimated 300,000 hip fractures in the U.S. each year. Four out of 10 women over 50 will experience a fracture at the hip, spine or wrist in their lifetime. Ten million people in the U.S. are estimated to have osteoporosis and 34 million more have low bone mass, placing them at greater risk for fracture.

"There are serious health consequences following hip fracture. Prevention of hip fracture is a key," said Wactawski-Wende. "Achieving adequate intake of calcium and vitamin D is one important factor in maintaining bone density and preventing hip fracture.

"Use of calcium with vitamin D supplements, along with a diet rich in calcium and vitamin D, may result in important benefits to bone density and hip fracture prevention," she said. "However, results of the WHI calcium plus vitamin D study do not support their use for colorectal cancer prevention."