The role of statins as potential targets for bone formation

Abstract

Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme have recently been shown to stimulate bone formation in rodents both in vitro and in vivo. In bone cells, these inhibitors increase the gene expression of bone morphogenetic protein-2, which is an autocrine-paracrine factor for osteoblast differentiation. The findings that statins increase bone formation and bone mass in rodents suggest a potential new action for these compounds, which may be beneficial in patients with established osteoporosis where marked bone loss has occurred. Recent clinical data suggest that they may reduce the risk of fracture in patients taking these drugs.

Figure 1

Cultures of murine neonatal calvaria incubated for either 4 or 7 days in the presence of simvastatin at 1 μM. Small amounts of new bone are present in control cultures whereas cultures exposed to simvastatin for 4 days show marked new bone formation and osteoblast accumulation. Cultures exposed for 7 days show further enhancement of bone formation.

Figure 2

Bone volume in the tibia of ovariectomized rats treated either by daily oral lavage with cerivastatin (0.1 mg/kg/day) or simvastatin (10 mg/kg/day) or subcutaneously with fibroblast growth factor (FGF) (80 μg/kg/day). The bone volume is expressed as per cent bone area (BA)/ total area measured (TA). ^*P < 0.05, versus control group.