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Title: Fracture healing in osteopenic bone and the influence of simvastatin
Author: Murray, Alastair W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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In part one of the study 20, 3-month-old female, Wistar rats underwent ovariectomy (Ovx) while a further 20 had a sham procedure to act as controls. Seven weeks later a transverse fracture was created in the proximal tibia of each animal by three-point bending with the resulting fractures supported by an intramedullary wire. Half of the animals in each group were euthanased at two weeks and the remainder at four weeks post fracture with tibiae removed post mortem. All tibiae were then x-rayed. The mechanical properties of half of the healing fractures were ascertained by four-point bending to failure while the remaining specimens were prepared for histological analysis and immunohistochemistry. There were no mechanical differences in the fracture calluses from the ovx animals compared with control at two weeks but by four weeks post fracture the ultimate load at failure of the fractures from the ovx animals were rescued to 71% of that from controls. Stiffness (54%) and stress at yield (74%) were also reduced while the strain at yield was increased by 40% in fractures from the ovx group. In the second part of the study the same animal model was used with the groups once again divided into ovx and sham controls. Half of each group received placebo while the other half received simvastatin 20mg/kg daily for 14 days post fatigue. The same time points and outcome measures were used as in the first part of the study. The dose and method of delivery of simvastatin had no apparent effect on the fracture healing in normal bone. However simvastatin appeared to have a deleterious effect on fracture healing in the osteopenic model causing a reduction in callus size and maturity and reducing the healing fractures’ ability to withstand load. This study does not support a role for simvastatin in the enhancement of fracture healing in osteopenia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available