Calcium and vitamin D supplementation associated with hypercalcemia, hypercalciuria in postmenopausal women

Postmenopausal women who take calcium and vitamin D supplements may be at higher risk for hypercalcemia and hypercalciuria, according to a new study.

Researchers conducted a 1-year randomized, placebo-controlled trial in which postmenopausal women received 400 to 1,800 IU of vitamin D per day, as well as calcium citrate supplements. All of the women in the study had vitamin D insufficiency at baseline. Serum and 24-hour urine calcium were measured every 3 months while the women were taking supplements, and any result that exceeded the upper reference range was classified as hypercalcemia or hypercalciuria. The study's primary outcome measures were dose responses to serum 25-hydroxyvitamin D and serum parathyroid hormone after vitamin D supplementation. Secondary outcomes were serum and 24-hour urine calcium levels. The study results were published online June 16 by Menopause.

A total of 163 women age 57 to 90 years were randomly assigned to 1 of 8 study groups: 400 IU of vitamin D daily, 800 IU, 1,600 IU, 2,400 IU, 3,200 IU, 4,000 IU, 4,800 IU, or placebo. The study participants also received calcium supplementation to ensure an intake of 1,200 to 1,400 mg/d after 7-day food diaries were used to determine usual dietary calcium levels. All of the women in the study had been postmenopausal for at least 7 years, and all were white. Of the women who were randomly assigned, 147 completed the study protocol, 5 were lost to follow-up, and 11 stopped taking the study medications but were included in the analysis. Mean adherence to the study medications over 12 months was 94% for vitamin D and 91% for calcium.

Overall, 8.8% of women experienced hypercalcemia and 30.6% experienced hypercalciuria. Hypercalciuria was transient in half of patients and recurred in the other half. The researchers did not detect a relationship between hypercalcemia or hypercalciuria and dose of vitamin D, and an equal proportion of patients in the placebo group also experienced hypercalciuria. Eleven women experienced serious adverse events, but none appeared to be related to vitamin D use, and no patients developed symptomatic kidney stones. A weak relationship was found between 24-hour urine calcium level and 12-month serum 25-hydroxyvitamin D level.

The researchers acknowledged that their results might not apply to other age or ethnic groups and that they did not use fixed-dose calcium or include a placebo group who did not take calcium supplements. However, they concluded that hypercalcemia and hypercalciuria are common in postmenopausal women who take calcium and vitamin D supplements and that these events are not related to dose of vitamin D or to serum 25-hydroxyvitamin D level. It is unclear whether these events are related to calcium alone or to calcium plus vitamin D, the authors said.

“Further investigation is needed to better define individuals who are likely to develop hypercalciuria and hypercalcemia, but a high baseline 24-hour urine calcium level is one predictor of hypercalciuria,” the authors wrote. “Before the start of calcium and vitamin D supplementation, it is advisable to measure blood and urine calcium levels and to perform a follow-up measurement within 3 months.”