Calcium and vitamin D supplements offer modest bone improvements, no colorectal cancer benefits

The results of a major clinical trial of the Women’s Health Initiative has found that calcium and vitamin D supplements in healthy post- menopausal women help preserve bone mass and prevent hip fractures in certain groups, including older women, but the supplements do not prevent other types of fractures or colorectal cancer. While generally well-tolerated, the supplements were associated with an increased risk of kidney stones. The findings are published in today’s issue of The New England Journal of Medicine.

“The overall results suggest that women, particularly those over 60, should consider taking calcium and vitamin D for bone health, but they should not expect these supplements to help prevent colorectal cancer,” said John Robbins, a professor of internal medicine at UC Davis Health System and on-site principal investigator of the Women’s Health Initiative study. Nearly 1,500 postmenopausal women of the 36,282 enrolled nationwide in the study were from the Sacramento area.

The study found a small but significant 1 percent higher hip bone density for those taking calcium combined with vitamin D compared to those taking a placebo. During the trial, 374 women had hip fractures with a fracture rate of 14 per 10,000 cases per year in the supplemented group, compared to 16 per 10,000 per year in the placebo group. This 12-percent reduction in hip fracture in those taking the calcium plus vitamin D supplement was not statistically significant; however, women who consistently took the full supplement dose experienced a significant 29 percent decrease in hip fracture. Women older than 60 had a significant 21 percent reduction in hip fracture. The supplements had no significant effect on spine or total fractures.

Calcium/vitamin D supplements provided no detectable effect on the incidence of colorectal cancer. There were similar rates of cancer in both the calcium/vitamin D and placebo groups (13 cases per 10,000 per year compared to 12 cases per 10,000 per year, respectively).

Overall, the supplements were well-tolerated by participants and the only adverse effect found was a 17 percent increase in kidney stones. Kidney stones were reported by 449 women (34 cases per 10,000 per year) in the CaD group compared to 381 women (29 cases per 10,000 per year) in the placebo group.

The trial was primarily designed to study the effect of calcium/vitamin D supplementation on preventing hip fracture, with secondary study objectives testing the effect of calcium and vitamin D on spine and other types of fracture and on colorectal cancer. Half of the over 36,000 participants in the trial received a daily dose of 1,000 milligrams of calcium carbonate combined with 400 IUs of vitamin D3. The other half of the study group received placebo pills in similarly marked bottles. Participants could choose between chewable or swallowable pills. During the study, a sub-set of participants had regular bone density scans. Study participants were followed for an average of 7 seven years, with three-quarters of them still taking their pills by the end of the study.

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. It contributes to an estimated 300,000 hip fractures in the United States 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 United States are estimated to have osteoporosis, and 34 million more have low bone mass, placing them at greater risk for fracture.

While study participants showed improvements in hip bone density, the reduction in hip fractures was smaller than expected and only statistically significant in certain groups – those over 60 and women who took the full intended dose of combined supplements.

“Not all women in the study group took the recommended number of supplements, which is equivalent to the recommended daily allowance of calcium and vitamin D,” said Robbins. “Fifty-nine percent of women who did take the recommended number of pills during the trial had a significant decrease (29 percent) in hip fracture risk – that’s four fewer hip fractures for every 10,000 women per year,” he said.

Robbins added that the low rates of hip fractures could be due to a number of other factors, such as the high body mass index of participants (heavier people have stronger bones), the inclusion of relatively few women over age 70, and the fact that many participants were already using calcium and vitamin D supplements, or were on hormone therapy.

The study findings, when translated to the U.S. population, would result in the prevention of two hip fractures per 10,000 women treated each year and would cause five cases of kidney stones. The number of hip fractures prevented would climb to four for compliant patients and six for women over 60. Because hip fractures are considered to be more serious than kidney stones, on balance, the public health benefit of the supplements outweighs the risks.

The study found no evidence of benefit from calcium/vitamin D for the prevention of colorectal cancer. Over an average of 7 seven years, 322 women in the study were diagnosed with invasive colorectal cancer. There was no statistically significant difference between the two groups in the number of cancer cases or in the characteristics or severity of tumors. There were also no differences between groups in the number of polyps reported by the participants. When the investigators analyzed only the data obtained from participants who were taking most of their study pills, there was still no benefit seen from calcium/vitamin D supplementation. The Women’s Health Initiative was a major 15-year research program launched in 1991 to address the most common causes of death, disability and poor quality of life in postmenopausal women – cardiovascular disease, cancer, and osteoporosis.