The use of delta-tocotrienol and lovastatin for anti-osteoporotic therapy

Aims: Statins are competitive inhibitors of HMGCoA reductase and are commonly used as anti-hypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin. Main methods: Forty-eight female Sprague Dawley rats were randomly divided into six groups: baseline control; sham-operated control; ovariectomised control; ovariectomised + 11 mg/kg lovastatin; ovariectomised + 60 mg/kg delta-tocotrienol and ovariectomised + 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given via oral gavage daily for eight weeks. After sacrificing the rats, the left and right femurs were dissected and processed for bone histomorphometric analysis and a bone biomechanical test, respectively. Key findings: Delta-tocotrienol in combination with lovastatin significantly improved the trabecular volume, trabecular number, trabecular thickness and trabecular separation; and it significantly increased bone strength in oestrogen-deficient rats. Delta-tocotrienol alone enhanced bone formation and maintained bone strength in ovariectomised rats. Delta-tocotrienol plus lovastatin treatment promoted better trabecular volume and trabecular number and received higher load than delta-tocotrienol alone. Lovastatin alone was not effective. Significance: Thus, the combination of delta-tocotrienol and lovastatin has the potential to be used for anti-osteoporotic therapy in postmenopausal women. (C) 2014 Elsevier Inc. All rights reserved.