OTA 2006 Posters

Scientific Poster #88 Basic Science

· · Can a Single High-Energy Impact Load Cause Development of Posttraumatic Osteoarthrosis?
Joseph Borrelli, Jr, MD (*); Melissa Zaegel (*); Matthew Silva, PhD (*); Linda Sandell, PhD (*); Washington University School of Medicine, St. Louis, Missouri, USA

Purpose: The development of posttraumatic osteoarthrosis (PTA) following injury causes pain, stiffness, and considerable morbidity. Mechanisms by which this occurs are actively being investigated in an effort to better understand the process and seek interventions for its prevention. This investigation was designed to assess the development of PTA in a validated in vivo rabbit model.

Methods: NZW rabbits (n = 36) underwent impaction of the right medial femoral condyle using a previously reported in vivo joint injury model. An impact load of either 70% (85 MPa) or 90% (105 MPa) of the fracture threshold was administered (time to peak load: 0.21 sec). The animals were allowed free cage activities and were euthanized at 0, 1, and 6 months. The left medial femoral condyle served as internal control. The cartilage was assessed histologically (hematoxylin & eosin, Safranin O), immunohistochemically (Col 2-3/4, AF-28, BMP-2, Type II collagen), and for changes in the mechanical properties (creep, thickness) of injured cartilage.

Results: Dose response and temporal changes were identified within the injured cartilage when compared to uninjured control cartilage. Histologically, advanced matrix deterioration was realized with near complete proteoglycan staining loss, in the 70% as well as the 90% specimens. In each of the 6-month specimens, chondrocyte cloning and drop-out (empty lacunae) were evident in the injured areas as well. Immunohistochemical assessment revealed significant decrease in BMP-2 production and in Type II collagen production, as well as increased collagen (COL 2-3/4) and proteoglycan (AF-28) degradation. Changes in the mechanical properties included increased creep deformation, decreased recovery, and significant thinning; each parameter worsened with increasing impact load and time from injury.

Conclusion/Significance: Based on these data, it is clear that PTA can be stimulated by application of a single, subfracture threshold, impact load. This deterioration was associated with obvious morphologic changes as well as a decrease in anabolic and an increase in catabolic activities of the chondrocytes. Changes in the cartilage extracellular matrix homeostasis correlated with the changes in its mechanical properties. Means to mitigate these changes should be sought in an effort to prevent the development of PTA following injury.

If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
· The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an "off label" use). · · FDA information not available at time of printing.