Quantification of arthritic bone degradation by analysis of 3D micro-computed tomography data

Abstract

The use of animal models of arthritis is a key component in the evaluation of therapeutic strategies against the human disease rheumatoid arthritis (RA). Here we present quantitative measurements of bone degradation characterised by the cortical bone profile using glucose-6-phosphate isomerase (G6PI) induced arthritis. We applied micro-computed tomography (μCT) during three arthritis experiments and one control experiment to image the metatarsals of the hind paws and to investigate the effect of experimental arthritis on their cortical bone profile. For measurements of the cortical profile we automatically identified slices that are orthogonal to individual metatarsals, thereby making the measurements independent of animal placement in the scanner. We measured the average cortical thickness index (CTI) of the metatarsals, as well as the thickness changes along the metatarsal. In this study we introduced the cortical thickness gradient (CTG) as a new measure and we investigated how arthritis affects this measure. We found that in general both CTI and CTG are able to quantify arthritic progression, whilst CTG was found to be the more sensitive measure.

Arthritis sensory and motor scale: predicting functional deficits from the clinical score in collagen-induced arthritis

“…We took advantage of the variable response to MTX to grade the prevention of functional deficits according to the clinical score. Like in previous imaging studies [12, 13], we showed that ankle bone degradation was increased in arthritic mice. Moreover, MTX poor responders exhibited the same bone degradation as untreated CIA mice, and significantly higher erosion compared with controls and also mild and MTX high responders.…”

“…Surprisingly, the relationship between clinical score and functional deficits has been scarcely studied. Although recent advances in image acquisition and analysis offer a large panel of non-invasive and automated techniques to characterize functional capacities in animals, these approaches have been rarely used to detect pain [5, 6], locomotion deficits [7–12], and bone erosion [12, 13] in different rodent models of arthritis. Moreover, no systematic and longitudinal study has been performed so far to precisely quantify sensory and motor deficits in mouse models of arthritis (under treatment or not) and to correlate them with the clinical score (i.e., the gold standard evaluation of arthritis severity).…”