Inflammatory Response Following Intraarticular Fracture (PTOA)

• Tibial Plateau Fracture [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

Post-traumatic osteoarthritis (PTOA) is a common cause of disability following a traumatic event involving a joint. It is estimated that PTOA may affect up to 12% of the population with symptomatic osteoarthritis, and it is associated with significant cost to the healthcare system (1). Given that the majority of trauma patients are younger, the impact of the condition can be particularly devastating for those in the prime of their working careers (2).

PTOA can develop following a variety of joint injuries, but it most predictably occurs with articular fracture. The initial traumatic injury involves a complex process of articular impaction or displacement and soft tissue disruption that leads to articular exposure to blood and marrow, a local inflammatory response, abnormal joint loading, and subsequent chondrocyte necrosis and apoptosis (3). However, the mechanism(s) that lead to progression from the initial injury to end-stage PTOA are largely unknown.

Inflammation can have deleterious effects on a joint. Though inflammatory cytokines have been shown to stimulate bone repair through osteoclastogenesis and recruitment of osteoblastic cells, multiple studies have demonstrated that these cytokines play a role in cartilage degradation (4-9). Increased IL-1 and TNF-a expression has been found in the cartilage of patients with osteoarthritis, and these cytokines are transiently increased after traumatic injury (10,11). Other matrix molecules including matrix metalloproteinase (MMP)-3 and cartilage oligomeric matrix protein (COMP) can be persistently elevated in synovial fluid after ACL injury (12,13)

The effect of the initial inflammatory response after intraarticular fracture on the development of PTOA remains unknown. Several authors have found elevated levels of cytokines in joints affected by trauma (14-16). However, these studies evaluated patients following an anterior cruciate ligament (ACL) injury. An intraarticular fracture likely subjects the joint to more of an inflammatory response and may place the joint at greater risk for developing osteoarthritis. There are currently no studies that link elevated levels of the inflammatory cytokines and chemokines in the setting of intraarticular trauma with PTOA. Investigating the cytokine profile in a joint immediately following intraarticular injury could lead to early targeted drug therapy with cytokine inhibitors to modify the progression of PTOA.