Progression Of Bone Marrow Lesions Research Articles

Post-traumatic and OA-related lesions in the knee at baseline and 2 years after traumatic meniscal injury: Secondary analysis of a randomized controlled trial

ObjectiveTo assess the presence of early degenerative changes on Magnetic Resonance Imaging (MRI) 24 months after a traumatic meniscal tear and to compare these changes in patients treated with arthroscopic partial meniscectomy or physical therapy plus optional delayed arthroscopic partial meniscectomy. DesignWe included patients aged 18-45 years with a recent onset, traumatic, MRI verified, isolated meniscal tear without radiographic osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with optional delayed arthroscopic partial meniscectomy. MRIs at baseline and 24 months were scored using the MRI Osteoarthritis Knee Score (MOAKS). We compared baseline MRIs to healthy controls aged 18-40 years. The outcome was the progression of bone marrow lesions (BMLs), cartilage defects and osteophytes after 24 months in patients. ResultsWe included 99 patients and 50 controls. At baseline, grade 2 and 3 BMLs were present in 26% of the patients (n=26), compared to 2% of the controls (n=1) (between group difference 24% (95% CI 15% to 34%)). In patients, 35% (n=35) had one or more cartilage defects grade 1 or higher, compared to 2% of controls (n=1) (between group difference 33% (95% CI 23% to 44%)). At 24 months MRI was available for 40 patients randomized to arthroscopic partial meniscectomy and 41 patients randomized to physical therapy. At 24 months 30% (n=12) of the patients randomized to arthroscopic partial meniscectomy showed BML worsening, compared to 22% (n=9) of the patients randomized to physical therapy (between group difference 8% (95% CI -11% to 27%)). Worsening of cartilage defects was present in 40% (n=16) of the arthroscopic partial meniscectomy group, compared to 22% (n=9) of the physical therapy group (between group difference 18% (95% CI -2% to 38%)). Of the patients who had no cartilage defect at baseline, 33% of the arthroscopic partial meniscectomy group had a new cartilage defect at follow-up compared to 14% of the physical therapy group. Osteophyte worsening was present in 18% (n=7) of the arthroscopic partial meniscectomy group and 15% (n=6) of the physical therapy group (between group difference 3% (95% CI -13% to 19%)). ConclusionsOur results might suggest more worsening of BMLs and cartilage defects with arthroscopic partial meniscectomy compared to physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up in young patients with isolated traumatic meniscal tears without radiographic OA.

Experimental models of bone marrow lesions in ovine femoral condyles.

To develop an in vivo experimental model for bone marrow lesions (BMLs) in ovine femorotibial joints. Randomized, prospective experimental study. Eighteen healthy, skeletally-mature Dorper cross ewes. One medial femoral condyle was penetrated with a 1.1 mm pin, and the contralateral medial femoral condyle was treated with transcutaneous extracorporeal shockwave (ESW) at 0.39 ± 0.04 mJ/mm2 . Clinical examination, magnetic resonance imaging (MRI), computed tomography (CT), and histopathological analyses were used to detect and characterize the development and progression of BMLs in the medial femoral condyle at 4, 8, and 12 weeks post-surgery. Pin penetration induced a BML detected on MRI within 2 weeks and lasted at least 12 weeks. BMLs were not observed in ESW-treated condyles. Histologically, BMLs were characterized by hemorrhage and inflammatory cellular infiltrate, and progressed to more dense fibrous tissue over time. Pathological changes were not observed in the articular cartilage overlying the region of BMLs. Direct, focal trauma to all layers of the osteochondral unit was sufficient to create an experimentally-induced BML which persisted for at least 90 days. The protocol used for ESW in this study did not induce BMLs. Experimental induction of BMLs is possible and mimicked naturally occurring disease states. Volumetric imaging is a sensitive method for characterization of the dynamic nature of these lesions.

Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo-Controlled Trial.

To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double-blind, placebo-controlled trial. Participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change -1.66% versus -2.17%, between-group difference 0.50% [95% confidence interval (95% CI) -0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score -36.0 versus -29.5, adjusted difference -2.7 [95% CI -27.1, 21.7]; mean change in stiffness score -14.2 versus -11.8, adjusted difference -0.2 [95% CI -12.2, 11.8]; mean change in function score -89.4 versus -87.5, adjusted difference 0.3 [95% CI -83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA.

Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women

To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA. 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n=260;+0.1±4.0kg,+0.2±4.4%), weight gain (n=43;+8.6±4.0kg,+9.8±4.1%) or weight loss (n=44;-9.0±7.2kg,-9.8±7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations. 687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39-5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92-2.84) and 53% (OR 1.53; 95%CI 0.92-2.56) in the weight gain vs the stable weight subgroup. In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.

Structural effects of intra-articular TGF-\u03b21 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial

BackgroundTo determine effects of allogeneic human chondrocytes expressing TGF-β1 (TG-C) on structural progression of MRI features of knee osteoarthritis over a 1 year period.MethodsThis phase II randomized controlled trial of TG-C included patients with moderate to advanced osteoarthritis. Patients were randomized to receive an intraarticular 3:1 mixture of non-transduced allogeneic human chondrocytes and TG-C or placebo. 3 T MRI was acquired for all patients at baseline and follow-up (3, 6 and 12 months). MRIs were assessed using the WORMS system including cartilage damage, bone marrow lesions (BMLs), meniscal damage/extrusion, Hoffa-, effusion-synovitis, and osteophytes. Analyses were performed on a whole knee level, compartmental level, and subregional level. Binary logistic regression with Generalized Estimating Equation was used to compare risks of progression, adjusting for baseline age and gender. Mann − Whitney − Wilcoxon tests were used to assess differences for continuous variables.ResultsFifty-seven Patients were included in the TG-C group and 29 in the placebo group. At 12 months, knees in the TG-C group showed less progression of cartilage damage compared to placebo on a whole knee level (34.6% vs. 47.9%; adjusted RR 0.7, 95%CI [0.5–1.1], p = 0.077). Less progression of Hoffa-synovitis and effusion-synovitis was observed in the TG-C group compared to placebo (9.6% vs. 21.1%, adjusted RR 0.5, 95%CI [0.2,1.2], p = 0.115). No statistically significant differences were seen for BMLs, meniscal damage and osteophytes.ConclusionsIntraarticular treatment with TG-C showed fewer patients in the treated group with progression in structural OA features and other MRI-defined inflammatory markers such as Hoffa-synovitis and effusion-synovitis. However, no differences were observed in regard to progression of BMLs and meniscal damage, or hypertrophic osteophyte formation.Trial registrationNCT01221441.Registered 13th October, 2010

The Influence of Joint Loading on Bone Marrow Lesions in the Knee

Background: Bone marrow lesions (BMLs) are considered as predictors of pain, disability, and structural progression of knee osteoarthritis. The relationship between knee loading and BMLs is not yet completely understood. Purpose: To summarize the available evidence regarding the relationship between joint loading and the prevalence and progression of BMLs in the tibiofemoral joint. Study Design: Meta-analysis. Methods: Three databases (PubMed, Web of Science, and The Cochrane Library) were systematically screened for studies encompassing BMLs and changes in knee loading. A methodological quality assessment was conducted, and a meta-analysis computing overall odds ratios (ORs) was performed where possible. Results: A total of 29 studies involving 7641 participants were included. Mechanical loading was categorized as body weight and composition, compartmental load, structural lesion, and physical activity. High compartmental loads and structural lesions increased the risk for BMLs (overall ORs ranging from 1.56 [95% CI, 1.13-2.15] to 8.2 [95% CI, 4.4-15.1]; P = .006). Body weight increased the risk for BMLs to a lesser extent (overall OR, 1.03; 95% CI, 1.01-1.05; P = .007). Contradictory results for the effect of physical activity on BMLs were found. Conclusion: Augmented compartmental loads and structural lesions increased the risk of the presence or progression of BMLs. Body weight increased the risk for BMLs to a lesser extent. Contradictory results for the effect of physical activity on BMLs may be explained by a dose-response relationship, knee alignment, and structural lesions. Clinical Relevance: It has been shown that unloading the knee temporarily may induce beneficial effects on osteoarthritis-related structural changes. Therefore, an early recognition of BMLs in the aging athlete’s knee may provide information to counter the onset and aggravation of symptomatic knee osteoarthritis by reducing the knee load.

How to define subregional osteoarthritis progression using semi-quantitative MRI Osteoarthritis Knee Score (MOAKS)

Recently, the MRI Osteoarthritis Knee Score (MOAKS), a new semi-quantitative magnetic resonance imaging (MRI) scoring tool, was introduced by a panel of experienced researchers in osteoarthritis (OA). The MOAKS is primarily applicable to quantify OA status, since the interpretation of change in the MOAKS features was not described. In order to enable longitudinal evaluation, we propose definitions for progression and improvement of the main MOAKS features. Clear definitions for progression and improvement of the main MOAKS features are given in this brief report. 687 baseline and 30 months follow-up MRIs of the knees of 348 overweight and obese middle-aged women, free of OA at baseline, were scored using the MOAKS. Baseline prevalence and the change of MOAKS features after 30 months follow-up, based on our definitions for progression and improvement, are presented. The proposed definitions showed 3% to 23% progression and 0% to 11% improvement in the MOAKS features during the 30 months follow-up. Overall, progression rates were higher in the medial than in the lateral tibiofemoral (TF) joint. Progression of bone marrow lesions (BMLs) and cartilage defects was highest in the patellofemoral (PF) joint. Inter-rater reliability of the MOAKS scores was moderate to nearly perfect (PABAK 0.77-0.88), with high percentage of agreement overall (89-94%). This brief report presents definitions for progression and improvement of the main MOAKS features for the longitudinal evaluation of knee OA features on MRI. We advocate uniform usage of the proposed definitions across studies, but welcome suggestions for optimization.

THU0224 Knee Effusion is A Risk Factor for Prevalence and Progression of Bone Marrow Lesions: A Population-Based Study

BackgroundBone marrow lesions (BML) occur commonly in knee osteoarthritis (OA) and may be a target for intervention in randomized controlled trials. The potential benefit of therapeutic interventions in OA is...

Does medial patellofemoral osteoarthritis matter? the relation of mri-detected structural damage in the medial and lateral patellofemoral joint to knee pain: the most and framingham osteoarthritis studies

s / Osteoarthritis and Cartilage 22 (2014) S7–S56 S54 groups (DEP þ GS, DEP þ placebo, DEP control þ GS) were compared separately with the DEP control þ placebo group as reference group. Results: 687 knees of 347 women with mean age 55.7 years ( 3.2 SD) and mean BMI 32.3kg/m2 ( 4.2 SD) had baseline and follow-up MRI available for analysis. There was no selective drop-out and the women were equally distributed over the 4 groups. ITT analysis showed a significant preventive effect in the DEP þ placebo group on overall progression of meniscus pathology (OR 0.61, 95% CI [0.38 0.99], p-value (p) 0.046). PP analysis showed a significant preventive effect in the DEP þ placebo group on overall progression of meniscus pathology (OR 0.43, 95% CI [0.22 0.84], p 0.014) and on overall progression of bone marrow lesions (OR 0.26, 95% CI [0.08 0.88], p 0.030). The 2 other groups (DEP þGS and DEP controlþGS) showed no significant effects on overall MRI OA-features. When differentiated according to location in the knee, all effects were seen in the medial meniscus or at the medial tibio-femoral compartment. (ITT: medial meniscus extrusion: OR 0.47, 95% CI [0.24 0.91], p 0.025; medial bone marrow lesion: OR 0.33, 95% CI [0.14 -0.77], p 0.011, PP: medial bone marrow lesion: OR 0.13, 95% CI [0.02 0.93], p 0.042). Evaluating the effects of the MRI OA-features on pain, 42 of 347 women (12%) met the definition of incident chronic knee pain in one or both knees (52 of 687 knees (6.7%)). Progression of bonemarrow lesions was significant associated with incident chronic knee pain (OR 2.1, 95% CI [1.02 4.46]). Conclusions: A diet and exercise program has preventive effects on progression of meniscus pathology and on bonemarrow lesions seen on MRI. Progression of bone marrow lesions is associated with incident chronic knee pain. 82 DOES MEDIAL PATELLOFEMORAL OSTEOARTHRITIS MATTER? THE RELATION OF MRI-DETECTED STRUCTURAL DAMAGE IN THE MEDIAL AND LATERAL PATELLOFEMORAL JOINT TO KNEE PAIN: THE MOST AND FRAMINGHAM OSTEOARTHRITIS STUDIES J. Stefanik y, K. Gross z, D. Felson y, J. Niu y, Y. Zhang y, C. Lewis x, N. Segal k, M. Nevitt{, F. Roemer#, A. Guermazi y, T. Neogi y. yBoston Univ., Boston, MA, USA; zMGH Inst. of Hlth.Professions, Boston, MA, USA; xUniv. of Alabama, Birmingham, AL, USA; kUniv. of Iowa, Iowa City, IA, USA; {UCSF, San Francisco, CA, USA; Klinikum Augsburg, Augsburg, Germany Purpose: Contrary to the expectations of biomechanical models, we previously demonstrated a high prevalence of MRI detected cartilage

OP0028 The Disease Modifying Effect of Strontium Ranelate in a Phase III Knee Osteoarthritis Study (SEKOIA) Using Quantitative Magnetic Resonance Imaging: Reduction in Bone Marrow Lesion Size Associated with Cartilage Protective Effect

ObjectivesTo explore using quantitative magnetic resonance imaging (qMRI) the disease modifying effect of strontium ranelate (SrRan) treatment on the cartilage volume loss and bone marrow lesions (BMLs) in a subgroup...

The natural history of bone marrow lesions in community-based adults with no clinical knee osteoarthritis

Objective:Although bone marrow lesions (BML) have been implicated in the pathogenesis of osteoarthritis, their natural history in a healthy population is unknown. This study in a healthy, pain-free population aimed...

Can [18F]fluorodeoxyglucose positron emission tomography imaging complement biopsy results from the iliac crest for the detection of bone marrow involvement in patients with malignant lymphoma?

To assess the usefulness of [18F]fluorodeoxyglucose positron emission tomography in the detection of bone marrow involvement in malignant lymphoma, and its impact in clinical management. One hundred and six consecutive patients with a confirmed diagnosis of lymphoma, referred for staging or restaging of Hodgkin's lymphoma (n=18) or non-Hodgkin's lymphoma (n=88), were reviewed retrospectively. A positron emission tomography scan and bone marrow biopsy of the iliac crest were performed in all patients. The assessment of bone marrow involvement by lymphoma was confirmed by histology and/or progression of bone marrow lesions in clinical follow-up. In 28 of 106 patients, bone marrow involvement was found. Positron emission tomography was more sensitive (86%) than bone marrow biopsy (57%). Positron emission tomography and bone marrow biopsy were concordant by positive correlation in 12 of 28 cases (43%) and by negative correlation in 77 of 78 cases (99%). Ten cases of non-Hodgkin's lymphoma and two cases of Hodgkin's lymphoma with positive positron emission tomography results and an initial negative bone marrow biopsy showed clinical progression of the bone marrow lesions and/or subsequent positive histology. These were considered as false-negative results for bone marrow biopsy. In seven of the 12 positive cases with negative bone marrow biopsy, positron emission tomography uptake distant from the site of the biopsy was seen. In four cases of follicular lymphoma, the bone marrow biopsy was positive and the positron emission tomography scan was normal. Positron emission tomography and bone marrow biopsy are complementary in assessing the presence of bone marrow involvement in patients with malignant lymphoma. In our series, positron emission tomography was more sensitive than bone marrow biopsy in Hodgkin's and non-Hodgkin's lymphoma, except in follicular lymphoma.