Gait Analysis Methods for Rodent Models of Osteoarthritis

Abstract

Patients with osteoarthritis (OA) primarily seek treatment due to pain and disability, yet the primary endpoints for rodent OA models tend to be histological measures of joint destruction. The discrepancy between clinical and preclinical evaluations is problematic, given that radiographic evidence of OA in humans does not always correlate to the severity of patient-reported symptoms. Recent advances in behavioral analyses have provided new methods to evaluate disease sequelae in rodents. Of particular relevance to rodent OA models are methods to assess rodent gait. While obvious differences exist between quadrupedal and bipedal gait sequences, the gait abnormalities seen in humans and in rodent OA models reflect similar compensatory behaviors that protect an injured limb from loading. The purpose of this review is to describe these compensations and current methods used to assess rodent gait characteristics, while detailing important considerations for the selection of gait analysis methods in rodent OA models.

Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations

“…Due to the rapidity of rodent gait, the human eye is often unable to detect subtle changes without assistance from videography, and these subtle gait compensations may be more likely to associate with diseases like osteoarthritis 3, 5, 9, 21 . Hence, we recommend video be used for observational scoring whenever possible.…”

“…In addition, since scoring is largely an assessment of self-selected behaviors, open arena testing is ideal to capture the animal’s natural gait. Some laboratories have used treadmills and food incentive for these tests, but these factors could mask some gait characteristics 3 . Finally, as with any behavioral analysis, investigators should learn proper techniques to handle and acclimate their animals to the experiment.…”

“…Spatial parameters are generally familiar variables (Figure 1A). Some gait systems also report variables such as the distance and angle between paws, but scientists should recognize these are not independent measures and can be geometrically derived from stride length, step length, stride length asymmetry, and step width 3 . In addition, novice users should remember the difference between step length and stride length; while the left and right step length can differ (spatially asymmetric), the stride length must be the same for all limbs if the animal is using a consistent gait pattern.…”

“…As such, several compensatory patterns are shared between quadrupeds and bipeds, including shuffle-stepping and limping 3 . The frequent challenge in rodent gait analysis is that these compensatory patterns can be difficult to detect due to the ability to re-distribute load to three limbs rather than one and the rapidity of the gait sequence.…”

“…Unfortunately, most commercial rodent gait analysis systems inundate users with large datasets – sometimes 50+ variables – to describe the rodent spatiotemporal gait pattern. Moreover, most of these variables are not independent and can be difficult to interpret without an understanding of quadrupedal gait 3 . The goal of this review is to describe the state of rodent gait analysis and highlight fundamental gait parameters needed to accurately evaluate preclinical arthritis models.…”