A joint contains many different tissues that can exhibit pathological changes, providing many pot... more A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in th...
Additional file 1: Table S1. Distribution of Pfirmanns type I-V cervical degenerative disc diseas... more Additional file 1: Table S1. Distribution of Pfirmanns type I-V cervical degenerative disc disease in athletes less than 20, 20–29 and > 30 years old by sport
Objective To describe the frequency and severity of magnetic resonance imaging (MRI) based periph... more Objective To describe the frequency and severity of magnetic resonance imaging (MRI) based peripheral osteoarthritis (OA) in athletes during the Rio de Janeiro 2016 Olympic Games. Methods All MRIs of the peripheral joints in Olympic athletes, performed at the centralized imaging facility, either following acute trauma or for non-traumatic joint pain, were included. All MRIs were retrospectively reviewed for presence and severity of MRI-based OA using an adapted Outerbridge classification for cartilage and adapted classifications for other tissues. Scoring of MRI abnormalities was independently and retrospectively performed without reference to the on-site clinical reports. The frequencies of MRI-detected OA were tabulated and grouped into sports categories, athletes’ age ( Results 11,274 athletes participated in the Games. 320 athletes underwent MRI of the peripheral joints. One hundred sixty (50.0%) were female, 109 (34.1%) were Conclusions MRI-defined OA was not uncommon among eli...
Objective To describe the frequency and the distribution of degenerative disc disease (DDD) detec... more Objective To describe the frequency and the distribution of degenerative disc disease (DDD) detected in athletes who underwent spine MRI in the 2016 Summer Olympic Games in Rio de Janeiro. Methods Data on spine MRI examinations from the 2016 Summer Olympics were retrospectively analyzed. We assessed the frequency of DDD of the cervical (Cs), thoracic (Ts), and lumbar (Ls) spine using Pfirrmann’s classification. Grade II and III were considered as mild, grade IV as moderate, and grade V as severe disc degeneration. Data were analyzed according to the location of the degenerative disc, type of sport, age-groups, and gender of the athletes. Results One hundred out of 11,274 athletes underwent 108 spine MRI’s (21 C, 6 T, and 81 L) (53% Females (F), 47% Males (M)). The frequency of DDD was 40% (42% F, 58% M) over the entire spine (28% mild, 9% moderate and 3% severe). There were 58% (12%F, 88%M) of the cervical spine discs that showed some degree of degeneration (44% mild, 13.5% moderate...
To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis... more To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (ROA) (i.e. 'early OA model') exhibit MRI-defined structural tissue pathology to a greater extent and show higher rates of progression compared to knees with bilateral radiographically normal knees without risk factors ('healthy reference'). Methods: We included 154 knees from the Osteoarthritis Initiative without ROA (Kellgren-Lawrence ¼ 0), but with definite ROA (Kellgren-Lawrence !2) in the contralateral knee, and 78 participants from the OAI healthy reference cohort (without any signs of radiographic OA, knee pain or risk factors in either knee). Effusionsynovitis, Hoffa-synovitis, bone marrow lesions (BMLs), cartilage lesions, meniscus morphology and-extrusion and osteophytes were assessed at year 1 (Y1) and year 4 (Y4). Frequencies of features for both groups at Y1 and rates of worsening from Y1 to Y4 were compared using Fisher's exact test. Results: 69% (early OA model) vs. 46% (healthy reference) had baseline Hoffa-synovitis, 26% vs. 19% effusionsynovitis, 27% vs. 13% femorotibial (FT) BMLs, 77% vs. 50% FT cartilage lesions, 36% vs. 9% meniscal damage, 51% vs. 24% meniscus extrusion, and 92% vs. 74% FT osteophytes. Apart from effusion-synovitis, all differences were statistically significant. For structural worsening, statistically significant differences were observed for FT cartilage (p ¼ 0.03) and FT osteophytes (p ¼ 0.01). Conclusion: MRI structural abnormalities are substantially more frequent and more progressive in radiographically normal knees with contralateral osteoarthritis than in 'healthy reference' controls. Compared with published data, they also are more frequent compared to radiographically normal knees "at risk", without contralateral knee OA.
Background: The evolution of pain in relation to damage in the synovium, bone and cartilage in os... more Background: The evolution of pain in relation to damage in the synovium, bone and cartilage in osteoarthritis (OA), coupled with their relation to wet biochemical markers are not well understood. Objectives: In this study we evaluated the relation between structural damage by MRI, clinical and pain sensitisation measures and wet biochemical biomarkers in knee OA. Methods: We recruited 130 participants fulfilling ACR criteria with advanced OA requiring total knee replacement (TKR) (n=80), mild OA having standard care (n=42) and non-OA controls (n=8). Knee MRI in 90 subjects (72 F, 18 M) was acquired and assessed by two radiologists with the MRI Knee Osteoarthritis Score (MOAKS). Overall MOAKS scores were created for Bone Marrow Lesions (BML), Cartilage Degradation (CD) and effusion/Hoffa synovitis (tSyn). Type II collagen cleavage products (CTX-II) were determined by ELISA. Clinical scoring was performed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain levels (WOMAC_P), Hospital Anxiety and Depression Scale (HADS), Body mass index (BMI) and pain sensitisation with pain pressure thresholds (PPT) of the patella by Quantitative Sensory Testing (QST). Results: The mild OA group had a mean age of 63 +/-9 yr and the advanced OA group 69 +/-9 yr. The advanced OA group had higher levels of pain, with a mean WOMAC_P of 58 +/-22 compared with the mild OA group who had a mean WOMAC_P of 40 +/-22. WOMAC_P correlated with the total number of regions with cartilage damage (nCD) (R=0.225, p=0.033) and total number of BMLs (nBML) (R=0.195, p=0.065) using BMI, age and HADS as covariates. Levels of CTX-II correlated with tSyn (R=0.313, p=0.03), nBML (R=0.252, p=0.019), number of osteophytes (R=0.33, p=0.002) and nCD (R=0.218, p=0.042), using BMI and age as covariates. The correlation for urinary CTX-II with tSyn (p=0.006) is shown in Figure 1 using a partial linear regression analysis of MOAKS, BMI and age. We also found CTX-II correlated with lesion load scores (total number of lesions multiplied by MOAKS size by% damage scores) for CD (R=0.277, p=0.009) and BML (r=0.308, p=0.004). PPT correlated with patella MOAKS scores for nBML (R=-0.221, p=0.038) and nCD (R=-0.279, p=0.009), with HADS, BMI and age as covariates. Conclusion: There is a direct correlation between the degree of cartilage damage and BMLs with pain in OA. Type II collagen degradation products were higher when there was more severe MRI-detected synovitis, BMLs and cartilage damage in the knee joint, suggesting that the source of enzymes degrading type II collagen in OA, including matrix metalloproteinases, are also likely to be produced by synovium and bone (1) and not just cartilage, as previously hypothesised in other studies. There was also a correlation between pain sensitisation and frequency of BMLs and cartilage degradation, suggesting that molecular mediators of pain sensitisation, which we have shown are produced by BMLs (1), are a cause of patient-reported OA pain. Conclusion: Our results demonstrate the prognostic value of effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage damage, and meniscal extrusion
Fig 2. Example UTE-T2* maps from (a) an asymptomatic subject (average ± SD UTE-T2* value = 8±2 ms... more Fig 2. Example UTE-T2* maps from (a) an asymptomatic subject (average ± SD UTE-T2* value = 8±2 ms), (b) ACL injury with surface intact medial meniscus (13±5 ms), and (c) ACL injury with visible tear to the medial meniscus (21±7 ms).
Author contributions: E. Macri was involved in conception and design of the present study, conduc... more Author contributions: E. Macri was involved in conception and design of the present study, conducted analyses, interpreted results, drafted and edited the article, and approved the final version of the manuscript. D. Felson, T. Neogi, J. Torner, C. Lewis and M. Nevitt were involved in original conception and design of the parent study (i.e. MOST study), assisted with interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. M. Ziegler provided guidance for statistical design and analyses, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. T. Cooke conducted data acquisition, assisted in study design and interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. A. Guermazi and F. Roemer were involved in original conception and design of the parent study (i.e., MOST study), conducted data acquisition, assisted with interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. J. Stefanik was involved in conception and design of the present study, conducted analyses, interpreted results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. J. Stefanik and E. Macri take responsibility for the integrity of the work as a whole.
There are few guidelines for clinical trials of interventions for prevention of post-traumatic os... more There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventio...
Aims were to assess (1) structural progression in knees with no/mild radiographic osteoarthritis ... more Aims were to assess (1) structural progression in knees with no/mild radiographic osteoarthritis (ROA) (i.e. Kellgren-Lawrence (K-L) grades 0 to 2) that will undergo knee replacement (KR) during a 5-year period; (2) differences in structural damage on MRI between knees with no/mild ROA vs. those with severe ROA (i.e. K-L 3 and 4) at baseline; and (3) differences in pain levels between those groups. All participants who underwent KR from baseline (BL) to 60 months were drawn from the Osteoarthritis Initiative. MRIs were assessed for bone marrow lesions (BMLs), Hoffa- and effusion-synovitis (i.e. hyperintensity signal changes in the fat pad and abnormal amount of capsular distension due to intraaticular joint fluid and/or synovial thickening) at BL and the time point before KR (T0). The measures of WOMAC and KOOS pain were used for pain characterization. WOMAC Activity of Daily Life (ADL) and KOOS Quality of Life (QoL) were applied to characterize functional status of the included par...
Purpose: Knee osteoarthritis (OA) occurs both in the patellofemoral (PFJ) and tibiofemoral joints... more Purpose: Knee osteoarthritis (OA) occurs both in the patellofemoral (PFJ) and tibiofemoral joints (TFJ). Previous authors have attempted to determine the compartmental prevalence and distribution of knee OA using x-ray and some have suggested that disease in the TFJ was more prevalent than in the PFJ. However, PFJ damage may be underestimated in x-ray studies. MRI can provide information on the compartmental distribution of cartilage and bone damage in both the TFJ and PFJ. The purpose of this study was to describe the prevalence of structural damage among compartments of the knee joint using MRI. Methods: 995 knees, one knee per subject, from the Framingham Community Cohort, a population-based sample of individuals aged 50 and over, who were recruited without regard for knee pain and underwent 1.5 T MRI with turbo spin-echo fat-suppressed images acquired in sagittal, coronal and axial planes. Cartilage damage and subchondral bone marrow lesions (BMLs) were assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Structural damage was defined in 3 ways: any cartilage damage (WORMS greater than 1; focal cartilage defect or superficial cartilage loss not extending to bone), severe cartilage damage (WORMS greater than 4; diffuse cartilage loss extending to bone), and any bone marrow lesion (WORMS greater than 0). The PFJ included medial and lateral patellar and anterior femoral (trochlear) regions. The medial and lateral TFJs included medial and lateral tibial plateaus (central, anterior, and posterior subregions) and opposing central and posterior subregions of the femur. We determined the prevalence of structural damage as isolated PFJ, isolated medial TFJ, isolated lateral TFJ, mixed (both PFJ and either medial or lateral TFJ), or no damage. Any subregion with damage defined structural damage in that compartment. PA and lateral weight bearing x-ray views were used to determine radiographic OA (ROA) compartmental involvement, defined as KL ≥ 2. We additionally performed a sub-analysis between males and females and in knees that were reported to have pain lasting at least a month in or around the knee to determine if the same patterns persisted. Results: The mean age was 63.4 years, mean BMI 28.6, and 57% were female. Isolated PFJ damage occurred in 20, 15 and 18% of knees depending on the definition used, respectively. Isolated PFJ damage was more common than isolated TFJ damage using any definition (see Table). Additionally, when using the severe cartilage damage definition, isolated PFJ damage was also more common than mixed involvement (damage in both the PFJ and TFJ). Mixed damage was the most common pattern when using the any cartilage damage and any BML definition. Further, among those with mixed damage using the any cartilage definition (n = 437), the most severe lesion was more often in the PFJ (n = 182) rather than the medial (n = 92) or lateral (n = 20) TFJ. This was also true among those with mixed damage using the any BML definition. Isolated PFJ structural damage was more common using MRI criteria than x-ray. Similar patterns were seen for both males and females and in knees with pain. Conclusions: Isolated PFJ structural damage is more common than isolated TFJ damage. Using MRI to directly visualize cartilage and bone yielded a greater prevalence of damage than ROA status. While the high prevalence and impact of PFJ has been recognized before, our data suggest it may be the predominant compartment affected by knee OA.
Objective. To determine the relationship between biochemical markers involved in bone turnover an... more Objective. To determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA). Methods. We analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n 5 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm 2) 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-Ia and CTX-Ib) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates. Results. At 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 R 2 5 0.032), and changes in bone shape over 24 months (partial R 2 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 R 2 5 0.028). Conclusion. We 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. This article was prepared using an Osteoarthritis Initiative (OAI) public-use data set, and its contents do not necessarily reflect the opinions or views of the OAI Study Investigators, the NIH, or the private funding partners of the OAI. The OAI is a public-private partnership between the NIH (contracts N01
Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investi... more Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW). A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2-3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries). Minimal tibiofemoral joint space and KL grade on plain radiograph of the knee were assessed at baseline and at yearly followup up to 3 years. In a subset, serial knee MRI examinations were performed. Individuals with a bone marrow lesion (BML) ≥ grade 2 at the tibiofemoral joint at baseline were classified as BML-positive. Relationships between change in JSW and risk factors were assessed using linear regression. The mean age of study participants was 62.8 (SD 7.5) years and 73% were female; 38.6% had BML. Mean baseline JSW was 3.65 mm. This reduced by 0.18 (0.30) mm/year in m...
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 2009
Letter to the Editor MRI-based semiquantitative assessment of subchondral bone marrow lesions in ... more Letter to the Editor MRI-based semiquantitative assessment of subchondral bone marrow lesions in osteoarthritis research We would like to comment on magnetic resonance imaging (MRI) assessment of bone marrow lesions (BMLs) in osteoarthritis (OA) research from a radiologic perspective. Selection of pulse sequences that are able to depict the maximum extent of BMLs is of paramount importance for subsequent correct assessment of the size of these lesions. A recently published article investigating a canine OA model by MRI suggested that to accurately assess semiquantitative size and extent of BMLs a combination of different pulse sequences should be used, and that this information could also apply to human clinical studies 1. In that study the authors used a protocol of T1-weighted threedimensional (3D) fast gradient recalled echo (GRE), sagittal fat-suppressed (FS) 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo (FSE) with fat saturation sequences and assessed BMLs using a semiquantitative scoring approach. Another article by the same research group published in ''Annals of the Rheumatic Diseases'' recently investigated subchondral bone lesions with a quantitative MRI approach 2. Acquisition of BMLs in that publication was performed on a 1.5 T system using a single 3D fast imaging with steady state precession (FISP) e sequence, a GRE-type sequence. While it has been shown that GRE-type sequences such as SPGR, fast low angle shot (FLASH), 3-point Dixon, double echo steady state (DESS) and others are very sensitive in delineating subchondral cysts, ''even with robust FS or WE [water excitation], these sequences are notoriously insensitive to marrow abnormality'' 3 due to trabecular magnetic susceptibility or T2* effects and will not show the true extent of these lesions (Fig. 1). Inferior demonstration of subchondral bone marrow changes on GRE-type sequences has also been acknowledged by other radiological research groups 4,5. This fact was summarized and published in a consensus statement by OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) in 2006 3. For these reasons research groups in the radiological community have been applying either T2-weighted, proton density (PD)-weighted, intermediate-weighted (IW) FS FSE or short tau inversion recovery (STIR) sequences to assess non-cystic BMLs in OA research 6e10. It has also been suggested that comparable results for BML assessment may be achieved for T1-weighted FS sequences after intravenous gadolinium
Purpose: To describe the anatomical distribution of synovitis and its association with joint effu... more Purpose: To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA). Methods: Baseline MRI was performed at 1.5 T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences. Results: 111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence. Conclusion: Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening.
Although there is an abundance of literature regarding the development of knee osteoarthritis fol... more Although there is an abundance of literature regarding the development of knee osteoarthritis following rupture of the anterior cruciate ligament (ACL), the exact mechanism underlying this link is still not clear. Recent studies have reported that a number of factors may be predictive of the subsequent development of osteoarthritis, with damage to the menisci and articular cartilage during the initial trauma, altered knee biomechanics post-injury, and episodic instability chief among them. This article summarizes recent developments in the understanding of the joint damage resulting from an ACL tear, and the influence that current and future treatment methods may have on the long-term progression to osteoarthritis.
between this source and the sites of EAG potential measurements on the skin. Results: The EAG rep... more between this source and the sites of EAG potential measurements on the skin. Results: The EAG repeatability was assessed with a test-retest protocol for 14 normal subjects. This protocol showed statistically significant high Intraclass Correlation Coefficients between the first and second tests for four electrode sites overlying the joint line (p < 0.05). These sites also showed the highest mean EAG values. In the control group, the mean amplitude of the EAG signals was statistically larger over the medial side than over the lateral side of the knee (0.231 AE 0.017 mV vs. 0.126 AE 0.042 mV for two sites over the joint line, p < 0.001), reflecting joint forces that are known to be higher on the medial side (mean AE standard error). For EAG signals recorded over the total knee replacement, their mean amplitude was statistically not different than zero, reflecting the absence of cartilage. For signals collected over the arthritic knees, their mean amplitude was statistically lower than in healthy subjects (0.057 AE 0.043 mV vs. 0.231 AE 0.017 mV for a medial site over the joint line, p < 0.001), reflecting the deterioration of cartilage caused by osteoarthritis. In the control group, the correlation coefficients between the amplitude of the EAG at each electrode site, and anthropometric variables such as age, weight, body mass index and height were not statistically significant; similarly, no significant differences were observed between men and women for the mean EAG values at each site. Finally, the finite element model computed electric potential distributions with maximum potential values located over the joint line, corresponding well to the maximum values that were measured experimentally in the Control subjects. Conclusions: Further analyses indicate that EAG signals arise from the 'streaming potentials' that can be measured directly on the surface of the articular cartilage during compression. Cartilage degradation, produced by a reduction in the concentration of glycosaminoglycans or collagen content, is known to decrease the amplitude of the streaming potentials. Therefore, electroarthrography constitutes a non-invasive method for measuring streaming potentials and for assessing cartilage degradation. The non-invasive nature of the EAG, its sensitivity to cartilage degradation, as well as its low cost make this approach very interesting for the early diagnosis of osteoarthritis and to monitor patients during the assessment of new treatments.
A joint contains many different tissues that can exhibit pathological changes, providing many pot... more A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in th...
Additional file 1: Table S1. Distribution of Pfirmanns type I-V cervical degenerative disc diseas... more Additional file 1: Table S1. Distribution of Pfirmanns type I-V cervical degenerative disc disease in athletes less than 20, 20–29 and > 30 years old by sport
Objective To describe the frequency and severity of magnetic resonance imaging (MRI) based periph... more Objective To describe the frequency and severity of magnetic resonance imaging (MRI) based peripheral osteoarthritis (OA) in athletes during the Rio de Janeiro 2016 Olympic Games. Methods All MRIs of the peripheral joints in Olympic athletes, performed at the centralized imaging facility, either following acute trauma or for non-traumatic joint pain, were included. All MRIs were retrospectively reviewed for presence and severity of MRI-based OA using an adapted Outerbridge classification for cartilage and adapted classifications for other tissues. Scoring of MRI abnormalities was independently and retrospectively performed without reference to the on-site clinical reports. The frequencies of MRI-detected OA were tabulated and grouped into sports categories, athletes’ age ( Results 11,274 athletes participated in the Games. 320 athletes underwent MRI of the peripheral joints. One hundred sixty (50.0%) were female, 109 (34.1%) were Conclusions MRI-defined OA was not uncommon among eli...
Objective To describe the frequency and the distribution of degenerative disc disease (DDD) detec... more Objective To describe the frequency and the distribution of degenerative disc disease (DDD) detected in athletes who underwent spine MRI in the 2016 Summer Olympic Games in Rio de Janeiro. Methods Data on spine MRI examinations from the 2016 Summer Olympics were retrospectively analyzed. We assessed the frequency of DDD of the cervical (Cs), thoracic (Ts), and lumbar (Ls) spine using Pfirrmann’s classification. Grade II and III were considered as mild, grade IV as moderate, and grade V as severe disc degeneration. Data were analyzed according to the location of the degenerative disc, type of sport, age-groups, and gender of the athletes. Results One hundred out of 11,274 athletes underwent 108 spine MRI’s (21 C, 6 T, and 81 L) (53% Females (F), 47% Males (M)). The frequency of DDD was 40% (42% F, 58% M) over the entire spine (28% mild, 9% moderate and 3% severe). There were 58% (12%F, 88%M) of the cervical spine discs that showed some degree of degeneration (44% mild, 13.5% moderate...
To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis... more To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (ROA) (i.e. 'early OA model') exhibit MRI-defined structural tissue pathology to a greater extent and show higher rates of progression compared to knees with bilateral radiographically normal knees without risk factors ('healthy reference'). Methods: We included 154 knees from the Osteoarthritis Initiative without ROA (Kellgren-Lawrence ¼ 0), but with definite ROA (Kellgren-Lawrence !2) in the contralateral knee, and 78 participants from the OAI healthy reference cohort (without any signs of radiographic OA, knee pain or risk factors in either knee). Effusionsynovitis, Hoffa-synovitis, bone marrow lesions (BMLs), cartilage lesions, meniscus morphology and-extrusion and osteophytes were assessed at year 1 (Y1) and year 4 (Y4). Frequencies of features for both groups at Y1 and rates of worsening from Y1 to Y4 were compared using Fisher's exact test. Results: 69% (early OA model) vs. 46% (healthy reference) had baseline Hoffa-synovitis, 26% vs. 19% effusionsynovitis, 27% vs. 13% femorotibial (FT) BMLs, 77% vs. 50% FT cartilage lesions, 36% vs. 9% meniscal damage, 51% vs. 24% meniscus extrusion, and 92% vs. 74% FT osteophytes. Apart from effusion-synovitis, all differences were statistically significant. For structural worsening, statistically significant differences were observed for FT cartilage (p ¼ 0.03) and FT osteophytes (p ¼ 0.01). Conclusion: MRI structural abnormalities are substantially more frequent and more progressive in radiographically normal knees with contralateral osteoarthritis than in 'healthy reference' controls. Compared with published data, they also are more frequent compared to radiographically normal knees "at risk", without contralateral knee OA.
Background: The evolution of pain in relation to damage in the synovium, bone and cartilage in os... more Background: The evolution of pain in relation to damage in the synovium, bone and cartilage in osteoarthritis (OA), coupled with their relation to wet biochemical markers are not well understood. Objectives: In this study we evaluated the relation between structural damage by MRI, clinical and pain sensitisation measures and wet biochemical biomarkers in knee OA. Methods: We recruited 130 participants fulfilling ACR criteria with advanced OA requiring total knee replacement (TKR) (n=80), mild OA having standard care (n=42) and non-OA controls (n=8). Knee MRI in 90 subjects (72 F, 18 M) was acquired and assessed by two radiologists with the MRI Knee Osteoarthritis Score (MOAKS). Overall MOAKS scores were created for Bone Marrow Lesions (BML), Cartilage Degradation (CD) and effusion/Hoffa synovitis (tSyn). Type II collagen cleavage products (CTX-II) were determined by ELISA. Clinical scoring was performed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain levels (WOMAC_P), Hospital Anxiety and Depression Scale (HADS), Body mass index (BMI) and pain sensitisation with pain pressure thresholds (PPT) of the patella by Quantitative Sensory Testing (QST). Results: The mild OA group had a mean age of 63 +/-9 yr and the advanced OA group 69 +/-9 yr. The advanced OA group had higher levels of pain, with a mean WOMAC_P of 58 +/-22 compared with the mild OA group who had a mean WOMAC_P of 40 +/-22. WOMAC_P correlated with the total number of regions with cartilage damage (nCD) (R=0.225, p=0.033) and total number of BMLs (nBML) (R=0.195, p=0.065) using BMI, age and HADS as covariates. Levels of CTX-II correlated with tSyn (R=0.313, p=0.03), nBML (R=0.252, p=0.019), number of osteophytes (R=0.33, p=0.002) and nCD (R=0.218, p=0.042), using BMI and age as covariates. The correlation for urinary CTX-II with tSyn (p=0.006) is shown in Figure 1 using a partial linear regression analysis of MOAKS, BMI and age. We also found CTX-II correlated with lesion load scores (total number of lesions multiplied by MOAKS size by% damage scores) for CD (R=0.277, p=0.009) and BML (r=0.308, p=0.004). PPT correlated with patella MOAKS scores for nBML (R=-0.221, p=0.038) and nCD (R=-0.279, p=0.009), with HADS, BMI and age as covariates. Conclusion: There is a direct correlation between the degree of cartilage damage and BMLs with pain in OA. Type II collagen degradation products were higher when there was more severe MRI-detected synovitis, BMLs and cartilage damage in the knee joint, suggesting that the source of enzymes degrading type II collagen in OA, including matrix metalloproteinases, are also likely to be produced by synovium and bone (1) and not just cartilage, as previously hypothesised in other studies. There was also a correlation between pain sensitisation and frequency of BMLs and cartilage degradation, suggesting that molecular mediators of pain sensitisation, which we have shown are produced by BMLs (1), are a cause of patient-reported OA pain. Conclusion: Our results demonstrate the prognostic value of effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage damage, and meniscal extrusion
Fig 2. Example UTE-T2* maps from (a) an asymptomatic subject (average ± SD UTE-T2* value = 8±2 ms... more Fig 2. Example UTE-T2* maps from (a) an asymptomatic subject (average ± SD UTE-T2* value = 8±2 ms), (b) ACL injury with surface intact medial meniscus (13±5 ms), and (c) ACL injury with visible tear to the medial meniscus (21±7 ms).
Author contributions: E. Macri was involved in conception and design of the present study, conduc... more Author contributions: E. Macri was involved in conception and design of the present study, conducted analyses, interpreted results, drafted and edited the article, and approved the final version of the manuscript. D. Felson, T. Neogi, J. Torner, C. Lewis and M. Nevitt were involved in original conception and design of the parent study (i.e. MOST study), assisted with interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. M. Ziegler provided guidance for statistical design and analyses, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. T. Cooke conducted data acquisition, assisted in study design and interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. A. Guermazi and F. Roemer were involved in original conception and design of the parent study (i.e., MOST study), conducted data acquisition, assisted with interpretation of results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. J. Stefanik was involved in conception and design of the present study, conducted analyses, interpreted results, contributed intellectually to manuscript revisions, and approved the final version of the manuscript. J. Stefanik and E. Macri take responsibility for the integrity of the work as a whole.
There are few guidelines for clinical trials of interventions for prevention of post-traumatic os... more There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventio...
Aims were to assess (1) structural progression in knees with no/mild radiographic osteoarthritis ... more Aims were to assess (1) structural progression in knees with no/mild radiographic osteoarthritis (ROA) (i.e. Kellgren-Lawrence (K-L) grades 0 to 2) that will undergo knee replacement (KR) during a 5-year period; (2) differences in structural damage on MRI between knees with no/mild ROA vs. those with severe ROA (i.e. K-L 3 and 4) at baseline; and (3) differences in pain levels between those groups. All participants who underwent KR from baseline (BL) to 60 months were drawn from the Osteoarthritis Initiative. MRIs were assessed for bone marrow lesions (BMLs), Hoffa- and effusion-synovitis (i.e. hyperintensity signal changes in the fat pad and abnormal amount of capsular distension due to intraaticular joint fluid and/or synovial thickening) at BL and the time point before KR (T0). The measures of WOMAC and KOOS pain were used for pain characterization. WOMAC Activity of Daily Life (ADL) and KOOS Quality of Life (QoL) were applied to characterize functional status of the included par...
Purpose: Knee osteoarthritis (OA) occurs both in the patellofemoral (PFJ) and tibiofemoral joints... more Purpose: Knee osteoarthritis (OA) occurs both in the patellofemoral (PFJ) and tibiofemoral joints (TFJ). Previous authors have attempted to determine the compartmental prevalence and distribution of knee OA using x-ray and some have suggested that disease in the TFJ was more prevalent than in the PFJ. However, PFJ damage may be underestimated in x-ray studies. MRI can provide information on the compartmental distribution of cartilage and bone damage in both the TFJ and PFJ. The purpose of this study was to describe the prevalence of structural damage among compartments of the knee joint using MRI. Methods: 995 knees, one knee per subject, from the Framingham Community Cohort, a population-based sample of individuals aged 50 and over, who were recruited without regard for knee pain and underwent 1.5 T MRI with turbo spin-echo fat-suppressed images acquired in sagittal, coronal and axial planes. Cartilage damage and subchondral bone marrow lesions (BMLs) were assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Structural damage was defined in 3 ways: any cartilage damage (WORMS greater than 1; focal cartilage defect or superficial cartilage loss not extending to bone), severe cartilage damage (WORMS greater than 4; diffuse cartilage loss extending to bone), and any bone marrow lesion (WORMS greater than 0). The PFJ included medial and lateral patellar and anterior femoral (trochlear) regions. The medial and lateral TFJs included medial and lateral tibial plateaus (central, anterior, and posterior subregions) and opposing central and posterior subregions of the femur. We determined the prevalence of structural damage as isolated PFJ, isolated medial TFJ, isolated lateral TFJ, mixed (both PFJ and either medial or lateral TFJ), or no damage. Any subregion with damage defined structural damage in that compartment. PA and lateral weight bearing x-ray views were used to determine radiographic OA (ROA) compartmental involvement, defined as KL ≥ 2. We additionally performed a sub-analysis between males and females and in knees that were reported to have pain lasting at least a month in or around the knee to determine if the same patterns persisted. Results: The mean age was 63.4 years, mean BMI 28.6, and 57% were female. Isolated PFJ damage occurred in 20, 15 and 18% of knees depending on the definition used, respectively. Isolated PFJ damage was more common than isolated TFJ damage using any definition (see Table). Additionally, when using the severe cartilage damage definition, isolated PFJ damage was also more common than mixed involvement (damage in both the PFJ and TFJ). Mixed damage was the most common pattern when using the any cartilage damage and any BML definition. Further, among those with mixed damage using the any cartilage definition (n = 437), the most severe lesion was more often in the PFJ (n = 182) rather than the medial (n = 92) or lateral (n = 20) TFJ. This was also true among those with mixed damage using the any BML definition. Isolated PFJ structural damage was more common using MRI criteria than x-ray. Similar patterns were seen for both males and females and in knees with pain. Conclusions: Isolated PFJ structural damage is more common than isolated TFJ damage. Using MRI to directly visualize cartilage and bone yielded a greater prevalence of damage than ROA status. While the high prevalence and impact of PFJ has been recognized before, our data suggest it may be the predominant compartment affected by knee OA.
Objective. To determine the relationship between biochemical markers involved in bone turnover an... more Objective. To determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA). Methods. We analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n 5 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm 2) 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-Ia and CTX-Ib) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates. Results. At 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 R 2 5 0.032), and changes in bone shape over 24 months (partial R 2 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 R 2 5 0.028). Conclusion. We 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. This article was prepared using an Osteoarthritis Initiative (OAI) public-use data set, and its contents do not necessarily reflect the opinions or views of the OAI Study Investigators, the NIH, or the private funding partners of the OAI. The OAI is a public-private partnership between the NIH (contracts N01
Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investi... more Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW). A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2-3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries). Minimal tibiofemoral joint space and KL grade on plain radiograph of the knee were assessed at baseline and at yearly followup up to 3 years. In a subset, serial knee MRI examinations were performed. Individuals with a bone marrow lesion (BML) ≥ grade 2 at the tibiofemoral joint at baseline were classified as BML-positive. Relationships between change in JSW and risk factors were assessed using linear regression. The mean age of study participants was 62.8 (SD 7.5) years and 73% were female; 38.6% had BML. Mean baseline JSW was 3.65 mm. This reduced by 0.18 (0.30) mm/year in m...
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 2009
Letter to the Editor MRI-based semiquantitative assessment of subchondral bone marrow lesions in ... more Letter to the Editor MRI-based semiquantitative assessment of subchondral bone marrow lesions in osteoarthritis research We would like to comment on magnetic resonance imaging (MRI) assessment of bone marrow lesions (BMLs) in osteoarthritis (OA) research from a radiologic perspective. Selection of pulse sequences that are able to depict the maximum extent of BMLs is of paramount importance for subsequent correct assessment of the size of these lesions. A recently published article investigating a canine OA model by MRI suggested that to accurately assess semiquantitative size and extent of BMLs a combination of different pulse sequences should be used, and that this information could also apply to human clinical studies 1. In that study the authors used a protocol of T1-weighted threedimensional (3D) fast gradient recalled echo (GRE), sagittal fat-suppressed (FS) 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo (FSE) with fat saturation sequences and assessed BMLs using a semiquantitative scoring approach. Another article by the same research group published in ''Annals of the Rheumatic Diseases'' recently investigated subchondral bone lesions with a quantitative MRI approach 2. Acquisition of BMLs in that publication was performed on a 1.5 T system using a single 3D fast imaging with steady state precession (FISP) e sequence, a GRE-type sequence. While it has been shown that GRE-type sequences such as SPGR, fast low angle shot (FLASH), 3-point Dixon, double echo steady state (DESS) and others are very sensitive in delineating subchondral cysts, ''even with robust FS or WE [water excitation], these sequences are notoriously insensitive to marrow abnormality'' 3 due to trabecular magnetic susceptibility or T2* effects and will not show the true extent of these lesions (Fig. 1). Inferior demonstration of subchondral bone marrow changes on GRE-type sequences has also been acknowledged by other radiological research groups 4,5. This fact was summarized and published in a consensus statement by OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) in 2006 3. For these reasons research groups in the radiological community have been applying either T2-weighted, proton density (PD)-weighted, intermediate-weighted (IW) FS FSE or short tau inversion recovery (STIR) sequences to assess non-cystic BMLs in OA research 6e10. It has also been suggested that comparable results for BML assessment may be achieved for T1-weighted FS sequences after intravenous gadolinium
Purpose: To describe the anatomical distribution of synovitis and its association with joint effu... more Purpose: To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA). Methods: Baseline MRI was performed at 1.5 T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences. Results: 111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence. Conclusion: Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening.
Although there is an abundance of literature regarding the development of knee osteoarthritis fol... more Although there is an abundance of literature regarding the development of knee osteoarthritis following rupture of the anterior cruciate ligament (ACL), the exact mechanism underlying this link is still not clear. Recent studies have reported that a number of factors may be predictive of the subsequent development of osteoarthritis, with damage to the menisci and articular cartilage during the initial trauma, altered knee biomechanics post-injury, and episodic instability chief among them. This article summarizes recent developments in the understanding of the joint damage resulting from an ACL tear, and the influence that current and future treatment methods may have on the long-term progression to osteoarthritis.
between this source and the sites of EAG potential measurements on the skin. Results: The EAG rep... more between this source and the sites of EAG potential measurements on the skin. Results: The EAG repeatability was assessed with a test-retest protocol for 14 normal subjects. This protocol showed statistically significant high Intraclass Correlation Coefficients between the first and second tests for four electrode sites overlying the joint line (p < 0.05). These sites also showed the highest mean EAG values. In the control group, the mean amplitude of the EAG signals was statistically larger over the medial side than over the lateral side of the knee (0.231 AE 0.017 mV vs. 0.126 AE 0.042 mV for two sites over the joint line, p < 0.001), reflecting joint forces that are known to be higher on the medial side (mean AE standard error). For EAG signals recorded over the total knee replacement, their mean amplitude was statistically not different than zero, reflecting the absence of cartilage. For signals collected over the arthritic knees, their mean amplitude was statistically lower than in healthy subjects (0.057 AE 0.043 mV vs. 0.231 AE 0.017 mV for a medial site over the joint line, p < 0.001), reflecting the deterioration of cartilage caused by osteoarthritis. In the control group, the correlation coefficients between the amplitude of the EAG at each electrode site, and anthropometric variables such as age, weight, body mass index and height were not statistically significant; similarly, no significant differences were observed between men and women for the mean EAG values at each site. Finally, the finite element model computed electric potential distributions with maximum potential values located over the joint line, corresponding well to the maximum values that were measured experimentally in the Control subjects. Conclusions: Further analyses indicate that EAG signals arise from the 'streaming potentials' that can be measured directly on the surface of the articular cartilage during compression. Cartilage degradation, produced by a reduction in the concentration of glycosaminoglycans or collagen content, is known to decrease the amplitude of the streaming potentials. Therefore, electroarthrography constitutes a non-invasive method for measuring streaming potentials and for assessing cartilage degradation. The non-invasive nature of the EAG, its sensitivity to cartilage degradation, as well as its low cost make this approach very interesting for the early diagnosis of osteoarthritis and to monitor patients during the assessment of new treatments.
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Papers by Frank Roemer