title: Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD) do not reveal adverse skeletal changes.
abstract: 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.
authors.affiliation: Division of Biochemical Toxicology and Cancerm, Research, Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-17177 Stockholm, Sweden. Monica.Lind@ki.se
authors.forename: P M
authors.initials: PM
authors.lastname: Lind
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: Rönn
authors.forename: H
authors.initials: H
authors.lastname: Melhus
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D002112:Calcifediol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006986:Hypervitaminosis A / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D024505:Tocopherols / Q000097:blood; D014801:Vitamin A / Q000009:adverse effects* / Q000633:toxicity; D010837:Vitamin K 1 / Q000097:blood
chemical_list: D014801:Vitamin A; D015652:25-Hydroxyvitamin D 2; D010837:Vitamin K 1; D002112:Calcifediol; D024505:Tocopherols