Upregulation of early inflammation to accelerate repair of fragility fractures. (360G-Wellcome-096035_Z_11_Z)

Fragility fractures as a result of osteoporosis are an enormous public health burden and are associated with excessive patient morbidity and mortality. The poor bone quality results in slower healing and predisposes to failure of orthopaedic implants used to stabilise the fractures. Currently there is currently no approved therapy for accelerating healing of fragility fractures. Thus, strategies to achieve this goal represent a major unmet medical need. We have previously reported that targe ted augmentation of the early inflammatory response at the fracture site can enhance fracture repair through the recruitment and differentiation of resident mesenchymal stromal cells in our murine model. This proposal aims to first, determine whether these findings also apply to osteoporotic bone, and second, dissect the pathways that lead to inflammatory cytokine production to determine the most effective point of intervention. The overall aim is to develop a clinically translatable strategy for accelerating the healing of fragility fractures by using a combination of primary human tissues and murine models.