Project description:Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.
Project description:Little is known about the temporal evolution of pain severity in persons with knee osteoarthritis (OA). We sought to describe the pain trajectory over 6 years in a cohort of subjects with radiographic, symptomatic knee OA.We used data from the Osteoarthritis Initiative (OAI), a multi-center, longitudinal study of subjects with diagnosed radiographic evidence of knee OA. Pain was assessed at baseline and annually for 6 years. Our analysis cohort included subjects with symptomatic knee OA at baseline, defined as baseline Kellgren-Lawrence (KL) score ?2 with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory modeling to identify distinct patterns of pain progression over a 6-year follow-up. Factors examined included sex, race, education, comorbidities, age, body mass index (BMI), alignment, KL grade, and depression.We used data from 1753 OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was 26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory modeling identified five distinct pain trajectories; baseline pain scores for each ranged from 15 to 62. None of the trajectories exhibited substantial worsening. One fifth of subjects in the two trajectories with the greatest pain underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity, depression, medical comorbidities, female sex, non-white race, lower education, and younger age were associated with trajectories characterized by greater pain.We found that knee pain changes little, on average, over 6 years in most subjects. These observations suggest knee OA is characterized by persistent rather than inexorably worsening symptoms.
Project description:OBJECTIVE:To investigate whether foot and/or ankle symptoms increase the risk of developing (1) knee symptoms and (2) symptomatic radiographic knee osteoarthritis (OA). DESIGN:1020 Osteoarthritis Initiative (OAI) participants who were at-risk of knee OA, but were without knee symptoms or radiographic knee OA, were investigated. Participants indicated the presence and laterality of foot/ankle symptoms at baseline. The main outcome was development of knee symptoms (pain, aching or stiffness in and around the knee on most days of the month for at least 1 month in the past year). A secondary outcome was development of symptomatic radiographic knee OA (symptoms plus Kellgren and Lawrence [KL] grade ?2), over the subsequent 4 years. Associations between foot/ankle symptoms and study outcomes were assessed by logistic regression models. RESULTS:Foot/ankle symptoms in either or both feet significantly increased the odds of developing knee symptoms (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.10 to 2.19), and developing symptomatic radiographic knee OA (adjusted OR 3.28, 95% CI 1.69 to 6.37). Based on laterality, contralateral foot/ankle symptoms were associated with developing both knee symptoms (adjusted OR 1.68, 95% CI 1.05 to 2.68) and symptomatic radiographic knee OA (adjusted OR 3.08, 95% CI 1.06 to 8.98), whilst bilateral foot/ankle symptoms were associated with developing symptomatic radiographic knee OA (adjusted OR 4.02, 95% CI 1.76 to 9.17). CONCLUSION:In individuals at-risk of knee OA, the presence of contralateral foot/ankle symptoms in particular increases risk of developing both knee symptoms and symptomatic radiographic knee OA.
Project description:BACKGROUND:Osteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development. PURPOSE:To develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI). STUDY TYPE:Retrospective. SUBJECTS:641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI. FIELD STRENGTH/SEQUENCE:MR images were obtained using 3.0T. ASSESSMENT:Compartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ?5 or total knee replacement [TKR]) over 8 years. STATISTICAL TESTS:Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA. RESULTS:Model 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08). DATA CONCLUSION:We established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance. LEVEL OF EVIDENCE:2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.
Project description:OBJECTIVES:Knee osteoarthritis (OA) onset and progression has been defined with transitions in Kellgren-Lawrence (KL) grade or Osteoarthritis Research Society International (OARSI) Joint Space Narrowing (JSN) grade. We quantitatively describe one-year transitions in KL grade and JSN, using fixed joint space width (fJSW), among knees with or at risk of OA. METHODS:Radiographic assessments from the Osteoarthritis Initiative (OAI) were used to identify transitions in KLG and JSN grade between consecutive annual visits. The fJSW was measured in the medial and lateral compartments. The distribution of change in fJSW for KLG and JSN transitions were described, and mean change in fJSW was estimated using mixed models. RESULTS:KL grade and JSN scores were available for about 20,000 annual transitions from 6047 knees contributed by 3389 participants. Knees that remained stable in KL or OARSI-JSN over 1 year had mean medial fJSW loss between -0.06 and -0.19 mm/year. Transition from KL grade 0 to 1, 0 to 2, and KL 1 to 2 were similar with respect to mean medial fJSW loss (0.18-0.28 mm). Greatest annual changes in medial fJSW corresponded to KL 0 to 3 (1.62 mm), KL 2 to 4 (1.23 mm) and JSN 0 to 2 (1.85 mm). CONCLUSIONS:Anchoring quantitatively measured loss of joint space width to transitions in KL grade and JSN provides reference values based on traditional definitions of knee OA onset and progression.
Project description:Objective: we aimed to identify circulating microRNAs associated with fast-progressing knee osteoarthritis (OA) as compared to slow-progressing knee OA and non-progressing knee OA using sujects from the Osteoarthritis Initiative (OAI) cohort. MicroRNA libraries were prepared from plasma using the QIAseq miRNA Library Kit (QIAGEN) and sequenced on the Illumina NextSeq550 using a single-end 75-base read protocol to an average depth of 11.6 ± 2.6 SD million reads per sample. Overall design: MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from N=20 fast-progressors (Kellgren-Lawrence [KL] grade 0/1 at baseline to KL 3/4 by 4-year follow-up), N=35 slow-progressors (KL 0/1 at baseline and 4-year follow-up to KL 2/3/4 by 8-year follow-up), and N=51 non-progressors (KL 0/1 at baseline through to 8-year follow-up).
Project description:Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of medication-treated diabetes on incidence and progression of knee OA. We analysed longitudinal data from the multi-center, longitudinal, prospective observational Osteoarthritis Initiative (OAI) study. The main outcomes were radiographic OA incidence (development of Kellgren-Lawrence grade 2 with joint space narrowing, JSN) and progression (increase in semiquantitative JSN or a new knee replacement). For the study of incidence, we selected participants with KL <2 or /KL?=?2 without JSN at baseline (incidence sample). To evaluate progression, we selected participants with baseline JSN <3 (progression sample). We used generalized estimating equations (GEE) logistic regression with adjustment for potential confounders to evaluate the effects of medication-treated diabetes on knee OA incidence and progression. We studied 3725 knees (3498 non-diabetic and 228 diabetic) in the incidence sample and 3594 knees (3335 non-diabetic and 259 diabetic) in the progression sample. Medication-treated diabetes did not have an effect on knee OA incidence (odds ratio, OR 0.53, 95% confidence interval, CI 0.23-1.5). There was an independent association between medication-treated diabetes and reduced progression of knee OA [OR 0.66, 95% CI (0.44-0.98)]. Medication-treated diabetes has no effect on knee OA incidence but reduces knee OA progression. The role of diabetes and anti-diabetic drugs in knee OA progression needs further exploration.
Project description:<h4>Objective</h4>Subjective crepitus is the reporting of hearing grating, cracking, or popping sounds in and/or around a joint. We aimed to evaluate whether there is an association between crepitus and incident symptomatic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), a multicenter longitudinal US cohort.<h4>Methods</h4>Knees without baseline symptomatic OA were included. Crepitus frequency was assessed using a question from the Knee Injury and Osteoarthritis Outcome Score at baseline and at 12, 24, and 36 months. Frequent knee pain and radiographs were assessed at baseline and at annual visits up to 48 months. Radiographic OA was defined as a tibiofemoral Kellgren/Lawrence grade ?2. Symptomatic OA was defined as a knee with both frequent symptoms and radiographic OA. We performed a repeated-measures analysis with a predictor of crepitus and outcome of incident symptomatic OA, adjusting for age, sex, and body mass index (BMI), with those never reporting crepitus as the referent group.<h4>Results</h4>There were a total of 3,495 participants (42.2% male), with mean ± SD age of 61.1 ± 9.2 years and a mean ± SD BMI of 28.2 ± 4.7 kg/m². The odds of incident symptomatic OA were higher with greater frequency of crepitus (never, rarely, sometimes, often, and always, with adjusted odds ratios of (referent), 1.5, 1.8, 2.2, and 3.0, respectively; P < 0.0001 for trend). The group with radiographic OA at OAI baseline but without symptoms contributed 26% of the observations but more than 75% of the incident symptomatic OA cases.<h4>Conclusion</h4>In those without symptomatic OA, subjective knee crepitus predicts incident symptomatic OA longitudinally, with most cases occurring in those with preexisting tibiofemoral radiographic OA but without frequent knee pain. However, an important limitation is that patellofemoral OA was not systematically evaluated within the OAI. Subjective crepitus offers utility for the identification of at-risk individuals, predictive modeling, and future research.
Project description:OBJECTIVE:To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). METHODS:The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on X-ray were assessed yearly over the subsequent 4 years. Associations between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using logistic regression. RESULTS:Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. CONCLUSION:The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent 4 years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.
Project description:OBJECTIVES:To assess whether initial or 12-18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months. METHODS:This was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ? 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics. RESULTS:Initial (odds ratio [95% confidence interval] = 2.13 [1.41-3.40]) and 12- 18-month change (3.76 [2.04-7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64-0.65], p = 0.003) and 12-18-month change (0.68 [0.68-0.68], p < 0.001) data. CONCLUSIONS:Initial and 12-18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12-18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA. KEY POINTS:• Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker. • In this study, subchondral bone texture was associated with knee osteoarthritis progression. • This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis. • This method may be useful in clinical trials with interventions targeting bone.