Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats.
OBJECTIVE
We investigated whether the local administration of simvastatin affected both the cellular events and the bone formation at surgically created bone defects in rat.


METHODS
Simvastatin (or a vehicle) was injected into a rat bony defect for 3 consecutive days from the day of surgery. Five or ten days after the injection, new bone tissue was collected, and the gene expressions of bone-related proteins were examined. For the histomorphometry, new bone area was measured.


RESULTS
At day 5, the statin group demonstrated significantly larger new bone area. The number of tartrate-resistant acid phosphatase-positive multinucleated cells in the statin group was less than in the control group. In the statin group, the expressions of both alkaline phosphatase and bone morphogenetic protein 2 mRNA significantly increased. In contrast, the expression of cathepsin K was significantly suppressed in the statin group. Although the levels of both RANK and osteoprotegerin were not affected by statin, the expression of RANKL was depressed. At day 10, there were no significant differences among the groups in either histomorphometric or reverse-transcription polymerase chain reaction analyses.


CONCLUSIONS
New bone area increased under the influence of simvastatin; however, the effect did not continue when the administration was terminated. Osteoclast suppression may be the consequence of RANKL depression.
Ayukawa
Yasunori
Y
Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. ayukawa@dent.kyushu-u.ac.jp
Yasukawa
Eisuke
E
Moriyama
Yasuko
Y
Ogino
Yoichiro
Y
Wada
Hiroko
H
Atsuta
Ikiru
I
Koyano
Kiyoshi
K
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism / Q000601:surgery; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors; D015870:Gene Expression; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D013977:Tibia / Q000601:surgery
D055396:Bone Morphogenetic Protein 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053245:RANK Ligand; D015675:Osteocalcin; D019821:Simvastatin; D000469:Alkaline Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat