Pilon Fracture With Intra-articular Injection of N-Acetylcysteine (Pilon NAC)

High energy intra-articular fractures of the distal tibia, or Pilon fracture, is a
devastating injury with multiple short and long term complications. The incidence of these
injuries is increasing as survival rates after motor vehicle collisions increase. The current
standard of care for high energy pilon fractures is to place an external fixator at the time
of injury and then provide definitive internal fixation when the soft tissue envelope allows,
which is usually around 10-14 days. Arguably, the most debilitating long term complication
after a high energy pilon fracture is the development of post-traumatic osteoarthritis
(PTOA), which occurs in 50% or more of pilon fractures within the first 2 years of surgery.
The development of osteoarthritis occurs even in the presence of adequate restoration of the
tibial plafond. Part of this issue lies in the fact that ankle joint cartilage is the
thinnest of any major articular joint and sustains a great deal of damage at the time of
injury. This impaction and injury initiates a cascade of events that ultimately result in
cartilage cell death, or chondrolysis. Chondrolysis occurs via necrosis or apoptosis.
Apoptosis occurs via a caspase pathway, while necrosis of chondrocytes likely occurs
secondary to overproduction of reactive oxidant species (ROS). Recent animal models have
demonstrated several things: chondrocyte death is highest along fracture lines, and likely
undergo necrosis as opposed to apoptosis. The reason that PTOA likely occurs in such a high
percentage of pilon fractures is because of this chondrolysis, and if a method can be
developed to decrease the rate of chrondrocyte necrosis, then the rate of PTOA could
potentially improve and improve patient outcomes overall. A recent bovine model examined the
injection of N-acetylcysteine (NAC) after an intra-articular knee fracture and its effect on
the cartilage cell viability. Their study demonstrated that chondrocyte cell viability after
an injection of NAC within four hours of injury decreased chondrolysis from roughly 60% to
about 30% at 48hrs. The effect was greater the closer to injury the injection occurred, and
was statistically significant for 2 weeks. This indicates that free radical scavengers can
potentially improve cartilage cell viability and help prevent the development of PTOA. No
studies have been published on humans regarding injection of NAC after a fracture. However, a
recent article examined the injection of NAC into osteoarthritic knees and found that it was
effective in lowering certain cartilage degradation markers and was comparable to hyaluronic
acid for both pain and function. NAC has been proven safe for both intra-articular injections
and systemic injections in humans. Our study will focus on the improvement of cartilage cell
viability with an injection of NAC. Our hypothesis is that the NAC intra-articular injection
will increase the percentage of viable cartilage cell after sustaining a pilon fracture, when
compared to a placebo injection of saline.

The goal of this study is to examine the effects of an intra-articular injection of the amino
acid NAC on cartilage cells after an intra-articular fracture of the ankle joint. The
long-term clinical goal of this research is to reduce the incidence of post-traumatic
osteoarthritis in the ankle joint after fracture.