Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D

Abstract

In the circulation 25-hydroxyvitamin D (25(OH)D) is bound to vitamin D-binding protein (DBP) and albumin. Only a small fraction is in the unbound, free form. According to the ‘free-hormone-hypothesis’ only the free form is biologically active. Genetic differences in DBP may affect the binding to 25(OH)D and thereby the amount of free 25(OH)D. In the present study sera were obtained from 265 postmenopausal women with low bone mass density (BMD). Serum 25(OH)D, DBP and albumin were measured and the free and bio-available (free + albumin-bound) 25(OH)D calculated. Based on genotyping of the polymorphisms rs7041 and rs4588, the six common DBP phenotypes were identified and the free and bio-available 25(OH)D calculated according to the corresponding binding coefficients. Relations between measures of 25(OH)D and PTH and BMD were evaluated with linear regression adjusted for age and BMI. The calculated amount of free and bio-available 25(OH)D was 0.03% and 13.1%, respectively, of the measured total serum 25(OH)D. Adjusting for DBP phenotype affected the calculated free and bio-available 25(OH)D levels up to 37.5%. All measures of 25(OH)D correlated significantly with PTH, whereas a significant association with BMD was only seen for the free and bio-available 25(OH)D measures. Adjusting for the DBP phenotypes improved the associations. These relations were almost exclusively seen in subjects not using vitamin D and/or calcium supplements. In conclusion, the free and bio-available forms of 25(OH)D may be a more informative measure of vitamin D status than total 25(OH)D. Adjustment for DBP phenotype may improve this further.

Key Words::

• Endocrinology
• polymorphism
• genetic
• vitamin D
• vitamin D-binding protein
• 25-hydroxyvitamin D

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Acknowledgements

The superb assistance by the staff at the Clinical Research Unit, from Marian Remijn and Line Wilsgaard at the DEXA laboratory, Inger Myrnes and Astrid Lindvall at the Department of Medical Biochemistry at the University Hospital of North Norway, Otto Bårholm at the Hormone Laboratory, Haukeland University Hospital, and Bente Holme at the Hormone Laboratory, Oslo University Hospital, is greatly appreciated.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The study was funded by a grant from The Norwegians Women Public Health Association in Troms, The North Norway Regional Health Authority, the University of Tromsø, and The Research Council of Norway.