Calcium plus vitamin D offered only modest improvement of bone mineral density

Reduction in fractures was insignificant.

Issue: January 2006

Taking calcium plus vitamin D supplements improved hip bone density in postmenopausal women.

A large-scale, randomized, double-blind, placebo-controlled trial — part of the Women’s Health Initiative — found that calcium with vitamin D supplementation diminished bone loss at the hip but did not significantly reduce the incidence of hip fracture. The results were published in the New England Journal of Medicine.

“The results support current recommendations of 1,200 mg elemental calcium and 400 to 600 IU of vitamin D, but they also allow clinicians to understand the impact supplementation actually has on fracture,” Rebecca D. Jackson, MD, told Endocrine Today. “[Supplements] are simply the foundation for bone health along with regular physical activity and reduction of other risk factors that can contribute to fracture.

“For women who have more significant bone disease, who already have low bone density or are at greater risk for fractures either due to medication that can contribute to osteoporosis or from personal history of fracture, additional diagnostic testing and the use of one of the seven FDA-approved bone active agents is certainly an important part of treatment,” said Jackson, professor of internal medicine in the divisions of endocrinology, diabetes and metabolism at Ohio State University and vice chair of the Women’s Health Initiative.

Bone mineral density

The trial enrolled 36,282 postmenopausal women aged 50 to 79 from the Women’s Health Initiative. Participants were randomly assigned to receive supplements or placebo. Active tablets contained 500 mg or elemental calcium and 200 IU of vitamin D.

Participants were told to take two tablets per day in divided doses and with meals. Women in either group could continue to take personal supplements.

At the end of the trial in March 2005, 1,551 participants had died and 2.7% were lost to follow-up. Seventy-six percent of participants were still taking the medication, but only 59% were taking 80% or more of it.

Throughout follow-up women receiving supplementation had greater preservation of total-hip BMD than those assigned placebo. Only insignificant differences were found in spine and whole-body BMD.

Researchers also found an insignificant 12% reduction in hip fractures in women assigned calcium and vitamin D supplementation compared with women assigned placebo. Women who adhered to the supplementation had a 29% reduction in hip fracture, and those 60 or older had a 21% reduction in fractures, however.

There was no significant reduction in fractures at other skeletal sites; there were 2,102 fractures among women assigned supplements and 2,158 among women assigned placebo.

The only adverse effect reported was a 17% increase in kidney stones among women taking supplements.

Effectiveness

Jackson said that the results were enlightening.

“Prior to the WHI trial, the majority of trials had focused on women with significant osteoporosis or individuals who were calcium plus vitamin D deficient. The WHI trial focused on more calcium replete, community dwelling, healthy postmenopausal women and showed modest benefit on the effects on bone mass and reduction in the risk of fractures in some subgroups,” she said.

“The surprise was the absolute lack of effectiveness at reducing fractures at other skeletal sites,” she said.

In addition, nearly half of the women enrolled in this trial were also enrolled in a hormone therapy trial. These women were taking a bone active agent through either the randomized clinical trial or through personal hormone supplements.

“This may have made it more difficult for us to pull out an independent calcium effect from our participants. The interaction of calcium plus vitamin D elucidated for us the fact that hormone therapy clearly reduces risk of hip, vertebral and total fractures,” Jackson said.

“Those women who also received active calcium in addition to hormone therapy had a further reduction in the risk of hip fractures,” she said.

“Clinicians and patients should be aware that even if a woman is receiving adequate calcium with vitamin D supplementation, she may still be at risk for fracture, particularly if she has a low bone mineral density,” wrote Joel S. Finkelstein, MD, in an accompanying editorial.

“With the widespread marketing of calcium and vitamin D, many women believe that they are completely protected against the development of osteoporosis if they are taking these supplements. This study should help correct this important misconception and allow more women to receive optimal therapy for bone health,” Finkelstein wrote. – by Leah Smith

For more information:

Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669-683.

Finkelstein JS. Calcium plus vitamin D for postmenopausal women — bone appétit? N Engl J Med. 2006;354:750-752.