Cortical and trabecular bone, bone mineral density, and resistance to ex vivo fracture are not altered in response to life-long vitamin A supplementation in aging rats.

High vitamin A (VA) intakes have been correlated with increased risk of bone fracture. Over 50% of the U.S. adult population reports use of dietary supplements, which can result in VA intakes > 200% of the RDA. In this study, 2 experiments were designed to determine the effect of dietary VA on cortical and trabecular bone properties and resistance to ex vivo fracture. In Expt. 1, we investigated whether orally administered VA accumulates in bone. Seven-week-old rats were treated daily with VA (6 mg/d for 14 d). Total retinol increased in both the tibia and femur (P < 0.01). In Expt. 2, we conducted a longitudinal study in which rats were fed 1 of 3 levels of dietary VA (marginal, adequate, and supplemented, equal to 0.35, 4, and 50 μg retinol/g diet, respectively) from weaning until the ages of 2-3 mo (young), 8-10 mo (middle-age), and 18-20 mo (old). Tibial trabecular and cortical bone structure, bone mineral density, and resistance to fracture were measured using micro-computed tomography and material testing system analysis, respectively. The VA-marginal diet affected measures of cortical bone dimension, suggesting bone remodeling was altered. VA supplementation increased medullary area and decreased cortical thickness in young rats (P < 0.05), but these changes were not present during aging. VA supplementation did not affect resistance to fracture or bone mineral content in old rats. From these results, we conclude that VA-marginal status affects trabecular bone more than cortical bone, and VA supplementation at a moderate level over the lifetime is unlikely to increase the risk of age-related bone fracture in rats.