Statins and bone metabolism.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are potent inhibitors of cholesterol biosynthesis. Cholesterol-lowering therapy using statins significantly reduces the risk of coronary heart disease. However, extensive use of statins leads to increases of other undesirable as well as beneficial effects, so-called pleiotropic effects. With respect to these effects, statins augment the expression of bone morphogenetic protein-2, a potent simulator of osteoblast differentiation and its activity, and promote mineralization by cultured osteoblasts, indicating that statins have an anabolic effect on bone. Chronic administration of statins in ovariectomized (OVX) rats modestly increases bone mineral density (BMD) of cancellous bone but not of compact bone. In clinical studies, there are conflicting results regarding the clinical benefits of this therapy for the treatment of osteoporosis. Observational studies suggest an association between statin use and reduction in fracture risk. Clinical trials reported no effect of statin treatment on BMD in hip and spine, and on bone turnover. Statins also may influence oral osseous tissues. Administration of statins in combination with osteoporosis therapy appears to improve alveolar bone architecture in the mandibles of OVX rats with maxillary molar extraction. Statins continue to be considered as potential therapeutic agents for patients with osteoporosis and possibly with periodontal disease. Development of new statins that are more specific and potent for bone metabolism will greatly increase the usefulness of these drugs for the treatment of bone diseases.
Section of Biochemistry, Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama, Japan. fwga4746@mb.infoweb.ne.jp
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N
Horiuchi
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T
Maeda
D000539:Alveolar Process / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D010006:Osteoblasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy; D016212:Transforming Growth Factor beta / Q000187:drug effects
D000924:Anticholesteremic Agents; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016212:Transforming Growth Factor beta