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Simvastatin Improves Fracture Healing in Mice
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
Department of Orthopedics, Lund University Hospital, Lund, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
2002 (English)In: Journal of bone and mineral research, ISSN 0884-0431, Vol. 17, no 111, 2004-2008 p.Article in journal (Refereed) Published
Abstract [en]

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 Scheffé’s post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biomechanical 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.

Place, publisher, year, edition, pages
2002. Vol. 17, no 111, 2004-2008 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-13037DOI: 10.1359/jbmr.2002.17.11.2004OAI: diva2:17704
Available from: 2008-03-14 Created: 2008-03-14 Last updated: 2009-06-04
In thesis
1. Following the mevalonate pathway to bone heal alley
Open this publication in new window or tab >>Following the mevalonate pathway to bone heal alley
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mevalonate pathway is an important biosynthetic pathway, found in all cells of virtually all known pro- as well as eukaryotic organisms. This thesis is an investigation into the use of two drugs, originally developed for different applications, but both affecting the mevalonate pathway, in to models of fracture repair.

Using two different rodent models of fracture repair, a commonly used cholesterol lowering drug (statin) and two drugs used to treat osteoporosis (bisphosphonate) were applied both systemically as well as locally in order to enhance fracture repair.

Papers I and II investigate the potential of simvastatin to improve the healing of femoral fractures in mice. Papers III and IV explore the use of two bisphosphonates to improve early fixation of stainless steel screws into rat bone.

The statin simvastatin lead to an increased strength of the healing cellus. The application of bisphosphonates increased early screw fixation.

It seems clear that both drugs have uses in orthopaedic applications. One interesting avenue of further research would be to combine the two classes of drugs and see if we can get the benefits while at the same time diminishing the drawbacks.

Place, publisher, year, edition, pages
Acta Orthopaedica, Volume 78, No. 328, 2007
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1033
Bone screws, coated materials, biocompatible, chemistry, diphosphonates, pharmacology, Equipment failure analysis methods, Femoral fractures, drug therapy, fracture fixation, instrumentation, Fracture fixation, fracture healing, drug effects, simvastatin, tibial fractures, physiopathologyial fractures, surgery
National Category
Medicinal Chemistry Other Veterinary Science
urn:nbn:se:liu:diva-11282 (URN)978-91-85895-30-4 (ISBN)
Public defence
2007-12-12, Linden, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Available from: 2008-03-14 Created: 2008-03-14 Last updated: 2009-08-21

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Skoglund, BjörnAspenberg, Per
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