WHI Study Results
Calcium and Vitamin D Supplements Offer Modest Bone Improvements,
No Benefits for Colorectal Cancer
Calcium and vitamin D supplements in healthy postmenopausal women
provide a modest benefit in preserving bone mass and prevent hip
fractures in certain groups including older women but do not prevent
other types of fractures or colorectal cancer, according to the
results of a major clinical trial, part of the Women’s Health
Initiative (WHI). While generally well tolerated, the supplements
were associated with an increased risk of kidney stones.
The study results are published in the February 16 issue of The
New England Journal of Medicine. The WHI is sponsored by the
National Heart, Lung, and Blood Institute (NHLBI) of the National
Institutes of Health.
“This important study provides guidance for women on the
risks and benefits of supplementing their diets with calcium and
vitamin D. 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 Elizabeth G. Nabel, M.D.,
NHLBI director and director of the Women’s Health Initiative.
The WHI Calcium with Vitamin D (CaD) trial of 36,282 postmenopausal
women ages 50 to 79 found a small but significant 1 percent higher
hip bone density for those taking calcium combined with vitamin
D compared to those taking 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/year compared to 12 cases per 10,000/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 WHI Calcium with Vitamin D 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 CaD on spine and other types of fracture and on colorectal cancer.
Participants in this study had previously enrolled in one or both
of the WHI trials of hormone therapy or dietary modification.
Half of the over 36,000 participants in the CaD trial received
a daily dose of 1000 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 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 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.
“Given the serious public health burden of fractures associated
with osteoporosis, it is important to learn as much as possible
about ways to prevent and treat bone loss,” said Joan McGowan,
Ph.D., of the NIH’s National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) and a co-author on the paper.
According to the study’s authors, there are several possible
reasons why despite 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.
”Although 76 percent of women were still taking study pills
at the end of the trial, only 59 percent were taking the intended
number of pills,” said Rebecca D. Jackson, M.D., endocrinologist
and the study’s lead investigator at Ohio State University
in Columbus. “In a secondary analysis, we found a significant
29 percent decrease in hip fracture risk among women who took most
of their study pills – that’s four fewer hip fractures
for every 10,000 women per year,” she said.
The rate of hip fractures was about half of what was expected,
and this decreased study power to show a significant finding, according
to Dr. Jackson. "The low rates could be due to a number of
factors, such as the high body mass index of participants (heavier
people have stronger bones), the inclusion of relatively few women
over age 70 years, and the fact that many participants were already
using calcium and vitamin D supplements, or were on hormone therapy,"
she said.
“If we look at all the findings together,” said McGowan,
“for every 10,000 women treated for one year, two hip fractures
would be prevented and five cases of kidney stones would be caused.
The number of hip fractures prevented would climb to four for compliant
patients and six for women over 60. Since 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’s findings of slowed bone loss and the reduction
in hip fractures for some groups suggest a role for these supplements
in preventing hip fracture in generally healthy postmenopausal women
and support the current Surgeon General’s recommendations
for these nutrients,” added McGowan, who is also the senior
scientific editor of the Surgeon General’s report on bone
health. She noted, however, that supplements may not be necessary
for healthy women whose diet meets recommended levels of calcium
and vitamin D.
The study found no evidence of benefit from calcium/vitamin D for
the prevention of colorectal cancer, according to Jean Wactawski-Wende,
Ph.D., epidemiologist and the study’s lead investigator at
the University at Buffalo.
Over an average of 7 years, 322 women in the study were diagnosed
with invasive colorectal cancer. There was no statistically significant
difference between the two groups in 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.
“As the third leading cause of cancer death and incidence
for women in the United States, there is great interest in the prevention
of colorectal cancer. Unfortunately, our findings do not validate
some previous studies and polyp prevention trials which showed a
benefit for calcium/vitamin D,” said Wactawski-Wende.
She added, however, that study design and population issues may
have limited the study’s ability to show a protective effect
of calcium/vitamin D. Since participants were not restricted from
taking personal calcium or vitamin D supplements, they had a relatively
high calcium and vitamin D intake at enrollment and intake rose
even higher during the trial so the impact of study supplementation
may have been muted.
Duration may have also been a factor, said Wactawski-Wende. “If
the benefit of CaD is for prevention of cancer at its early stages
and colorectal cancer takes 10 to 20 years to develop, 7 years of
supplementation and follow-up may not be enough time to show a benefit.
Still, we found no trend toward protection in the later years of
follow-up,” she said. She added that the ongoing 5-year WHI
extension study will continue to track occurrences of colorectal
cancer – as well as other diseases – and may provide
answers on later effects of the WHI CaD supplementation.
“The WHI will continue to provide us with answers about the
major health conditions affecting women for years to come,”
said Nabel, “The study’s participants and investigators
have made major contributions to disease prevention in postmenopausal
women.”
- Resources:
To interview Dr. Nabel or WHI project officer Jacques Rossouw,
M.D. of NHLBI, contact the NHLBI Communications Office at 301-496-4236.
To interview Dr. Donna Griebel of NCI’s Division of Cancer
Prevention, contact the NCI Press Office at 301-496-6641; to interview
Dr. McGowan, contact the National Institute of Arthritis and Musculoskeletal
and Skin Diseases Office of Communications at 301-496-8190. To interview
Dr. Jackson, contact Michelle Gailiun at Ohio State University at
614-293-6054; to interview Dr. Wactawski-Wende, contact Lois Baker
at the University at Buffalo Office of News Services at 716-645-5000,
ext. 1417.
WHI—a Legacy to Future Generations, a conference on
the past, present, and future of WHI (including synthesis of
findings generated from the WHI observational study and all
four clinical trials --estrogen plus progestin, estrogen alone,
dietary modification, and calcium/vitamin D --will be held February
28-March 1, 2006 on the NIH campus. For more information and
a conference agenda, go to: http://www.nhlbi.nih.gov/whi/references.htm.
For more information on the Women's Health Initiative, see http://www.nhlbi.nih.gov/whi.
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NHLBI, NIAMS, and NCI are part of the National Institutes of
Health (NIH), the Federal Government’s primary agency for
biomedical and behavioral research. NIH is a component of the U.S.
Department of Health and Human Services. For more information, go
to: www.nhlbi.nih.gov, www.niams.nih.gov,
www.nci.nih.gov. |