Locally applied simvastatin promotes fracture healing in ovariectomized rat.
Simvastatin solution was injected subcutaneously to the site of fractured tibiae of ovariectomized rats. Afterwards healing quality was evaluated by morphologic, radiographic, biomechanical, histological and histomorphometric methods at 1, 2 and 4 weeks after fracture. Results showed that locally applied simvastatin improved fracture healing.


BACKGROUND
Many studies have documented an anabolic effect of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, on undisturbed bone. Reports of their effects, however, on fractured skeletal systems have been limited. A study was, therefore, conducted to check the effects of statins on fracture healing.


METHODS
Simvastatin (10 mg/kg/day) was injected subcutaneously to tissue overlying the site of fractured tibiae of ovariectomized rats for a treatment period of 5 days. Vehicle reagent was used as a control. Healing quality was evaluated at 1, 2 and 4 weeks after fracture.


RESULTS
Compared with that in the vehicle group, the callus cross-section area in simvastatin-treated rats was significantly enlarged by 21.3% (p < 0.05) at 1 week and by 21.5% (p < 0.05) at 2 weeks; new woven bone was relatively substantive and arranged more tightly and regularly at 2 and 4 weeks; and maximal load was increased by 57.5% (p < 0.05) at 2 weeks and by 31.4% (p < 0.05) at 4 weeks. Histomorphometrically, simvastatin was associated with a significant (p < 0.05) increase of mineralization width (MLW), mineralization volume (MLV) and mineral apposition rate (MAR).


CONCLUSIONS
The current study suggests that local application of simvastatin could promote fracture healing in ovariectomized rats.
Wang
J W
JW
Department of Orthopaedics, the Second Affiliated Hospital, Medical School of Zhejiang University, No.88, Jiefang Road, Hangzhou, China 310009.
Xu
S W
SW
Yang
D S
DS
Lv
R K
RK
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D010024:Osteoporosis / Q000150:complications; D010052:Ovariectomy; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013977:Tibia / Q000473:pathology; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin; D000469:Alkaline Phosphatase