Higher Vitamin D in Menopause Linked to Big Reduction in Fracture

Nancy A. Melville

September 15, 2014

HOUSTON — Women who maintain high vitamin-D levels throughout menopause have a more than 40% reduced risk for fracture during the transition than those whose levels are lower, according to new research presented here at the American Society for Bone and Mineral Research (ASBMR) 2014 annual meeting.

"Women at midlife with higher 25(OH)D have a lower risk of nontraumatic fracture over the menopausal transition, independent of bone-mineral density [BMD] and other covariates," said lead author Jane Cauley, PhD, of the University of Pittsburgh Graduate School of Public Health, Pennsylvania.

While circulating levels of 25(OH)D are known to be associated with fracture risk in general, and specifically hip fracture, most studies have involved subjects aged 65 or older. The question of the role of vitamin D in menopause is relevant, however, due to the host of changes that can set women up for an increased fracture risk, Dr. Cauley explained.

"We know [from previous studies] that bone loss accelerates in the transmenopausal period, and further research [J Clin Endocrinol Metab. 2013;98:E654- E663] has shown menopausal bone-mineral density changes to correlate with changes in estradiol and [follicle-stimulating hormone] FSH."

And studies have also shown women to require more than 500 mg of calcium per day to achieve neutral calcium balance compared with women on hormone therapy.

Asked to comment, session moderator Catherine Gordon, MD, director of the division of adolescent medicine at Hasbro Children's Hospital and a professor and vice chair for clinical research in the Alpert Medical School of Brown University's department of pediatrics, Providence, Rhode Island, said: "The authors had the opportunity in this study to work with a novel sample — women going through the menopausal transition.

"In my view, the results emphasize the need for empiric vitamin-D supplementation, treatment of vitamin-D deficiency, and surveillance for the deficiency in perimenopausal women, a group known to be a high risk for bone loss," she told Medscape Medical News.

Higher Vitamin-D Levels Almost Halved Risk of Nontraumatic Fracture

To evaluate the role of serum 25(OH)D in the equation, Dr. Cauley and her colleagues assessed 1620 women who were enrolled in the bone cohort of the Study of Women's Health Across the Nation (SWAN), funded by the US National Institutes of Health.

Most of the women (74.5%) were premenopausal or early menopausal, 7.2% were late perimenopausal, and 4.8% were postmenopausal, early in the course of the study, 2 years after enrolling.

The women had mean 25(OH)D levels at the 2-year visit of 21.6 ng/mL; however, there was notable variance according to ethnicity, with mean levels among whites of 25.2 ng/mL, 14.1 ng/mL among blacks, 20.1 ng/mL among Chinese, and 23.5 ng/mL among Japanese. As many as 703 (43%) of women had mean levels below 20 ng/mL.

The mean age of the women at time of 25(OH)D measure was 48.5 years, with no difference by race.

With an average follow-up of 9.5 years, 88 of the women had experienced an incident nontraumatic fracture. But those maintaining 25(OH)D levels of greater than 20 ng/mL had as much as a 45% lower risk of fracture, compared with those with lower levels.

Even after adjusting for important variables including the women's BMD and body mass index (BMI) and excluding postmenopausal women, the researchers found that each 10-ng/mL increase in mean serum 25(OH)D was associated with a 25% lower nontraumatic fracture risk (defined as a fracture resulting from a fall from standing height or less).

No association was seen between 25(OH)D levels and traumatic fractures (defined as a break occurring from a fall from greater than standing height, from playing sports or  from a motor vehicle accident, or because something fell on the subject).

In further evaluating rates of spine- and hip-BMD changes in a subgroup of 791 women for whom data was available from 5 years to 1 year before their final menstrual period, the researchers found no associations between 25(OH)D levels and bone loss that occurred across menopause.

In responding to an audience member's question regarding the mechanisms that could explain vitamin D not appearing to be associated with BMD but showing a link to nontraumatic fracture, Dr. Cauley speculated on the role of its possible effect on skeletal integrity.

"It could be that vitamin D affects bone quality, but we couldn't measure that," she said. "We do hope to get measures of trabecular score in future research, and hopefully that will help us better understand the issue."

The study nevertheless offers important insights on the specific changes that occur during menopause using a unique population, Dr. Gordon told Medscape Medical News.

Dr. Cauley and Dr. Gordon have reported no relevant financial relationships.

American Society for Bone and Mineral Research 2014 Annual Meeting; September 13, 2014; Houston, Texas. Abstract 1076.

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