Kwong Yuen Chiu, Y. Eric Yu, Yan Chen, Weiwei Zhao, Kyle K. Nishiyama, Ji Wang, Xingjian Zhang, Frankie K. L. Leung, Bin Zhou, William Macaulay, Ting Wang, Elizabeth Shane, X. Edward Guo, Xu Cao, William W. Lu, Tezita Watts, Yizhong Hu
Developing effective treatment for osteoarthritis (OA), a prevalent and disabling disease, has remained a challenge, primarily due to limited understanding of its pathogenesis and late diagnosis. In the subchondral bone, rapid bone loss following traumatic injuries and bone sclerosis at the advanced stage of OA are well-recognized hallmarks of the disease. Recent studies have further demonstrated the crucial contribution of subchondral bone in the development of OA. However, the microstructural basis of these bone changes has not been examined thoroughly, and the paradox of how abnormal resorption can eventually lead to bone sclerosis remains unanswered. By applying a novel microstructural analysis technique, Individual Trabecula Segmentation (ITS), to micro computed tomography (μCT) images of human OA knees, we have identified a drastic loss of rod-like trabeculae and thickening of plate-like trabeculae that persisted in all regions of the tibial plateau, underneath both severely damaged and still intact cartilage. The simultaneous reduction in trabecular rods and thickening of trabecular plates provide important insights to the dynamic and paradoxical subchondral bone changes observed in OA. Furthermore, using an established guinea pig model of spontaneous OA, we discovered similar trabecular rod loss and plate thickening that preceded cartilage degradation. Thus, our study suggests that rod-and-plate microstructural changes in the subchondral trabecular bone may play an important role in the development of OA, and that advanced microstructural analysis techniques such as ITS are necessary in detecting these early but subtle changes. With emerging high-resolution skeletal imaging modalities such as the high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular rod loss identified by ITS could potentially be used as a marker in assessing the progression of OA in future longitudinal studies or clinical diagnosis. This article is protected by copyright. All rights reserved
