Inflammation-Induced Osteogenesis in a Rabbit Tibia Model

Abstract

Pathologic conditions associated with bone formation can serve as models to identify bone-promoting mediators. The inflammatory response to bacterial infections generally leads to osteolysis and impaired bone healing, but paradoxically, it can also have pro-osteogenic effects. As a potential model to investigate pro-osteogenic stimuli, this study characterizes the bone formation in an established rabbit tibia model of periprosthetic infection. Our hypothesis was that the infection with Staphylococcus aureus (S. aureus) correlates with bone formation as a response to local inflammation. Fluorochromes showed excessive subperiosteal bone formation in infected tibiae, starting the first week and continuing throughout the study period. Despite the observed cortical lysis on micro-CT after 28 days, infection resulted in a twofold higher bone volume in the proximal tibiae compared to uninfected controls. The ipsilateral fibulae, nor the contralateral fibulae or tibiae were affected by infection. Next, we sought to confine the cause of stimulated bone formation to the isolated S. aureus cell wall. In absence of virulent bacterial infection, the S. aureus cell wall extract induced bone in a more favorable way without cortical lysis. This suggests that the sterile inflammatory reaction to bacterial antigens may be harnessed for bone regenerative purposes. Future investigations in this rabbit tibia model can lead to further identification of effective stimuli for clinical application.

Keywords: Staphylococcus aureus; animal model; bone tissue regeneration; inflammatory/immune response.