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Locally applied Simvastatin improves fracture healing in mice.

Skoglund B, Aspenberg P - BMC Musculoskelet Disord (2007)

Bottom Line: With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined.Continuous systemic delivery resulted in a 160% larger force at failure.Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Orthopedics and Sports Medicine, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, SE 581 85 Linkoping, Sweden. bjorn.skoglund@ltv.se

ABSTRACT

Background: HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.

Methods: Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg) or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test.

Results: With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.

Conclusion: This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.

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Related in: MedlinePlus

Photographs taken at evaluation to illustrate the three-point bending.
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Figure 2: Photographs taken at evaluation to illustrate the three-point bending.

Mentions: A lateral incision was made along the distal femur. The patella was dislocated medially with the blunt side of the scalpel, so that the femoral condyles were exposed. Using an intercondylar approach, a hole was drilled through the medullary canal of the femur using a cannula (diameter 0.4 mm). A wider cannula (0.6 mm) was then inserted into the canal made. The sharp end of the cannula was blunted in order not to penetrate through to the hip. The cannula was cut off, so that the remaining bit was inside the bone and no end extended beyond the bone. A specially made pair of scissors with semi-lunar cutting edges were then slid along the bone to mid-diaphysis and the femur cut to produce a fracture (Figures 1, 2 &3). The patella was then repositioned over the knee-joint and the muscles and skin sutured separately.


Locally applied Simvastatin improves fracture healing in mice.

Skoglund B, Aspenberg P - BMC Musculoskelet Disord (2007)

Photographs taken at evaluation to illustrate the three-point bending.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200653&req=5

Figure 2: Photographs taken at evaluation to illustrate the three-point bending.
Mentions: A lateral incision was made along the distal femur. The patella was dislocated medially with the blunt side of the scalpel, so that the femoral condyles were exposed. Using an intercondylar approach, a hole was drilled through the medullary canal of the femur using a cannula (diameter 0.4 mm). A wider cannula (0.6 mm) was then inserted into the canal made. The sharp end of the cannula was blunted in order not to penetrate through to the hip. The cannula was cut off, so that the remaining bit was inside the bone and no end extended beyond the bone. A specially made pair of scissors with semi-lunar cutting edges were then slid along the bone to mid-diaphysis and the femur cut to produce a fracture (Figures 1, 2 &3). The patella was then repositioned over the knee-joint and the muscles and skin sutured separately.

Bottom Line: With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined.Continuous systemic delivery resulted in a 160% larger force at failure.Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Orthopedics and Sports Medicine, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, SE 581 85 Linkoping, Sweden. bjorn.skoglund@ltv.se

ABSTRACT

Background: HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.

Methods: Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg) or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test.

Results: With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.

Conclusion: This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.

Show MeSH
Related in: MedlinePlus