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Title: The effects of bisphosphonate on direct fracture healing
Author: Savaridas, Terence
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Fractures repair by two distinct mechanism; indirect fracture healing via an endochondral stage and direct fracture healing with primary bone formation via osteonal remodelling units ('cutting cones'). Bisphosphonates are recommended by national clinical guidelines to reduce the risk of osteoporotic fractures. Despite bisphosphonate therapy, osteoporotic fractures continue to occur. A proportion of these fractures require rigid fixation, whereby bone repairs by direct fracture healing. The effects of bisphosphonate therapy on direct fracture healing have not been previously reported. With indirect fracture healing, therapeutic doses of bisphosphonate led to a delay in callus remodelling and a larger callus volume without detrimental effects on the physical property of healing fractures. A model of direct fracture healing with rigid tibial plating in the rat was developed. In addition, a non-rigid model of external fixation that used the same number and size of screw holes to that of the plating model was used for comparison. Implants were designed and tested in cadavers prior to preliminary studies in rats. Within these two groups, animals were randomly allocated either to receive daily injections of bisphosphonate (Ibandronate) or saline (Control) for nine weeks. Following three weeks of injections a transverse tibial osteotomy was created and stabilised. Plain radiographs were obtained at fortnightly intervals. Animals were sacrificed at six weeks post fracture stabilisation. On sacrifice, fracture healing was assessed on contact radiographs, with a 4-point bend to failure and histologically. The mechanical properties of the uninjured diaphyseal bone in the contra-lateral limb were also assessed following bisphosphonate therapy. The mean bending stress at failure of diaphyseal bone in the uninjured limb was increased by 20% following only nine weeks of bisphosphonate treatment. The increase in strength of the uninjured diaphyseal bone has relevance when normalising the strength of fracture repair in a limb when comparing it to the unfractured limb as frequently reported in animal studies of fracture repair. In direct fracture healing bisphosphonate therapy resulted in impaired fracture healing as evident on plain radiographs based on the visibility of the fracture line. At six weeks post fracture the failure stress on application of a 4-point bend was decreased and histology revealed delayed bone healing compared to controls. Ibandronate treatment had an inhibitory effect on direct fracture healing in a rodent model. In clinical practice, the treating surgeon may need to consider using non-rigid fixation methods in patients already on bisphosphonate therapy. When rigid fixation is essential patients on bisphosphonates will need to be monitored for features of delayed or non-union and the use of fracture healing adjuncts should be considered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available