Changes In Bone Marrow Lesions Research Articles

The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. Purpose: To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. Results: Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, –9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. Conclusion: In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.

Comparative validation of the knee inflammation MRI scoring system and the MRI osteoarthritis knee score for semi-quantitative assessment of bone marrow lesions and synovitis-effusion in osteoarthritis: an international multi-reader exercise.

Bone marrow lesions (BMLs) and synovitis on magnetic resonance imaging (MRI) are associated with symptoms and predict degeneration of articular cartilage in osteoarthritis (OA). Validated methods for their semiquantitative assessment on MRI are available, but they all have similar scoring designs and questionable sensitivity to change. New scoring methods with completely different designs need to be developed and compared to existing methods. To compare the performance of new web-based versions of the Knee Inflammation MRI Scoring System (KIMRISS) with the MRI OA Knee Score (MOAKS) for quantification of BMLs and synovitis-effusion (S-E). Retrospective follow-up cohort. We designed web-based overlays outlining regions in the knee that are scored for BML in MOAKS and KIMRISS. For KIMRISS, both BML and S-E are scored on consecutive sagittal slices. The performance of these methods was compared in an international reading exercise of 8 readers evaluating 60 pairs of scans conducted 1 year apart from cases recruited to the OA Initiative (OAI) cohort. Interobserver reliability for baseline status and baseline to 1 year change in BML and S-E was assessed by intra-class correlation coefficient (ICC) and smallest detectable change (SDC). Feasibility was assessed using the System Usability Scale (SUS). Mean change in BML and S-E was minimal over 1 year. Pre-specified targets for acceptable reliability (ICC ⩾ 0.80 and ⩾ 0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. Mean (95% CI) ICC for change in BML was 0.88 (0.83-0.92) and 0.69 (0.60-0.78) for KIMRISS and MOAKS, respectively. KIMRISS mean SUS usability score was 85.7 and at the 95th centile of ranking for usability versus a score of 55.4 and 20th centile for MOAKS. KIMRISS had superior performance metrics to MOAKS for quantification of BML and S-E. Both methods should be further compared in trials of new therapies for OA.

EVALUATION OF METABOLIC RESPONSE IN BONE MARROW LESIONS AFTER EXERCISE IN RELATION TO CHANGES IN ADJACENT CARTILAGE T2 VALUES

Patellofemoral pain syndrome (PFPS) is one of the most common causes of anterior knee pain in active populations. Due to its multifactorial nature, patellofemoral pain is hard to diagnose and treat. Increased stress in the subchondral bone is associated with PFPS and is correlated to elevated bone remodelling. [18F]NaF PET-MR imaging can localize regions of elevated bone remodelling and provide information about the metabolic processes involved (1, 2). Further, [18F]NaF uptake changes after exercise, thus showing that it is sensitive to changes in bone physiology resulting from acute bone loading (3, 4). For cartilage, T2 relaxation times have been used to study cartilage hydration and microstructure changes after exercise. While some studies have observed a decrease in T2 times after exercise, changes are usually transient and have largely been evaluated in the context of healthy subjects (5). An early sign of persistent abnormal mechanical stress is Bone Marrow Lesions (BMLs), which are strongly associated with pain and structural disease progression. We aimed to reproduce prior work which has shown that acute loading results in a large physiological response in bone regions with BMLs. Further, we wanted to explore if there is breakdown of the cartilage microstructure, either at baseline or in response to loading in cartilage regions adjacent to BMLs. The purpose of this study is to detect changes in the functional response of the knee joint to loading using [18F]NaF PET-MR imaging after a stair-climbing exercise in subjects with unilateral patellofemoral pain. The aims of this feasibility study are 1) to detect acute loading-induced changes in [18F]NaF uptake in bone regions with BMLs and 2) compare consequent T2 values in the cartilage adjacent to BMLs at baseline and in response to loading. 4 subjects (3 F, aged 39.5±15.0 years, BMI 26.1±5.9 kg/m2) with unilateral knee pain and BMLs (3 in patella, 1 in femur) underwent two consecutive 30-min [18F]NaF PET/MRI scans of both knees, at baseline and then repeated after a stair-climbing exercise [112 stairs, up and down]. Bone metabolic activity was quantified by calculating maximum standardized uptake values (SUVmax) in areas of BMLs in the painful leg and the corresponding region in the contralateral leg. T2 maps were calculated from quantitative DESS images [TE(1,2)=6.04, 30.44 ms] in the cartilage regions adjacent to the BMLs and in the same regions in the contralateral leg. Segmentations of cartilage were done manually in MATLAB, while SUVmax in BMLs was calculated using ROIs drawn in Horos. Pre- and post-exercise changes in SUVmax and T2 values were compared to account for loading-induced response in both metabolic and structural parameters in painful vs healthy knees. Increased [18F]NaF uptake was observed post-exercise in areas with BMLs (as compared to contralateral leg regions), confirming that PET findings correspond to structural changes observed in MRI (Fig-1). The average SUVmax values increased from 6.35±3.98 to 10.49±5.42 in the painful leg and from 1.71±1.96 to 4.04±3.21 in the contralateral leg after exercise. The average T2 relaxation times increased from 30.61±1.87 ms to 31.61±1.55 ms in the painful leg and from 27.17±2.73 ms to 27.65±2.29 ms in the contralateral leg (Fig-2). The mean change in SUVmax due to exercise was 4.15±2.42 in the BML vs 2.34±2.06 in the contralateral leg. In adjacent cartilage, a mean change in T2 values of 1.01±1.45 ms in the BML region of the painful leg and 0.47±0.48 ms in the contralateral leg was observed. In this feasibility study, [18F]NaF PET-MR showed acute loading-induced changes in BMLs, with a 2-fold increase in SUVmax in the painful leg vs the contralateral leg. While there seemed to be a higher cartilage T2 in regions adjacent to BMLs compared to the contralateral leg, the change induced by exercise was small.

Association Between Structural Change Over Eighteen Months and Subsequent Symptom Change in Middle-Aged Patients Treated for Meniscal Tear.

Middle-aged subjects with meniscal tear treated with arthroscopic partial meniscectomy (APM) experience greater progression of damage to joint structures on imaging than subjects treated nonoperatively. It is unclear whether these changes are clinically relevant. The goal of this study was to assess whether worsening in magnetic resonance imaging (MRI)-assessed tissue damage over 18 months leads to subsequent worsening in knee pain over the subsequent 3.5 years. We used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of APM versus physical therapy for subjects ages ≥45 years with knee pain, cartilage damage, and meniscal tear. We assessed whether change in cartilage surface area damage score (and other structural measures) from baseline to 18 months, assessed on MRI with the MRI Osteoarthritis Knee Score (MOAKS) system, was associated with change in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (range 0-100; 100=worst) from 18 to 60 months. The primary analysis included 168 subjects with complete MRI data at baseline and 18 months and KOOS data at 18 and 60 months. We did not observe clinically important associations between change in cartilage surface area score between baseline and 18 months and change in pain scores from 18 to 60 months. Pain scores in the worst tertile for cartilage surface area damage score progression worsened by 0.45 points more than in the best tertile (95% confidence interval -4.45, 5.35). Similarly, we did not observe clinically important associations between changes in bone marrow lesions, osteophytes, or synovitis and subsequent pain. We did not observe clinically important associations between early changes in cartilage damage and other structural measures and worsening in pain over the subsequent 3.5 years. Further follow-up is required to assess this association over a longer follow-up period.

Why do obese patients with oa have more pain?

The prevalence of obesity, osteoarthritis (OA) and chronic pain are rising globally and are major contributors to a progressive decline in physical function and quality of life. There is an established positive association between obesity and chronic pain. While substantial evidence supports this association in individuals with OA, the reasons underlying it remain unclear, with considerable insights gained from studying the effects of weight loss. Research on the impact of obesity in OA has mainly focused on its effects on joint loads, joint alignment, changes on imaging and biomarkers, with fewer studies considering the mediating role of these aspects on symptomatic change. In addition to increased joint loads, obesity creates low-grade systemic inflammation and in local adipose tissues (e.g. infrapatellar fat pad (IFP)) via the proliferation of pro-inflammatory cytokines and adipokines. The generation of OA pain through mechanical and inflammatory stimuli is well established via the activation of nociceptors in most joint tissues. Pain is a hallmark of OA disease progression, ranging from intermittent mechanical pain with activity to constant pain, thought to be largely due to low-grade inflammation. In addition, it is known that a subset of individuals with OA will have altered nociceptive signalling, manifesting in peripheral or central sensitization of pain, a process potentially enhanced in obese individuals. Historically, study of the relationship between obesity and pain in people with OA has used BMI ≥30kg/m2 as an indicator of obesity. A dose-response relationship has been observed between BMI and pain severity. Studies report that weight loss of as little as 5%, achieved either naturally or surgically, results in joint pain reduction. However, BMI is limited as a marker of obesity as it does not account for type of adipose tissue (i.e. subcutaneous or visceral), its distribution (abdomen vs extremities), or type of mass (muscle vs fat). These limitations are important since adipose tissue is metabolically active, a storer of macrophages, producing and releasing pro-inflammatory cytokines and adipokines (e.g. TNF-α, IL-6, leptin, adiponectin). Cytokines and adipokines are known contributors to extracellular matrix degradation, a process that ultimately leads to joint space narrowing. Adipokines are prominent in serum and can be considered a central driver of inflammation, while some are found in synovial fluid or the IFP, presenting a mechanism for a local effect. Thus it is unclear if pain improvement after weight loss is due to lower joint loads, lower levels of inflammation or a combination of both. Complicating the issue further is the prescription of opioids, which is higher for those who are obese compared to non-obese individuals and can lead to opioid-induced hyperalgesia. Despite OA clinical guidelines opposing their use, rates of opioid consumption continue to be a problem. Studies from preclinical models investigating obesity, pain, and OA are limited, but have contributed to evidence supporting the role of systemic and local inflammation being associated with pain sensitization to thermal and mechanical stimuli. Most recently, the critical role of signaling from fat cells in the development of pain sensitization was highlighted in a study of mice models with lipodystrophy. Initially protected from pain sensitization, lipodystrophic mice with transplanted adipose tissue developed hyperalgesia and allodynia. Knowledge from clinical studies has progressed with use of more detailed measurements of obesity, such as the type of adiposity. Recent advances include evidence on the contribution of visceral or subcutaneous adiposity, measured by dual x-ray absorptiometry, to pain in people with knee OA, indicating that visceral but not subcutaneous fat is associated with worsening knee pain. These results which accounted for BMI, support the systemic effects of obesity on pain in OA and implicate visceral fat as a driver of pain. In addition, there has been further study of the presence of bone marrow lesions (BMLs) and synovitis/effusion, which have been associated with pain or sensitization, and these changes can be more severe in obese individuals. Conflicting evidence exists regarding changes in BMLs and improvement in pain after weight loss. Evidence for the mediating role of synovitis/effusion in pain improvement after weight loss is limited, indicating a non-significant indirect effect. However, combined evidence regarding changes in cytokines, IFP volume and pain severity in obese individuals suggest that further research into synovitis/effusion is warranted. Gaps and opportunities for expanding our understanding of the mechanisms underlying the relationship between obesity and pain in individuals with OA will be discussed.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms.

To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.

Does cartilage loss cause pain in osteoarthritis and if so, how much?

ObjectivesAlthough treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved.MethodsUsing...

Early Magnetic Resonance Imaging–Based Changes in Patients With Meniscal Tear and Osteoarthritis: Eighteen‐Month Data From a Randomized Controlled Trial of Arthroscopic Partial Meniscectomy Versus Physical Therapy

The present study was undertaken to evaluate changes in knee magnetic resonance imaging (MRI) findings over the course of 18 months in subjects with osteoarthritic change and meniscal tear treated with arthroscopic partial meniscectomy (APM) or nonoperatively with physical therapy (PT). We used 18-month follow-up data from the Meniscal Tear in Osteoarthritis Research Trial. MRI results were read with reference to the MRI Osteoarthritis Knee Score. We focused on 18-month change in bone marrow lesions (BMLs), cartilage thickness, cartilage surface area, osteophyte size, effusion-synovitis, and Hoffa-synovitis. We used multinomial logistic regression to assess associations between MRI-based changes in each feature and treatment type. A total of 351 subjects were randomized, and 225 had both baseline and 18-month MRI results. In both treatment groups, patients experienced substantial changes in several MRI-based markers. In 60% of the APM group, versus 33% of the PT group, cartilage surface area damage advanced in ≥2 subregions (adjusted odds ratio 4.2 [95% confidence interval 2.0-9.0). Patients who underwent APM also had greater advancement in scores for osteophytes and effusion-synovitis. We did not find significant associations between treatment type and change in cartilage thickness, BMLs, or Hoffa-synovitis. This cohort of patients with meniscal tear and osteoarthritis showed marked advancement in MRI-based features over 18 months. Patients treated with APM showed more advancement in some features compared to those treated nonoperatively. The clinical relevance of these early findings is unknown and requires further study.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms - results from the ZAP2 trial

Purpose: Subchondral bone marrow lesions (BMLs) are an early sign of knee osteoarthritis (OA) that predicts both cartilage loss and symptomatic progression of OA. Previous studies have suggested targeting BMLs in short-term structure modification trials. A key hypothesis is that shrinkage of BMLs is associated with reduced cartilage loss and improved knee symptoms, but this has been debated. This study used data from a multicentre randomised controlled trial (ZAP2), in which all participants had symptomatic knee OA and BMLs, and the aim was to describe the association between change in BMLs and change in tibiofemoral cartilage volume and knee symptoms.

Development of a novel histological scoring system for bone marrow lesions - the osteoarthritis bone score

Purpose: Bone marrow lesions (BMLs) are a known feature of osteoarthritis (OA) and are well described on Magnetic Resonance Imaging (MRI) analysis. However, little is known about the histological changes in BMLs and how histological changes relate to pain in OA BML tissue. We have previously demonstrated that BMLs are highly metabolically active structures, with features of angiogenesis, fibrous connective tissue, cartilage expression and bone resorption. In this work we aimed to develop a novel histological scoring system for BMLs by comparing BML versus non-BML OA tissue and normal bone.

Association of bone marrow lesions localisation with weight bearing pain in people with knee osteoarthritis: data from the osteoarthritis initiative

Purpose: Subchondral bone contributes to pain in knee osteoarthritis (OA). OA structural change particularly affects weight-bearing components of the joint, most notably the medial femorotibial compartment in people with varus angulation. Subchondral bone marrow lesions (BMLs) detected on MRI in knee OA are strongly associated with pain. BMLs typically occur in regions of the joint with the most severe structural change, for example, full-thickness cartilage lesions. However, the association between subchondral BMLs in weight-bearing components and weight-bearing pain has not been clarified. The purpose of this study was to assess association between BMLs location and weight bearing knee pain using data from the Osteoarthritis Initiative (OAI). We hypothesized that BMLs at the medial femorotibial joint compartment were associated with weight bearing pain, independent of non-weight bearing pain, and that changes in size of the BMLs over time were associated with change in weight bearing pain. Methods: The OAI is a publicly available multi-center, longitudinal, prospective observational study of knee OA. We examined the knees of OAI participants with MRI readings using the MRI Osteoarthritis Knee Score (MOAKS). BMLs, articular cartilage, osteophytes, Hoffa’s synovitis, effusion, meniscal morphology and anterior cruciate ligament tears were scored using the MOAKS, and femorotibial angle (FTA) and Body Mass Index (BMI) were examined. BML scores using MOAKS were available for 4 articular sub-regions (median and lateral femorotibial, and medial and lateral patellofemoral joint) and the subspinous region. Knee pain was assessed at baseline (cross-sectional) and baseline and 2 years (longitudinal) using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We defined weight bearing pain as the sum of three WOMAC questions (pain on climbing stairs, on walking, and on standing) and non-weight bearing pain as the sum of two WOMAC questions (pain in bed and with sitting/lying down). Negative binomial regression was performed, using SPSS version 23 software. Results: 1412 participants were included in the cross-sectional analysis (from OAI project 22, 30 and 65), mean age 62 (±9) years, mean BMI 30 (±5), 61% female, median weight and non-weight bearing WOMAC score 2 (IQR 0, 4) and 0 (IQR 0, 1), and median total BML score 3 (IQR 1, 6). Weight bearing pain was associated with total BML score was r = 0.35 (p < 0.0001), and with BML scores at medial (r=0.29, p < 0.0001) and lateral (r=0.09, p = 0.0009) femorotibial joint compartments. Weight bearing pain was also associated with BML score at medial and lateral patellofemoral joint compartments (r = 0.03, p = 0.3 and 0.13, p < 0.0001, respectively). The association between weight bearing pain and BML scores at medial femorotibial and lateral patellofemoral joint compartments remained significant after adjusting for non-weight bearing pain, age, sex, BMI, FTA, BML scores at the other 4 joint compartments and the other OA related MRI features (osteophyte score, cartilage defect score, medial meniscus extrusion, anterior cruciate ligament tears, synovitis and effusion) (Table 1). 600 participants were included in the longitudinal study (OAI project 22), mean age 62 (± 9) years, mean BMI 31 (± 5), 57% female, median weight and non-weight bearing WOMAC score 1 (IQR 0, 3) and 0 (IQR 0, 1), and median total BML score 3 (IQR 2, 5). From baseline to 2 years, the changes in the mean weight and non-weight bearing 0.5 (±2.2) and 0.1 (±1.4), and mean total BML score were 0.7 (±1.9). The correlation between changes in weight bearing pain and changes in total BML score was r = 0.13 (p = 0.002); between changes in weight-bearing pain and BML score at medial and lateral femorotibial joint compartment were r = 0.16 (p < 0.0001) and -0.03 (p = 0.45), between changes in weight-bearing pain and changes in BML score at medial and lateral patellofemoral joint compartment were r = 0.04 (p = 0.3) and -0.03 (p = 0.5). The association between the changes in BML score at medial femorotibial joint compartment and changes in weight-bearing pain remained significant after adjusting for changes in non-weight bearing pain, age, sex, BMI, BML change at the other four joint compartments and osteophyte score change (Table 2). Conclusions: In this cross sectional and longitudinal study, BMLs at medial femorotibial joint compartment in varus knee OA participants were highly associated with the severity and the change in severity of weight bearing pain. The associations persisted when mutually adjusting for other feature of OA related MRI features, and adjusting for non-weight bearing pain, age, sex and BMI. Our findings suggest that BMLs in weight-bearing areas might contribute to weight bearing pain. Reducing BMLs or weight bearing in joint compartments with BMLs are candidate treatment targets in knee OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA). HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts. HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56). HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

The effect of intra-articular glucocorticosteroids and exercise on symptoms and bone marrow lesions in knee osteoarthritis: a secondary analysis of results from a randomized controlled trial

To evaluate if the relative volume of bone marrow lesions (BMLs) changed in patients with knee osteoarthritis (OA) during a therapeutic study. This study is a sub-study to a larger clinical trial which compared the clinical effects of intra-articular corticosteroid injection in knee OA to placebo injection, both given prior to exercise therapy. Clinical assessment using the Knee injury and Osteoarthritis Outcome Score (KOOS) and magnetic resonance imaging (MRI) examinations with BML assessments were performed at baseline and follow-up after 14 weeks and 26 weeks, respectively. The BML volume was determined using a computer assisted method focusing on participants with valid baseline and follow-up MRI examinations. Any changes in BML and KOOS were analyzed and investigated for associations. Fifty participants received steroid and placebo injection, respectively, of which 41 and 45 had complete MRI examinations at week 14, and 36 and 33 at week 26, respectively. All participants received 12 weeks of exercise. A significant change in relative BML volume was observed between the corticosteroid group and the placebo group after 14 weeks [-1.1% vs2.7%; between-group difference, 3.8% (95% CI 0.5-7.0)] but not after 26 weeks [0.8% vs1.6%; between-group difference, 0.8% (95% CI -2.8 to 4.4)]. No significant association was found between changes in relative BML volume and KOOS. Despite the statistically significant difference in BML volume at 14 weeks after corticosteroid injection and 12 weeks exercise therapy compared to placebo injection and exercise, there is very little evidence on a relationship between corticosteroids and BML volume. EudraCT number: 2012-002607-18.

Association Between Biochemical Markers of Bone Turnover and Bone Changes on Imaging: Data From the Osteoarthritis Initiative

To determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA). We analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm2 ) and shape (position on 3-D vector) were assessed on magnetic resonance images, and bone trabecular integrity (BTI) was assessed on radiographs. Serum and urinary markers (serum C-terminal crosslinked telopeptide of type I collagen [CTX-I], serum crosslinked N-telopeptide of type I collagen [NTX-I], urinary NTX-I, urinary C-terminal crosslinked telopeptide of type II collagen [CTX-II], and urinary CTX-Iα and CTX-Iβ) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates. 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 R2 = 0.032), and changes in bone shape over 24 months (partial R2 range 0.008 to 0.024). Overall, biochemical markers were not predictive of changes in BMLs or osteophytes. Serum NTX-I was inversely associated with BTI of the vertical trabeculae (quadratic slope) in all analyses (highest partial R2 = 0.028). 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.

Evolution of synovitis in osteoarthritic knees and its association with clinical features

To investigate the course of synovitis on contrast-enhanced magnetic resonance images (CE-MRI) in osteoarthritic knees over 2 years, and its association with pain and cartilage deterioration. Consecutive patients (n=39, mean age 61 years, 79% woman, median (range) body mass index (BMI) 29 (24-48)kg/mm2) with clinical osteoarthritis (OA) were included. Baseline and follow-up CE-MRI (3T) were scored paired in chronological order for synovitis (semi-quantitatively at 11 sites (range 0-22)), cartilage deterioration and bone marrow lesions (BMLs) (semi-quantitatively according to Knee Osteoarthritis Scoring System (KOSS)). Changes in sum scores were calculated. Cartilage deterioration was defined as change of ≥2 above the smallest detectable change (SDC). Pain was assessed by standardized questionnaires. Analysis of covariance (ANCOVA) and linear regression models were used to investigate association between synovitis change and cartilage deterioration and between synovitis change or cartilage deterioration and change in pain. The total synovitis score did not change over 2 years (mean change 0.2 (standard deviation (SD) 3.2)), although changes in individual patients were observed. Cartilage deterioration was observed in 51% of patients. Synovitis change score was lower in patients without compared to patients with cartilage deterioration, taking BML change in account (mean difference -2.1 (-4.1 to-0.1)). Change in synovitis was not associated with change in pain, whereas cartilage deterioration was associated with change in Intermittent and Constant OsteoArthritis Pain (ICOAP) constant pain in adjusted models (unstandardised coefficient (B) (95% confidence interval (CI)) 2.8 (0.4-5.3)). In individual patients synovitis fluctuates during disease course. Synovitis change was not associated with change in pain. Increase in synovitis is associated with cartilage deterioration, suggesting a role for synovitis as a target for disease-modifying treatment.

Natural history and clinical significance of meniscal tears over 8years in a midlife cohort.

BackgroundThere is limited longitudinal data available on the natural history of meniscal tears especially in middle-aged adults with a low prevalence of osteoarthritis (OA). The aim of this study was to describe the natural history of meniscal tears over 8 years and the relationship with change in knee pain and structures.MethodsOne hundred ninety eight participants [mean age 47 (28–63); 57 % female] were studied at baseline and 8 years later. Approximately half were the adult offspring of subjects who had a knee replacement performed for knee OA and the remainder were randomly selected controls. Meniscal tears/extrusion, cartilage volume/defects, bone marrow lesions (BMLs) and effusion were assessed on MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index.Results22 % of the participants had at least one meniscal tear at any site at baseline. Over 8 years, 16 % of the participants had an increase in severity of meniscal tears while none improved. Increase in meniscal tear score was associated with worsening knee pain (β = +2.81 (+1.40, +4.22)), with offspring having a significantly greater increase in pain severity compared to controls. BMI and presence of osteophytes at baseline, but not knee injury, predicted change in tears, whereas change in meniscal tears was independently associated with cartilage volume loss, change in BMLs and change in meniscal extrusion.ConclusionChange in meniscal tears shares risk factors with knee OA and is independently associated with worsening knee pain and structural damage suggesting that meniscal tears are on the knee OA causal pathway.

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

Familial effects on structural changes relevant to knee osteoarthritis: a prospective cohort study

Genetic factors play an important role in the pathogenesis of knee osteoarthritis (OA), but which knee structural changes mediate this is unclear. This study aimed to describe the differences in knee structural changes over 8-10 years between offspring having at least one parent with total knee replacement (TKR) for severe primary knee OA and controls with no family history of knee OA. 115 offspring (mean age 45 years) with a family history of TKR for severe knee OA were compared with 104 (mean age 46 years) controls. T1 or T2-weighted fat saturated magnetic resonance imaging (MRI) was performed respectively to evaluate knee cartilage defects, bone marrow lesions (BMLs), meniscal extrusion and tears at baseline and 10 years. Multivariate logistic regression model was used to adjust for potential confounders. Offspring had a greater increase in cartilage defect score (1.03 vs 0.52, P = 0.007) and meniscal extrusion score (0.28 vs 0.10, P = 0.027) over 10 years, and a greater increase in meniscal tear score (0.40 vs 0.10, P = 0.012) over 8 years in the medial but not the lateral tibiofemoral compartment. Changes in BMLs over 8-years were not different between the two groups. These associations were independent of potential confounders, and strengthened after further adjustment for each other. With the exception of BMLs, offspring with a family history of knee OA have a greater risk of increases in multiple knee structural abnormalities in the medial tibiofemoral compartment suggesting pleiotropic familial effects.

THU0223 Vastus Medialis Muscle FAT Content as Assessed by Magnetic Resonance Imaging is A Risk Factor for Knee Osteoarthritis Progression: Relevance in A Clinical Trial

BackgroundRecent osteoarthritis (OA) studies propose vastus medialis (VM) muscle surface as a variable associated with cartilage volume loss over time. However, such muscle area may also include a significant proportion...

Bone marrow lesions may not respond to anti-inflammatory treatments in knee osteoarthritis(OA)

Bone marrow lesions may not respond to anti-inflammatory treatments in knee osteoarthritis(OA)