title: The use of delta-tocotrienol and lovastatin for anti-osteoporotic therapy.
abstract: OBJECTIVE
  Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic 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.
  
  
  METHODS
  Forty-eight female Sprague Dawley rats were randomly divided into six groups: baseline control; sham-operated control; ovariectomised control; ovariectomised+11mg/kg lovastatin; ovariectomised+60mg/kg delta-tocotrienol and ovariectomised+60mg/kg delta-tocotrienol+11mg/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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Thus, the combination of delta-tocotrienol and lovastatin has the potential to be used for anti-osteoporotic therapy in postmenopausal women.
authors.affiliation: Department of Life Sciences, School of Pharmacy, International Medical University, No. 126, Jalan 19/155b, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
authors.forename: Saif
authors.initials: S
authors.lastname: Abdul-Majeed
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Hospital UKM, Jalan Ya'acob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Norazlina
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Hospital UKM, Jalan Ya'acob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia. Electronic address: imasoel@medic.ukm.my.
authors.forename: Ima-Nirwana
authors.initials: IN
authors.lastname: Soelaiman
mesh_terms: D000818:Animals; D004357:Drug Synergism; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014810:Vitamin E; C082097:tocotrienol, delta; D008148:Lovastatin
keywords: Biomechanical test; Bone histomorphometry; Bone strength; HMGCoA reductase; Lovastatin; Osteoporosis; Ovariectomised; Postmenopausal women; Statins; Tocotrienols; Trabecular