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


CONCLUSIONS
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.
Department of General Internal Medicine, University Hospital Bern and University of Bern, Bern, Switzerland;
Andreas
A
Schild
Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, and.
Isabelle
http://orcid.org/0000-0003-0134-6217
I
Herter-Aeberli
Department of General Internal Medicine, University Hospital Bern and University of Bern, Bern, Switzerland;
Karin
K
Fattinger
Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, and.
Sarah
S
Anderegg
Laboratory of Ion Beam Physics, ETH Zurich, Zurich, Switzerland;
Tim
T
Schulze-König
Laboratory of Ion Beam Physics, ETH Zurich, Zurich, Switzerland;
Christof
C
Vockenhuber
Laboratory of Ion Beam Physics, ETH Zurich, Zurich, Switzerland;
Hans-Arno
HA
Synal
Centre on Aging and Mobility, University of Zurich and Waid City Hospital, Zurich, Switzerland; Geriatric Clinic and.
Heike
H
Bischoff-Ferrari
Human Nutrition and Health, DSM Nutritional Products, Kaiseraugst, Switzerland; and.
Peter
P
Weber
Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
Arnold
A
von Eckardstein
Laboratory of Human Nutrition, Institute of Food, Nutrition, and Health, and michael.zimmermann@hest.ethz.ch.
Michael B
MB
Zimmermann
D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016723:Bone Remodeling; D002112:Calcifediol / Q000097:blood*; D002118:Calcium / Q000652:urine; D002132:Calcium Radioisotopes; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012307:Risk Factors; D012621:Seasons; D013557:Switzerland / Q000453:epidemiology
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D002132:Calcium Radioisotopes; D002762:Cholecalciferol; D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol; D002118:Calcium
41Ca; bone health; calcium; postmenopausal women; serum 25(OH) vitamin D; skeletal labeling; vitamin D