Background: Osteoarthritis is generally a slowly progressive disorder. However, at least 1 in 7 people with incident knee osteoarthritis develop an abrupt progression to advanced-stage radiographic disease, many within 12 months. We summarize what is knownprimarily based on findings from the Osteoarthritis Initiativeabout the risk factors and natural history of accelerated knee osteoarthritis (AKOA)defined as a transition from no radiographic knee osteoarthritis to advanced-stage disease < 4 yearsand put these findings in context with typical osteoarthritis (slowly progressing disease), aging, prior case reports/series, and relevant animal models. Summary: Risk factors in the 2 to 4 years before radiographic manifestation of AKOA (onset) include older age, higher body mass index, altered joint alignment, contralateral osteoarthritis, greater pre-radiographic disease burden (structural, symptoms, and function), or low fasting glucose. One to 2 years before AKOA onset people often exhibit rapid articular cartilage loss, larger bone marrow lesions and effusion-synovitis, more meniscal pathology, slower chair-stand or walking pace, and increased global impact of arthritis than adults with typical knee osteoarthritis. Increased joint symptoms predispose a person to new joint trauma, which for someone who develops AKOA is often characterized by a destabilizing meniscal tear (e.g., radial or root tear). One in 7 people with AKOA onset subsequently receive a knee replacement during a 9-year period. The median time from any increase in radiographic severity to knee replacement is only 2.3 years. Despite some similarities, AKOA is different than other rapidly progressive arthropathies and collapsing these phenomena together or extracting results from one type of osteoarthritis to another should be avoided until further research comparing these types of osteoarthritis is conducted. Animal models that induce meniscal damage in the presence of other risk factors or create an incongruent distribution of loading on joints create an accelerated form of osteoarthritis compared to other models and may offer insights into AKOA. Conclusion: Accelerated knee osteoarthritis is unique from typical knee osteoarthritis. The incidence of AKOA in the Osteoarthritis Initiative and Chingford Study is substantial. AKOA needs to be taken into account and studied in epidemiologic studies and clinical trials.

Objectives. To determine whether greater effusion-synovitis volume and infrapatellar fat pad (IFP) signal intensity alteration differentiate incident accelerated knee OA (KOA) from a gradual onset of KOA or no KOA. Methods. We classified three sex-matched groups of participants in the Osteoarthritis Initiative who had a knee with no radiographic KOA at baseline (recruited 200406; KellgrenLawrence <2; n = 125/group): accelerated KOA: 51 knee progressed to KellgrenLawrence grade 53 within 48 months; common KOA: 51 knee increased in radiographic scoring within 48 months; and no KOA: both knees had the same KellgrenLawrence grade at baseline and 48 months. The observation period included up to 2 years before and after when the group criteria were met. Two musculoskeletal radiologists reported presence of IFP signal intensity alteration and independent readers used a semi-automated method to segment effusion-synovitis volume. We used generalized linear mixed models with group and time as independent variables, as well as testing a group-by-time interaction. Results. Starting at 2 years before disease onset, adults who developed accelerated KOA had greater effusion-synovitis volume than their peers (accelerated KOA: 11.94 ± 0.90 cm 3 , KOA: 8.29 ± 1.19 cm 3 , no KOA: 8.14 ± 0.90 cm 3) and have greater odds of having IFP signal intensity alteration than those with no KOA (odds ratio = 2.07, 95% CI = 1.143.78). Starting at 1 year prior to disease onset, those with accelerated KOA have greater than twice the odds of having IFP signal intensity alteration than those with common KOA. Conclusion. People with IFP signal intensity alteration and/or greater effusion-synovitis volume in the absence of radiographic KOA may be at high risk for accelerated KOA, which may be characterized by local inflammation.

Objective. To determine whether accelerated knee osteoarthritis (KOA) is preceded by, and characterized over time by, destabilizing meniscal tears or other pathologic changes.Methods. We selected 3 sex-matched groups of subjects from the first 48 months of the Osteoarthritis Initiative, comprising adults who had a knee without KOA (Kellgren/Lawrence [K/L] radiographic grade <2) at baseline. Subjects in the accelerated KOA group developed KOA of K/L grade ≥3, those with typical KOA showed increased K/L radiographic scores, and those with no KOA had the same K/L grade over time. An index visit was the visit when the radiographic criteria for accelerated KOA and typical KOA were met (the no KOA group was matched to the accelerated KOA group). The observation period was up to 2 years before and after an index visit. Radiologists reviewed magnetic resonance (MR) images of the index knee and identified destabilizing meniscal tears (root tears, radial tears, complex tears), miscellaneous pathologic features (acute ligamentous or tendinous injuries, attrition, subchondral insufficiency fractures, other incidental findings), and meniscal damage in >2 of 6 regions (3 regions per meniscus: anterior horn, body, posterior horn). In addition, bone marrow lesions (BMLs) and cartilage damage on MR images were quantified. Linear mixed regression models were performed to analyze the results.Results. At 1 year before the index visit, >75% of adults with accelerated KOA had meniscal damage in ≥2 regions (odds ratio 3.19 [95% confidence interval 1.70-5.97] versus adults with typical KOA). By the index visit, meniscal damage in ≥2 regions was ubiquitous in adults with accelerated KOA, including 42% of subjects having evidence of a destabilizing meniscal tear (versus 14% of subjects with typical KOA). These changes corresponded to findings of larger BMLs and greater cartilage loss in the accelerated KOA group.Conclusion. Accelerated KOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, and also characterized by the presence of large BMLs and greater cartilage loss.

We assessed which combinations of risk factors can classify adults who develop accelerated knee osteoarthritis (KOA) or not and which factors are most important. We conducted a case-control study using data from baseline and the first four annual visits of the Osteoarthritis Initiative. Participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL]<2). We classified three groups (matched on sex): (i) accelerated KOA: >1 knee developed advance-stage KOA (KL = 3 or 4) within 48 months; (ii) typical KOA: >1 knee increased in radiographic scoring (excluding those with accelerated KOA); and (iii) No KOA: no change in KL grade by 48 months. We selected eight predictors: Serum concentrations for C-reactive protein, glycated serum protein (GSP), and glucose; age; sex; body mass index; coronal tibial slope, and femorotibial alignment. We performed a classification and regression tree (CART) analysis to determine rules for classifying individuals as accelerated KOA or not (no KOA and typical KOA). The most important baseline variables for classifying individuals with incident accelerated KOA (in order of importance) were age, glucose concentrations, BMI, and static alignment. Individuals <63.5 years were likely not to develop accelerated KOA, except when overweight. Individuals >63.5 years were more likely to develop accelerated KOA except when their glucose levels were >81.98 mg/dl and they did not have varus malalignment. The unexplained variance of the CART = 69%. These analyses highlight the complex interactions among four risk factors that may classify individuals who will develop accelerated KOA but more research is needed to uncover novel risk factors. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:876-880, 2018.

Background Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. Methods The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade < 1). Participants were classified into 2 groups based on radiographic progression from baseline to 48 months: AKOA (KL grade change from < 1 to > 3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. Results At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. Conclusions Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers.

Objective To examine if adults who develop accelerated knee osteoarthritis (KOA) have greater knee symptoms with certain activities than those with or without incident common KOA. Methods We conducted a case-control study using data from baseline and the first 4 annual visits of the Osteoarthritis Initiative. Participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL] <2). We classified 3 groups: 1) accelerated KOA: ≥1 knee developed advance-stage KOA (KL=3 or 4) within 48 months, 2) common KOA: ≥1 knee increased in radiographic severity (excluding those with accelerated KOA), and 3) No KOA: no change in radiographic severity by 48-months. We focused on individual items from the WOMAC pain/function subscales and KOOS pain/symptoms subscales. The index visit was a year before a person met the definition for accelerated, common, or no KOA. To examine group difference in knee symptoms we used ordinal logistic regression models for each symptom. Results are reported as odds ratios (OR) and 95% confidence intervals (CI). Results Individuals who developed accelerated KOA were more likely to report greater difficulty with lying down (OR=2.10, 95% CI=1.04 to 4.25), pain with straightening the knee fully (OR=2.04, 95% CI=1.08, 3.85), and pain walking (OR=2.49, 95% CI=1.38, 4.84) than adults who developed common KOA. Conclusion Individuals who develop accelerated KOA report greater symptoms with certain activities than those with common KOA. Our results may help identify individuals at risk for accelerated KOA or with early-stage accelerated KOA.

We aimed to determine if knees with incident accelerated knee osteoarthritis (AKOA) were more likely to receive a knee replacement (KR) than those with common knee osteoarthritis (KOA) or no KOA. We conducted a nested cohort study using data from baseline and the first 9 years of the Osteoarthritis Initiative (OAI). Eligible knees had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2). We classified 3 groups using KL grades from the first 8 years of the OAI: 1) AKOA: knee progressed to advance-stage KOA (KL 3/4) in ≤ 4 years, 2) common KOA: knee increased in KL grade (excluding AKOA), and 3) No KOA: no change in KL grade by 8 years. The outcome was a KR (partial or total) at or before the 9-year OAI visit. We conducted a logistic regression with generalized linear mixed model and adjusted for age, body mass index, and sex. Overall, 14% of knees with AKOA received a KR by the 9th year compared with 1% and < 1% of those with common or no KOA, respectively. Knees that developed AKOA were > 80x and ~ 25x more likely to receive a KR than knees with no KOA or incident common KOA (adjusted odds ratio = 25.08; 95% confidence interval = 9.63-65.34). In conclusion, approximately 1 in 7 knees that develop AKOA received a KR; however, KRs were rare in the OAI among other knees with no radiographic KOA at baseline. Urgent steps are needed to identify adults at high-risk for AKOA and develop prevention strategies regarding the modifiable risk factors.

We assessed whether adding magnetic resonance (MR)‐based features to a base model of clinically accessible participant characteristics (i.e., serological, radiographic, demographic, symptoms, and physical function) improved classification of adults who developed accelerated radiographic knee osteoarthritis (AKOA) or not over the subsequent 4 years. We conducted a case–control study using radiographs from baseline and the first four annual visits of the osteoarthritis initiative to define groups. Eligible individuals had no radiographic KOA in either knee at baseline (Kellgren–Lawrence [KL] grade <2). We classified two groups matched on sex (i) AKOA: at least one knee developed advanced‐stage KOA (KL = 3 or 4) within 48 months and (ii) did not develop AKOA within 48 months. The MR‐based features were assessments of bone, effusion/synovitis, tendons, ligaments, cartilage, and menisci. All characteristics and MR‐based features were from the baseline visit. Classification and regression tree analyses were performed to determine classification rules and identify statistically important variables. The CART models with and without MR features each explained approximately 40% of the variability. Adding MR‐based features to the model yielded modest improvements in specificity (0.90 vs. 0.82) but lower sensitivity (0.62 vs. 0.70) than the base model. There was consistent evidence that serum glucose, effusion‐synovitis volume, and cruciate ligament degeneration are statistically important variables in classifying individuals who will develop AKOA. We found common MR‐based measures failed to dramatically improve classification. These findings also show a complex interplay among participant characteristics and a need to identify novel characteristics to improve classification. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2420–2428, 2019