Abstract
There is controversy over whether bone or cartilage is primarily involved in osteoarthritis (OA) pathogenesis; this is important for targeting early interventions. We explored evidence from animal models of knee OA by preforming a systematic review of PubMed, Scopus, and Web of Science for original articles reporting subchondral bone and cartilage pathology in animal models with epiphyseal closure. Extracted data included: method of induction; animal model; cartilage and bone assessment and method; meniscal assessment; skeletal maturity; controls; and time points assessed. Quality scoring was performed. The best evidence was synthesized from high‐quality skeletally mature models, without direct trauma to tissues of interest and with multiple time points. Altogether, 2849 abstracts were reviewed. Forty‐seven papers were included reporting eight different methods of inducing OA, six different species, six different methods of assessing cartilage, five different bone structural parameters, and four assessed meniscus as a potential initiator. Overall, the simultaneous onset of OA in cartilage and bone was reported in 82% of datasets, 16% reported bone onset, and 2% reported cartilage onset. No dataset containing meniscal data reported meniscal onset. However, using the best evidence synthesis (n = 8), five reported simultaneous onset when OA was induced, while three reported bone onset when OA occurred spontaneously; none reported cartilage onset. In summary, there is a paucity of well‐designed studies in this area which makes the conclusions drawn conjectures rather than proven certainties. However, within the limitation of data quality, this review suggests that in animal models, the structural onset of knee OA occurs either in bone prior to cartilage pathology or simultaneously.
Highlights
Osteoarthritis (OA) is typically diagnosed and treated when pathology becomes detectable by conventional radiography, but the OA process begins long before this as evidenced by magnetic resonance imaging (MRI)‐detectable structural pathology.[1]
The concept of early OA in humans is imprecisely defined, and limited data exist on the timing and sequence of events that occur at the onset of human knee OA
There were three datasets ranked as high quality that were in skeletally mature animals and used multiple time points; since the criteria were all met in these three datasets, they were included in the best evidence synthesis analysis
Summary
Osteoarthritis (OA) is typically diagnosed and treated when pathology becomes detectable by conventional radiography, but the OA process begins long before this as evidenced by magnetic resonance imaging (MRI)‐detectable structural pathology.[1]. Mice and rats are commonly used for biomaterials testing at early stages of OA, their thin cartilage layer (3‐ 5 cells thick) and the small nature of their joints[10,11,12,13,14] make it difficult to discern changes in bone structural parameters that are comparable to the human OA disease Their lack of growth plate fusion makes it difficult to distinguish whether changes in bone structural parameters result solely from OA or from the influence of persistent growth plate patency.[15,16,17] while these rodent models are useful for basic research because they are small, inexpensive, easy to manipulate on a genetic level, feature short reproduction cycles and lifespans, and produce meaningful and relevant data,[18] several articles and reviews highlight the poor correlation of rodent models with a variety of different human conditions by demonstrating failure to successfully translate rodent‐based findings into successful clinical practice.[15,16,17] To remain focused and avoid ambiguity, we have decided to exclude these animal models. In contrast, were included in this review because OA in guinea pigs more closely resembles human knee OA pathogenesis 19 and because guinea pig growth plates fully fuse
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