Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women

Abstract

Objective: This study aims to prospectively assess the incidence of hypercalciuria and hypercalcemia with different doses of vitamin D and with a calcium intake of approximately 1,200 mg/day.

Methods: This was a 1-year randomized placebo-controlled study of vitamin D (400-4,800 IU/d) in 163 white women aged 57 to 90 years. Calcium citrate tablets (200 mg) were added to the diet to achieve a total calcium intake of approximately 1,200 mg/day in all groups. All women had vitamin D insufficiency at baseline, with serum 25-hydroxyvitaminD levels lower than 20 ng/mL (50 nmol/L). Serum and 24-hour urine calcium were collected every 3 months on supplementation, any test result above the upper reference range represented an episode of hypercalcemia or hypercalciuria. Mixed-effects models and multivariate logistic regression were used in the analysis.

Results: Hypercalcemia (>10.2 mg/dL [2.55 mmol/L]) occurred in 8.8% of white women. Hypercalciuria (>300 mg/d [7.5 mmol]) occurred in 30.6% of white women. Episodes of hypercalciuria were transient in half of the group and recurrent in the other half. No relationship between hypercalcemia or hypercalciuria and vitamin D dose was found, and hypercalciuria was equally common in the placebo group.

Conclusions: Hypercalciuria and hypercalcemia commonly occur with vitamin D and calcium supplements. Whether hypercalciuria and hypercalcemia are caused by calcium, vitamin D, or both is unclear. These findings may have relevance to the reported increase in kidney stones in the Women's Health Initiative trial. Because calcium 1,200 mg and vitamin D 800 IU/day are widely recommended in postmenopausal women, systematic evaluation of the safety of supplements is warranted in clinical management and in future studies.

Trial registration: ClinicalTrials.gov NCT00472823.

Figure 1

Incidence of hypercalcemia compared to placebo and vitamin D dose. The dotted line indicates the upper normal range of 10.2mg/dl. There were 20 episodes of hypercalcemia in 14 women. There is no significant association between episodes of hypercalcemia and vitamin D dose.

Figure 2

The change in mean (95% CL) 24h urine calcium over time and has been adjusted for dose, estimated by a mixed-effects model. * indicates that the result is significantly different from baseline with p<0.0001.

Figure 3

Incidence of hypercalciuria and vitamin D dose.The dotted line indicates an upper normal range of 300mg.There were 81 episodes of hypercalciuria > 300mg in 47 women (32%) and were unrelated to vitamin D dose.

Figure 4

All serum calcium and 24h urine calcium values during study. The upper normal range for serum calcium and 24h urine calcium is indicated by the dotted lines. Only 2 women had both hypercalcemia and hypercalciuria ; most have either one or the other.