TY - JOUR
T1 - Simvastatin improves fracture healing in mice
AU - Skoglund, B
AU - Forslund, Carina
AU - Aspenberg, Per
PY - 2002
Y1 - 2002
N2 - Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffe's post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biornechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p = 0.001), the force required to break the bone was 63% greater (p = 0.001), and the energy uptake was increased by 150% (p = 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures.
AB - Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffe's post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biornechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p = 0.001), the force required to break the bone was 63% greater (p = 0.001), and the energy uptake was increased by 150% (p = 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures.
KW - bone
KW - mice
KW - statins
KW - fracture repair
U2 - 10.1359/jbmr.2002.17.11.2004
DO - 10.1359/jbmr.2002.17.11.2004
M3 - Article
SN - 1523-4681
VL - 17
SP - 2004
EP - 2008
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 11
ER -