Subtrochanteric fracture non-unions: development of a risk scoring system for predicting non-unions and biological characterisation of the non-union tissue

The aim of this thesis was three-fold. Firstly, to investigate the characteristics of patients presenting with subtrochanteric fractures treated with intra-medullary fixation and describe their outcomes, with a special reference to the development of non-union; secondly, to identify risk factors predisposing to non-union and to develop a scoring system that could predict the development of this complication; thirdly, to analyse the biological and molecular profile of fracture non-union tissue. Between January 2009 and December 2016 (eight years), 545 consecutive patients (561 fractures) were treated for proximal femoral fractures extending into the subtrochanteric area, fulfilling the inclusion criteria. Their management and outcomes were reported, with subgroup analysis identifying associations for developing common complications (including non-union; infection; effect of open reduction / osteoporosis / bisphosphonates; atypical fractures; type of nail used; transfusion requirements; presence of a ‘weekend effect’, medical complications and mortality). Regression analysis identified several factors associated with an increased risk non-union (deep infection; self-dynamisation; presence of an atypical fracture; diabetes; and malreduction, as demonstrated by a lateral cortex fracture gap size and varus malalignment), with another factor (moderate comminution) being associated with a decreased risk. Based on these findings, a risk scoring system for predicting non-unions was developed. Additionally, open reduction of subtrochanteric fractures was not associated with an increased risk of deep infection and non-union. The use of cerclage wiring however was found to be associated with a decreased incidence of non-union without an increase in complications. Regarding the laboratory part, following ethics committee approval, ten patients undergoing revision surgery as part of their treatment for atrophic non-union were recruited. Functional assays and gene analysis were performed on the isolated osteoprogenitor cells to elucidate their biological and molecular profile. Comparing the samples’ gene expression at baseline, three genes were found to be over-expressed in non-union tissue mesenchymal stem cells (MSCs) (ICAM1, MMP10 and GLI1), whilst another four genes were under-expressed (EGF, IGF2, MMP8 and COL14A1). Comparing non-union versus bone MSCs following osteogenic stimulation (i.e. osteoblastic differentiation), only IGF2 and EGF were significantly under-expressed in non-union MSCs.