Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

Abstract

In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C-telopeptide of type II collagen (CTX-II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro-computed tomography (mCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTX-II levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint. ß

Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study

“…CTX-II is seen as a marker of articular cartilage degradation 26 , but is also suggested to be involved in calcified cartilage layer changes or even bone metabolism 27,28 . The rapid elevation seen after a joint bleed is in accordance with studies demonstrating release of CTX-II into synovial fluid within 1 week after joint injury in humans 29 and a rise in uCTX-II levels in two different canine OA models 30 .…”

Strontium ranelate: ready for clinical use as disease-modifying osteoarthritis drug?

“…Importantly, owing to unloading of the affected unstable joint in this model, the osteopenic trabecular bone changes are extended to the metaphyseal area 31. This makes it not likely that the observed histological and biochemical changes in cartilage are secondary to the bone changes in this prevention protocol.…”

“…Of interest in this respect is the recent observation that strontium ranelate stimulates differentiation of bone marrow mesenchymal stem cells into osteoblasts 33. Unfortunately, not all data on bone changes were provided in detail in this in vivo animal study, and more sophisticated analyses of bone by microCT31 32 or MRI—with which the group has extensive experience34—were lacking. As for the clinical trial, no relations between bone and cartilage changes were provided.…”

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model

“…Volumetric shapes include strips (Batiste et al, 2004), cylinders (Boudenot et al, 2014; Iijima et al, 2015; Intema et al, 2010; McErlain et al, 2008; Sniekers et al, 2008), and cubes (Florea et al, 2015). Sizes vary from small 2 x 2 x 4mm 3 cubes (Florea et al, 2015) to large anatomical contours that include the medial or lateral compartments of the tibia (Hamann et al, 2012; Maerz et al, 2016; Mohan et al, 2016).…”