Effects of mevastatin on grafted bone in MRL/MpJ mice.

Statins, lipid-lowering drugs, have been reported to influence bone metabolism. However, the available information about their effects on bone formation and resorption in vivo is still limited. The present study was undertaken to determine whether the topical administration of mevastatin could increase the bone mass of isografted bone. The tibiae were bilaterally dissected from a donor MRL/MpJ mouse and transplanted subcutaneously in the dorsal region of a recipient mouse. One grafted tibia was topically infused for either 1, 2, 3, or 4 weeks with mevastatin, using an osmotic minipump at a dose of 2.5 pmol/hr. The other tibia was infused with 0.9% NaCl (control). Our three results were: (1) Topical mevastatin stimulated bone formation and numerous cuboidal osteoblasts appeared on the surface of newly formed bone. Bone mineral density and bone area in mevastatin-treated bone were significantly increased. (2) Topical mevastatin increased the number of osteoclasts. (3) The expression of bone morphogenetic protein-2 (BMP-2) mRNA and receptor activator of NF-kB ligand (RANKL) mRNA were upregulated in mevastatin-treated bone. These results suggest that the topical infusion of mevastatin increases bone mass of isografted bone by increasing bone turnover and, at least in part, by promoting the expression of BMP-2 and RANKL mRNA.