ECTS2016 Poster Presentations Nutrition (13 abstracts)
Effects of clinically relevant doses of vitamin A on bone in mice
Vikte Lionikaite 1 , Karin Gustafsson 1 , Anna Westerlund 1 , Antti Koskela 2 , Juha Tukkanen 2 , H Herschel Conaway 3 , Claes Ohlsson 1 , Petra Henning 1 & Ulf Lerner 1,
1University of Gothenburg, Gothenburg, Sweden; 2University of Oulu, Oulu, Finland; 3University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; 4Umea University, Umea, Sweden.
Excess vitamin A has been associated with decreased cortical bone thickness and increased fracture risk. While most studies in rodents have been done using very high doses of vitamin A for a few days, we here investigate how clinically relevant doses of vitamin A, calculated from the Recommended Daily Allowance (RDA) in humans, affects the bone phenotype in mice after longer exposure.
C57BL/6 mice were fed either a control diet (15 IU/g retinyl acetate), or diets enriched with 67 IU/g (medium), or 200 IU/g (high) retinyl acetate for 4 or 10 weeks.
Serum retinol levels increased at 4 and 10 weeks with the high dose vs control, however, retinyl esters have been reported to be a more sensitive measurement of excess vitamin A, with levels over 200 nM indicating potential hypervitaminosis A in humans. Mice fed the high diet had retinyl ester levels of 343±65 nM and 325±96 nM at 4 and 10 weeks respectively, significantly exceeding the control of 65±17 nM and 45±4 nM respectively and indicating potential hypervitaminosis A. Tibial periosteal circumference decreased which resulted in reduced cortical bone area (−11±2%; P<0.01) and decreased cortical thickness (−6±2%; P<0.05) after 10 weeks of high diet. These reductions in the amount of cortical bone, measured by CT, resulted in a non-significant trend towards reduced bone strength as analysed by three point bending, maximal load at failure. In contrast, trabecular bone was not affected in the metaphyseal region of long bones or vertebrae as measured by CT. At 4 weeks, a decrease in the cortical bone expression of osteoblastic genes, with no effect on osteoclastic genes, was observed. This suggests that the reduction in cortical bone mass may be mediated by bone forming osteoblasts.
In conclusion, our results suggest that even clinically relevant doses of vitamin A have a negative impact on cortical bone, with the trabecular bone unaffected.
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Bone Abstracts
ISSN 2052-1219 (online)
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