title: A review on the use of statins and tocotrienols, individually or in combination for the treatment of osteoporosis.
abstract: Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jln Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia. imasoel@medic.ukm.my.
authors.forename: Saif
authors.initials: S
authors.lastname: Abdul-Majeed
authors.forename: Norazlina
authors.initials: N
authors.lastname: Mohamed
authors.forename: Ima-Nirwana
authors.initials: IN
authors.lastname: Soelaiman
mesh_terms: D000818:Animals; D001682:Biological Availability; D001862:Bone Resorption / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000188:drug therapy / Q000517:prevention & control; D024508:Tocotrienols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D024508:Tocotrienols