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Cystic lesions around the knee are a diverse group of entities, frequently encountered during routine MRI of the knee. These lesions range from benign cysts to complications of underlying diseases such as infection, arthritis, and malignancy. MRI is the technique of choice in characterizing lesions around the knee: to confirm the cystic nature of the lesion, to evaluate the anatomical relationship to the joint and surrounding tissues, and to identify associated intra-articular disorders. We will discuss the etiology, clinical presentation, MRI findings, and differential diagnosis of various cystic lesions around the knee including meniscal and popliteal (Baker's) cysts, intra-articular and extra-articular ganglia, intra-osseous cysts at the insertion of the cruciate ligaments and meniscotibial attachments, proximal tibiofibular joint cysts, degenerative cystic lesions (subchondral cyst), cystic lesions arising from the bursae (pes anserine, prepatellar, superficial and deep infrapatellar, iliotibial, tibial collateral ligament, and suprapatellar), and lesions that may mimic cysts around the knee including normal anatomical recesses. Clinicians must be aware about the MRI features and the differential diagnosis of cystic lesions around the knee to avoid misdiagnosis.

ObjectiveTo determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression.MethodsThe present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of

ObjectiveUse of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA.MethodsWe used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren-Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW.ResultsOf 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = -0.042, 95% CI -0.08, -0.0004). No other associations were observed.ConclusionsIn current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

ObjectiveTo examine the associations of knee injury, radiographic osteoarthritis severity, and quadriceps strength with knee pain exacerbation during walking.DesignWithin-person knee-matched case-control study.MethodsParticipants from the Osteoarthritis Initiative who completed a 20-m walking test at the 24-month visit were included. Pain exacerbation was defined as an increase in pain intensity of 1 or more on a numeric rating scale (0 as no pain and 10 as the worst imaginable pain) while completing the 20-m walking test. We used conditional logistic regression to assess the relation of recent knee injury, Kellgren-Lawrence (KL) grade, and quadriceps strength to unilateral knee pain exacerbation during walking.ResultsWe included 277 people who experienced unilateral knee pain exacerbation during the walking test. Recent knee injury was associated with pain exacerbation during walking, with an odds ratio of 3.4 (95% confidence interval [CI]: 1.3, 9.2). Compared with knees with a KL grade of 0, the odds ratios of pain exacerbation during walking were 1.3 (95% CI: 0.7, 2.7), 3.3 (95% CI: 1.5, 7.1), and 8.1 (95% CI: 3.1, 21.1) for knees with KL grades of 2, 3, and 4, respectively. Painful knees with a deficit in quadriceps strength of greater than or equal to 4% had a 1.4-fold (95% CI: 1.0, 1.9) higher risk of pain exacerbation during walking than their pain-free counterparts.ConclusionRecent knee injury, more severe radiographic osteoarthritis, and lower quadriceps strength were associated with an increased risk of knee pain exacerbation during walking. J Orthop Sports Phys Ther 2021;51(6):298-304. Epub 10 May 2021. doi:10.2519/jospt.2021.9735.

ObjectivesTo examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults.MethodsWe used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations).ResultsHeavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression.ConclusionHeavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

OBJECTIVE:Osteoarthritis (OA) is a disease with a substantial public health burden. Quantitative assessments of periarticular bone may be a biomarker capable of monitoring early disease progression. The purpose of this study was to evaluate whether measures of periarticular bone associate with longitudinal structural progression. METHODS:We conducted a 12-18 months longitudinal study using the Osteoarthritis Initiative (OAI). Participants received knee dual-energy x-ray absorptiometry (DXA), trabecular magnetic resonance (MR) imaging, and x-rays. Knee DXAs generated proximal tibial medial:lateral periarticular bone mineral density (paBMD) measures. Proximal tibial trabecular MR images were assessed for trabecular morphometry: apparent bone volume fraction (BVF), trabecular number, thickness, and spacing. Weight-bearing x-rays were assessed for medial tibiofemoral joint space narrowing (JSN). Chi-squared analyses assessed whether periarticular bone measures were predictive of worsening medial tibiofemoral JSN, adjusted for age, sex, and BMI. RESULTS:In all, 444 participants, mean age 64.2 ± 9.2 years, BMI 29.5 ± 4.6kg/m2, and 52% male at baseline. Medial JSN (radiographic progression) occurred in 40 participants (9%). Higher baseline medial:lateral paBMD, apparent BVF, trabecular number and thickness, and lower baseline and decreased trabecular spacing were all associated with more progression of JSN in the medial compartment. From lowest to highest baseline medial:lateral paBMD quartile groups, 2%, 5%, 11%, and 18% had medial JSN progression, respectively, between the 36- and 48-month visits, p-values = 0.001 and 0.002 unadjusted and adjusted. The rate of change in medial:lateral paBMD, apparent BVF, and spacing were associated with more medial JSN. For rate of medial:lateral paBMD change from lowest to highest quartile, the proportion of each group that experienced medial JSN progression were 5%, 5%, 11%, and 18%, with an unadjusted and adjusted p-value of 0.005. CONCLUSION:Baseline and most rates of periarticular bone change associate with knee OA structural progression, highlighting the close relationship between subchondral bone and JSN. Future studies should focus on developing these measures as predictive and pathophysiological biomarkers, and evaluating their deployment in clinical trials testing bone-targeted therapeutics.

ObjectiveTo evaluate radiographic subchondral trabecular bone texture (TBT) as a predictor of clinically relevant osteoarthritis (OA) progression (combination of symptom and structural worsening).MethodsThe Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of progressive knee OA cases (n = 194 knees with both radiographic and pain progression over 24-48 months) and comparators (n = 406 OA knees not meeting the case definition). TBT parameters were extracted from a medial subchondral tibial region of interest by fractal signature analysis of radiographs using validated semiautomated software. Baseline TBT and time-integrated values over 12 and 24 months were evaluated for association with case status and separately with radiographic and pain progression status, adjusted for age, sex, body mass index, race, baseline Kellgren/Lawrence grade, baseline joint space width, Western Ontario and McMaster Universities Osteoarthritis Index pain score, and pain medication use. C statistics were generated from receiver operating characteristic curves.ResultsRelative to comparators, cases were characterized by thinner vertical and thicker horizontal trabeculae. The summed composite of 3 TBT parameters at baseline and over 12 and 24 months best predicted case status (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT composite score (0.633-0.649) was improved modestly but statistically significantly over the use of covariates alone (0.608). One TBT parameter, reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and 24 months, predicted risk of any progression (radiographic and/or pain progression).ConclusionAlthough associations are modest, TBT could be an attractive means of enriching OA trials for progressors since it can be generated from screening knee radiographs already standard in knee OA clinical trials.

BackgroundThe aim was to assess serum magnesium levels in relation to prevalence of knee chondrocalcinosis in two population-based Chinese studies.MethodsData included in this analysis consisted of two population-based cross-sectional studies, i.e., the Xiangya Hospital Health Management Center Study and the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was present if there was definite linear cartilage calcification. Serum magnesium concentration was measured using the chemiluminescence method. We examined the relation of serum magnesium levels to prevalence of knee chondrocalcinosis using generalized estimating equations.ResultsThe prevalence of knee chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40-0.87) and 0.49 (95% CI 0.33-0.72) in the second and the third tertiles of serum magnesium, respectively (P for trend

ObjectiveTo determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA).MethodsWe analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm2 ) and shape (position on 3-D vector) were assessed on magnetic resonance images, and bone trabecular integrity (BTI) was assessed on radiographs. Serum and urinary markers (serum C-terminal crosslinked telopeptide of type I collagen [CTX-I], serum crosslinked N-telopeptide of type I collagen [NTX-I], urinary NTX-I, urinary C-terminal crosslinked telopeptide of type II collagen [CTX-II], and urinary CTX-Iα and CTX-Iβ) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates.ResultsAt baseline, most biochemical markers were associated with BMLs, with C statistics for the presence/absence of any BML ranging from 0.675 to 0.688. At baseline, urinary CTX-II was the marker most consistently associated with BMLs (with odds of having ≥5 subregions affected compared to no BML increasing by 1.92-fold [95% confidence interval (95% CI) 1.25, 2.96] per 1 SD of urinary CTX-II), large osteophytes (odds ratio 1.39 [95% CI 1.10, 1.77]), bone area and shape (highest partial R2  = 0.032), and changes in bone shape over 24 months (partial R2 range 0.008 to 0.024). Overall, biochemical markers were not predictive of changes in BMLs or osteophytes. Serum NTX-I was inversely associated with BTI of the vertical trabeculae (quadratic slope) in all analyses (highest partial R2  = 0.028).ConclusionWe found multiple significant associations, albeit mostly weak ones. The role of systemic biochemical markers as predictors of individual bone anatomic features of single knees is limited based on our findings.

ObjectiveTo investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression.MethodsEighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p

BackgroundTo describe the scoring methodology and MRI assessments used to evaluate the cross-sectional features observed in cases and controls, to define change over time for different MRI features, and to report the extent of changes over a 24-month period in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium study nested within the larger Osteoarthritis Initiative (OAI) Study.MethodsWe conducted a nested case-control study. Cases (n = 406) were knees having both radiographic and pain progression. Controls (n = 194) were knee osteoarthritis subjects who did not meet the case definition. Groups were matched for Kellgren-Lawrence grade and body mass index. MRIs were acquired using 3 T MRI systems and assessed using the semi-quantitative MOAKS system. MRIs were read at baseline and 24 months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. We provide the definition and distribution of change in these biomarkers over time.ResultsSeventy-three percent of the cases had subregions with BML worsening (vs. 66 % in controls) (p = 0.102). Little change in osteophytes was seen over 24 months. Twenty-eight percent of cases and 10 % of controls had worsening in meniscal scores in at least one subregion (p

ObjectiveTo determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA).MethodsWe undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis.ResultsThe most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively).ConclusionTwenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA.

ObjectiveTo evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.MethodsKnees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2 years before T0 (T-2) were compared using conditional logistic regression.ResultsOne hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 ± 8.7 [mean ± SD] years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95 % CI: 1.23-2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement.ConclusionsDiscrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement.Key points• Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. • MRI predicts knee replacement with similar accuracy to radiographic JSW. • MRI reveals greater cartilage thinning and thickening prior to knee replacement.

PurposeTo assess whether magnetic resonance (MR) imaging-based cross-sectional measures of structural joint damage can be used to predict knee replacement during the following year.Materials and methodsParticipants were drawn from the Osteoarthritis Initiative, a longitudinal observational study that includes 4796 participants who have knee osteoarthritis or are at risk. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. During the 5 years of follow-up, 199 knees underwent knee replacement and were matched with 199 control knees that did not undergo knee replacement. Knees were matched according to radiographic disease stage and patient sex and age. All knees that underwent knee replacement and had MR images available from the year before surgery were included. MR images were assessed for cartilage damage, bone marrow lesions, meniscal damage, meniscal extrusion, synovitis, and effusion prior to reported knee replacement. Conditional logistic regression was applied to assess the risk of knee replacement. Analyses were performed on a compartmental and knee level.ResultsParticipants had a mean age ± standard deviation of 64.2 years ± 8.4 (range, 47-82 years) and were predominantly women (232 of 398 participants, 58.3%). Risk for knee replacement was significantly increased for knees that exhibited two or more subregions with severe cartilage loss (odds ratio [OR], 16.5; 95% confidence interval [CI]: 3.96, 68.76), more than two subregions with bone marrow lesions (OR, 4.00; 95% CI: 1.75, 9.16), medial meniscal maceration (OR, 1.84; 95% CI: 1.13, 2.99), effusion (OR, 4.75; 95% CI: 2.55, 8.85), or synovitis (OR, 2.17; 95% CI: 1.33, 3.56), but not extrusion (OR, 1.00; 95% CI: 0.60,1.67), when compared with knees that did not exhibit these features as the reference standard.ConclusionApart from meniscal extrusion, all features of tissue abnormalities at MR imaging were related to clinical prognosis and could be used to predict knee replacement in the following year.

ObjectiveThe impact of increasing utilization of total knee arthroplasty (TKA) on lifetime costs in persons with knee osteoarthritis (OA) is understudied.MethodsWe used the Osteoarthritis Policy Model to estimate total lifetime costs and TKA utilization under a range of TKA eligibility criteria among US persons with symptomatic knee OA. Current TKA utilization was estimated from the Multicenter Osteoarthritis Study and calibrated to Health Care Cost and Utilization Project data. OA treatment efficacy and toxicity were drawn from published literature. Costs in 2013 dollars were derived from Medicare reimbursement schedules and Red Book Online. Time costs were derived from published literature and the US Bureau of Labor Statistics.ResultsEstimated average discounted (3% per year) lifetime costs for persons diagnosed with knee OA were $140,300. Direct medical costs were $129,600, with $12,400 (10%) attributable to knee OA over 28 years. OA patients spent a mean ± SD of 13 ± 10 years waiting for TKA after failing nonsurgical regimens. Under current TKA eligibility criteria, 54% of knee OA patients underwent TKA over their lifetimes. Estimated OA-related discounted lifetime direct medical costs ranged from $12,400 (54% TKA uptake) when TKA eligibility was limited to Kellgren/Lawrence grades 3 or 4 to $16,000 (70% TKA uptake) when eligibility was expanded to include symptomatic OA with a lesser degree of structural damage.ConclusionBecause of low efficacy of nonsurgical regimens, knee OA treatment-attributable costs are low, representing a small portion of all costs for OA patients. Expanding TKA eligibility increases OA-related costs substantially for the population, underscoring the need for more effective nonoperative therapies.

IntroductionOur objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs).MethodsWe conducted an analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS). Knee magnetic resonance images were scored for BMLs using a semiquantitative grading scheme. In addition, a subset of persons with BMLs underwent quantitative volume measurement of their BML, using a proprietary software method. Within the BOKS population, 80 people with BMLs and 80 without BMLs were selected for the purposes of this case-control study. Bone biomarkers assayed included type I collagen N-telopeptide (NTx) corrected for urinary creatinine, bone-specific alkaline phosphatase, and osteocalcin. The same methods were used and applied to a nested case-control sample from the Framingham study, in which BMD assessments allowed evaluation of this as a covariate. Logistic regression models were fit using BML as the outcome and biomarkers, age, sex, and body mass index as predictors. An receiver operating characteristic curve was generated for each model and the area under the curve assessed.ResultsA total of 151 subjects from BOKS with knee OA were assessed. The mean (standard deviation) age was 67 (9) years and 60% were male. Sixty-nine per cent had maximum BML score above 0, and 48% had maximum BML score above 1. The only model that reached statistical significance used maximum score of BML above 0 as the outcome. Ln-NTx (Ln is the natural log) exhibited a significant association with BMLs, with the odds of a BML being present increasing by 1.4-fold (95% confidence interval = 1.0-fold to 2.0-fold) per 1 standard deviation increase in the LnNTx, and with a small partial R2 of 3.05. We also evaluated 144 participants in the Framingham Osteoarthritis Study, whose mean age was 68 years and body mass index was 29 kg/m2, and of whom 40% were male. Of these participants 55% had a maximum BML score above 0. The relationship between NTx and maximum score of BML above 0 revealed a significant association, with an odds ratio fo 1.7 (95% confidence interval = 1.1 to 2.7) after adjusting for age, sex, and body mass index.ConclusionsSerum NTx was weakly associated with the presence of BMLs in both study samples. This relationship was not strong and we would not advocate the use of NTx as a marker of the presence of BMLs.

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4C(short) or C1,2C), type II cleavage only with Col2:3/4C(longmono) (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels.

To study the association of quantitative medial meniscal position measures with radiographic and symptomatic knee osteoarthritis (OA) progression over 2–4 years. The FNIH OAI Biomarkers study comprised 600 participants in four subgroups: 194 case knees with combined structural (medial minimum joint space width (minJSW) loss ≥0.7 mm) and symptomatic (persistent Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale increase ≥9 [0–100 scale]) progression; 200 knees with neither structural nor symptomatic progression; 103 knees with isolated structural and 103 with isolated symptomatic progression. Coronal double echo at steady state (DESS) MRIs were used for segmenting five central slices of the medial meniscus. Associations with progression were examined using logistic regression (adjusted for demographic and clinical data). Greater baseline medial meniscal extrusion was associated with combined structural/symptomatic progression (OR 1.59; 95%CI: [1.25,2.04]). No relationship was observed for tibial plateau coverage or meniscal overlap distance. The two-year increase in meniscal extrusion (OR 1.48 [1.21, 1.83]), and reduction in tibial plateau coverage (OR 0.70 [0.58,0.86]) and overlap distance (OR 0.73 [0.60,0.89]) were associated with combined progression. Greater baseline extrusion was associated with isolated structural and less extrusion with isolated symptomatic progression. The longitudinal increase in meniscal extrusion, and reduction in tibial plateau coverage and overlap distance were associated with structural, but not with symptomatic progression. Baseline measures of medial meniscal extrusion were consistently positively associated with combined radiographic/symptomatic progression and with isolated structural, but not with isolated symptomatic progression. These measures may therefore allow one to assess the risk of structural knee OA progression and to monitor interventions restoring meniscal position and function. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether baseline joint space narrowing (JSN) predicted disease remission, knee pain, and physical function changes in persons with knee osteoarthritis (OA). Methods: This study is a secondary analysis of a two‐armed randomized controlled trial. Participants were aged ≥50 years (n = 171) with a body mass index ≥28 kg/m2 and radiographic medial tibiofemoral OA. Participants in the intervention group received diet and exercise programs and special treatment (cognitive behavioral therapy, knee brace, and muscle strengthening exercises) according to the disease remission. Remission of pain and remission of patient global assessment of disease activity and/or functional impairment were used to define the disease remission. The control group were provided with an education pamphlet. The primary outcome was disease remission at 32 weeks, and the secondary outcomes were the changes in knee pain and physical function at 20 and 32 weeks. Baseline JSN was scored from 0 to 3, and the association between baseline JSN and outcomes was assessed using multiple regression. Results: There was no association of baseline JSN with disease remission at 32 weeks when the disease remission has been achieved. The baseline JSN grade 3 was associated with changes in knee pain at 20 weeks (p <.05). There was no association between baseline JSN and physical function. Conclusion: Baseline JSN severity predicted changes in knee pain but not the disease remission or changes in physical functions. Identification of baseline radiographic severity may be helpful in identifying differences in response to diet and exercise programs in knee OA. [ABSTRACT FROM AUTHOR]

The study aimed to determine the associations between the morphological types of proximal tibiofibular joint (PTFJ) and the risk of total knee replacement (TKR) in a cohort of participants with progressive osteoarthritis. A nested case–control design was performed in Osteoarthritis Initiative study. The case knees were those with TKR at 24–60 months follow up (cases), and were 1:1 matched with control knees by age, sex, and Kellgren‐Lawrence grade at baseline. The morphological type of each PTFJ was identified according to the coronal and sagittal MR images. Conditional logistic regression models were used to examine the association of the PTFJ types with the risk of TKR at baseline and the time point before TKR (T0). A total of 193 case knees at baseline and 148 case knees at T0 time point had matched controls between 12 and 60 M. Seven types of the PTFJ were identified and classified into three categories: plane, trochoid, and irregular types. The prevalence of the irregular type was higher in case knees than in controls both at baseline (cases vs. controls, 35.8% vs. 26.9%) and at T0 time point (cases vs. controls, 33.1% vs. 27.0%). The irregular type of the PTFJ at baseline (odds ratio: 1.62, 95% confidence interval: 1.01–2.59) rather than at T0 time point was significantly associated with increased odds of TKR. The irregular types of the PTFJ at baseline are associated with increased risk of TKR, suggesting PTFJ may play a role in knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Metformin has been shown to modulate meta-inflammation, an important pathogenesis in knee osteoarthritis (OA). The study aimed to test the association between regular metformin use with total knee replacement (TKR) in patients with diabetes. This is a retrospective study with electronic records retrieved in Hong Kong public primary care. Patients with diabetes aged ≥ 45 who visited during 2007 to 2010, were followed up for a four-year period from 2011 to 2014 to determine the incidence of TKR. Propensity score matching based on age, sex, co-medications and chronic conditions was conducted to adjust for confounding. Cox regression was implemented to examine the association between metformin use and TKR. In total, 196,930 patients were eligible and 93,330 regular metformin users (defined as ≥ 4 prescriptions over the previous year) and non-users were matched. Among 46,665 regular users, 184 TKRs were conducted, 17.1% fewer than that among non-users. Cox regression showed that regular metformin users had a 19%-lower hazard of TKR [hazard ratio (HR) = 0.81, 95% confidence interval: 0.67 to 0.98, P = 0.033], with a dose–response relationship. Findings suggest a potential protective effect of metformin on knee OA progression and later TKR incidence among diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA).Methods: In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)-100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients' global assessment of disease impact.Results: 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI -0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups.Conclusion: In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks.Trial Registration Number: NCT03843931. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome is a major health problem worldwide associated with obesity, thus drawing attention to its relation to osteoarthritis (OA). However, it is still uncertain whether metabolic syndrome or body fat distribution is associated with knee OA. The aim of this longitudinal study was to elucidate the association between metabolic obesity and adverse structural changes of knee OA assessed by magnetic resonance imaging (MRI). Methods: Participants were recruited from the Hallym Aging Study cohort in Korea. Knee MRI scans, along with dual‐energy X‐ray absorptiometry, were assessed in 226 participants at baseline and after 3 years. The structural progression in the tibiofemoral joint was evaluated using the semi‐quantitative Whole‐Organ MRI Score (WORMS) for cartilage morphology and bone marrow lesions (BML). Logistic regression with generalized estimating equation was performed for associations of metabolic risk factors with worsening of WORMS scores at the subregional level. Results: In the medial compartment, fat mass in women was associated with cartilage loss, but the statistical significance disappeared after adjusting for body mass index. Metabolic syndrome and each of its components were not associated with cartilage loss or increase of BML. On the other hand, the interaction effects of metabolic syndrome on the association between obesity and knee OA progression were not significant. Conclusion: In this cohort, metabolic effects of obesity on knee cartilage damage and BML were not demonstrated. Further large‐scale studies are required to prove the causal relationship between metabolic obesity and knee OA. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a major problem globally. First-line management comprises education and self-management strategies. Online support groups may be a low-cost method of facilitating self-management. Objective: The aim of this randomized controlled pilot study is to evaluate the feasibility of the study design and implementation of an evidence-informed, expert-moderated, peer-to-peer online support group (My Knee Community) for people with knee OA. The impacts on psychological determinants of self-management, selected self-management behaviors, and health outcomes were secondary investigations. Methods: This mixed methods study evaluated study feasibility (participant recruitment, retention, and costs), experimental intervention feasibility (acceptability and fidelity to the proposed design, including perceived benefit, satisfaction, and member engagement), psychological determinants (eg, self-efficacy and social support), behavioral measures, health outcomes, and harms. Of a total of 186, 63 (33.9%) participants (41/63, 65% experimental and 22/63, 35% control) with self-reported knee OA were recruited from 186 volunteers. Experimental group participants were provided membership to My Knee Community, which already had existing nonstudy members, and were recommended a web-based education resource (My Joint Pain). The control group received the My Joint Pain website recommendation only. Participants were not blinded to their group allocation or the study interventions. Participant-reported data were collected remotely using web-based questionnaires. A total of 10 experimental group participants also participated in semistructured interviews. The transcribed interview data and all forum posts by the study participants were thematically analyzed. Results: Study feasibility was supported by acceptable levels of retention; however, there were low levels of engagement with the support group by participants: 15% (6/41) of participants did not log in at all; the median number of times visited was 4 times per participant; only 29% (12/41) of participants posted, and there were relatively low levels of activity overall on the forum. This affected the results for satisfaction (overall mean 5.9/10, SD 2.7) and perceived benefit (17/31, 55%: yes). There were no differences among groups for quantitative outcomes. The themes discussed in the interviews were connections and support, information and advice, and barriers and facilitators. Qualitative data suggest that there is potential for people to derive benefit from connecting with others with knee OA by receiving support and assisting with unmet informational needs. Conclusions: Although a large-scale study is feasible, the intervention implementation was considered unsatisfactory because of low levels of activity and engagement by members. We recommend that expectations about the support group need to be made clear from the outset. Additionally, the platform design needs to be more engaging and rewarding, and membership should only be offered to people willing to share their personal stories and who are interested in learning from the experiences of others. [ABSTRACT FROM AUTHOR]

Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.Design, Setting, and Participants: This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.Interventions: Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).Main Outcomes and Measures: The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.Results: Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.Conclusions and Relevance: Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347. [ABSTRACT FROM AUTHOR]

Objectives Emerging evidence suggests a potential link between OA and gout; however, the association between serum uric acid (UA) itself and knee OA remains uncertain due to a lack of longitudinal studies. Here, we investigated the association between serum UA and knee OA according to cartilage status in elderly community residents without gout. Methods In this longitudinal study, participants without a history of gout were recruited from among the Korean cohort of the Hallym Aging Study (n  = 296 for radiography study and n  = 223 for MRI study). Weight-bearing knee radiographs and 1.5-T MRI scans, along with blood collection for analysis of serum UA, were performed at baseline and after 3 years. The severity and structural progression of knee OA were evaluated using the Kellgren–Lawrence grading system and the Whole-Organ MRI Score (WORMS) cartilage scoring method. Multivariable logistic regression analysis was conducted using generalized estimating equation (GEE) models. Results Serum UA levels were not associated with radiographic progression after adjusting for age, sex and BMI. There was no significant association between serum UA and tibiofemoral cartilage loss on MRI. However, baseline serum UA levels were negatively associated with patellofemoral cartilage loss over 3 years (adjusted odd ratio 0.70 per 1 mg/dl increase, 95% CI: 0.49, 0.98). Conclusion In this population-based cohort, serum UA was not a risk factor for knee OA progression. Further large-scale longitudinal studies in other populations are needed to validate the effects of UA on cartilage damage. [ABSTRACT FROM AUTHOR]

The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24–60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren–Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle α), sagittal inclination angle (angle β), fibular contacting area (S), load‐bearing area (Sτ), lateral stress‐bolstering area (Sφ), and posterior stress‐bolstering area (Sυ) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR (T0) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty‐three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline and T0 time point. While baseline angle α was positively associated with TKR risk, other measures at baseline and all measures at T0 were not significantly associated with TKR risk. Changes in S, Sτ, and Sυ were significantly and negatively associated with the risk of TKR (ΔS, odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19–0.76; ΔSτ, OR = 0.37, 95% CI: 0.16–0.87; ΔSυ, OR = 0.22, 95% CI: 0.08–0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.Methods: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling.Discussion: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.Trial Registration: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019. [ABSTRACT FROM AUTHOR]

Flare in knee and hip osteoarthritis (OA) is more than just an exacerbation of pain. Unstructured, semistructured, and focus group interviews followed by Delphi surveys with patients and health professionals (HP) generated candidate domains of an OA flare. Content analysis of interviews with 29 patients and 16 HP extracted 180 statements, which were grouped into 9 clusters. Delphi consensus with 50 patients (Australia, Canada, and France) and 116 HP (17 countries on 4 continents) identified 5 flare domains: pain, swelling, stiffness, psychological aspects, and effect of symptoms. Elements for a preliminary definition of an OA flare are proposed. Registered at clinicaltrials.gov NCT02892058. [ABSTRACT FROM AUTHOR]

* BACKGROUND: Knowledge of patellofemoral osteoarthritis (OA) pain trajectories is vital to helping clinicians and patients make shared disease-specific decisions regarding treatment options and coping strategies. * OBJECTIVES: To describe the pain trajectories of people living with patellofemoral OA who present to a chronic care management program, and to explore baseline characteristics associated with different trajectories. * METHODS: In this prospective longitudinal cohort study, 88 participants who presented to a chronic care management program reported their worst pain over the previous week at baseline and at 6,12,18, and 26 weeks using a 10-cm visual analog scale. Trajectories (classes) were identified using latent class growth analysis. Demographics, pain, physical performance, strength, quality of life, mental health, and lower limb/foot structural measures obtained at baseline were assessed for association with trajectory class membership. * RESULTS: Individuals in class 1 (28%) exhibited high, persistent pain from baseline (7.8 ± 1.7 cm), which continued over time (P = .52). Class 2 (57%) displayed moderate baseline pain (4.8 ± 1.8 cm), which also remained persistent (P = .97). Individuals in class 3 (15%) showed low, improving pain (baseline pain, 2.6 ± 1.2 cm) over time (P = .017). At baseline, poor Knee injury and Osteoarthritis Outcome Score (KOOS) scores, local and proximal sensitivity to pressure, and lower knee extensor strength were associated with increased odds of following the high-pain trajectory (range [95% confidence interval], 1.03 [1.00,1.07] to 16.24 [2.53,104.34]). * CONCLUSION: Distinct pain trajectories appear to exist in people with patellofemoral OA presenting to a chronic care management program. Baseline variables may be useful for identifying individuals at risk of poorer prognosis. Larger studies are needed to confirm the efficacy of this finding. * LEVEL OF EVIDENCE: Prognosis, level 2b. [ABSTRACT FROM AUTHOR]

Objective: To determine whether infrapatellar fat pad (IPFP) signal intensity measures are predictive of incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative study.Methods: Case knees (n = 355), as defined by incident ROA, were matched 1:1 with control knees, according to sex, age, and radiographic status. T2-weighted magnetic resonance images were assessed at P0 (the visit when incident ROA was observed on a radiograph), P1 (1 year prior to P0), and baseline and used to assess IPFP signal intensity semiautomatically. Conditional logistic regression analyses were performed to assess the risk of incident ROA associated with IPFP signal intensity alteration, after adjustment for covariates.Results: The mean age of the participants was 60.2 years, and most (66.7%) were female and overweight (mean body mass index 28.3 kg/m2 ). Baseline IPFP measures including the mean value and standard deviation of IPFP signal intensity, the mean value and standard deviation of IPFP high signal intensity, median and upper quartile values of IPFP high signal intensity, and the clustering effect of high signal intensity were associated with incident knee ROA over 4 years. All P1 IPFP measures were associated with incident ROA after 12 months. All P0 IPFP signal intensity measures were associated with ROA.Conclusion: The quantitative segmentation of high signal intensity in the IPFP observed in our study confirms the findings of previous work based on semiquantitative assessment, suggesting the predictive validity of semiquantitative assessment of IPFP high signal intensity. The IPFP high signal intensity alteration could be an important imaging biomarker to predict the occurrence of ROA. [ABSTRACT FROM AUTHOR]

Objective: To determine whether 3D meniscal measures had similar sensitivity to longitudinal change as cartilage thickness; to what extent these measures are associated with longitudinal joint space width (JSW) change; and whether the latter associations differ between minimum (mJSW) and fixed-location JSW.Methods: Two-year changes in medial meniscal position and morphology, cartilage thickness (MRI) and minimum and fixed-location JSW (radiography) were determined in 35 Osteoarthritis Initiative knees [12 men, age: 67 (51-77) years; 23 women, age: 65 (54-78) years], progressing from baseline Kellgren-Lawrence grade ≤2 to knee replacement within 3-5 years. Multiple linear regression assessed the features contributing to JSW change.Results: Meniscal measures, cartilage thickness and JSW displayed similar sensitivity to change (standardised response mean≤|0.76|). Meniscal changes were strongly associated with JSW change (r≤|0.66|), adding ≤20% to its variance in addition to cartilage thickness change. Fixed-location JSW change (multiple r2=72%) was more strongly related to cartilage and meniscal change than mJSW (61%). Meniscal morphology explained more of fixed-location JSW and meniscal position more of mJSW.Conclusion: Meniscal measures provide independent information in explaining the variance of radiographic JSW change. Fixed-location JSW appears to be more reflective of structural change than mJSW and, hence, a potentially superior measure of structural progression.Key Points: • 3D positional/morphological meniscal measures change in rapidly progressing knees. • Similar sensitivity to 2-year change of quantitative meniscal/cartilage measures in rapid progression. • Changes in meniscal measures are strongly associated with radiographic JSW change. • Meniscal change provides information to explain JSW variance independent of cartilage. • Fixed-location JSW reflects structural disease stage more closely than minimum JSW. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to examine the difference in the pattern of articular damage in persons with either a partial anterior cruciate ligament (ACL) tear; a complete ACL tear or no ACL tear. Methods Our study included 600 individuals (of the 600 individuals, 25 with a partial, 12 with a complete ACL tear and 563 with no ACL tear) from the progression sub-cohort of the Osteoarthritis Initiative. Individuals had a mean age of 61.8 years (range 45-79 years). Chi-square tests were used to compare the location of meniscal pathology, bone marrow lesions (BMLs) and regional cartilage morphology between individuals with a partial or complete ACL tear, as seen on magnetic resonance imaging, as well as to a control group of 563 knees. Results Individuals with either a complete or partial ACL tear displayed predominantly medial tibiofemoral damage. Individuals with complete ACL tears were more likely to have cartilage lesions in the lateral posterior tibia ( P = 0.03) and the medial anterior femur ( P = 0.008) as well as BMLs in the medial posterior tibia ( P = 0.007). However, no significant difference in meniscal morphology was found in either compartment. Individuals with no history of knee trauma or ACL injury displayed predominantly medial tibiofemoral compartment damage. Conclusion Individuals with prevalent ACL disruptions exhibited concomitant osteoarthritic changes in the medial tibiofemoral compartment, as seen on MRI. As the changes in joint tissues were predominantly located in the medial compartment, it is thought that these ACL tears may represent a manifestation of the overall disease process rather than the precipitant for osteoarthritis incidence. [ABSTRACT FROM AUTHOR]

Background: This study was performed to determine if the effectiveness of patellofemoral bracing as a treatment for patellofemoral osteoarthritis is influenced by patellofemoral joint alignment and trochlear morphology. We hypothesized that those with more extreme patellar malalignment would benefit more from bracing.Methods: Thirty-eight patients who had received bracing as part of a comprehensive treatment plan for patellofemoral osteoarthritis were selected for this study. Ten measures of patellar alignment were taken from X-rays. These alignment measures were divided into percentile groups (tertiles) for contingency table analysis. Treatment outcome was measured by Western Ontario and Macmasters Universities Osteoarthritis Index (WOMAC) scores and these were dichotomised into two groups according to "Improved" or "Not Improved" according to the minimum clinically important difference (MCID). Spearman's rho test was performed for continuous variables and Fisher's exact test was performed for correlation between tertile groups and MCID categories.Results: Thirty-eight patients (9 male and 29 female) between the ages of 51 to 89 were included in this study. WOMAC scores ranged from -25 to 41.67, with a mean change of -3.97, 31.6, 44.7 and 31.6% of patients falling into the "Improved" group for Global, Pain and Function scores respectively. We found a non-significant trend shown (p = 0.058, correlation coefficient 0.31) between bisect offset and change in WOMAC global, indicating a trend for higher change in WOMAC scores with increasing bisect offset. Statistically significant correlations were found between mean MCID categories for the WOMAC global and function groups when analysed against percentile groups for bisect offset (p < 0.01) and patellar subluxation distance (p < 0.05), indicating those in higher percentile groups were more likely not to improve after six months.Conclusion: Higher bisect offset and patellar subluxation distance measures were associated with poorer outcomes. However, due to the limited sample size, more studies are required to fully examine this relationship. [ABSTRACT FROM AUTHOR]

Objectives: Investigating the association between baseline cartilage volume measurements (and initial 24th month volume loss) with medial compartment Joint-Space-Loss (JSL) progression (>0.7 mm) during 24-48th months of study.Methods: Case and control cohorts (Biomarkers Consortium subset from the Osteoarthritis Initiative (OAI)) were defined as participants with (n=297) and without (n=303) medial JSL progression (during 24-48th months). Cartilage volume measurements (baseline and 24th month loss) were obtained at five knee plates (medial-tibial, lateral-tibial, medial-femoral, lateral-femoral and patellar), and standardized values were analysed. Multivariate logistic regression was used with adjustment for known confounders. Artificial-Neural-Network analysis was conducted by Multi-Layer-Perceptrons (MLPs) including baseline determinants, and baseline (1) and interval changes (2) in cartilage volumes.Results: Larger baseline lateral-femoral cartilage volume was predictive of medial JSL (OR: 1.29 (1.01-1.64)). Greater initial 24th month lateral-femoral cartilage volume-loss (OR: 0.48 (0.27-0.84)) had protective effect on medial JSL during 24-48th months of study. Baseline and interval changes in lateral-femoral cartilage volume, were the most important estimators for medial JSL progression (importance values: 0.191(0.177-0.204), 0.218(0.207-0.228)) in the ANN analyses.Conclusions: Cartilage volumes (both at baseline and their change during the initial 24 months) in the lateral femoral plate were predictive of medial JSL progression.Key Points: • Baseline lateral femoral cartilage volume is directly associated with medial JSL progression. • 24-month lateral femoral cartilage loss is inversely associated with medial JSL progression. • Lateral femoral cartilage volume is most important in association with medial JSL progression. [ABSTRACT FROM AUTHOR]

Source Citation: Noorduyn JCA, van de Graaf VA, Willigenburg NW, et al. Effect of physical therapy vs arthroscopic partial meniscectomy in people with degenerative meniscal tears: five-year follow-up of the ESCAPE randomized clinical trial. JAMA Netw Open. 2022;5:e2220394. 35802374. [ABSTRACT FROM AUTHOR]

Background: The development of radiographic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) rupture has long been studied and proven in the adolescent population. However, similar exhaustive investigations have not been conducted in mature-aged athletes or in older populations. Purpose: To identify whether an older adult population had an increased risk of incident radiographic knee OA after a traumatic knee injury compared with a young adult population. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with ACL ruptures who underwent primary reconstruction were enrolled in a prospective, longitudinal single-center study over 15 years. The adult cohort was defined as participants aged ≥35 years who had a knee injury resulting in an ACL tear, the adolescent-young cohort suffered similar knee injuries and were aged ≤25 years, and a third cohort of participants aged 26 to 34 years who suffered a knee injury was included to identify the existence of any age-related dose-response relationship for the onset of radiographic knee OA. A Kaplan-Meier survival analysis was employed to determine the occurrence of incident radiographic OA across the study populations at 2, 5, 10, and 15 years after reconstruction. Significance at each time point was analyzed using chi-square tests. Results: A total of 215 patients, including 112 adolescents (mean age, 20.4 years; 50.9% female), 71 patients aged 26 to 34 years (mean age, 29.2 years; 42.3% female), and 32 adults (mean age, 40.2 years; 59.4% female), were assessed for International Knee Documentation Committee (IKDC) grading on knee radiographs. It was found that 53.0% and 77.8% of adults at a respective 10 and 15 years after reconstruction had an IKDC grade of B or greater compared with 17.7% and 61.6% of the adolescent-young cohort. Chi-square testing found that adults developed OA earlier than adolescents at 5 and 10 years after reconstruction (P = .017 and P < .0001, respectively). However, survival analysis did not demonstrate that adults were more likely to develop radiographic knee OA at 15 years after reconstruction compared with the adolescent-young cohort (P = .4). Conclusion: The age at which an ACL injury is sustained does not appear to influence the rate of incident radiographic knee OA, although mature-aged athletes are likely to arrive at the OA endpoint sooner. [ABSTRACT FROM AUTHOR]

Objective To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. Methods Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. Results Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA ( P < 0.01 for 24 months), 24-month change in tibial ( P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW ( P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated ( P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. Conclusion BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To investigate how different types of meniscal tears predispose to different patterns of meniscal position in subjects with and without symptomatic knee osteoarthritis (OA).Methods: A cross-sectional analysis of 161 women participating in an observational study to evaluate knee OA progression was performed using baseline MRI data. Meniscal morphologic features were scored in three separate locations. Meniscal position measures were determined for extrusion and proportion of coverage. Analysis was performed using multiple linear regression models treating each tear type as an individual variable with a binary response.Results: Complex tears, cysts and maceration of the medial meniscus were associated with more medial (p = 0.0004, p = 0.004, p < 0.0001, respectively) and anterior extrusion (p = 0.03, p = 0.03, p < 0.0001, respectively) than normal menisci. Horizontal tears of the lateral meniscus had more lateral (p = 0.005) and anterior extrusion (p < 0.0001) than normal menisci. Anterior and body tears of the medial meniscus were associated with more anterior extrusion (p = 0.0006, p = 0.01, respectively), whereas meniscal body tears alone had more medial extrusion than normal menisci (p = 0.0002). Meniscal body tears of the lateral meniscus had more lateral extrusion than normal menisci (p = 0.01).Conclusion: Anterior horn and meniscal body tears and the more severe macerated and complex tear types predisposed to more medial meniscal extrusion. Laterally, only meniscal body and horizontal tears significantly affected extrusion, potentially reflecting a lower overall prevalence of lateral meniscal tears. These results may have important implications in identifying tear types associated with more meniscal dysfunction, with the ultimate goal of identifying those at greatest risk for knee OA progression. [ABSTRACT FROM PUBLISHER]

Background: Knee buckling is common in persons with advanced knee osteoarthritis and after orthopedic procedures. Its prevalence in the community is unknown. Objective: To examine the prevalence of knee buckling in the community, its associated risk factors, and its relation to functional limitation. Design: Cross-sectional, population-based study. Setting: The Framingham Osteoarthritis Study. Participants: 2351 men and women age 36 to 94 years (median, 63.5 years). Measurements: Participants were asked whether they had experienced knee buckling or ‘giving way’ and whether it led to falling. They were also asked about knee pain and limitations in function by using the Short Form-12 and Western Ontario and McMaster Universities Osteoarthritis Index, had isometric tests of quadriceps strength, and underwent weight-bearing radiography and magnetic resonance imaging of the knee. Radiographs were scored for osteoarthritis by using the Kellgren—Lawrence scale, and magnetic resonance images were read for anterior cruciate ligament tears. The relationship of buckling to functional limitation was examined by using logistic regression that adjusted for age, sex, body mass index, and knee pain severity. Results: Two hundred seventy-eight participants (11.8%) experienced at least 1 episode of knee buckling within the past 3 months; of these persons, 217 (78.1%) experienced more than 1 episode and 35 (12.6%) fell during an episode. Buckling was independently associated with the presence of knee pain and with quadriceps weakness. Over half of those with buckling had no osteoarthritis on radiography. Persons with knee buckling had worse physical function than those without buckling, even after adjustment for severity of knee pain and weakness. For example, 46.9% of participants with buckling and 21.7% of those without buckling reported limitations in their work (adjusted odds ratio, 2.0 [95% CI, 1.5 to 2.7]). Limitation: Causal inferences are limited because of the study's cross-sectional design. Conclusion: In adults, knee buckling is common and is associated with functional loss. [ABSTRACT FROM AUTHOR]

The article reports on the administration of physical therapy, and its efficacy, in the treatment of patients with osteoarthritis of the knee (OK). Topics discussed include results of a clinical trial in one military hospital in the U.S. involving patients with OK who underwent physical therapy, comparison with a treatment using glucocorticoid injections, and impact on the patients' well-being and the quality of care.