Presence Of Bone Marrow Lesions Research Articles

Preoperative patellar bone marrow lesions with full thickness cartilage defects correlate with residual anterior knee pain in total knee arthroplasty without patellar resurfacing.

Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. III.

Comparison of evaluation metrics of deep learning for imbalanced imaging data in osteoarthritis studies

To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage Values in Hips With Bone Marrow Lesions.

Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population-based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. Study participants (n=128) were recruited from a cross-sectional population-based study of people ages 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. Thirty-two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval -149.69, -0.81; P=0.048) (9%) in the BML compared to the no-BML group. Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

Gastrointestinal amyloidosis in a patient with smoldering multiple myeloma: A case report

BACKGROUNDSmoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma (MM). Amyloidosis (light chain) (AL) is the most common form of systemic amyloidosis. There are few reports of SMM coexisting with AL involving the digestive tract. CASE SUMMARYA 63-year-old woman presented with lower limb edema, abdominal distension, abdominal pain, and hematochezia. Gastroscopy showed gastric retention, gastric angler mucosal coarseness, hyperemia, and mild oozing of blood. Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers, submucosal ecchymosis, and hematoma. Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining. MM was confirmed by bone marrow biopsy and immunohistochemistry. The patient had no hypercalcemia, renal dysfunction, anemia, bone lesions or biomarkers of malignancy defined as plasma cells > 60% in bone marrow. Additionally, no elevated serum free light chain ratio, or presence of bone marrow lesions by magnetic resonance imaging (SLiM criteria) were detected. The patient was finally diagnosed with SMM coexisting with AL. She received chemotherapy and was discharged when the symptoms were relieved. She is doing well at nearly five years of follow up.CONCLUSIONThis case highlights that high index of suspicion is required to diagnose gastrointestinal AL. It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa, ecchymosis, and submucosal hematoma. Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

COMPARISON OF VARIOUS METRICS FOR EVALUATING THE PERFORMANCE OF DEEP LEARNING BINARY CLASSIFICATION, PARTICULARLY WHEN UNDERLYING IMAGING DATA ARE IMBALANCED

Subchondral bone marrow lesions (BMLs) are associated with symptoms and structural progression of knee OA. Automated detection of BMLs using deep learning approaches may help in screening potential participants in clinical trials and enrich study samples for fast structural progressors or for a specific pain phenotype. The metric commonly used to evaluate the performance of deep learning binary classification (i.e., receiver operating characteristic (ROC)) might not be as informative as other metrics of performance, especially when the underlying data used to train and validate the deep learning models are imbalanced as in the case when the outcomes of interest are rare. To compare the evaluation of deep learning binary classification of BMLs based on imbalanced data from the OAI study using various performance metrics. We used the sagittal intermediate-weighted (IW) fat-suppressed (FS) MRI data of 2,467 participants from the OAI study in the data analysis. We dichotomized the MOAKS (MRI Osteoarthritis Knee Score) BML grades (scored from 0-3) into presence or absence classes. The split was done by categorizing grades > 0 as presence and grades = 0 as absence. After the deep learning models were trained, we obtained the status of BMLs from MRI images on each of 13 subregions in femur and tibia (e.g., Femur Central Medial (FemCentMed), Tibia Anterior Lateral (TibAntLat), Tibia Posterior Medial (TibPostMed)). We applied ROC, precision-recall (PR), precision-recall gain (PRG), F1, and the Matthews correlation coefficient (MCC) to summarize the prediction performance of the deep learning models using the test data. The available MOAKS data from the OAI are imbalanced. The class imbalance ratios (i.e., presence of BMLs vs absence of BMLs) are 569:2427, 49:2947, and 191:2805 in the FemCentMed, TibAntLat, and TibPostMed, respectively. When the data are this severely imbalanced, metrics such as the area under the ROC curve (ROC-AUC) and PR-AUC show conflicting performance results in TibAntLat and TibPostMed (see Table 1). In general, a binary classifier with a ROC-AUC value of 0.8 to 0.9 is considered excellent and has an outstanding performance with a value of more than 0.9. The ROC metric (ROC-AUC = 0.84) is too optimistic since the precision and sensitivity are nearly zero, indicating that almost all data are assigned to the absence of BMLs class. The PR curve (PR-AUC = 0.10) is more informative compared to the ROC as it is consistent with the values of precision and sensitivity. The MCC and F1 results are also consistent with those of the PR curve for high- (TibAntLat) or low-class (FemCentMed) imbalance ratios. The class imbalance ratio coupled with results of the ROC, PR, and MCC should be reported for deep learning models of binary classification, particularly in the circumstance where the underlying data are imbalanced. To properly interpret the prediction performance of deep learning models of binary classification, an expanded set of performance metrics should be reported. None. AG is consultant to Pfizer, Novartis, Regeneron, TissueGene, Merck Serono, and AstraZeneca. AG and FWR are shareholders of BICL, LLC. FWR is consultant to Calibr –California Institute of Biomedical Research and Grunenthal. KK is consultant to Regeneron, LG Chem, and Express Scripts. He is principal investigator for pharma sponsored clinical trials to Abbvie, Cumberland, and GSK and DSMB to Kolon TissueGene and Avalor Therapeutics.

The interactions between MRI-detected osteophytes and bone marrow lesions or effusion-synovitis on knee symptom progression: an exploratory study

To investigate the longitudinal association between MRI-detected osteophyte scores and progression of knee symptoms, and whether the association was modified in the presence of bone marrow lesions (BMLs) or effusion-synovitis. Data from Vitamin D Effects on Osteoarthritis (VIDEO) study, a randomized, double-blinded and placebo-controlled clinical trial in symptomatic knee osteoarthritis (OA) patients, were analyzed as an exploratory study. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess knee symptoms. Osteophytes, BMLs and effusion-synovitis were measured using MRI. 334 participants with MRI information and WOMAC score (baseline and follow-up) were included in the analyses, with 24.3% of them having knee pain increased 2 years later. Statistically significant interactions were found between MRI-detected osteophytes and BMLs or effusion-synovitis on increased knee symptoms. In participants with BMLs, higher baseline scores of MRI-detected osteophytes in most compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and effusion-synovitis. In participants with effusion-synovitis, higher baseline scores of MRI-detected osteophytes in almost all the compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and BMLs. In contrast, MRI-detected osteophyte scores were generally not associated with knee symptom progression in participants without baseline BMLs or effusion-synovitis. MRI-detected OPs are associated with increased total knee pain, weight-bearing knee pain, stiffness and physical dysfunction in participants presenting BMLs or effusion-synovitis, but not in participants lacking BMLs or effusion-synovitis. This suggests they could interact with bone or synovial abnormalities to induce symptoms in knee OA.

A novel osteochondral explant model to study bone and cartilage responses to damage in PTOA

Purpose: Osteoarthritis (OA) is a progressive joint disease, which was traditionally associated with degradation of articular cartilage, but is now known to affect other joint tissues including subchondral bone. Indeed, changes in subchondral bone have been shown to precede the process of cartilage degradation and may contribute to it. One specific example of this is the presence of bone marrow lesions (BMLs) in acute joint injury, and their potential role in development of post-traumatic osteoarthritis (PTOA). This process of bone-cartilage cross-talk can be challenging to study in vivo due to its complexity, thus multi-tissue explant model systems are crucial. Traditional osteo-chondral explant models (femoral head, or cylindrical cored specimens) are useful in capturing certain aspects of this process but are limited in that bone damage is necessarily created, during the process of isolation. Thus, in this study we used a novel bone-cartilage explant model, where no bone damage was created during harvest. Then, experimental damage was introduced by either chemical or mechanical means, and the subsequent effects on cartilage and bone tissue status were determined. Methods: First, we characterised the rat patella (n=12) as an osteo-chondral explant system, with no initial bone damage, by comparing with the state-of-the-art femoral head explant in terms of baseline viability assays. The baseline viability of both explant models was evaluated using biochemical, histological and microstructural assays. Then samples were subjected to either chemical or mechanical damage and the individual tissue damage responses were assessed. For chemical damage, explants were exposed to 10ng/ml of IL-1β for 0, 1, 3 and 7 days. For mechanical damage, tissues were exposed to mechanical compression at 0.5 Hz, 10 % strain for 10 cycles. In both cases, Sulfated glycosaminoglycan (sGAG), and MMP-13 were measured as an assessment of representative cartilage responses while and alkaline phosphatase (ALP) was assessed as a representative bone response. Furthermore, histomorphometric, and immunohistochemical, evaluations of each explant system were also carried out. Results: Our results demonstrate that the patellar explant is an excellent ex vivo model system to study bone-cartilage crosstalk, and one which does not induce any bone damage at the time of tissue harvest. We also established culture conditions to maintain viability in these explants in standard media for up to 28 days in culture (data not shown). In the histological sections, haematoxylin and eosin were used to show general morphology of patella explant and femoral head (Fig. 1C). Rat patellae exposed to IL-1β showed that both proteoglycan content and bone metabolism markers were significantly increased (p<0.05) after 7 days of treatment when compared with the controls (Fig.1 A-B). To confirm this finding, qualitative immunohistochemical staining showed chondrocytes increased expression of MMP13 after treatment with IL-1β. Mechanically compressed patellae showed a decrease in compressive moduli from day 3 to day 7 (Fig. 2A), this suggested that subchondral bone remodelling may have taken place as a compensatory mechanism to repair microdamage. To fully validate these findings additional bone microstructural parameters need to be assessed by computer tomography (μCT) (data not shown). In addition to this, increase in MMP13 release was observed three days after samples were mechanically damaged when compared with the control (Fig. 2B). Conclusions: In summary, these initial Results showed that patella explant is a useful model to study bone cartilage cross-talk. We used this system to study the effects of chemical and mechanical damage, to both tissue types. The aim of this project was to establish a system to recapitulate the subchondral bone damage associated with joint injury and PTOA. We used a novel patellar explant model, which does not involve the creation of basal bone damage during isolation. IL-1β was used as a surrogate for bone damage and resulted in cartilage and bone specific changes. It is well known that cartilage has poor reparative potential and overloading has catabolic effects in the osteochondral tissue. In summary, this study demonstrates that the explant model can be useful for bone-cartilage crosstalk in a model of PTOA.

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.

Management of Bone Marrow Lesions of the Hip With Subchondral Calcium Phosphate Injection: Surgical Technique and Tips

Bone marrow lesions (BMLs) are localized areas of edema within subchondral bone, which are often due to early chondromalacia changes, subchondral insufficiency stress or microfractures, and/or avascular necrosis. The presence of BMLs worsen outcomes after arthroscopy and arthroplasty, thus making their management important in the preservation of hip function. In recent years, the advent of Subchondroplasty (SCP; Zimmer Knee Creations Incorporated, Exton, PA)—a minimally invasive surgical technique that involves injecting an isothermic calcium phosphate solution to stabilize BMLs—has shown promising results in managing pain from osteoarthritis (OA). The SCP material (AccuFill Bone Substitute Material, Zimmer Knee Creations Incorporated) has a similar physical and chemical structure to native bone mineral. In this Technical Note, we discuss a surgical approach for managing acetabular and femoral head BMLs with SCP. We also review the prior clinical trials reporting on SCP for knee OA. SCP may be a promising technique as part of the treatment algorithm for managing hip OA, and clinical trial enrollment has begun for hip SCP. On the basis of these results, further investigations into this procedure may be warranted.

Effect of atorvastatin on knee structure and pain in patients with knee osteoarthritis: a randomised controlled trial

Purpose: Observational studies have shown an effect of oral statin on reducing structural progression of knee osteoarthritis. However, no randomised controlled trials have been performed. This study examined the effect of atorvastatin compared to placebo on reducing structural progression and improving symptoms in participants with symptomatic knee osteoarthritis. Methods: A multicentre, randomised, parallel-group, double-blind, placebo-controlled trial was conducted in Melbourne, Hobart, and Adelaide, Australia. Participants aged 40-70 years with symptomatic knee osteoarthritis assessed by the American College of Rheumatology criteria were randomly assigned in a 1:1 ratio to receive oral atorvastatin 40 mg (n=151) or inactive matching placebo (n=153) once daily over two years. The primary outcome was annual percentage change in tibial cartilage volume assessed using magnetic resonance imaging (MRI) over two years. Secondary outcomes were worsening of tibiofemoral cartilage defects and bone marrow lesions (BMLs) assessed using MRI and change in knee pain and function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over two years. Intention-to-treat analyses were performed. Analysis of intervention effects according to the absence or presence of BMLs at baseline was pre-specified. Results: Of 304 participants (mean age 55.7 years, 55.6% female), 248 (81.6%) completed the trial. Annual change in tibial cartilage volume was not significantly different between groups [atorvastatin: -0.26% (95% CI -0.92% to 0.41%) vs. placebo: -0.91% (95% CI -1.52% to -0.30%), p=0.15]. No significant between-group differences were observed in worsening of cartilage defects (atorvastatin: 59.6% vs. placebo: 63.4%, p=0.56) or BMLs (57.6% vs. 57.5%, p=0.99), or change in WOMAC pain (-35.9 vs. -31.6, p=0.78) or function score (-90.7 vs. -92.8, p=0.97). In those without BMLs at baseline (n=105), annual change in tibial cartilage volume was significantly different between the atorvastatin and placebo groups [0.50% (95% CI -0.88% to 1.87%) vs. -1.19% (95% CI -2.09% to -0.30%)] where significant cartilage volume loss was observed in the placebo group but not in the atorvastatin group with a between-group difference of -1.69% (95% CI -3.36% to -0.02%, p=0.047) (Table 1). There were no significant differences in adverse events between groups. Conclusions: Among participants with symptomatic knee osteoarthritis, oral atorvastatin 40 mg once daily did not reduce knee cartilage loss or knee pain over two years. However, atorvastatin reduced cartilage loss in those without BMLs, suggesting atorvastatin may have a disease-modifying effect in those with knee osteoarthritis and without BMLs.Table 1Change in cartilage volume, cartilage defects, bone marrow lesions, knee pain and functionWithin-group change, mean (95% CI)Between-group difference Atorvastatin - PlaceboP for interaction between BMLs and treatmentAtorvastatin (n=151)Placebo (n=153)Mean difference (95% CI)PAnnual % change in tibial cartilage volume-0.26 (-0.92 to 0.41)-0.91 (-1.52 to -0.30)0.66 (-0.24 to 1.55)0.15Without BMLs0.50 (-0.88, 1.87)-1.19 (-2.09, -0.30)-1.69 (-3.36, -0.02)0.0470.11With BMLs-0.61 (-1.37, 0.16)-0.75 (-1.54, 0.04)-0.14 (-1.19, 0.91)0.79Change in WOMAC pain (0-500)-35.9 (-60.1 to -11.7)-31.6 (-49.2 to -14.0)-4.3 (-34.9 to 26.4)0.78Without BMLs-36.0 (-84.1, 12.2)-26.9 (-59.0, 5.1)-9.0 (-69.4, 51.4)0.760.83With BMLs-35.9 (-62.6, -9.1)-34.4 (-56.2, -12.6)-1.4 (-36.4, 33.5)0.94Change in WOMAC function (0-1700)-90.7 (-169.5 to -11.9)-92.8 (-152.3 to -33.4)2.1 (-99.7 to 103.9)0.97Without BMLs-80.3 (-234.5, 73.8)-58.8 (-168.7, 51.1)-21.5 (-226.1, 183.0)0.830.74With BMLs-95.6 (-182.9, -8.2)-113.0 (-185.4, -40.7)17.4 (-97.5, 132.4)0.77No (%)No (%)Odds ratio (95% CI)Atorvastatin vs. PlaceboPP for interaction between BMLs and treatmentWorsening of cartilage defects90 (59.6)97 (63.4)0.86 (0.51, 1.44)0.56Without BMLs25 (52.1)34 (59.6)0.72 (0.30, 1.69)0.440.64With BMLs65 (63.1)63 (65.6)0.92 (0.49, 1.72)0.79Worsening of BMLs87 (57.6)88 (57.5)1.00 (0.62, 1.63)0.99Without BMLs18 (37.5)30 (52.6)0.50 (0.20, 1.29)0.150.09With BMLs70 (68.0)58 (60.4)1.38 (0.74, 2.55)0.31 Open table in a new tab

Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis

IntroductionObservational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin...

Patellofemoral alignment and geometry and early signs of osteoarthritis are associated in patellofemoral pain population.

BackgroundPatellofemoral pain (PFP) patients show increased prevalence of patellar malalignment. Structural and alignment abnormalities of the patellofemoral joint (PFJ) may play a role in development of PFP and patellofemoral osteoarthritis (PFOA).ObjectivesEvaluating associations of patellofemoral alignment and femoral geometry with bony and cartilaginous abnormalities in PFP patients and healthy control subjects.MethodsData from a case‐control study were used (64 PFP subjects, 70 control subjects, 57% female, age 23.2 (6.4)). Alignment and femoral geometry measures in the PFJ were determined using MRI. Structural abnormalities in the PFJ associated with OA (bone marrow lesions, osteophytes, minor cartilage defects and Hoffa‐synovitis), quantified cartilage composition (T1ρ relaxation times) in the PFJ and perfusion within the patellar bone were examined using different MRI techniques. Associations were analyzed using regression analyses, adjusted for potential confounders.ResultsLateral patellar tilt was negatively associated with presence of osteophytes on both patella (OR 0.91; 95% CI 0.84 to 0.98), anterior femur (OR 0.92; 95% CI 0.84 to 0.99) and minor cartilage defects on patella (OR 0.91; 95% CI 0.84 to 0.99). Patella alta was positively associated with the presence of bone marrow lesions in the patella and minor cartilage defects (OR 48.33; 95% CI 4.27 to 547.30 and OR 17.51; 95% CI 1.17 to 262.57, respectively). Patella alta and medial patellar translation were positively associated with T1ρ relaxation times within trochlear cartilage (β 5.2; 95% CI 0.77 to 9.58, and 0.36; 95% CI 0.08 to 0.64, respectively). None of the alignment and geometry measures were associated with bone perfusion.ConclusionOur study implies that associations between patellofemoral alignment and geometry and structural joint abnormalities linked to OA are already present in both PFP patients and healthy control subjects.

Single-source dual-energy computed tomography for the detection of bone marrow lesions: impact of iterative reconstruction and algorithms.

To compare the diagnostic performance of different reconstruction algorithms of single-source dual-energy computed tomography (DECT) for the detection of bone marrow lesions (BML) in patients with vertebral compression fracture using MRI as the standard of reference. Seventeen patients with an age over 50 who underwent single-source DECT of the spine were included. The raw data (RD) were reconstructed using filtered back-projection (FBP) and iterative reconstruction (IR) with three iteration levels (IR1-IR3). Bone marrow images were generated using a three-material decomposition (3MD) and a two-material decomposition (2MD) algorithm and an RD-based approach. Three blinded readers scored the images for image quality and the presence of bone marrow lesions (BML). Only vertebrae with height loss were included. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The different reconstructions were compared using Dunn's multiple comparison test. Thirty-nine vertebrae were included. IR(1-3) showed superior sensitivity (87.5%) compared to FBP (75%) using 3MD but was comparable to RD (83.3%). All 2MD images were inferior (sensitivity < 38%). The image quality score was significantly higher for 3MD-IR(1-3) compared to 3MD-FBP (p < 0.0001) and all 2MD data sets (p < 0.03). This pattern was also supported by the SNR and CNR measurements. RD showed no significant improvement compared to IR. The image quality of bone marrow images acquired with DECT can be improved by using IR compared with FBP. RD-based reconstruction does not offer significant improvement over image data-based reconstruction. 2MD algorithms are not suitable for BML detection.

The clinical trajectory of people with knee osteoarthritis: secondary analysis of a follow-up assessment following a two-year supplemental intervention

Purpose: To report the clinical trajectory of physical function in people with knee osteoarthritis (OA) four years following a two-year daily intervention involving daily glucosamine and chondroitin sulfate supplements. Secondary objective is to determine if baseline patellofemoral OA features identified on magnetic resonance imaging (MRI) at baseline predict changes in physical function, pain and quality of life two and four years following a supplement intervention. Methods: This is a secondary analysis of a two-year randomised placebo-controlled trial, the Long-term Evaluation of Glucosamine Sulfate (LEGS) trial. Physical function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, two (2011; post-intervention) and four years (2013; two years after formal treatment) with a mailed survey. The minimal clinically important difference of 9.1 was used to identify symptomatic improvement/worsening. Patellofemoral OA features at baseline were evaluated for bone marrow lesions (BMLs), full thickness cartilage loss and osteophytes using the MRI Osteoarthritis Knee Score. Generalised estimating equations determined if patellofemoral OA features were associated with symptomatic improvement/worsening. Results: Of 303 participants, 87% completed two year and 56% completed four year follow-up questionnaires. There were no differences in the number of people followed up between the supplemental groups. From baseline, 41% improved in physical function at two year follow-up, 47% had no change and 13% worsened (Fig 1). From post-intervention, 20% demonstrated further improvement at four years, 60% had no change and 20% worsened. Of people who improved at two-year follow up, 67% had no further changes at four year follow-up (Fig 1). Presence of BMLs in the patellofemoral joint predicted functional improvement at two-year follow-up (OR 0.44, 95% CI 0.24-0.82), and no other patellofemoral features on MRI were associated with clinical changes over time. Conclusions: Majority of people remained the same or improved in physical function, pain and quality of life scores over four years (range=20-60%), indicating that people with knee OA were not likely to functionally decline after an intervention. Most OA features in the patellofemoral joint did not predict symptomatic changes. However, the presence of patellofemoral BMLs predicted improvement in physical function at two-year follow up. Although this finding may be incidental, baseline physical function scores could have potentially influenced the results. However, since baseline physical function scores were adjusted for in the model and the model remained significant, a true effect of patellofemoral BMLs on improved physical function was demonstrated. Overall, the findings from this study demonstrate the importance of understanding the clinical trajectory of people with knee OA. Patients and clinicians need to be made aware of the high proportion of participants who do not have clinical worsening four years following initial start of treatment with supplements, as well as the moderate number of participants likely to demonstrate improvement in physical function either within two or four years.

Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis

IntroductionRandomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo....

The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the Osteoarthritis Initiative

SummaryObjectiveBone shape and bone marrow lesions (BMLs) represent different features of Magnetic resonance imaging (MRI)-detected subchondral pathology in osteoarthritis (OA). The aim of this study was to determine how these features are related and how they change in OA progression.Methods600 participants from the Osteoarthritis Initiative (OAI) FNIH Biomarkers Initiative were included, having Kellgren–Lawrence grade 1–3, at baseline and MRI data at baseline and 24 months. The associations between 3D quantitative bone shape vectors and presence of (MRI Osteoarthritis Knee Score) MOAKS semi-quantitative BMLs (total BML size ≥1) were analysed for femurs and tibias using linear regression. Responsiveness over 24 months was calculated for both features in four pre-defined progression groups and reported as standardised response means (SRMs). Multilevel models investigated the longitudinal relationship between change in BML size and change in bone shape.ResultsMean age was 61.5, 59% female and mean body mass index (BMI) 30.7. Correlation between baseline femur vector and BML was r = 0.28, P < 0.001. The presence of BMLs was associated with higher bone shape vector; coefficient (95% CI) 0.75 (0.54, 0.96) and 0.57 (0.38, 0.77) for femur and tibia respectively, both P < 0.001. After covariate adjustment, only the femur remained significant [coefficient 0.49, (95% CI 0.30, 0.68)]. Longitudinally bone vector demonstrated more responsiveness to change than BMLs (SRM 0.89 vs 0.13) while multilevel models revealed that increase in BML size was related to a more positive bone shape vector (representing worsening OA).ConclusionThere is a relationship between bone shape and BMLs, with prevalence of BMLs associated with increasing OA bone shape. Bone shape demonstrated greater responsiveness than semi-quantitative BMLs.

The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the osteoarthritis initiative

Purpose: Magnetic resonance imaging (MRI) has provided great insights into the development of OA, and helped highlight the importance of subchondral bone pathology. Bone shape and bone marrow lesions (BMLs) represent different features of MRI-detected subchondral pathology in osteoarthritis (OA) and while BMLs are well studied the relationship between these two remains poorly understood. It is important to understand if they represent a single construct or different parts of the OA process, and to further explore their use as imaging biomarkers. The aim of this study was to determine how these features are related and how they change in OA progression. Methods: 600 participants from the FNIH Biomarkers Initiative of the OAI were included, having Kellgren–Lawrence (KL) 1, 2 or 3 at baseline and MRI data at baseline and 24 months. MRI images obtained from the OAI were scored for BMLs using the semi-quantitative MOAKS system that scores 3 features using an ordinal scale for size, number of BMLs and percentage of lesion that is a BML as opposed to a cyst. Quantitative 3D bone shape data was provided by Imorphics (Manchester, UK) using active appearance models (AAMs) applied separately for femur and tibia from 3T DESS-we images. The shape vector for each bone was calculated by taking the principal components of the mean non-OA shape and the mean OA shape and the vector was normalised by setting the mean OA shape to +1 and mean non-OA shape as −1, with each unit increase of 1 representing 1 standard deviation (SD) calculated in non-OA knees. Four BML scores were computed: “BML total size”, “BML total number”, “BML total sub regions” and BML maximum size”. At baseline the correlation between the BML scores and bone shape measures were assessed using Spearman`s correlation coefficients. The association between 3D quantitative bone shape vectors and BMLs at baseline was analysed using linear regression. Presence of a BML was defined as BML total size ≥ 1. Responsiveness was calculated for both features in 4 pre-defined progression groups and reported as standardised response means (SRMs).Due to nesting of repeated measurements within individuals, multilevel linear modelling was used to assess the longitudinal relationship between change in BML size and change in bone shape vector. Results: Mean age was 61.5, 59% were female and mean BMI was 30.7. Correlation between baseline femur shape vector and femur BML total size was r = 0.28, P < 0.001 and similar for the tibia. Linear models revealed an association between presence of a femur BML at baseline and baseline 3D femur vector in both univariable and multivariable models (adjusted coefficient 0.49, 95% CI 0.30, 0.68) indicating a more positive femur vector (indicative of “increased OA”) in individuals with BMLs at baseline, with a difference equivalent to 0.5 × SD of non-OA knees. Longitudinally bone shape demonstrated more responsiveness to change than all BML measures (SRM 0.89 vs 0.13) for femur bone shape vector vs BML total size respectively (Table 1). Univariable growth models revealed that bone shape vector tended to be more positive over time (indicating worsening) while BML total size reduced over time. Multilevel models also showed that an increase in BML size was related to a more positive bone shape vector (representing worsening OA). Conclusions: There is a relationship between bone shape and BMLs, with increasing OA bone shape vector associated with higher prevalence of BMLs. Bone shape vector demonstrated greater responsiveness than semi-quantitative BMLs over time periods typical of a clinical trial.Table 1Responsiveness of bone shape and BML measures over 24 monthsRadiographic and pain progression N = 194Radiographic progression only N = 103Pain progression only N = 103No progression N = 2002 year responsiveness, SRM (95%CI)Bone shapeFemur0.89 (0.72,1.02)1.02 (0.85,1.20)0.46 (0.31,0.61)0.61 (0.49,0.72)Tibia0.84 (0.70,0.97)0.76 (0.56,0.96)0.26 (0.07,0.43)0.47 (0.33,0.69)BMLsFemur BML total size−0.13 (−0.26,0.02)−0.15 (−0.35,0.07)−0.31 (−0.51,−0.13)−0.24 (−0.37,0.13)Femur BML total number0.38 (0.26,0.50)0.20 (−0.02,0.41)0.17 (−0.04,0.35)0.27 (0.14,0.38)Tibia BML total size0.11 (−0.02,0.26)0.14 (−0.04,0.31)−0.04 (−0.23,0.15)−0.01(−0.16,0.11)Tibia BML total number0.37 (0.24,0.51)0.31 (0.12,0.51)0.19 (0.00,0.33)0.16 (0.02,0.29)Femur BML maximum size−0.05 (−0.19,−0.09)−0.01 (−0.19,0.21)−0.20 (−0.38,0.01)−0.11 (−0.25,0.02)BML total sub regions−0.02 (−0.15,0.13)−0.03 (−0.23,0.15)−0.13 (−0.32,0.07)−0.06 (−0.20,0.08) Open table in a new tab

Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative

BackgroundGreater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA.MethodsWe conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores.ResultsWe included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML.ConclusionsAmong individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.

Novel Surgical Technique for Bone Marrow Lesion — Case Report

Abstract Introduction: Bone marrow lesions (BMLs) are commonly described as magnetic resonance imaging (MRI) findings associated with stress injuries or trauma. The presence of BMLs closely correlates with pain and rapid joint deterioration. Case presentation: A 51-year-old healthy man presented to our clinic with severe knee pain due to BMLs. After 3 months of conservative treatment, arthroscopy and subchondroplasty (SCP) of the medial femoral condyle was performed. The IKDC (International Knee Documentation Committee) score improved from 39.9 to 66.7 at 6 months, and to 87.4 at 1 year after surgery. The KOOS (Knee Injury and Osteoarthritis Outcome) score improved from 38.5 to 77.7 at 6 months, and to 92.6 at 1 year after surgery. The Tegner Lysholm score improved from 23 to 80 at 6 months, and to 95 at 1 year after surgery. Conclusion: SCP may provide a viable approach to reduce pain associated with BML, with minimal risk of significant complications.