title: The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency.
abstract: Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p< 0.05). There was a parallel increase in BMP-2 gene expression in the rats receiving combined treatment (p< 0.05). The combination of annatto tocotrienol and lovastatin exerted either additively or synergistically on selected bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.
authors.affiliation: Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Cheras 56000, Malaysia. chinkokyong@ppukm.ukm.edu.my.
authors.forename: Kok-Yong
authors.initials: KY
authors.lastname: Chin
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, PA 19104, USA. saif_saad83@yahoo.com.
authors.forename: Saif
authors.initials: S
authors.lastname: Abdul-Majeed
authors.affiliation: Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Cheras 56000, Malaysia. azlina@ppukm.ukm.edu.my.
authors.forename: Norazlina
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Cheras 56000, Malaysia. imasoel@ppukm.ukm.edu.my.
authors.forename: Soelaiman
authors.initials: S
authors.lastname: Ima-Nirwana
mesh_terms: D000818:Animals; D031212:Bixaceae / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002338:Carotenoids / Q000737:chemistry; D019587:Dietary Supplements; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D008148:Lovastatin / Q000008:administration & dosage*; D010052:Ovariectomy; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D024508:Tocotrienols / Q000008:administration & dosage*
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D004967:Estrogens; D010936:Plant Extracts; D024508:Tocotrienols; D002338:Carotenoids; C054041:annatto; D008148:Lovastatin
keywords: calcium; menopause; mevalonate; mineralization; osteopenia; osteoporosis; vitamin E