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Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD) do not reveal adverse skeletal changes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical pharmacogenetics and Osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical pharmacogenetics and Osteoporosis)
2006 (English)In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 159, no 1, 73-80 p.Article in journal (Refereed) Published
Abstract [en]

We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet containing 12IU Vitamin A per g pellet (control, C), or a standard diet supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12 weeks. At the end of the study, serum retinyl esters were elevated 4- and 20-fold. Although neither average food intake nor final body weights were significantly different between groups, a dose-dependent reduction in serum levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the length of the humerus was the same as in controls, but the diameter was reduced (-4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the diaphysis showed that bone mineral density (BMD) was unchanged and that periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight of the humerus was not affected, but since bone volume decreased, volumetric BMD, as measured by the bone ash method, even increased (+2.5%, p<0.05). In conclusion, interference with other fat-soluble Vitamins is a possible indirect mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since the WHO criterium for osteoporosis is based on BMD, further studies are warranted to examine whether this is also true in humans.

Place, publisher, year, edition, pages
2006. Vol. 159, no 1, 73-80 p.
Keyword [en]
25-Hydroxyvitamin D 2/blood, Animals, Bone Density/*drug effects/physiology, Calcifediol/blood, Dose-Response Relationship; Drug, Female, Hypervitaminosis A/*chemically induced/*physiopathology, Rats, Rats; Sprague-Dawley, Research Support; Non-U.S. Gov't, Tocopherols/blood, Vitamin A/*adverse effects/toxicity, Vitamin K 1/blood
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-80220DOI: 10.1016/j.cbi.2005.10.104PubMedID: 16289060OAI: oai:DiVA.org:uu-80220DiVA: diva2:108134
Available from: 2007-02-28 Created: 2007-02-28 Last updated: 2010-05-06Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16289060&dopt=Citation

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Melhus, Håkan
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