[Study on local implantation of simvastatin for repairing rabbit radial critical size defects].
OBJECTIVE
To find an ideal material for repairing bone defect by local implanting simvastatin compounded with poly-lactic acid (PLA) into the radial critical size defects of rabbits, and to observe the reparative effect and type of bone formation induced by simvastatin.


METHODS
Twelve 4-months-old male New Zealand white rabbits (2.3-2.8 kg) with 22 mm radial critical size defects on both sides were randomized into 4 groups (all n=3). Right side and left side of every rabbit were set as controls with each other. The left defects (experimental groups) of groups A, B, and C were implanted with cylinder-like compound scaffolds containing 50, 100, and 200 mg of simvastatin (fixed with 250 mg PLA), or auto-bone graft as group D, respectively. The right defects of groups A, B, and C were implanted with scaffolds containing only 250 mg PLA. The right defects of group D were left without any treatment. Digital X-ray images of bone defects were taken 8 and 16 weeks after operation, X-ray was scored double blind and X-ray pixel value was measured. Animals were euthanized 16 weeks postoperatively. CT was applied to analyze new bone formation volume in the defects. In addition, morphological characters of new bones were observed through micro-CT and histology.


RESULTS
X-ray films showed that the bone defect of each experimental side had much cloud-like callus, and the bone stump were not clear 8 weeks after operation; and the cortex in the defect was continuous and the medullary was recanalized 16 weeks after operation. In control sides, the cortexes were discontinuous and the ends of fractures were sclerified. At 8 and 16 weeks after operation, the X-ray scores, pixel values and the CT volume percentage of new bone in experiment sides were all significantly higher than those in control sides (P < 0.05). The X-ray scores of experimental sides in groups C and D were significantly higher than those in groups A and B 8 weeks after operation (P < 0.05), and the X-ray scores of experimental sides in groups B and D were significantly higher than those in groups A and C 16 weeks after operation (P < 0.05). The X-ray pixel values of experimental sides of group B were significantly higher than those of groups A, C, and D 8 weeks after operation (P < 0.05). The new bone formation volume of experimental side of groups B and D was higher than that of groups A and C (P < 0.05), and group D was significantly higher than that of group B (P < 0.05). Micro-CT showed bone defects of experimental sides of group B had totally healed, with connected medullary cavities and continuous bone cortex, on the contrary bone defects of control sides of group B did not healed completely. Histological observation showed better bone remodeling effects of the experimental sides than control sides, with connected medullary cavities and continuous bone cortex. And the osteogenetic type was endochondral ossification.


CONCLUSIONS
Local implantation of simvastatin can promote repairing rabbit radial critical bone defect, 100 mg is the best dose of repairing the bone defects.
Zhu
Jinglin
J
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, P.R. China.
Song
Quansheng
Q
Wang
Jingying
J
Han
Xiaoguang
X
Yang
Yanlin
Y
Liao
Jing
J
Song
Chunli
C
D000818:Animals; D001861:Bone Regeneration; D018786:Bone Substitutes; D016025:Bone Transplantation; D019344:Lactic Acid; D008297:Male; D011091:Polyesters; D011108:Polymers; D011817:Rabbits; D011884:Radius / Q000293:injuries*; D011885:Radius Fractures / Q000601:surgery*; D019821:Simvastatin / Q000627:therapeutic use*
D018786:Bone Substitutes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D019821:Simvastatin