Subchondral Bone Loss And Articular Cartilage Damages In Patients With Knee Osteoarthritis PDF Download

This dissertation, "Subchondral Bone Loss and Articular Cartilage Damages in Patients With Knee Osteoarthritis" by Yan, Chen, 陳炎, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Subchondral bone loss and articular cartilage damages in patients with knee osteoarthritis" Submitted by CHEN Yan for the degree of Doctor of Philosophy at the University of Hong Kong in August 2015. Osteoarthritis (OA) is the most prevalent form of arthritis, and characterized by articular cartilage damage and subchondral bone sclerosis. Subchondral bone sclerosis has been demonstrated to lead to cartilage degradation. However, clinical studies showed that treatment of antiresorptive drugs enhance subchondral bone quality, and thus attenuate OA cartilage degeneration. These results suggest a role of subchondral bone loss in OA pathogenesis. Thus, the changes of subchondral bone in OA are still unclear. We aimed to examine subchondral bone changes and their role in human knee OA. Firstly, we examined the effect of risk factors, i.e., hypertension and type 2 diabetes mellitus (T2DM) which are associated with knee OA, and further, with bone loss, on OA subchondral bone. We found significant lower bone mineral density (BMD) and higher porosity at subchondral plate in OA patients with hypertension and T2DM. Furthermore, hypertensive patients had significantly lower bone volume fraction (BV/TV), trabecular number (Tb.N) and higher structure model index (SMI) than non-hypertensive patients. In addition, hypertensive patients showed higher Osteoarthritis Research Society International + (OARSI) score, higher number of Tartrate-resistant acid phosphatase (TRAP) + osteoclasts and lower Osteocalcin osteoblasts. These findings suggest that subchondral bone loss occurs in knee OA patients with hypertension and T2DM, and is associated with exuberated articular cartilage damage. Secondly, because subchondral bone cyst (SBC), a hallmark of OA, is characterized by focal bone loss and surrounding bone sclerosis, we investigated changes in bone and articular cartilage localized in cyst regions in knee OA. We found that cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. OARSI score, the numbers of TRAP osteoclasts, + + Osterix osteoprogenitors, Osteocalcin osteoblasts and expression of SOX9, were higher in cyst group. These findings further support the association between subchondral bone loss (associated with SBCs) and articular cartilage damage in knee OA. Finally, to differentiate subchondral bone loss from bone sclerosis, we evaluated subchondral trabecular plate and rod microstructural changes in human OA knees, based on the individual trabecula segmentation technique. We found that in Lateral, Anterior and Posterior subvolumes on lateral condyle, OARSI score, BV/TV, trabecular plate number and volume fraction (pBV/TV), and elastic moduli did not differ between OA and normal control groups. However, OA group had significantly lower trabecular rod number and volume, and increased rod thickness, increased trabecular plate thickness and axial volume fraction, lower plate-plate, plate-rod and rod-rod junction density. These changes occurred similarly in all subvolumes on medial condyle and Medial and Central subvolumes on lateral condyle, excepted that OARSI score, BV/TV, pBV/TV and elastic moduli were higher in OA group. These results suggest that subchondral trabecular rod loss and plate stiffening precedes OA changes in cartilage, and that trabecular rod loss probably precedes trabecular plat