Multiple roles of tumor necrosis factor-alpha in fracture healing

•Secondary fracture healing is an inflammatory process that is driven by immune cytokines.•Tumor Necrosis Factor-Alpha (TNF-α) is a central mediator in this inflammatory response•Disease states associated with poor bone healing such as osteoporosis and diabetes have abnormal TNF-α physiology•Appreciation of TNF-α's role in secondary bone healing may lead to new therapies to augment fracture healing

This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications.