The present study examined the dose-dependent effect of vitamin E in reversing bone loss in ovariectomized (Ovx) rats. Sprague-Dawley rats were either Sham-operated (Sham) or Ovx and fed control diet for 120 days to lose bone. Subsequently, rats were divided into 5 groups ( /group): Sham, Ovx-control, low dose (Ovx + 300？mg/kg diet; LD), medium dose (Ovx + 525？mg/kg diet; MD), and high dose (Ovx + 750？mg/kg diet; HD) of vitamin E and sacrificed after 100 days. Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase compared to the Ovx-control group. Bone histomorphometry analysis indicated a decrease in bone resorption as well as increased bone formation and mineralization in the Ovx groups supplemented with MD and HD of vitamin E. Microcomputed tomography findings indicated no effects of vitamin E on trabecular bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced fourth lumbar vertebra quality as evidenced by improved ultimate and yield load and stress when compared to Ovx-control group. These findings demonstrate that vitamin E improves bone quality, attenuates bone resorption, and enhances the rate of bone formation while being unable to restore bone density and trabecular bone structure. 1. Introduction Ovarian hormone deficiency is a major risk factor for osteoporosis in women [1, 2]. Although there are several FDA-approved medications to either prevent or reverse osteoporosis, women continue to look for safer and more feasible preventative and therapeutic alternatives [3]. In postmenopausal women, the rate of bone turnover increases with the rate of bone resorption exceeding that of bone formation which results in net bone loss [4]. These events, in part, have been linked to the modulation of immune cell mediators (cytokines and prostaglandins) and oxygen-derived free radical (ODFR) formation either in the bone microenvironment or in the cells that serve as osteoclastic precursors such as those of the monocyte-macrophage lineage [5]. A plethora of local cytokines and lipid mediators such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-α), lymphotoxin, leukotrienes, and prostaglandins of the E series (PGE) are involved in regulating bone metabolism [6–8]. Ovarian hormone deficiency is associated with increased activation of certain immune cells leading to an increase in inflammatory mediators, such as IL-1 [9, 10], IL-6 [9, 11], and in particular PGE2 [12–17], which is in part responsible for suppressing osteoblastic activity stimulating osteoclastic differentiation, and activity
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