Calcium and Vitamin D Boost HRT Effect on Hip Fracture Risk

Marlene Busko

June 28, 2013

According to new data from the Women's Health Initiative (WHI), postmenopausal women who took hormone replacement therapy (HRT) had a lower risk for hip fracture than women who received placebo, and they had an even lower risk if they also took calcium and vitamin D. Taking these supplements without HRT, however, did not lower the risk for hip fracture.

The study, by John A. Robbins, MD, from the University of California, Davis, in Sacramento, and colleagues was published online June 26 in Menopause.

"Our further investigation of the WHI data shows that [calcium and vitamin D supplementation] — although, by itself, may not be of statistically proven benefit for fracture prevention — may have a significant effect when used with [hormone therapy]," the authors write. "The current study provides evidence that supplemental [calcium and vitamin D] augments the protective effects of [hormone therapy] against hip fracture, and vice versa."

At first blush, these findings may seem to contradict recent US Preventive Services Task Force (USPSTF) recommendations advising against routine calcium and vitamin D supplementation, However, Michael L. LeFevre, MD, USPSTF co-vice chair from the University of Missouri School of Medicine, Columbia, explained in an interview with Medscape Medical News that the study results and the recommendations are consistent with one another.

"The recommendations of the task force against routine supplementation with calcium and vitamin D for all postmenopausal women should not be interpreted to mean that there are no women who might benefit from calcium and vitamin D supplementation," Dr. LeFevre, MD, explained. "This article would suggest that women who are taking [HRT] might be a category of women who may benefit from a dose of calcium and vitamin D in terms of enhancing hip fracture prevention."

Benefits vs Harms of Calcium, Vitamin D, and HRT

The literature about supplemental calcium and vitamin D to prevent fractures "is full of conflicting reports and strong opinions," and using postmenopausal HRT to treat osteoporosis is equally controversial, the authors write.

The researchers analyzed data from the WHI of 16,089 women (aged 50 - 79 years at baseline) who received both hormone therapy or placebo and calcium/vitamin D supplements or placebo for a mean follow-up of 7.2 years. Women who received HRT received estrogen alone if they had had a hysterectomy, or estrogen and progestin if they had an intact uterus. Those who received the vitamin and mineral supplements received 1000 mg/day calcium and 400 IU/day vitamin D.

The primary outcomes were hip fractures and bone mineral density changes.

Taking calcium and vitamin D supplements on top of HRT was not linked with changes in hip or spine bone mineral density.

During follow-up, 83 women randomly assigned to receive HRT (31 who also received calcium and vitamin D and 52 who received a placebo instead of the supplement) and 131 women randomly assigned to receive placebo (70 who received calcium and vitamin D and 61 who received the placebo supplement) had a hip fracture. Calcium/vitamin D supplementation reduced the risk of fracture among women who received HRT, but not among women who received placebo (hazard ratio, 0.59 vs 1.20; P = .01).

The rate of hip fractures per 10,000 person-years was:

  • 11 for women taking HRT and calcium and vitamin D supplements,

  • 18 for women taking HRT only,

  • 25 for women taking calcium and vitamin D supplements only, and

  • 22 for women taking both placebos.

According to Dr. LeFevre, determining optimal prevention strategies is important, as about 15% of postmenopausal women will experience a hip fracture during their lifetime, and more will have any type of osteoporotic fracture. Although it is well-established that HRT reduces the risk for fracture, it also increases the risk for breast cancer (especially in women taking both estrogen and progestin), pulmonary embolism, heart disease, stroke, and gall bladder disease.

After the publication of these earlier WHI trials, "we saw a dramatic decline in the recommendation for and the use of HRT in the US," he continued. "Now, I think most would agree that we should be targeting symptomatic women and trying to relieve suffering, and if in the process we can prevent some fractures, that's great." Conventional wisdom has also shifted away from giving calcium and vitamin D supplements to all postmenopausal women to prevent fractures.

"This article says that [for a select group of postmenopausal women] already taking HRT, the benefit in terms of reduction in hip fractures is greater if [they] also take calcium and vitamin D," Dr. LeFevre summarized.

The "benefit seems to increase with increasing total [calcium and vitamin D] intake" for all levels of diet intake, the authors report, adding that "[d]ose choice should be made to minimize adverse effects." Further research is needed to determine whether calcium and vitamin D supplements would have a synergistic effect with other therapies for osteoporosis, they conclude.

This research was partially funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. One coauthor has received a grant from Novo Nordisk, and one coauthor has received a grant from Pfizer. The other authors and Dr. LeFevre have disclosed no relevant financial relationships.

Menopause. Published online June 26, 2013. Abstract

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