Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention

Abstract

Even with current treatments of acute joint injuries, more than 40% of people who suffer significant ligament or meniscus tears, or articular surface injuries, will develop osteoarthritis (OA). Correspondingly, 12% or more of all patients with lower extremity OA have a history of joint injury. Recent research suggests that acute joint damage that occurs at the time of an injury initiates a sequence of events that can lead to progressive articular surface damage. New molecular interventions, combined with evolving surgical methods, aim to minimize or prevent progressive tissue damage triggered by joint injury. Seizing the potential for progress in the treatment of joint injuries to forestall OA will depend on advances in (1) quantitative methods of assessing the injury severity, including both structural damage and biologic responses, (2) understanding of the pathogenesis of post-traumatic OA, taking into account potential interactions among the different tissues and the role of post-traumatic incongruity and instability, and (3) application of engineering and molecular research to develop new methods of treating injured joints. This paper highlights recent advances in understanding of the structural damage and the acute biological response following joint injury, and it identifies important directions for future research.

Figure 1

CT-based fracture severity metric values are shown for 20 tibial plafond fracture patients. This metric combines normalized values of overall fracture energy and the energy released at the articular surface into a single measure of fracture severity. The bars are colored according to minimum 2-year follow-up Kellgren-Lawrence OA scores. Mild to severe OA developed in all patients with a combined severity metric > 40, but in none with severity less than this apparent threshold.

Figure 2

Chondrocyte viabilities are shown for explants exposed to rotenone for varying periods of time from before until after impact (the hours before and after are labeled on the horizontal axis). Black columns are for impact sites; white columns for nonimpact sites. The untreated controls (0/0) are included for reference. Asterisks indicate significant differences between impact sites that were rotenone-treated and those that were not (p < 0.001).

Figure 3

Factors involved in the development of PTOA after injury. The clinical manifestation of PTOA depends upon a number of factors at the cellular and molecular, joint, and systemic levels. Currently, surgical intervention primarily occurs at the joint or systemic level, although a more thorough understanding of the pathologic events at the cell and tissue level may provide insight into new therapeutic approaches to prevent joint degeneration.

Figure 4

Histologic sections of control (left) and experimentally fractured (right) mouse knee joints at 8 (A,B) and 50 (C,D) wks following fracture. By 8 wks, severe loss of safranin O staining for proteoglycan was evident in (B) the experimental tibial (T) and femoral (F) articular cartilage. At 50 wks, severe loss of cartilage to the subchondral bone was observed (D) in the experimental tibia (T) and femur (F). [Reprinted with permission from Furman BD et al. Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis. J Orthop Res. 25(5):578–92, 2007.]

Figure 5

This conceptual framework depicts the immediate cellular responses to acute joint trauma and facilitates the identification of targets for early interventions. Catabolic and anabolic processes are involved in the response to the injury and overlap with one another.

Figure 6

Quantitative assessment of cell survival between impacted samples of human ankle cartilage treated with a single (▲) dose or multiple (▼) doses of P-188 (8μg/ml) and non-treated controls (■). The single dose was administered once at Day 0 and was present in culture media for 48 hrs. For the multiple dose, P-188 was added to culture media every 48 hrs. (*) represents significant difference between treated and non-treated groups (p<0.05).