Inflammatory Response Following Intraarticular Fracture

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. 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.

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. 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. 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.
Other matrix molecules including matrix metalloproteinase (MMP)-3 and cartilage oligomeric
matrix protein (COMP) can be persistently elevated in synovial fluid after ACL injury.

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. 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.

Inclusion Criteria:

- 18 years of age or older

- Radiographic evidence of tibial plateau fracture

Exclusion Criteria:

- Less than 18 years of age

- Greater than 60 years of age

- Any history of pre-existing knee osteoarthritis based on previous diagnosis or
suggestive history

- Any history of autoimmune disease

- Any history of contralateral intra-articular knee injury