Examination of osteoarthritis and subchondral bone alterations within the stifle joint of an ovariectomised ovine model

Abstract

The exact relationship between osteoporosis and osteoarthritis is still a matter for debate for many. The ovariectomised ewe is frequently used as a model for osteoporosis, resulting in significant alterations in bone morphometry and turnover in both trabecular and subchondral bone after 1 year. This study examines whether ovariectomy has any impact on development of osteoarthritis within the ovine stifle joint at the same time point. In addition, we investigate whether there are any significant correlations present between articular cartilage degeneration and alterations in microstructural parameters or turnover rates in the underlying bone. Twenty-two sheep were examined in this study; 10 of the sheep underwent ovariectomy and 12 were kept as controls. Five distinctive fluorochrome dyes were administered intravenously at 12-week intervals to both groups, to label sites of bone turnover. All animals were then sacrificed 12 months postoperatively. Although most specimens showed some evidence of osteoarthritis, no measurable difference between the two study groups was detected. Osteoarthritis was associated with a thinning of the subchondral plate, specifically the subchondral cortical bone; however, whereas previous studies have suggested a link between trabecular thinning and osteoarthritis, this was not confirmed. No correlation was found between osteoarthritis and bone turnover rates of either the subchondral trabecular bone or bone plate. In conclusion, despite the fact that ovariectomy results in marked morphological and structural changes in the ovine stifle joint at 1-year postoperatively, no evidence was found to suggest that it plays a direct role in the aetiology of osteoarthritis.

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

“…However, it needs to be pointed out that although the OP‐related changes in subchondral bone may accelerate cartilage damage in patients with OP‐OA, there is no evidence showing that OP is an initiating factor for the occurrence of OA . The pathogenic factors of OA are complicated and numerous, but OP was not confirmed as a causative factor in animal models . Our study indicates that a synergism between OA and OP could promote the progression of OA when OA has already occurred.…”

“…(47) The pathogenic factors of OA are complicated and numerous, but OP was not confirmed as a causative factor in animal models. (48,49) Our study indicates that a synergism between OA and OP could promote the progression of OA when OA has already occurred. Moreover, the current study supported some studies on the treatment of OP and OA focusing on biomechanics, (50,51) and reasonably suggests that treatment with bone metabolism agents (ie, bisphosphonates or estrogen) could reverse the dominance of resorption over formation in subchondral bone remodeling, thus exerting a beneficial effect on microstructure and biomechanical properties, which may mitigate the OA development in patients with OP-OA.…”

Advances and challenges in gene‐based approaches for osteoarthritis

“…Although the fatal infection was not related to rAAV exposure, this case highlights the need for the utmost care in patient monitoring during such trials . Other critical issues, such as duration of transgene expression, the need for long‐term analyses in clinically relevant animal models , the benefits of indirect versus direct approaches, and the identification of optimal therapeutic factors, need to be addressed. Clear answers to many of these questions are still lacking and will likely have significant impact on the field.…”

Evaluating pharmacological models of high and low anxiety in sheep

“…Sheep are used broadly in medical research, including highly invasive procedures and pharmacological trials ( Holland et al, 2013 ; Yates et al, 2010 ), are farmed in extensive conditions and in large numbers globally ( Dwyer, 2009 ), and are a useful model species for other production animals as they are easy to maintain and have well-developed cognitive abilities ( Greiveldinger, Veissier & Boissy, 2011 ). Pharmacological models of high and low anxiety states in this species would thus be of use in a range of research areas.…”