Studies of indirect and direct effects of hypervitaminosis A on rat bone by comparing free access to food and pair-feeding

  • Thomas Lind Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University, Uppsala, Sweden http://orcid.org/0000-0003-2791-688X
  • P. Monica Lind Department of Medical Sciences, Section of Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
  • Lijuan Hu Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University, Uppsala, Sweden
  • Håkan Melhus Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University, Uppsala, Sweden
Keywords: Bone, bone turnover serum biomarkers, pair-fed, pQCT, rat, vitamin A

Abstract

Background: The most prominent features of hypervitaminosis A in rats are spontaneous fractures and anorexia. Since caloric restriction induces alterations in bone, some effects could be secondary to loss of appetite. To clarify the mechanisms behind vitamin A-induced bone fragility it is necessary to distinguish between direct and indirect effects.

Materials and methods: In this study we compared rats fed high doses of vitamin A both with pair-fed controls, which were fed the same amount of chow as that consumed by the vitamin A group to keep food intake the same, and to controls with free access to food.

Results: In contrast to the pair-fed animals, rats in the free access group fed high doses of vitamin A for 7 days had 13% lower food intake, 15% lower body weight, and 2.7% shorter femurs compared with controls. In addition, serum biomarkers of bone turnover were reduced. Peripheral quantitative computed tomography of the femurs showed that the bone mineral content, cross sectional area, and periosteal circumference were similarly reduced in the pair-fed and free access groups. However, bone mineral density (BMD) and cortical parameters were only significantly decreased in the free access group.

Conclusions: Our data indicate that the major direct short-term effect of high doses of vitamin A on rat bone is a reduced bone diameter, whereas the effects on bone length, serum biomarkers of bone turnover, BMD, and bone cortex appear to be mainly indirect, caused by a systemic toxicity with loss of appetite, reduced food intake, and general effects on growth.

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Published
2018-04-26
How to Cite
Lind T., Lind P. M., Hu L., & Melhus H. (2018). Studies of indirect and direct effects of hypervitaminosis A on rat bone by comparing free access to food and pair-feeding. Upsala Journal of Medical Sciences, 123(2), 82–85. https://doi.org/10.1080/03009734.2018.1448020
Section
Original Articles