Calcium supplements: Stone risk up, fracture risk down

May 1, 2006

Bethesda, MD-In the largest randomized clinical trial ofcalcium and vitamin D in postmenopausal women, researchers havefound that women taking calcium with vitamin D supplementation had17% more kidney stones than did women on placebo.

But a study author overseeing the research-part of the National Institutes of Health's Women's Health Initiative-advises urologists: "Stay tuned."

Joan A. McGowan, PhD, director of the Musculoskeletal Diseases Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases at NIH, said further analysis is being done now.

Dr. McGowan pointed out that previous, prospective observational studies, including work using the Nurses Health Study data, have shown that increasing dietary calcium may be protective in those at risk of stones and that supplements may have the opposite effect.

7-year study

The calcium-vitamin D arm of the Women's Health Initiative followed 36,282 women, ages 50 to 79 years, for an average of 7 years. Half were given daily calcium carbonate, 1,000 mg, and vitamin D3, 400 international units. The other half was given a placebo. Both groups were allowed to take limited amounts of calcium and/or vitamin D supplements on their own. Study results were published recently in the New England Journal of Medicine (2006; 354:669-83) and were discussed during a Women's Health Initiative conference attended by Urology Times.

The women in the active calcium with vitamin D supplementation group had 12% fewer hip fractures than those on placebo, but the researchers say that the number was smaller than expected and could be attributed to chance. However, for the subgroup of women who actually took their assigned pills regularly (59%), the data showed 29% fewer hip fractures. Also, among women 60 years and older, there was a 21% decreased hip facture risk for those in the calcium-vitamin D group.

Risk of renal stones increased with calcium-vitamin D supplementation (hazard ratio, 1.17, 95% CI, 1.02 to 1.34)

Dr. McGowan noted that the researchers asked the participants to take the calcium-vitamin D in divided doses (twice daily) and to take them with food, but she does not think the researchers will be able to know whether that's what the women actually did.

"Certainly, if you take a very large dose at the same time and you don't take it with food, you may be causing a greater risk of calcium precipitation than if you took them as directed," she said.

Glenn Preminger, MD, professor of urology and director of the Comprehensive Kidney Stone Center at Duke University, Durham, NC, recommends that if a physician sees a woman who wants or needs to be on calcium supplementation and there is concern about stone formation, the safest course is to conduct a 24-hour urine analysis for elevated urinary calcium after the patient has been on supplementation for 4 months. If the calcium excretion is elevated, he would recommend the patient be put on a thiazide diuretic.

"Thiazide will block the excretion of calcium into the urine," Dr. Preminger told Urology Times. "Studies have shown that the excess calcium that is being absorbed actually gets put into the bone by the thiazide. The only other thing the physician must be aware of is that one of the potential side effects of thiazide therapy is loss of potassium and the potential for hypocitrituria. Therefore, potassium supplementation may also be necessary."