Femorotibial Compartment Research Articles

Serum ARGS-aggrecan in a phase 2 clinical trial targeting osteoarthritis

OBJECTIVETo monitor serum concentrations of the aggrecan ARGS neoepitope in a clinical trial of ADAMTS-5 inhibition as disease-modifying therapy of knee osteoarthritis, and to investigate relationships between reduction in ARGS and change in cartilage thickness, knee related pain and function. DESIGNROCCELLA trial participants received once-daily oral S201086 75, 150 or 300 mg, or placebo, for 52 weeks. Serum was collected at baseline, 4, 12, 28 and 52 weeks, and 2 weeks post treatment with ARGS measured by an in-house immunoassay. Change from baseline to week 52 in central medial femorotibial compartment cartilage thickness was measured by MRI, function and pain by WOMAC subscores. Associations between cumulative change in ARGS and change in cartilage thickness or WOMAC subscores were evaluated by linear regression. RESULTSS201086 reduced serum levels of ARGS in a dose-dependent manner throughout the treatment period. Maximal reduction was at 4 weeks with a 58.5% [95% CI 60.8%, 56.2%] reduction of ARGS compared to baseline for 300 mg S201086. Two weeks post treatment, ARGS concentrations rebounded with a dose-dependent overshoot compared to baseline levels. Cumulative change of ARGS concentration from baseline to week 52 had no effect on change in cartilage thickness (slope -0.8x10-6 [-2.9x10-6, 1.3x10-6]) or change in WOMAC pain and function (slopes -30x10-6 [-64x10-6, 5.2x10-6] and -97x10-6 [-214x10-6, 20x10-6], respectively) at week 52. CONCLUSIONSystemic inhibition of ADAMTS-5 resulted in markedly reduced serum ARGS, but change in serum ARGS concentrations showed no association with the progression of cartilage thinning, or patient reported pain and function. ClinicalTrials.govNCT03595618.

Micro-computed tomography reveals high-density mineralised protrusions and microstructural lesions in equine stifle joint articular cartilage.

Stifle osteoarthritis (OA) lesions are most common in the medial femorotibial (MFT) compartment. Their characterisation and mapping will inform equine veterinarians towards an accurate diagnosis of OA. Investigate and map micro-CT (μCT) changes in the hyaline articular cartilage (HAC) in the medial femoral condyle (MFC) and medial tibial plateau (MTP). Ex vivo cadaveric. Stifles (n = 7 OA and 17 control [CO]) were retrieved from a tissue bank. The MFC and MFT were imaged with μCT. Regions of interest (ROIs) were cranial (MFCcr; MTPcr) and caudal (MFCca; MTPca) sites. In each ROI, μCT images were scored for HAC fibrillation, surface mineralisation and for the presence of high-density mineralised protrusions (HDMP). The lesions were mapped, and site-matched histology was performed. The microstructure of healthy and abnormal HAC was discernible on μCT images and confirmed with histology. HAC fibrillation was more prevalent (p = 0.019) in the MFCcr of the OA group (n = 7/7, 100%) when compared with the CO group (n = 7/17, 41%). Score 1 HAC surface mineralisation was more prevalent (p = 0.038) in the OA MFCca (n = 4/7, 57%) when compared with the CO group (n = 2/17, 12%). HDMP were heterogenous and hyperdense mineralised material protruding into the HAC and were more frequent (p = 0.033) in MFCs (n = 12/24, 50%) compared with MTPs (n = 5/24, 20%). Score 3 HDMPs were also more prevalent (p = 0.003) in the MFCcr (n = 7/24, 29%) compared with MFCca (n = 0/24, 0%) and in MFCs (n = 7/24, 29%) compared with MTPs (n = 3/24, 12.5%) (p = 0.046). Clinical history was not available for all specimens. Equine HDMP and HAC surface mineralisation are imaged for the first time in the MFT joint. HAC fibrillation and erosion and HDMP are more frequent in the cranial aspect of the MFC. μCT images of OA in equine stifle joints provide a novel perspective of lesions and improve understanding of OA.

No correlation found between palpation and ultrasound for evaluation of effusion in the medial femorotibial and femoropatellar joint compartments of horses.

To compare palpation and ultrasound scores of effusion of the medial femorotibial and femoropatellar joints of horses. 40 horses (80 stifles) were evaluated over a 12-week period. Horses > 1 year of age without history of stifle disease were enrolled from September to December 2022. Palpation of right and left medial femorotibial and femoropatellar joint compartments was performed. Amount of effusion was scored by a board-certified large animal surgeon, a third-year large animal surgery resident, and an equine sports medicine intern. Effusion of right and left medial femorotibial and femoropatellar joints was quantified with ultrasound by a board-certified equine sports medicine and rehabilitation clinician. Amount of effusion on palpation and ultrasound was graded as none-mild (1), moderate (2), or severe (3). A 2-way intraclass correlation coefficient evaluated interrater reliability of palpation scores. The Spearman rank correlation determined association between palpation and ultrasound scores. Interrater reliability for palpation of effusion was poor between all observers for all joint compartments. No significant correlation was identified between palpation and ultrasound scores for any joint compartment for any observer. Clinicians often rely on palpation of joint effusion as an indication of stifle pathology. We found interrater reliability to be poor for palpation scores, indicating low agreement for palpation of joint effusion between clinicians within our group. No correlation was found between palpation and ultrasound scores for joint effusion, indicating that clinicians should not rely on palpation alone to quantify joint effusion of the medial femorotibial and femoropatellar joints.

Prospective Observational Study of a Non-Arthroscopic Autologous Cartilage Micrografting Technology for Knee Osteoarthritis.

Autologous micrografting technology (AMT®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons® SRT in 4.0 mL of saline solution, and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37-84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing, and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p ≤ 0.05). Autologous auricular cartilage micrografts obtained by AMT® procedure (using Rigenera® technology) is an effective and safe protocol in the treatment of early stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population and in a randomized clinical trial (RCT).

Which Knee Phenotypes Exhibit the Strongest Correlation With Cartilage Degeneration?

Although articular wear has been thoroughly investigated, the effects of abnormal limb alignment on cartilage degeneration over time remain poorly understood. An exact assessment of the correlation between lower limb alignment abnormalities and MRI-observed articular degradation may be helpful for understanding the progression of osteoarthritis and planning future treatment. In patients with moderate to advanced osteoarthritis, (1) is there a correlation between overall alignment of the knee and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (2) Is there a correlation between tibial alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (3) Is there a correlation between femoral alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? Between April 2020 and September 2022, we retrospectively evaluated 3106 patients aged 45 to 79 years who were at risk of experiencing knee osteoarthritis. Of those, we considered as potentially eligible 600 symptomatic index knees with radiographic evidence of osteoarthritis-Kellgren-Lawrence Grades 2 or 3-at the baseline visit. Of those, 22% (134 of 600) were excluded because of a lack of proper alignment measurements, leaving 466 knees with measurements of radiologic alignment angles and quantitative MRI cartilage measurements of 16 subregions of the femorotibial compartment at baseline and 12 and 24 months, and 64 knees at the 48-month visit for investigation in the current study. Data regarding cartilage measurements of the patellofemoral compartment were not available for analysis. The knees were categorized into one of the possible 25 different phenotypes of the lower extremity established by previous research, based on the neutral, valgus, or varus distal mechanical angle of the femur and proximal tibial mechanical angle on full-limb radiographs. We applied ANOVA to estimate the effect size of the overall, femoral, and tibial alignments on the location of cartilage degradation over time, as measured by cartilage metrics on MRI. We found that the overall combinations of a valgus femur with valgus tibia or a valgus femur with varus tibia were associated with the highest loss of cartilage in the internal medial tibial subregion and anterior lateral tibial subregion (η 2 p = 0.39 and 0.17, respectively). For the tibia, we found that the combination of a valgus femur with valgus tibia was associated with an increase in the area of subchondral bone denuded of cartilage in the central lateral tibial subregion (η 2 p = 0.2). For the femur, we found that the combination of a valgus femur with valgus tibia was associated with loss of cartilage thickness in the central weightbearing lateral femorotibial compartment (η 2 p = 0.15). We found that certain alignment patterns are associated with rapid deterioration of cartilage and exposure of subchondral bone, even over short time periods. In particular, the valgus femur with valgus tibia and valgus femur with varus tibia phenotypes deserve special attention, because they exhibited a strong, atypical correlation with the internal medial tibial subregion and anterior lateral tibial subregion, respectively. This is important because valgus and varus malalignment cause isolated lateral and medial compartment disease, respectively. Therefore, these findings suggest that a more individualized approach for limb axis deformities is valuable, and hint at a more meticulous radiologic and clinical investigation, perhaps using different imaging modalities, especially when assessing the exact cartilage state and planning an intervention. Future studies, ideally biomechanical, might help in assessing the long-term effects of the various phenotypes on cartilage degradation and their relevance in reconstructive surgery. Level II, prognostic study.

Clinical and radiological efficacy of single-dose intra-articular high-molecular-weight hyaluronic acid in knee osteoarthritis.

While visco-supplementation is being used for the treatment of knee osteoarthritis (OA), the published reports vary widely in benefits afforded by this treatment. It was therefore proposed to assess the objective parameters along with subjective outcomes. Our study assessed the radiological and clinical efficacy of single-dose high-molecular-weight intra-articular hyaluronic acid (HMW-IAHA) injection in knee OA. This interventional cohort study was conducted in a calculated sample size of 44 patients with knee OA. Visual analog scale (VAS) and knee OA and outcome score (KOOS) were used for clinical assessment, and whole organ magnetic resonance imaging score (WORMS) for radiological assessment. The subjects were given a single dose of HMW-IAHA injection, 90 mg/3 ml, and were assessed on day 0 and day 90. Statistical Package for Social Sciences (SPSS) software was used. At the day 90 follow-up, there was an improvement in mean ± standard deviation values of VAS score (day 0: 8.53 ± 0.81, day 90: 5.97 ± 0.87), KOOS score (day 0: 27.33 ± 15.18, day 90: 57.26 ± 14.26), and the cartilage signal and morphology in the medial femorotibial joint (day 0: 11.02 ± 6.26 and day 90: 10.91 ± 6.22) and patellofemoral joint (day 0: 10.35 ± 4.36 and day 90: 10.28 ± 4.39) compartments. There was a decrease in synovitis score from 2.3 ± 1.61 to 1.3 ± 1.3 in the medial femorotibial joint compartment and total WORMS score (day 0: 66.57 ± 36.06, day 90: 65.14 ± 35.62). A single dose of intra-articular injection with high-molecular-weight hyaluronic acid produces improvement in the clinical symptoms and quality of life as well as is effective in maintaining the articular cartilage integrity and reducing synovial inflammation.

Lateral meniscus with tears or with histologic calcification does not increase the risk of lateral osteoarthritis after medial unicompartmental arthroplasty.

Meniscal tears or histological meniscal calcifications (in the absence of radiological chondrocalcinosis) are frequent in osteoarthritis. Whether lateral meniscal lesions influence clinical outcomes after medial unicompartmental knee arthroplasty (UKA) is unknown. We analyzed 130 patients (130 knees) with medial unicompartmental knee arthroplasties between 2005 and 2015. These 130 knees had full articular cartilage thickness in the lateral compartment and no radiological chondrocalcinosis on preoperative radiographs. The lateral meniscus was analyzed with preoperative MRI and a biopsy of the anterior horn at the time of surgery. Synovial fluid was collected and analyzed for calcium pyrophosphate dihydrate crystal deposition (CPPD crystals). Lateral meniscal tears were untreated when detected on MRI or during surgery, with the hypothesis that these tears on the opposite compartment would remain asymptomatic in medial UKA. At average 10-year follow-up, patients were evaluated with clinical and radiographic outcome, with a focus on the risk of joint space narrowing of the lateral femorotibial compartment. CPPD crystals were present in the synovial fluid of 70 knees. Lateral meniscal tears were seen on MRI in 34 (49%) normal meniscuses of the 60 knees without CPPD crystals and in six other knees without histological meniscal calcification despite CPPD crystals. Histological calcification was present on 61 lateral meniscuses with 53 meniscal tears. The results showed no significant differences in the clinical outcomes between knees with lateral meniscal tears or lateral meniscal histological chondrocalcinosis or both lesions and those without these conditions. Additionally, radiographic progression of osteoarthritis in the opposite femorotibial compartment of the knee was not more frequent in patients with these meniscal issues. The tenyear cumulative survival rates, measured by the need for total knee arthroplasty, were 91% for knees without meniscal lesions and 92% for knees with these lesions. On this basis, treatment of meniscal tears of the lateral compartment and routine aspiration of the knee to assess for birefringent crystals in the planning of medial UKA do not appear necessary.

Efficacy and Safety of Stempeucel in Osteoarthritis of the Knee: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled Study

Background: Osteoarthritis is a chronic, progressive, and degenerative condition with limited therapy options. Recently, biologic therapies have been an evolving option for the management of osteoarthritis. Purpose: To assess whether allogenic mesenchymal stromal cells (MSCs) have the potential to improve functional parameters and induce cartilage regeneration in patients with osteoarthritis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 146 patients with grade 2 and 3 osteoarthritis were randomized to either an MSC group or placebo group with a ratio of 1:1. There were 73 patients per group who received either a single intra-articular injection of bone marrow–derived MSCs (BMMSCs; 25 million cells) or placebo, followed by 20 mg per 2 mL of hyaluronic acid under ultrasound guidance. The primary endpoint was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. The secondary endpoints were WOMAC subscores for pain, stiffness, and physical function; the visual analog scale score for pain; and magnetic resonance imaging findings using T2 mapping and cartilage volume. Results: Overall, 65 patients from the BMMSC group and 68 patients from the placebo group completed 12-month follow-up. The BMMSC group showed significant improvements in the WOMAC total score compared with the placebo group at 6 and 12 months (percentage change: −23.64% [95% CI, −32.88 to −14.40] at 6 months and −45.60% [95% CI, −55.97 to −35.23] at 12 months P < .001; percentage change, −44.3%). BMMSCs significantly improved WOMAC pain, stiffness, and physical function subscores as well as visual analog scale scores at 6 and 12 months (P < .001). T2 mapping showed that there was no worsening of deep cartilage in the medial femorotibial compartment of the knee in the BMMSC group at 12-month follow-up, whereas in the placebo group, there was significant and gradual worsening of cartilage (P < .001). Cartilage volume did not change significantly in the BMMSC group. There were 5 adverse events that were possibly/probably related to the study drug and consisted of injection-site swelling and pain, which improved within a few days. Conclusion: In this small randomized trial, BMMSCs proved to be safe and effective for the treatment of grade 2 and 3 osteoarthritis. The intervention was simple and easy to administer, provided sustained relief of pain and stiffness, improved physical function, and prevented worsening of cartilage quality for ≥12 months. Registration: CTRI/2018/09/015785 (National Institutes of Health and Clinical Trials Registry–India).

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

To describe associations between MRI markers with knee symptoms in young adults. Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial

To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75mg, P=0.165; vs 150mg, P=0.939; vs 300mg, P=0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

Selection of Knees With Subsequent Cartilage Thickness Loss Based on Magnetic Resonance Imaging Semiquantitative Grading: Data From the Osteoarthritis Initiative Foundation for the National Institutes of Health Biomarker Cohort.

To investigate which magnetic resonance imaging (MRI)-based articular pathologies are predictive of subsequent medial femorotibial compartment quantitative cartilage thickness loss and therefore suitable for enrichment of clinical trials with participants showing a high likelihood for structural progression. Semiquantitative MRI Osteoarthritis Knee Score (MOAKS) assessments at baseline and quantitative cartilage thickness measurements at baseline and year-2 follow-up were performed in 599 participants (age 62 years; body mass index 31 kg/m2 ; 59% female) from the Osteoarthritis Initiative-based Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Knees were classified as medial femorotibial compartment (MFTC) progressors or nonprogressors based on MFTC cartilage thickness change (smallest detectable change threshold -111 μm). Logistic regression was used to investigate the association between baseline presence and severity of MFTC MOAKS pathologies with subsequent MFTC progression. The standardized response mean (SRM) was computed to estimate the sensitivity to change that can be achieved when selecting knees based on MOAKS pathologies. Presence of MFTC MOAKS cartilage damage (odds ratio [OR] 2.77 [95% confidence interval (95% CI) 1.76, 4.36]), MFTC bone marrow lesions (OR 2.69 [95% CI 1.89, 3.83]), medial meniscus extrusion or damage (OR 2.21 [95% CI 1.37, 3.55]), as well as MOAKS severity subscales for cartilage and meniscus damage were associated with subsequent progression. The SRM was greater in knees with than in knees without the presence of these pathologies and was associated with the severity of those pathologies. MRI-based grading of articular pathologies makes it possible to specifically select progressor knees suitable for inclusion in clinical trials but also to identify knees in which treatment is not indicated (e.g., knees without cartilage damage despite presence of radiographic osteoarthritis).

PREVALENCE OF STRUCTURAL LESIONS AND OSTEOARTHRITIS IN FEMOROTIBIAL JOINTS OF ASYMPTOMATIC PARTICIPANTS FROM THE LAUSANNE KNEE STUDY

Structural lesions of the cartilage, menisci, and bone are prevalent on knee MRIs in the asymptomatic population. The presence of such lesions may lead to the diagnosis of osteoarthritis (OA) according to imaging criteria. The prevalence of OA at imaging may depend on the definition criteria used (radiographic vs. MRI criteria). 1) To determine the prevalence of structural lesions of the femorotibial joint in two groups of young and older asymptomatic participants with healthy knees from the Lausanne Knee Study (LKS). 2) To determine the prevalence of OA in that population using radiographic and MRI definitions of OA. Asymptomatic volunteers were prospectively enrolled in this IRB-approved HIPPA-compliant study. Inclusion criteria: age between18-35 or 45-70 years, no knee symptoms in the past 12 months, no history of severe lower limb injury requiring surgery or not, no impairment that might affect gait, BMI≤30. All participants (n=430, 47.8 years ±16.17 (SD), range 18-70 y, 192 (44.6%) male) underwent a clinical evaluation, including KOOS and WOMAC scores to evaluate pain and knee function, radiographic imaging (weight-bearing Schuss and lateral radiographs of both knees, full spine and lower extremity weight-bearing low dose 3D biplanar radiographs (EOS)), and 3T MRI of a randomly selected knee. MRI protocol included 2D fat-suppressed FSE IW images (sagittal, coronal, and transverse planes), isotropic 3D DESS, high-resolution 3D T1. One musculoskeletal radiologist with 6 years of experience graded radiographs (KL score) and knee MRIs for all structural lesions included in the MOAKS criteria. For this study, only femorotibial compartments will be presented. OA was defined as a KL score≥2 at radiography, or using the criteria proposed by Hunter et al (2011) at MRI. There were 137 participants in the young (Y) (26.2y±4.7; 65 male (47.4%)) and 293 in the older (O) group (57.9y±7.23; 127 male (43.3%)). Participants had no knee pain or functional impairment (average KOOS 97.6±2.51 vs 97.2±3.78 in Y vs O group (p=0.26); average WOMAC 97.8±5.48 vs 96.7±8.23 in Y vs O group (p=0.16)). Structural lesions were highly prevalent in the femorotibial joints (decreasing order of prevalence): 190 (44.2%) cartilage damage (7 vs 183 in Y vs. O, p<10−5), 132 (30.7%) BML (5 vs 127 in Y vs. O, p<10−5), 111 (25.8%) meniscal damage (2 vs 109/ in Y vs. O, p<10−5), 110 (25.6%) had peri-articular cysts (13 vs 97 in Y vs. O, p<10−5), 104 (24.2%) participants had osteophytes (3 vs 101/ in Y vs. O, p<10−5), 68 (15.8%) Hoffa synovitis (3 vs 65 in Y vs. O, p<10−5), 38 (8.8%) synovitis/effusion (3 vs 35 in Y vs. O, p<10−3), and 17 (4%) had loose bodies (1 vs 16 in Y vs. O, p=0.019). 76 (17.7%) participants (1 young) had radiographic OA (60 KL2; 16 KL3; 0 KL4), while 24 (5.6%) participants (all from the older group) had femorotibial OA based on MRI criteria, 198 (46%) had normal MRI, and 208 (48.4%) had structural lesions of variable severity that did not fulfill MRI criteria of OA. In a cohort of 430 asymptomatic volunteers with clinically healthy knees, structural lesions were present in up to 54% of femorotibial joints, with their prevalence increasing with age. The prevalence of OA at imaging in healthy knees may be high and depends on the criteria used (prevalence of 5.6% vs. 17.7% when using MRI vs. radiographic criteria).

AGREEMENT AND PRECISION OF FEMOROTIBIAL CARTILAGE TRANSVERSE RELAXATION TIME (T2) OBTAINED AT FOUR DIFFERENT MAGNETIC FIELD STRENGTHS

Spin-spin (transverse) relaxation time (T2) is considered to reflect cartilage composition, such as hydration, collagen content and orientation. It can be computed from multi-echo spin-echo (MESE) MRI and is associated with age, sex, and structural joint pathology. Cartilage T2 is dependent on the magnetic field strength. Lower field strength is characterized by lower signal to noise ratios (SNR) compared to standard 1.5Tesla (T) and 3T systems, resulting in longer acquisition times, while access to ultra-high field 7T MRI is still limited. A direct comparative evaluation of cartilage T2 across different field strengths has not been performed to date. To analyze the agreement and the intra-reader test-retest precision of laminar femorotibial cartilage T2, acquired from four different scanner models with 0.55T,1.5T, 3T, and 7T. Six healthy volunteers (5 female, age 21.5±3.5 y) without knee pain had two MESE MRIs acquired each, with repositioning of the knee between test and retest scans, using a 1) MAGNETOM Free.Max 0.55T (acquisition matrix (AM) 304 × 248, slice thickness [ST] 3mm, TR 3020ms, 6 echoes from 16.1 to 96.6ms, acquisition time (AT) 14 min 56 sec) 2) MAGNETOM Sola 1.5T (AM 384 × 384, ST 3mm, TR 2700ms, 7 echoes from 11.7 to 81.9ms, AT 10 min 31 sec) 3) MAGNETOM Vida 3T (AM 384 × 384, ST 3mm, TR 3210ms, 9 echoes from 11.5 to 103.5ms, AT 8 min 17 sec) 4) MAGNETOM Terra 7T (AM 384 × 384, ST 3mm, TR 4490ms, 9 echoes from 8.1 to 72.9ms, AT 8 min 22 sec) (Fig. 1). The field of view was 12 × 12cm for all MESE MRIs. Segmentation of the medial and lateral femorotibial compartment cartilage (MFTC/LFTC) was performed manually by an expert reader; the T2 values were computed for each voxel using custom software. The cartilage layers were divided into the top 50% (superficial [sf]) and bottom 50% (deep) layer, based on the local distance between the cartilage surface and bone interface. The test-retest precision across the entire femorotibial joint (FTJ), the MFTC, and the LFTC was measured using the root mean square coefficient of variation (RMS CV in %). The absolute values of laminar T2 were compared between field strengths using ANOVA, with Bonferroni-Dunn post-hoc correction. The RMS CV across the FTJ was lowest at 3T (0.9%/1.4% sf/deep) and greatest at 0.55T (3.2%/4.0%). The RMS CV was 1.3%/3.4% at 1.5T and 2.3%/1.4% at 7T. Sf RMS CV at 0.55/1.5/3/7T was 3.9/1.7/1.0/3.5% for the MFTC, and 3.0/1.7/1.2/2.7% for the LFTC. The deep layer RMS CV was 5.4/3.4/3.1/2.6% for the MFTC and 5.0/4.1/1.1/2.9% for the LFTC. Sf and deep layer T2 differed significantly between field strengths for the FTJ, the MFTC, and the LFTC (all p<0.001). Both sf and deep layer T2 across the FTJ, the MFTC and also the LFTC were shortest at 7T and longest at 0.55T (Fig. 2). Interestingly, T2 was shorter at 1.5T than at 3T, but this difference reached statistical significance only for the deep layer in the FTJ and in the MFTC (Fig. 2). Based on the protocols implemented in this study, laminar cartilage T2 systematically varied with magnetic field strength. The shortest values were observed at 7T, and the longest at 0.55T. These findings suggest that cartilage T2 measurements in multicenter studies are not directly comparable when different field strengths (potentially also different manufacturer and scanner models) are included. The test-retest precision error was lowest at 3T and highest at 0.55T, suggesting that, in clinical studies, measurements should be performed at 3T. However, test-retest precision is highly dependent on the protocol and might be improved for lower field strengths, applying different acquisition parameters (e.g. longer acquisition times and higher resolution). Implementation on the 7T magnet may require further improvement to leverage the full potential benefit of the higher field strength.

Kinematic alignment fails to achieve balancing in 50% of varus knees and resects more bone compared to functional alignment.

Evidence is emerging that tibio-femoral compartmental balancing is related to clinical outcomes after total knee arthroplasty (TKA). The purpose of this study was to assess if kinematic alignment (KA) delivered a balanced knee in flexion and extension after TKA on varus deformity, compared to functional alignment (FA). This single-centre retrospective cohort study assessed 110 consecutive TKAs performed with an image-based robotic system for pre-operative varus deformity. The ligament balancing in the medial and lateral femorotibial compartments was assessed intra-operatively with a robotic system to evaluate if a KA plan would deliver a balanced knee. Balance was considered achieved if tibio-femoral compartments (medial/lateral) were equal to or less than 1.5mm, or if the estimated final gap position more than 2mm from the global implant thickness (17mm). Implant positioning was modified within limits previously defined for a FA philosophy to achieve balancing. Resection thickness and implant positioning were compared with the KA plan and after the FA adjustments; and also, between the patients with a final balanced knee in extension and at 90° of flexion. A total of 102 patients were eligible for final analysis. Mean age was 67.3 ± 8.2years, average BMI was 29.1 ± 5.2kg/m2, mean pre-operative coronal alignment was 174.0° ± 3.3° and sagittal alignment 3.4° ± 5.9°. Mean post-operative coronal alignment was 177.7° ± 1.0° and sagittal alignment 0.8° ± 1.9°. A KA plan delivered medial-lateral tibio-femoral compartment balancing in 67 cases (65.7%) for the extension gap and in 50 cases (49.1%) for the flexion gap. All measured bone resection depths were significantly less for FA compared to KA. To achieve balancing targets, final femoral component position was more externally rotated relative to the posterior condylar axis, (0.5° with KA compared to 1.7° with FA (p < 0.0001), and the tibia in more varus (3.0° KA vs. 3.5° FA p = 0.0024). Only one soft tissue release was required. KA failed to deliver a balanced TKA in more than 50% of cases, especially regarding the flexion gap. Consideration of soft tissue laxity led to significantly less bone resection, with more externally rotated femoral component and more varus tibial component.

Association of Superficial Cartilage Transverse Relaxation Time With Osteoarthritis Disease Progression: Data From the Foundation for the National Institutes of Health Biomarker Study of the Osteoarthritis Initiative.

To study whether layer-specific cartilage transverse relaxation time (T2) and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression. The Foundation for the National Institutes of Health Biomarker Consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.7 mm) and a persistent increase in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (≥9 on a 0-100 scale) at 24-48 months from baseline (n=194). Multiecho spin-echo (MESE) magnetic resonance images (MRIs) for cartilage T2 analysis had been acquired in the right knees only (97 progressor knees). These were compared to 104 control knees without JSW or pain progression. Fifty-three knees had JSW progression, and 57 pain progression only. Cartilage thickness segmentations obtained from double-echo steady-state MRI were matched to MESE MRI to extract superficial and deep femorotibial cartilage T2. Superficial medial femorotibial compartment (MFTC) T2 at baseline was the primary, and change in deep MFTC T2 between baseline and 12 months was the secondary analytic outcome of this post hoc exploratory study. Baseline superficial MFTC T2 was significantly elevated in progressor knees (adjusted mean 47.2 msec [95% confidence interval (95% CI) 46.5, 48.0]) and JSW progression only knees (adjusted mean 47.3 msec [95% CI 46.3, 48.3]), respectively, versus non-progressor knees (45.8 msec [95% CI 45.0, 46.5]) after adjustment for age, sex, body mass index, WOMAC pain score, and medial joint space narrowing grade (analysis of covariance). Change in T2 was not significantly associated with case status. Baseline superficial, but not deep, medial cartilage T2 is associated with clinically relevant disease progression in knee OA.

Lumbar spine metastasis from squamous cell carcinoma of tongue

Introduction: Acute anterior poliomyelitis (AAP) is an endemic human disease caused by a worldwide spreading enterovirus. The late consequences of AAP include a new picture of muscle weakness together with abnormal muscle fatigue, amyotrophy, and myoarticular pain, configuring a condition known as post-polio syndrome (PPS). This new condition comprises a specific set of health problems due to the polio virus, resulting in decreased functional capacity and/or the onset of new disabilities. Case Report: A 53-year-old female, human resources analyst, reported that she had been shaken by AAP at the age of 2. Currently she was presented with gait on the knees, osteo-myoarticular pain, inadequate synergies of movements. Imaging exams showed great disproportion in the pelvic region with marked amyotrophy and liposubstitution of the muscle, more evident in the left leg. Although there was some preservation of the plantar flexor muscles, interstitial edema was evident. In the thighs there was amyotrophy with liposubstitution of the muscle, more evident on the left. In the left knee joint there was a lesion of the cruciate ligaments with extensive deep chondral erosions in the load area of the femorotibial compartment, with exposure of the subchondral bone, without edema. Osteopenia also affected it. Conclusion: Through the data obtained in this study, it can be seen that there are many reasons why patients affected by post-polio syndrome develops bone deformities and joint interferences that cause the individual to suffer losses and aggravations in health and quality of life. Nevertheless, there is a lack of theoretical framework available in the literature, justifying the importance of further studies on this topic.

A painful skeleton disarticulated by acute anterior poliomyelitis

Introduction: Acute anterior poliomyelitis (AAP) is an endemic human disease caused by a worldwide spreading enterovirus. The late consequences of AAP include a new picture of muscle weakness together with abnormal muscle fatigue, amyotrophy, and myoarticular pain, configuring a condition known as post-polio syndrome (PPS). This new condition comprises a specific set of health problems due to the polio virus, resulting in decreased functional capacity and/or the onset of new disabilities. Case Report: A 53-year-old female, human resources analyst, reported that she had been shaken by AAP at the age of 2. Currently she was presented with gait on the knees, osteo-myoarticular pain, inadequate synergies of movements. Imaging exams showed great disproportion in the pelvic region with marked amyotrophy and liposubstitution of the muscle, more evident in the left leg. Although there was some preservation of the plantar flexor muscles, interstitial edema was evident. In the thighs there was amyotrophy with liposubstitution of the muscle, more evident on the left. In the left knee joint there was a lesion of the cruciate ligaments with extensive deep chondral erosions in the load area of the femorotibial compartment, with exposure of the subchondral bone, without edema. Osteopenia also affected it. Conclusion: Through the data obtained in this study, it can be seen that there are many reasons why patients affected by post-polio syndrome develops bone deformities and joint interferences that cause the individual to suffer losses and aggravations in health and quality of life. Nevertheless, there is a lack of theoretical framework available in the literature, justifying the importance of further studies on this topic.

Detection of Differences in Longitudinal Cartilage Thickness Loss Using a Deep-Learning Automated Segmentation Algorithm: Data From the Foundation for the National Institutes of Health Biomarkers Study of the Osteoarthritis Initiative.

ObjectiveTo study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (OA), we evaluated the sensitivity to change in progressor knees from the Foundation for the National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and we determined whether differences in progression rates between predefined cohorts can be detected by the fully automated approach.MethodsThe OA Initiative Biomarker Consortium was a nested case–control study. Progressor knees had both medial tibiofemoral radiographic joint space width loss (≥0.7 mm) and a persistent increase in Western Ontario and McMaster Universities Osteoarthritis Index pain scores (≥9 on a 0–100 scale) after 2 years from baseline (n = 194), whereas non‐progressor knees did not have either of both (n = 200). Deep‐learning automated algorithms trained on radiographic OA knees or knees of a healthy reference cohort (HRC) were used to automatically segment medial femorotibial compartment (MFTC) and lateral femorotibial cartilage on baseline and 2‐year follow‐up magnetic resonance imaging. Findings were compared with previously published manual expert segmentation.ResultsThe mean ± SD MFTC cartilage loss in the progressor cohort was –181 ± 245 μm by manual segmentation (standardized response mean [SRM] –0.74), –144 ± 200 μm by the radiographic OA–based model (SRM –0.72), and –69 ± 231 μm by HRC‐based model segmentation (SRM –0.30). Cohen's d for rates of progression between progressor versus the non‐progressor cohort was –0.84 (P < 0.001) for manual, –0.68 (P < 0.001) for the automated radiographic OA model, and –0.14 (P = 0.18) for automated HRC model segmentation.ConclusionA fully automated deep‐learning segmentation approach not only displays similar sensitivity to change of longitudinal cartilage thickness loss in knee OA as did manual expert segmentation but also effectively differentiates longitudinal rates of loss of cartilage thickness between cohorts with different progression profiles.

Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults

To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years. Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n=156) and 10-13 year follow-up at CDAH-3 (n=167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n=313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML. In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (β:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (β:-141.548; 95%CI:-254.917,-28.179) and total bone area (β:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (β:-0.001; 95%CI:-0.002,-0.00004), and total bone area (β:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (β:-0.001; 95%CI:-0.001,-0.0001) and total bone area (β:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA. COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.

Comparison of conventional MRI, MR arthrography, MR arthrography with traction, MR arthrography with pressure in the evaluation of articular distension

ObjectiveTo evaluate the performance of conventional MRI, standard MR arthrography, MR arthrography with traction and MR arthrography with pressure in articular distension in patients with ACL injury. Design and patientsThe consecutive patients (7 female, 21 male) with acute ACL injured conventional MRI, MR arthrography, MR arthrography with traction and MR arthrography with pressure were evaluated. ResultsThe amount of distension in the joint was evaluated in the posterior, femorotibial and anterior compartments. Medially, between the meniscus posterior horn and the tibial corner, MRA with pressure was found to be more effective in showing this distance than MRA with traction (p < 0,05). Laterally, in measurements made between the posterior horn of the meniscus and the capsule, MRA with traction and MRA with pressure are more effective showing this distance than conventional MRI and standard MRA (p < 0,05). In measurements made medially, between the posterior horn of the meniscus and the capsule, MRA with traction is more effective in showing this distance than standard MRA (p < 0,05). In all three different MRA modalities, the lateral femorotibial joint distance was found to be statistically higher than conventional MRI (p < 0,05). Medial femorotibial joint distance was found to be statistically higher in MRA with pressure than in conventional MRI and standard MRA (p < 0,05). The medial infrapatellar distance was found to be statistically higher in MRA with pressure than standard MRA and MRA with traction (p < 0,05). The lateral infrapatellar distance is higher in MRA with pressure than in MRA with traction, and this height is statistically significant (p < 0,05). ConclusionTraction and pressure applications added to MRA will increase the effectiveness of the method by increasing the distension in the knee joint. Although both seem to be effective in creating distension in posterior compartment and femorotibial joint distance, MRA with pressure is more effective especially in anterior compartment.