Abstract
Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments. This study introduces a three-dimensional method for bone surface roughness measurement from micro-computed tomographic data obtained from rats subjected to collagen-induced arthritis (CIA), in which the degree of bone erosion is related to the severity and the duration of the disease. In two studies of rat CIA, the surface roughness of the talus bone following 21 days of disease increased 559% and 486% from the control group. At 41 days following disease induction, the roughness of the bone surface increased 857% above baseline. The roughness of the control samples was similar from each study (less than 4% different), demonstrating the robustness of the algorithm. Treatment with methotrexate at 0.1 mg/kg daily demonstrated significant protection from bone erosion, whereas the 0.05 mg/kg daily dose was not efficacious (98% versus 22% inhibition of roughness-measured bone erosion). The main advantage of such an algorithm is demonstrated in the preclinical drug study of rat CIA with methotrexate treatment, indicating the immediate utility of this approach in drug development studies.
Highlights
Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments
This figure contains three-dimensionally rendered views of the normal eraser, the damaged eraser, and the normal eraser with the small hole imposed by voxel deletion
The eroded surface of the bones in arthritic joints is a hallmark of the disease,[1,2] and conventional radiography has limited ability to quantify pathology on the surface of bones.[4,5]
Summary
Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments. The limitations of standard radiography for the characterization of arthritis in humans may pose insurmountable challenges in preclinical rodent studies since the anatomy is so much smaller, disease progression is accelerated, and robust, well-characterized assays are often required for monitoring drug therapy. The latter requires clinically relevant animal models and reliable quantitative analysis, which imparts added demands on the dependability of the imaging techniques. The ability to distinguish between object form versus roughness is innate; training a computer to make the same classifications is more challenging
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