To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI).
The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders.
Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]).
Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA.
Bone marrow; cartilage; knee; osteoarthritis; magnetic resonance imaging
We studied the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression.
We measured mechanical axis from long limb radiographs from the MOST Study and the Osteoarthritis Initiative (OAI) to define valgus limbs (>1° valgus) and examined the effect of valgus vs. neutral (neither varus nor valgus) on OA structural outcomes. Posteroanterior x-rays and knee MRIs were obtained in subjects at the time of the long limb x-ray and at follow-up examinations. Lateral progression was defined by an increase in joint space narrowing (on a semiquantitative scale) and incidence as new lateral narrowing in knees without x-ray OA. We defined lateral cartilage damage and progressive meniscal damage when WORMS (MOST) or BLOKS (OAI) scores for cartilage or meniscus increased at follow-up. We used logistic regression with adjustment for age, sex, BMI and Kellgren and Lawrence grade and used GEE to evaluate the effect of valgus vs. neutral alignment on disease outcomes.
We studied 5046 knees (881 valgus) from MOST and 5953 knees (1235 valgus) from OAI. In both studies, all strata of valgus malalignment including 1.1 to 3° valgus were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment above 3° was associated with incidence (for example in MOST, adjOR = 2.7 (95% 1.1, 6.8)). Valgus 3° or more was also associated with cartilage damage on MRI in knees without OA (for example in OAI, adjOR = 5.9 (95% CI, 1.3, 30.3)). We found a strong relation of valgus with progressive lateral meniscal damage.
Valgus malalignment increases the risk of knee OA x-ray progression, incidence and of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.
Knee Osteoarthritis (OA) and pain are assumed to be barriers for meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportion of people with and without knee OA and knee pain who met recommended physical activity levels through walking.
Cross-sectional analysis of community dwelling adults who have or who are at high risk of knee OA from The Multicenter Osteoarthritis Study. Participants wore a StepWatch activity monitor to record steps/day over 7 days. The proportion that met the recommended physical activity levels was determined as those accumulating ≥150 minutes/week at ≥100 steps/minute in bouts lasting ≥10 minutes. These proportions were also determined for those with and without knee OA, as classified by radiograph, and by severity of knee pain.
Of the 1788 study participants (age 67 sd 8 yrs, BMI 31 sd 6 kg/m2, 60% female), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and without knee OA; 7.3% and 10.1% of men (p=0.34), and 6.3% and 7.8% of women (p=0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe pain versus no pain, 12.9% and 10.9% of men (p=0.74) and 6.7% and 11.0% (p=0.40) of women met recommended physical activity levels.
Disease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA.
Mechanics means relating to or caused by movement or physical forces. In this paper, I shall contend that OA is almost always caused by increased physical forces causing damage to a joint. While examples of joint injury causing osteoarthritis are numerous, I shall contend that most or almost all osteoarthritis is caused in part by mechanically induced injury to joint tissues. Further, once joint pathology has developed, as is the case for almost all clinical osteoarthritis, pathomechanics overwhelms all other factors in causing disease progression. Treatments which correct the pathomechanics have long lasting favorable effects on pain and joint function compared with treatments that suppress inflammation which have only temporary effects. I shall lastly contend that the mechanically induced joint injury leads to variable inflammatory responses but that the role of this inflammation in worsening structural damage in an already osteoarthritic joint has not yet been proven.
osteoarthritis; biomechanics; inflammation
To assess risk of cartilage loss in the tibiofemoral joint in relation to baseline damage severity, and to analyze the association of nearby pathologic findings on the risk of subsequent cartilage loss.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of individuals with or at high risk for knee osteoarthritis. Magnetic resonance imaging (MRI) examinations were assessed according to the Whole Organ Magnetic Resonance Imaging Score (WORMS). Included were all knees with available baseline and 30 months MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in each subregion in relation to the number of associated articular features including bone marrow lesions, meniscal damage and extrusion and also in regard to baseline damage severity, respectively.
13524 subregions of 1365 knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow-up. Risk of cartilage loss was increased for subregions with associated features (ORs 2.53, 95% confidence interval [CI] 2.03-3.15 for one, 4.32 95% CI 3.42-5.47 for two and 5.30 95% CI 3.95-7.12 for three associated features; p for trend <0.0001). Subregions with prevalent cartilage damage showed increased risk for further cartilage loss compared to subregions with intact cartilage at baseline with small superficial defects exhibiting highest risk.
Risk of cartilage loss is increased for subregions with associated pathology and further increased when more than one type of associated feature is present. In addition, prevalent cartilage damage increases risk for subsequent cartilage loss.
magnetic resonance imaging; osteoarthritis; risk factors; cartilage loss; meniscal damage; mensical extrusion; bone marrow lesions
To describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population.
Framingham osteoarthritis (OA) study participants obtained bilateral hand radiographs at baseline and 9-year follow-up. The authors defined radiographic HOA at joint level as Kellgren–Lawrence grade (KLG)≥2, erosive HOA as KLG≥2 plus erosion and symptomatic HOA as KLG≥2 plus pain/aching/stiffness. Presence of HOA at individual level was defined as ≥1 affected joint. The prevalence was age-standardised (US 2000 Population 40–84 years).
Mean (SD) baseline age was 58.9 (9.9) years (56.5% women). The age-standardised prevalence of HOA was only modestly higher in women (44.2%) than men (37.7%), whereas the age-standardised prevalence of erosive and symptomatic OA was much higher in women (9.9% vs 3.3%, and 15.9% vs 8.2%). The crude incidence of HOA over 9-year follow-up was similar in women (34.6%) and men (33.7%), whereas the majority of those women (96.4%) and men (91.4%) with HOA at baseline showed progression during follow-up. Incident metacarpophalangeal and wrist OA were rare, but occurred more frequently and from an earlier age in men than women. Development of erosive disease occurred mainly in those with non-erosive HOA at baseline (as opposed to those without HOA), and was more frequent in women (17.3%) than men (9.6%).
The usual female predominance of prevalent and incident HOA was less clear for radiographic HOA than for symptomatic and erosive HOA. With an ageing population, the impact of HOA will further increase.
In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis. The aim of this study was to examine the validity provided by within-grade scoring.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of subjects with or at risk of knee osteoarthritis. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30 month changes in cartilage and bone marrow lesion assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and bone marrow lesions, using ordinal logistic regression.
1867 knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (aOR 4.4, 95%CI 2.2,8.7) but not ≥ full grade (aOR 1.3, 95%CI 0.8,2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95%CI 3.6,25.1) and ≥ full grade (aOR 5.1, 95%CI 3.2,8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsicompartmental within-grade (medial cartilage damage: aOR 5.5, 95%CI 2.6,11.6; medial worsening of BMLs: aOR 4.9, 95%CI 2.0,12.3) but not full grade worsening of BMLs and cartilage damage.
Within-grade changes in semiquantitative MRI assessment of cartilage and bone marrow lesions are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures.
osteoarthritis; MRI; semiquantitative scoring; WORMS; within grade; validity
Varus and valgus alignment are associated with progression of knee osteoarthritis, but their role in incident disease is less certain. Radiographic measures of incident knee osteoarthritis may be capturing early progression rather than disease development. We tested the hypothesis: in knees with normal cartilage morphology by MRI, varus is associated with incident medial cartilage damage and valgus with incident lateral damage.
In MOST, a prospective study of persons at risk for or with knee osteoarthritis, baseline full-limb x-rays and baseline and 30-month MRIs were acquired. In knees with normal baseline cartilage morphology in all tibiofemoral subregions, we used logistic regression with GEE to examine the association between alignment and incident cartilage damage adjusting for age, gender, BMI, laxity, meniscal tear, and extrusion.
Of 1881 knees, 293 from 256 persons met criteria. Varus vs. non-varus was associated with incident medial damage (adjusted OR 3.59, 95% CI: 1.59, 8.10), as was varus vs. neutral, with evidence of a dose effect (adjusted OR 1.38/1° varus, 95% CI: 1.19, 1.59). Findings held even excluding knees with medial meniscal damage. Valgus was not associated with incident lateral damage. Varus and valgus were associated with a reduced risk of incident lateral and medial damage, respectively.
In knees with normal cartilage morphology, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment. These results support that varus increases the risk for initial development of knee osteoarthritis.
To examine whether erosive hand osteoarthritis (OA) is associated with knee subchondral bone attrition (SBA) and systemic bone mineral density (BMD).
Associations of MRI-defined knee SBA with radiographic erosive hand OA were evaluated in 1253 Framingham participants using logistic regression with generalised estimating equations. We also examined the association between the number of erosive OA finger joints and SBA adjusted for the number of non-erosive OA finger joints. Associations between erosive hand OA and femoral neck BMD were explored in 2236 participants with linear regression. Analyses were adjusted for age, sex and body mass index.
Participants with erosive hand OA had increased odds of knee SBA (OR=1.60, 95% CI 1.07 to 2.38). The relation between the number of erosive OA finger joints and SBA became non-significant when adjusted for the number of non-erosive OA joints as a proxy for the burden of disease. There was a non-significant trend towards higher BMD in erosive hand OA compared with participants without hand OA.
Erosive hand OA was associated with knee SBA, but the relation might be best explained by a heightened burden of disease. No significant relation of erosive hand OA with BMD was found.
This nonsystematic literature review provides an overview of magnetic resonance imaging (MRI) of subchondral bone marrow lesions (BMLs) in association with osteoarthritis (OA), with particular attention to the selection of MRI sequences and semiquantitative scoring systems, characteristic morphology, and differential diagnosis. Histologic basis, natural history, and clinical significance are also briefly discussed.
PubMed was searched for articles published up to 2011, using the keywords bone marrow lesion, osteoarthritis, magnetic resonance imaging, bone marrow edema, histology, pain, and subchondral.
BMLs in association with OA correspond to fibrosis, necrosis, edema, and bleeding of fatty marrow as well as abnormal trabeculae on histopathology. Lesions may fluctuate in size within a short time and are associated with the progression of articular cartilage loss and fluctuation of pain in knee OA. The characteristic subchondral edema-like signal intensity of BMLs should be assessed using T2-weighted, proton density-weighted, intermediate-weighted fat-suppressed fast spin echo or short tau inversion recovery. Several semiquantitative scoring systems are available to characterize and grade the severity of BMLs. Quantitative approaches have also been introduced. Differential diagnoses of degenerative BMLs include a variety of traumatic or nontraumatic pathologies that may appear similar to OA-related BMLs on MRI.
Subchondral BMLs are a common imaging feature of OA with clinical significance and typical signal alteration patterns, which can be assessed and graded by semiquantitative scoring systems using sensitive MRI sequences.
bone marrow lesion; bone marrow edema; osteoarthritis; MRI; knee
The knee can be injected at different anatomic sites with or without image-guidance. We undertook a systematic review to determine the accuracy of intra-articular knee injection (IAKI) and whether this varied by site, use of image-guidance, and experience of injectors, and whether accuracy of injection, site, or use of image-guidance influenced outcomes following IAKIs.
Medline, Embase, AMED, CINAHL, Web of Knowledge, Cochrane Central Registers for Controlled Trials up to Dec 2012 were searched for studies that evaluated either accuracy of IAKIs or outcomes related to accuracy, knee injection sites, or use of image-guidance. Within-study and between-study analyses were performed.
Data from 23 publications were included. Within-study analyses suggested IAKIs at the superomedial patellar, medial midpatellar (MMP), superolateral patellar (SLP) and lateral suprapatellar bursae sites were more accurate when using image-guidance than when blinded (ranges of pooled risk difference 0.09–0.19). Pooling data across studies suggested blinded IAKIs at the SLP site were most accurate (87%) while MMP (64%) and anterolateral joint line (ALJL) sites were (70%) least accurate. Overall about one in five blinded IAKIs were inaccurate. There was some evidence that experience of the injector was linked with improved accuracy for blinded though not image-guided injections. Based on a small number of studies, short but not longer-term outcomes for ultrasound-guided were found to be superior to blinded IAKIs.
Image-guided IAKIs are modestly more accurate than blinded IAKIs especially at the MMP and ALJL sites. Blinded injections at SLP site had good accuracy especially if performed by experienced injectors. Further studies are required to address the question whether accurate localization is linked with an improved response.
Osteoarthritis of the knee; Clinical trials; Injection; Aspiration; Accuracy; Systematic review
While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.
Cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1018 participants (mean age 63.1 ± 7.8 years, 60% female) who had radiographic knee OA and had worn a StepWatch monitor to record steps/day. High- and low- positive affect, and depressive symptoms were based on the Center for Epidemiologic Studies-Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screen.
Compared to respondents with low positive affect (27% of respondents), those with high positive affect (63%) walked similar steps/day while those with depressive symptoms (10%) walked less (adjusted beta coefficients = −32.6 [−458.9, 393.8] and −579.1 [−1274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (p= 0.0045). Among respondents with knee pain (39%), those with high positive affect walked significantly more steps/day (711.0 [55.1, 1366.9]) than those with low positive affect.
High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider to promote physical activity among people with painful knee OA.
Physical Activity; Positive Affect; Depressive Symptoms; Knee Pain; Walking
Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
We conducted a cross-sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by gender and ethnic groups, and if it does, to what extent such a difference is accounted for by knee malalignment.
The NIH-funded Multicenter Osteoarthritis (MOST) Study is an observational study of persons age 50 to 79 years with either symptomatic knee OA or at high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full-limb films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women as well as Caucasians (CC) and African Americans (AA) using a logistic regression model adjusting for covariates (race or gender and BMI, age, education, clinic site), and used generalized estimating equations to account for correlation between two knees within a person.
Of 5202 knees (2652 subjects), 1532 (29.5%) had medial JSN, and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in women’s than in men’s knees (OR=1.9, 95% CI 1.5–2.4) and was also higher in knees of AA than in CC (OR=2.4, 95% CI: 1.7–3.3). Further adjustment for malalignment attenuated the OR for gender but not the OR for race.
Women and AA are more likely to have lateral JSN than men and Caucasians. Valgus malalignment may contribute to the higher prevalence in women.
An association between rheumatoid factor (RF) and increased mortality has been described in individuals with rheumatoid arthritis. The objective of this study was to determine the effect of RF on mortality and coronary heart disease (CHD) in the general population.
Subjects were participants in a population-based study focused on cardiovascular disease who attended for a study visit during the years 1974–84. RF was measured and information obtained on cardiovascular risk factors, joint symptoms and erythrocyte sedimentation rate (ESR). The subjects were followed with respect to mortality and incident CHD through 2005. Adjusted comparison of overall survival and CHD event-free survival in RF-positive versus RF-negative subjects was performed using Cox proportional hazards regression models.
Of 11 872 subjects, 140 had positive RF. At baseline RF was associated with diabetes mellitus and smoking and inversely associated with serum cholesterol. RF-positive subjects had increased all-cause mortality (HR 1.47, 95% CI 1.19 to 1.80) and cardiovascular mortality (HR 1.57, 95% CI 1.15 to 2.14) after adjusting for age and sex. Further adjustment for cardiovascular risk factors and ESR only modestly attenuated this effect. An increase in CHD among the RF-positive subjects did not reach statistical significance (HR 1.32, 95% CI 0.96 to 1.81, adjusted for age and sex). Subjects with RF but without joint symptoms also had increased overall mortality and cardiovascular mortality (HR for overall mortality 1.33, 95% CI 1.01 to 1.74, after adjustment).
In a general population cohort, RF was associated with increased all-cause mortality and cardiovascular mortality after adjustment for cardiovascular risk factors, even in subjects without joint symptoms.
Enthesopathy has been reported as a feature of osteoarthritis (OA) in the distal interphalangeal (DIP) joints. We previously reported that central bone marrow lesions (BML) on magnetic resonance imaging (MRI) scans are associated with OA. In this study, we evaluated whether hand and knee enthesopathy were related.
We studied knee and hand radiographs of subjects from the Framingham Osteoarthritis Study. Subjects seen in 2002–2005 had bilateral posteroanterior hand radiographs, weight-bearing knee radiographs, and knee MRI scans. Hand radiographs were read for enthesophytes at the juxtaarticular non-synovial areas of metacarpophalangeal (MCP), proximal interphalangeal (PIP), and DIP joints, and midshafts of the phalanges. We selected 100 cases of knees with central BML and 100 matched controls. Conditional logistic regression was used to assess associations.
Subjects with enthesophytes of at least 1 score ≥ 2 at DIP, PIP, and/or MCP were not more likely to have central knee BML (OR 0.49, 95% CI 0.17–1.40) than those without enthesophytes. Similarly, having at least 1 score ≥ 2 on the shafts was not significantly associated with having a central knee BML (OR 0.59, 95% CI 0.23–1.51). Adjustment for the presence of diabetes mellitus did not affect these results, but there was an increased prevalence of diabetes in those with hand enthesophytes (OR 3.09, 95% 1.29–7.40, enthesophyte score ≥ 2).
We found no increase in the prevalence of hand enthesophytes among persons with central knee BML on their knee MRI scans. This provides evidence against a systemic enthesopathic disorder in association with knee OA.
OSTEOARTHRITIS; ENTHESOPHYTE; CENTRAL BONE MARROW LESIONS
To determine the effect of quadriceps strength in individuals with knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee pain and function.
We studied 265 subjects (154 men and 111 women, mean ± SD age 67 ± 9 years) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospective, 30-month natural history study of knee OA. Quadriceps strength was measured at baseline, isokinetically, during concentric knee extension. MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints, with medial and lateral compartments assessed separately. At baseline and at followup visits, knee pain was assessed using a visual analog scale, and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index.
There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint. Results were similar in malaligned knees. However, greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain and better physical function over followup (P < 0.001).
Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint, including in malaligned knees. We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint, a finding that requires confirmation. Subjects with greater quadriceps strength also had less knee pain and better physical function over followup.
Given the inconsistency of remission definitions in rheumatoid arthritis (RA) trials, the goal of this American College of Rheumatology/European League Against Rheumatism committee was to define remission.
The committee instructed a working group that a new remission definition, among other requirements, needed to allow for little, if any, active clinical disease and to be defined using the core set of outcome measures for RA trials and that those in remission at one time needed to have a low risk of later worsening function or radiograph progression. Remission was to be defined using trial data for use in trials but needed to anticipate use in a practice setting.
The working group started by evaluating the thresholds for core set measures compatible with remission and determined that patient-reported outcomes contributed importantly to the ability of outcome assessment to distinguish more from less effective treatments. The group created a candidate group of remission definitions to test, including Boolean versions and widely used indexes. Testing how well these candidate definitions predicted later good outcomes, the group found that Disease Activity Score 28 thresholds for remission performed worse than Simplified Disease Activity Index/Clinical Disease Activity Index or Boolean versions. Also, persons with low Disease Activity Score 28 occasionally had high joint counts, which were incompatible with remission. The parent committee chose two definitions: one Boolean (patient had to have all of the following: tender joint count, swollen joint count ≤1, C reactive protein ≤1 mg/dl) and patient global assessment ≤1 (on a 0–10 scale) and one Simplified Disease Activity Index ≤3.3.
The American College of Rheumatology/European League Against Rheumatism has promulgated two new similar definitions of remission for RA trials.
In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST).
MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5T MRI of one knee. Synovitis was scored in 6 compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-contrast enhanced MRI, read for cartilage morphology according to the WORMS method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI.
472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosohexanoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis.
In conclusion, systemic levels of n3 and n6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.
knee osteoarthritis; synovitis; cartilage; fatty acids; inflammation
To describe the association of osteophytes with concomitant cartilage damage in a population-based cohort using semiquantitative MRI assessment and to describe the prevalence of atrophic and hypertrophic phenotypes of tibio-femoral knee osteoarthritis.
Participants of the Framingham Knee Osteoarthritis Study were examined with a 1.5 T MRI system using triplanar intermediate-weighted fat suppressed sequences. Cartilage and osteophytes were assessed according to the WORMS scoring system. Overall prevalence of knees with severe cartilage damage and concomitant osteophyte status was described. The odds ratios of severe cartilage damage according to osteophyte size were estimated using a logistic regression model. An additional analysis assessed knees with absent or only tiny osteophytes (≤2 on a 0-7 scale) in all 10 tibio-femoral subregions but with severe cartilage damage (atrophic phenotype) and knees with large osteophytes (≥5 on a 0-7 scale) and without substantial cartilage damage (hypertrophic phenotype) in regard to radiographic osteoarthritis status.
1597 knees of 1248 subjects were included. 54 of 67 (80.6%) knees with large osteophytes exhibited severe cartilage damage. The risk of severe cartilage damage increased markedly with increasing osteophyte size. 21 knees (1.3%) showed an atrophic phenotype. Only 3 knees (0.2%) exhibited a hypertrophic phenotype.
The majority of knees with severe tibio-femoral cartilage damage exhibit moderate to large osteophytes. The larger the osteophyte, the more likely there was severe cartilage damage. A minority of knees exhibits the so-called atrophic phenotype, which also includes knees without radiographic osteoarthritis. The hypertrophic phenotype is extremely rare
Osteophytes; Magnetic Resonance Imaging; Osteoarthritis; Knee; Cartilage
Objective. IA steroid injections (IASIs) have been shown to relieve pain in knee OA and are widely used in clinical practice. There is, however, evidence of some variation in response. Knowledge of predictors of response could aid in the selection of patients for this therapy. The aim of this systematic review was to determine factors associated with response to IASI in knee OA.
Methods. Medline, Embase, AMED, CINAHL, Web of Science and Cochrane Central Registers for Controlled Trials up to January 2012 were searched with additional hand searches of relevant articles. Studies included were those that involved adults diagnosed with knee OA in whom IASIs were administered and factors that predicted treatment response were investigated.
Results. Eleven publications meeting these criteria were reviewed and relevant information extracted. It was not possible to pool the results because of the different predictors studied, variable outcome measures, different criteria for symptom change and missing data. Given the relative paucity of data and small heterogeneously designed studies, it was difficult to identify predictors of response. Data from individual publications, although not consistent across studies, suggest that the presence of effusion, withdrawal of fluid from the knee, severity of disease, absence of synovitis, injection delivery under US guidance and greater symptoms at baseline may all improve the likelihood of response to IASI.
Conclusion. Further larger-scale studies using standardized methods are required to characterize predictors of response and should focus on synovitis, effusion, pain and structural severity of disease. Such data would help in better targeting therapy to those most likely to benefit.
osteoarthritis of the knee; clinical trials; treatment response; predictors of response; systematic review
To evaluate if two different measures of synovial activation, baseline Hoffa-synovitis and effusion-synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis (OA) of the knee.
Non-contrast enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a STIR sequence in the coronal plane. Hoffa-synovitis, effusion-synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic OA nor MRI-detected tibio-femoral cartilage damage at the baseline visit. Presence of Hoffa-synovitis was defined as any grade ≥2 (range from 0–3) and effusion-synovitis as any grade ≥2 (range from 0–3). We performed logistic regression to examine the relation of presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders of cartilage loss.
Of 514 knees included in the analysis, prevalence of Hoffa-synovitis and effusion-synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion-synovitis was associated with an increased risk for cartilage loss (odds ratio (OR) = 2.7, 95% confidence intervals 1.4–5.1, p=0.002); however, no such an association was observed for baseline Hoffa-synovitis (OR =1.0, 95% confidence intervals 0.5–2.0).
Baseline effusion-synovitis, but not Hoffa-synovitis, predicted cartilage loss. Our findings suggest that effusion-synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in future development of cartilage lesions in knees without OA.
Osteoarthritis; magnetic resonance imaging; effusion; synovitis; cartilage loss
To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs.
Subjects from the Multicenter Osteoarthritis Study aged 50–79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month MRI of knees (n=1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form ‘more loaded’ compartment, while lateral compartment in valgus and medial compartment in varus were combined to form ‘less loaded’ compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline.
Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment (adjusted RRs [95%CI]: 1.5 [1.2–1.9]) and valgus alignment in the lateral compartment (1.4 [1.0–2.1]). Increase in BML score was more likely in the more loaded compartments (1.7 [1.4–2.0]) in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees (0.8, [0.7–1.0]).
Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.
bone marrow lesion; malalignment; osteoarthritis; knee; MRI