GAIT-2-OA · Can biomechanical measurements of joints predict severity of osteoarthritis?
FP7 — People (Marie Curie Actions)
- Duration
- 2013-09-01 → 2014-08-31
- EU contribution
- €154,618
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Can biomechanical measurements of joints predict severity of osteoarthritis?
Gait changes may non-invasively monitor osteoarthritis (OA) progression. We have recently found that OA-prone Str/ort mice show increasing non-compliance in a treadmill task with age and OA development. The aim herein was to evaluate use of asymmetry and imbalance indices, as predictors of treadmill task non-compliance in Str/ort mouse OA development. Twenty-two male Str/ort and 20 CBA mice (non-OA prone) were monitored longitudinally and gait measurements (DigigaitTM system) taken at 4wk intervals from age 8-36wks or until treadmill task non-compliance; a period encompassing pre-OA and overt, active OA phases in Str/ort mice. Spatiotemporal gait measurements including swing, brake, propel and stance times, stride length and frequency, and paw area were each used to calculate: symmetry index (SI), and symmetry ratio (SR) bewteen right and left contralateral hind- or fore-limbs. We also defined gait moderation index (GMI) as an imbalanced measures between contralateral hind-fore limbs (diagonal limbs). Linear mixed effects models were employed to assess difference in gait symmetry between CBA and Str/ort mice. Models included the effects of strain, age and strain/age interaction, as well as random mouse effect. Time-dependent Cox regression models were used to assess effects of SI, SR and GMI on early treadmill task non-compliance in Str/ort aged 16-28wks. All 20 CBA, but only 3/22 Str/ort mice completed treadmill tasks until 36wks of age; 9 Str/ort mice dropped-out between 16-28wks and a further 10 at 32 wks. Results were consistent for both SI and SR for all gait characteristics. Longitudinal pattern of SI differed in hind- and fore-limbs for swing:stance ratio, in hind-limb paw area and stance time in CBA and Str/ort mice. Str/ort had lower fore-paw area SI than CBA mice. SI did not differ in CBA and Str/ort for stride length, frequency, swing, propel or brake time; the majority remained stable in hind- but not in fore-limbs. Longitudinal GMI patterns differed between strains (swing:stance, paw area and propel time) except stride length and frequency. SI for hind-limb swing:stance and GMI for paw area were predictors of treadmill non-compliance in Str/ort mice. Longitudinal differences in symmetry and imbalance patterns between CBA and Str/ort mice indicate different gait modification during normal growth periods and OA development. Assuming treadmill task non-compliance is linked with OA, our data suggest that hind-limb asymmetry is more closely related to OA development, but that fore-limb asymmetry tempers these hind-limb OA effects. Vitally, capacity for swing:stance asymmetry and paw area gait moderation index to predict Str/ort mouse non-compliance in the treadmill task supports their use as early OA markers.
Data: CORDIS, © European Union
Project objective
Osteoarthritis (OA) is a painful and disabling, multi-factorial disease with strong genetic and environmental determinants. The natural form of OA that arises spontaneously in Str/ort mice has been used as a model for human OA joint degeneration. This model is limited, however, because it is impossible to grade OA incidence and severity non-invasively in mice. Locomotor biomechanics provides a unique tool for non-invasively assessing knee dynamics, and has already been used to detect gait modifications in humans. Such gait analyses are directly transferable to mice. Our pilot data suggest that OA-prone Str/ort mice, in which the joints deteriorate rapidly with ageing, can readily be categorised by temporal changes in gait. Our hypothesis is that deterioration or deviation in individual mouse gait from normal will provide a non-invasive measure of joint degeneration.Our first aim is to examine the heritability of histological osteoarthritis (OA) severity and drop-out age, and their genetic and phenotypic correlations. Our second aim is to assess the relationship between different aspects of gait measurements and OA severity in Str/ort mice, and to assess the predictability of gait measurements on drop-out age. The third aim is to assess the degrees of asymmetry of individuals’ gait measurements (left versus right and front versus rear limbs) during the development of OA in Str/ort mice and compare these to changes in gait during normal healthy ageing in non OA-prone, mice.Identifying new statistically-defined and robust methods of OA detection in the mouse that do not require sacrifice would radically change how OA research might be conducted using this species and accelerate translation of new therapies.""
Original text from CORDIS.
Participants
- THE ROYAL VETERINARY COLLEGE · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union