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.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of the adult population leading to pain, disability and, if not treated, significantly decreased life span[1,2]
Bone degradation caused by different types of arthritis is well documented[4,5] but the severity is normally longitudinally judged by manual scoring, which is a semi-quantitative method
The thickness higher up on the bone, towards the tarsals, seems to be largely unchanged. This led to the idea that the gradient of the linear function Ψ (ξ), cortical thickness gradient (CTG), should be larger for arthritic bones than for non-arthritic ones
Summary
Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of the adult population leading to pain, disability and, if not treated, significantly decreased life span[1,2]. Bone degradation caused by different types of arthritis is well documented[4,5] but the severity is normally longitudinally judged by manual scoring, which is a semi-quantitative method. A standard approach to evaluate the effects of experimental arthritis on bones is to measure the bone mineral density (BMD) using μCT7,8. Allows for longitudinal studies of the disease in single animals or in patients[10,11], without the use of histological approaches applied to characterize BMD and malformations[5,12]. We examined the thickness and the gradient of the cortical bone in the metatarsals of mice, which is among the earliest-affected regions in animals immunised with glucose-6-phosphate isomerase (G6PI), inducing poly-arthritic disease[23]
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