Initiating factors for the onset of OA: A systematic review of animal bone and cartilage pathology in OA

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.