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Vitamin A Antagonizes Calcium Response to Vitamin D in Man
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
2001 In: J Bone Miner Res, Vol. 16, no 10, 1899-1905 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. Vol. 16, no 10, 1899-1905 p.
URN: urn:nbn:se:uu:diva-92404OAI: oai:DiVA.org:uu-92404DiVA: diva2:165463
Available from: 2004-11-17 Created: 2004-11-17Bibliographically approved
In thesis
1. Vitamin A and Osteoporosis: Experimental and Clinical Studies
Open this publication in new window or tab >>Vitamin A and Osteoporosis: Experimental and Clinical Studies
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Vitamin A in high doses is severely toxic to the rat skeleton, and the active metabolite retinoic acid (RA) can induce bone resorption in vitro. An excessive dietary intake of vitamin A has been associated with reduced bone mineral density and an increased risk of hip fracture. In this thesis, mechanisms of vitamin A toxicity have been investigated.

In the human osteosarcoma cell line MG-63 and in human primary osteoblast-like cultures, stimulation with RA decreased expression of osteoprotegerin (OPG), a potent inhibitor of osteoclast formation and activity. Expression of receptor activator of NF-κΒ ligand (RANKL), which stimulates osteoclastogenesis, was induced. This increase of the RANKL/OPG ratio is a likely mechanism of RA-induced bone resorption.

An interaction between vitamin A and D was demonstrated in humans for the first time. Fifteen mg retinyl palmitate antagonized the serum calcium-increasing effect of 2 μg 1,25-(OH)2-D3. This antagonism did not appear to be mediated via PTH.

Rats with subclinical hypervitaminosis A after 3 months’ exposure to approximately 9,000 IU retinyl palmitate per day had decreased bone strength, as measured by three-point-bending analysis of femur. Bone diameter and volume, but not bone mineral density, were reduced, suggesting the use of measurements other than BMD for evaluation of early hypervitaminosis A. Indirect mechanisms of toxicity may develop over time, since serum levels of other fat-soluble vitamins were decreased.

In summary, vitamin A can increase bone fragility in the rat at doses considerably lower than previously shown. The regulation of RANKL/OPG is a likely pathway for direct effects of vitamin A in bone. An antagonistic effect between vitamin A and vitamin D has been demonstrated in humans, suggesting indirect mechanisms for vitamin A toxicity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 65 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1392
Internal medicine, vitamin A, bone, osteoporosis, Invärtesmedicin
National Category
Clinical Medicine
urn:nbn:se:uu:diva-4677 (URN)91-554-6100-X (ISBN)
Public defence
2004-12-10, Enghoffsalen, UAS, Uppsala, 13:15
Available from: 2004-11-17 Created: 2004-11-17Bibliographically approved

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