Incidence of Hypercalciuria and Hypercalcemia during a Vitamin D Trial in Postmenopausal Women

Endocr Rev, Vol. 33 (03_MeetingAbstracts): OR38-1
Copyright © 2012 by The Endocrine Society ENDO 2012: June 23-26, 2012, Houston, Texas
Vinod Yalamanchili, MBBS1 and John Gallagher, MD1
1 Bone Metabolism Unit, Creighton University Medical Center Omaha, NE

Background: Long-term use of vitamin D and calcium supplements is common in older women. But there is no long-term data on hypercalcemia and hypercalciuria on supplements. In the WHI study there was a significant increase in renal stones in women on 400 IU/d dose of vitamin D3 and 1000mg extra calcium after 7 years but no biochemical data. We collected serum and urine calcium data every 3 months during a one-year trial of different doses of vitamin D.

Methods: Participants in this study were 163 Caucasian postmenopausal women, ages 57-85 years, randomized to one of the several doses of vitamin D3 - 400, 800, 1600, 2400, 3200, 4000, 4800 IU/day or placebo.

Calcium intake was increased to 1200-1400mg/d using calcium citrate from a baseline average of 691 mg/d. The main inclusion criterion was vitamin insufficiency -serum 25OHD < 20ng/ml (Diasorin assay).

Exclusion criteria were illness or medications known to affect vitamin D metabolism.
Serum and urine calcium were measured at baseline and every 3 months for one year. Multiple regression including age, dose, calcium intake, weight, serum 25OHD was used to analyze serum and urine calcium results separately.

Definition of hypercalcemia was a value > normal range (8.9-10.3 mg/dl) and
hypercalciuria a 24h urine calcium > normal (300mg).
Any abnormal event was verified after one week and if high values continued then calcium supplements were reduced or vitamin D was stopped.

Results: Mean baseline serum 25OHD was 15.6 ng/ml and increased on the highest dose of vitamin D to 45 ng/ml. Mean baseline serum calcium was 9.47 mg/dl and increased to 9.52 mg/dl; mean 24-hr urine calcium was 142 mg and increased to 186 mg. Final 24h urine calcium increased with vitamin D dose.

There were 88 episodes of hypercalciuria and 25 episodes of hypercalcemia.
There was no significant association between episodes of hypercalcemia or hypercalciuria and vitamin D dose or serum 25OHD and no kidney stones.
Prolonged hypercalciuria led to discontinuation of calcium in 2 and vitamin D in 1 subject.

Conclusion: About 33 percent of subjects had an episode of hypercalciuria and 10 percent an episode of hypercalcemia on vitamin D and calcium.
These changes were not related to vitamin D dose.
If these changes occur frequently with long-term use it could explain the increase in kidney stones seen in the WHI study.
Limitation of calcium supplements and measurement of 24h urine calcium is advisable with long-term use of vitamin D and calcium.

Nothing to Disclose: VY, JG
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Typically should limit Calcium to 500 mg/day

See also VitaminDWiki

• IoM again fails to look at interactions - Nov 2010 had the following chart
• Note: the existing knowledge indicates a 50% increase in absorption with high level of vitamin D

Supplements which combine vitamin D and Calcium (as of Jan-2010) = green diamonds
RDA of Vitamin D and Calcium is safe = green square

• Interaction between Vitamin D and calcium – April 2012
• Overview Calcium and Vitamin D which includes the following notional chart