γ-
Tocotrienol (GT3), an analogue of
vitamin E, has gained increasing scientific interest recently as it provides significant health benefits. GT3 exerts its biological effects not only by virtue of
antioxidant properties but also by inhibiting hydroxy-methyl-
glutaryl-coenzyme A (
HMG-CoA) reductase. Studies have reported that the
mevalonate pathway is relevant for bone metabolism and
HMG-CoA reductase inhibitors can increase bone mass and are useful in
osteoporosis therapy. However, whether it is involved in the bone anabolic activity of GT3 is not clear. This study was conducted to investigate the ability of GT3 to protect against
ovariectomy-induced bone loss, as well as the correlation between the protections and
mevalonate pathway. Results showed that mice supplemented with 100mg/kg emulsified GT3 via
subcutaneous injection once per month for three months were significantly protected from
ovariectomy-induced bone loss as evaluated by various bone structural parameters, bone metabolic gene expression levels and serum levels of
biochemical markers for
bone resorption and bone formation. Importantly, the effect of GT3 on preventing against
ovariectomy-induced bone loss could be reversed by daily supplementation with
mevalonate, indicating that GT3 may via an
HMG-CoA reductase-dependent mechanism to protect against
ovariectomy-induced bone loss. Our results suggest that GT3 is suitable as dietary supplement and has potential as an alternative drug to treat or prevent
osteoporosis.