Bone health best with 40 nanograms of vitamin D – Oct 2015

Oral Vitamin D Supplements Increase Serum 25-Hydroxyvitamin D in Postmenopausal Women and Reduce Bone Calcium Flux Measured by 41Ca Skeletal Labeling.

J Nutr. 2015 Oct;145(10):2333-40. doi: 10.3945/jn.115.215004. Epub 2015 Sep 2.
Schild A1, Herter-Aeberli I2, Fattinger K1, Anderegg S2, Schulze-König T3, Vockenhuber C3, Synal HA3, Bischoff-Ferrari H4, Weber P5, von Eckardstein A6, Zimmermann MB7.
1 Department of General Internal Medicine, University Hospital Bern and University of Bern, Bern, Switzerland;
2 Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, and.
3 Laboratory of Ion Beam Physics, ETH Zurich, Zurich, Switzerland;
4 Centre on Aging and Mobility, University of Zurich and Waid City Hospital, Zurich, Switzerland; Geriatric Clinic and.
5 Human Nutrition and Health, DSM Nutritional Products, Kaiseraugst, Switzerland; and.
6 Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
7 Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, and michael.zimmermann@hest.ethz.ch.

BACKGROUND:
Ensuring adequate vitamin D status in older adults may reduce the risk of osteoporosis. The serum 25-hydroxyvitamin D 25(OH)D concentration is the recommended biomarker of vitamin D status, but the optimal serum 25(OH)D concentration for bone health in postmenopausal women remains unclear.

OBJECTIVE:
The aim of this study was to apply the highly sensitive (41)Ca skeletal labeling technique and the measurement of urinary (41)Ca:(40)Ca ratios to determine the serum 25(OH)D concentration that has greatest benefit on bone calcium flux in postmenopausal women.

METHODS:
We administered a mean intravenous (41)Ca dose of 870 pmol to healthy postmenopausal women n = 24, age (mean ± SD): 64 ± 6.0 y without osteoporosis. After 6 mo, at the nadir of their wintertime serum 25(OH)D status, each of the women sequentially consumed daily oral cholecalciferol supplements of 10, 25, and 50 μg/d (in this order), each for 3 mo. We assessed serum 25(OH)D concentrations monthly and urinary (41)Ca:(40)Ca ratios biweekly. (41)Ca:(40) Ca ratios were measured with low-energy accelerator mass spectrometry. With the use of pharmacokinetic analysis, we determined the effect of varying serum 25(OH)D concentrations on (41)Ca transfer rates.

RESULTS:
At baseline, the mean (95% CI) serum 25(OH)D concentration was 16.2 (13.5, 18.8) μg/L. After the first, second, and third intervention periods, mean (95% CI) serum 25(OH)D increased to 29.8 (27.2, 32.4), 36.9 (34.2, 39.7), and 46.6 (41.2, 52.0) μg/L, respectively. Supplementation was associated with a downward shift in the urinary (41)Ca: (40)Ca ratio compared with the predicted (41)Ca: (40)Ca ratio without vitamin D supplementation. In the model, the most likely site of action of the increase in serum 25(OH)D was transfer from the central compartment to a fast exchanging compartment. At this transfer rate, predicted values were a concentration with half-maximal effect of 2.33 μg/L and an estimate of the maximal effect of 31.7%. After the first, second, and third intervention periods, the mean changes in this transfer rate were +18.0%, +25.7%, and +28.5%, respectively.

CONCLUSION:
In healthy postmenopausal women, increasing serum 25(OH)D primarily affects calcium transfer from the central compartment to a fast exchanging compartment; it is possible that this represents transfer from the extracellular space to the surface of bone. A serum 25(OH)D concentration of ∼40 μg/L achieves ∼90% of the expected maximal effect on this transfer rate. This trial was registered at clinicaltrials.gov as NCT01053481.

PMID: 26338885

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