Instability dependency of osteoarthritis development in a rabbit model of graded anterior cruciate ligament transection

Abstract

Background: Joint instability has long been empirically recognized as a leading risk factor for osteoarthritis. However, formal mechanistic linkage of instability to osteoarthritis development has not been established. This study aimed to support a clinically accepted, but heretofore scientifically unproven, concept that the severity and rapidity of osteoarthritis development in unstable joints is dependent on the degree of instability. In a survival rabbit knee model of graded joint instability, the relationship between the magnitude of instability and the intensity of cartilage degeneration was studied at the organ level in vivo.

Methods: Sixty New Zealand White rabbits received either complete or partial (medial half) transection of the anterior cruciate ligament or sham surgery (control) on the left knee. At the time that the animals were killed at eight or sixteen weeks postoperatively (ten animals for each treatment and/or test-period combination), the experimental knees were subjected to sagittal plane stability measurement, followed by whole-joint cartilage histological evaluation with use of the Mankin score.

Results: Sagittal plane instability created in the partial transection group was intermediate between those in the complete transection and sham surgery groups. The partial and complete transection groups exhibited cartilage degeneration on the medial femoral and/or medial tibial surfaces. The average histological score (and standard deviation) for the medial compartment in the partial transection group (2.9 ± 0.9) was again intermediate, significantly higher than for the sham surgery group (1.9 ± 0.8) and significantly lower than for the complete transection group (4.5 ± 2.3). The average histological scores for the medial compartment in the partial transection group correlated significantly with the magnitude of instability, with no threshold effect being evident. The significance level of alpha was set at 0.05 for all tests.

Conclusions: The severity of cartilage degeneration increased continuously with the degree of instability in this survival rabbit knee model of graded instability.

Fig. 1

Custom anteroposterior (A-P) loading device for sagittal plane stability measurement, analogous to a clinical so-called drawer test. (Reprinted, with permission, from: Heiner AD, Rudert MJ, McKinley TO, Fredericks DC, Bobst JA, Tochigi Y. In vivo measurement of translational stiffness of rabbit knees. J Biomech. 2007;40:2313-7.)

Fig. 2

Load-displacement relationships in a stable control knee (left) and an unstable knee after partial ACL transection (right). Sagittal plane stability was quantified in terms of anterior drawer stiffness (ADS: regression slope from +7.5 N to the maximum force) and neutral zone length (NZL: displacement length between ±7.5 N data points). Higher instability was characterized by a decrease of anterior drawer stiffness and an increase of neutral zone length.

Fig. 3

Individual animal data plots for sagittal plane stability measures: anterior drawer stiffness (horizontal axis) and neutral zone length (vertical axis). The mean values for each treatment group from both eight-week and sixteen-week animals are indicated by the blank square plots at the right (anterior drawer stiffness) or at the bottom (neutral zone length) of the graph. The dispersion bars indicate standard deviations (SD). ACLT = anterior cruciate ligament transection.

Fig. 4

Results of histological evaluation for each individual articular surface. The scores on the histological histochemical grading scale (HHGS) for each individual animal are plotted, along with the mean values (from both eight-week and sixteen-week animals) and the standard deviation (SD) for each treatment group. ACLT = anterior cruciate ligament transection.

Fig. 5

Comparisons of global histological findings for individual compartments across treatment groups. Average scores on the histological histochemical grading scale (HHGS) for the compartments for each individual animal are plotted, along with the mean values (from both eight-week and sixteen-week animals) and the standard deviation for each treatment group. ACLT = anterior cruciate ligament transection.

Fig. 6

Correlations of global cartilage degeneration in the medial compartment with instability in the twenty knees that had partial transection of the ACL (including both eight-week and sixteen-week animals), as assessed by means of anterior drawer test stiffness (left) and of neutral zone length (right). Note that both the negative slope in the left graph and the positive slope in the right graph indicate positive correlation of cartilage degeneration with instability. No threshold effect is evident. HHGS = histological histochemical grading scale, and ACLT = anterior cruciate ligament transection.