MRI-Detected Damage Shows Up 2 years Before Knee OA Dx by Pam Harrison Knees that exhibit certain MRI features of structural damage, especially within 2 years prior to the actual onset of osteoarthritis (OA), are at increased risk of developing radiographic OA compared with matched knees that do not exhibit the same features, results from the Osteoarthritis Initiative indicate. In a large, ongoing observational study of knee OA, the trajectory of the presence of structural damage at specific time points from 1 to 4 years prior to incident radiographic OA showed that at 2 years prior to the case-finding or diagnostic visit, the presence of Hoffa-synovitis increased the risk of incident radiographic OA by 76% (HR 1.76 (95% CI 1.18-2.64).Incident radiograph OA was defined as the first occurrence of radiographic findings compatible with OA. The presence of effusion synovitis on MRI 2 years prior to the actual diagnosis increased the risk of incident radiographic OA by 81% (HR 1.81, 95% CI 1.18-2.78) while the presence of medial meniscal damage increased the risk of incident radiographic OA by 83% (HR 1.83, 95% CI 1.170-2.89). One year prior to the case-finding visit, multiple structural features predicted radiographic OA, the strongest risk factors at this time point being medial bone marrow lesions (BMLs), tibio-femoral BMLs, and effusion synovitis. The presence of a medial BML 1 year prior to the diagnostic visit increased the risk of incident radiographic OA more than six-fold (HR 6.50, 95% CI 2.27-18.62), the presence of tibio-femoral BMLs by close to fourfold (HR 3.70, 95% CI 1.84-7.44), and effusion synovitis by 2.5-fold (HR 2.50; 95% CI 1.76-3.54). At the time of incident radiographic OA when knee OA was diagnosed, all structural features were significant except for patella-femoral BMLs (HR 1.41, 95% CI 0.98-2.03) and lateral meniscal extrusion (HR 5.50, 95% CI 1.22-24.81). "Knowledge about the early stages of knee OA is sparse," Frank Roemer, MD, Boston University School of Medicine, and colleagues write in Arthritis and Rheumatology. "We found that knees exhibiting structural features in the 2 years prior to developing disease had an increased risk [of OA] and that the number of features present increased the risk further -- i.e., lesion load -- seems potentially more relevant than the presence of any specific feature alone." The Osteoarthritis Initiative (OAI) is an ongoing longitudinal cohort study designed to identify biomarkers for the onset or progression of knee OA. Both knees of 4,796 participants were studied using 3 Tesla (MRI) and fixed-flexion radiography at baseline, 12, 24, 36, and 48 months of follow-up. OAI participants were between 45 and 79 years of age at baseline with symptomatic knee OA in at least one knee or who were at increased risk of developing symptomatic knee OA. They also had to have two of the following risk factors for OA, namely being overweight, a history of knee injury or surgery, a family history of knee replacement, or Heberden's nodes. Cases were defined as study participants who had at least one knee that developed incident radiographic OA during the 4 years of follow-up. Altogether 355 case knees and 355 matched control knees were included in the analysis. "An increasing number of positive features markedly increased risk for radiographic OA particularly for the baseline visits, the visits 2 years and 1 year prior to the case-defining visit as well as the case defining visit itself," investigators observed. Thus, the presence of five or six concomitant features 2 years prior to the diagnosis of knee OA increased the risk of having knee OA by almost six-fold and by almost 12-fold 1 year prior to the diagnosis compared with knees with only one feature or without any features present at the same time points, they add. An increase in the number of concomitant features was also highly associated with an increased risk of incident OA for the baseline, years two, years one, and the diagnostic visit (P<0.0001). "We showed that new presence and persistence of a feature prior to the case-defining visit but not at baseline bears a higher risk than knees exhibiting that feature at every time point," the authors note. "And we demonstrated that knees exhibiting MRI features, especially within the 2 years prior to disease onset, exhibiting several features concomitantly and experiencing new occurrences of these features at one or more time points are associated with increased risk for developing incident radiographic OA." In an accompanying editorial Timothy McAlindon, MD, MPH, Tufts Medical Center, Boston, laments that despite recent evidence to the contrary, the paradigm of OA as primarily a degenerative disorder of hyaline auricular cartilage remains dominant. "Hyaline cartilage is a largely aneural structure and an unlikely source of pain," McAlindon writes. "And cumulative research has demonstrated that knee OA (and perhaps all OA) is fundamentally a disorder of deranged biomechanics manifesting with damage throughout articular structures." The advent of MRI in the study of OA has been a "disruptive innovation" he adds, "revealing aspects to which we had been agnostic and are difficult to fit into the prevailing paradigm." These included pathologies in the subchondral bone, and effusion synovitis. In addition, observation studies using MRI have shown that several of these features relate to pain in knee OA. The fact that other features are often evident in early disease raises questions about the centrality of hyaline cartilage involvement and, more broadly, about the pathological steps in the development of knee OA. "Knee OA can no longer be viewed as a monotonic disorder of hyaline cartilage [when], in fact, other processes appear to be more influential including the presence of inflammation and structural damage to the meniscus and subchondral bone," McAlindon concludes. "It is clear that we need to change the construct of OA ... as that old paradigm has arguably stifled research and progress in this field for decades." The study was funded by the OAI, a public-private partnership involving the National Institutes of Health, a branch of the Department of Health and Human Services. Private funding partners of the OAI include Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. None of the authors declared any potential conflicts of interest although Roemer is chief medical officer and shareholder of the Boston Imaging Core Lab.Dr. McAlindon declared no conflicts of interest.
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