Abstract
Introduction: It has been suggested that statins may influence bone turnover via an effect on bone morphogenic protein 2 (BMP-2). While the effect on statins in the prevention of osteoporosis remains controversial there is some evidence that they may exert a significant effect on fracture healing.
Using a newly developed fracture model of the proximal tibia of the rat, the effect of simvastatin on osteoporotic and non-osteoporotic fracture healing was investigated. The fracture model was used as it provided a useful model of metaphyseal fracture healing which is particularly relevant to osteoporotic fracture.
Methods: Four groups of 20 3-month-old female Wistar rats were used. Half underwent ovariectomy (ovx) while the remainder had a sham procedure. 8 weeks later a fracture was created in the proximal tibia of each animal by three point bending. The fractures were supported by a narrow intramedullary k-wire. 20 sham and 20 ovx animals were then fed 20mg/kg simvastatin by gavage for 14 days while the rest received placebo. 10 animals from each group were sacrificed at 2 weeks post surgery while the rest were sacrificed at 4 weeks.
X-rays of the healing fractures were taken. Both the intact and fractures tibiae were then taken for mechanical testing by four point bending.
Results: Six animals (7.5%) were excluded because of fracture comminution (5) or loss of stabilisation (1). There was a similar radiological appearance in all 4 groups at each time point. At two weeks: there was no difference in the mechanical properties of the healing bone between the groups. At 4 weeks the fractured and intact tibiae from the sham animals had an equal ultimate load at failure to their intact tibiae. However, the fractured tibiae from the ovx animals remained weaker (ovx & placebo 68%, ovx & statin 60.5% of ultimate load at failure compared with intact tibia). The difference between the fractures ultimate load in ovx and sham animals was statistically significant (p=0.0105). No difference was seen between the statin and placebo group.
Discussion: This work provides evidence that a metaphyseal fracture in the osteoporotic rat model is able to withstand significantly less load at 4 weeks than a fracture from a sham ovx animal suggesting fracture healing is slower in osteoporotic individuals. Simvastatin at 20mg/kg had no effect on the mechanical properties of normal or osteoporotic fracture healing in this study.
Correspondence should be addressed to Mr Carlos Wigderowitz, Honorary Secretary BORS, University Dept of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School, Dundee DD1 9SY.
