Femoral cartilage thickness measured on MRI varies among individuals: Time to deepen one of the principles of kinematic alignment in total knee arthroplasty. A systematic review.

PURPOSE: Kinematically aligned total knee arthroplasty (KA TKA), as a pure resurfacing procedure, is based on matching implant thickness with bone cut and kerf thickness, plus cartilage wear. However, the assumption of a consistent 2 mm femoral cartilage thickness remains unproven. This study aimed to systematically review the available literature concerning magnetic resonance imaging (MRI) assessment of femoral cartilage thickness in non-arthritic patients. Our hypothesis was that cartilage thickness values would vary significantly among individuals, thereby challenging the established KA paradigm of 'one-cartilage-fits-all'. METHODS: Systematic literature searches (Pubmed, Scopus and Cochrane Library) followed PRISMA guidelines. English-language studies assessing distal and posterior femoral cartilage thickness using MRI in non-arthritic adults were included. Studies lacking numerical cartilage thickness data, involving post-operative MRI, considering total femoro-tibial cartilage thickness, or failing to specify the compartment of the knee being studied were excluded. RESULTS: Overall, 27 studies comprising 8170 MRIs were analysed. Weighted mean femoral cartilage thicknesses were: 2.05 ± 0.62 mm (mean range 1.06-2.6) for the distal medial condyle, 1.95 ± 0.4 mm (mean range 1.15-2.5) for the distal lateral condyle, 2.44 ± 0.5 mm (mean range 1.37-2.6) for the posterior medial condyle and 2.27 ± 0.38 mm (mean range 1.48-2.5) for the posterior lateral condyle. DISCUSSION: Femoral cartilage thickness varies significantly across patients. In KA TKA, relying on a fixed thickness of 2 mm may jeopardize the accurate restoration of individual anatomy, leading to errors in implant coronal and rotational alignment. An intraoperative assessment of cartilage thickness may be advisable to express the KA philosophy at its full potential. LEVEL OF EVIDENCE: Level IV.

Cartilage thickness in the medial compartment of the knee joint evaluated by MRI three-dimensional analysis correlates with weight-bearing line ratio and joint line convergence angle.

PURPOSE: The correlation between cartilage thickness evaluated by 3D MRI and knee alignment has not been elucidated. The study's purpose was to retrospectively verify whether average cartilage thickness calculated by the automatic MRI 3D analysis system for each subregion was correlated with knee alignment. METHODS: A total of 53 patients underwent medial meniscus repair or high tibial osteotomy for medial knee osteoarthritis. Cartilage thickness was automatically calculated using 3D MRI software. Knee alignment, weight-bearing line ratio (WBLR), joint line convergence angle (JLCA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were calculated on a weight-bearing long-leg radiograph using digital planning software. The association between knee alignment and the average cartilage thickness at 18 subregions in the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using Spearman's rank correlation coefficient. RESULTS: Cartilage thickness of the MFC had moderately positive correlations with WBLR at four subregions and weak correlations at two subregions. Cartilage thickness of the MTP had moderately positive correlations with WBLR at four subregions. Cartilage thickness of the MFC had moderately negative correlations with JLCA at six subregions. Cartilage thickness of the MTP had moderately negative correlations with JLCA at four subregions and a weak correlation at one subregion. Conversely, cartilage thickness had weak correlations with MPTA or LDFA. CONCLUSIONS: In knees with pathological conditions in the medial compartment, cartilage thicknesses by 3D MRI had positive correlations with WBLR and JLCA at almost all subregions of the MFC and at the anterior-middle and central-external of the MTP. Treatment strategies should be considered in light of these regions. LEVEL OF EVIDENCE: Cross-sectional study (diagnosis); Level of evidence, 2.

Biomechanical properties of articular cartilage in different regions and sites of the knee joint: acquisition of osteochondral allografts.

Osteochondral allograft (OCA) transplantation involves grafting of natural hyaline cartilage and supporting subchondral bone into the cartilage defect area to restore its biomechanical and tissue structure. However, differences in biomechanical properties and donor-host matching may impair the integration of articular cartilage (AC). This study analyzed the biomechanical properties of the AC in different regions of different sites of the knee joint and provided a novel approach to OCA transplantation. Intact stifle joints from skeletally mature pigs were collected from a local abattoir less than 8 h after slaughter. OCAs were collected from different regions of the joints. The patella and the tibial plateau were divided into medial and lateral regions, while the trochlea and femoral condyle were divided into six regions. The OCAs were analyzed and compared for Young's modulus, the compressive modulus, and cartilage thickness. Young's modulus, cartilage thickness, and compressive modulus of OCA were significantly different in different regions of the joints. A negative correlation was observed between Young's modulus and the proportion of the subchondral bone (r = - 0.4241, P < 0.0001). Cartilage thickness was positively correlated with Young's modulus (r = 0.4473, P < 0.0001) and the compressive modulus (r = 0.3678, P < 0.0001). During OCA transplantation, OCAs should be transplanted in the same regions, or at the closest possible regions to maintain consistency of the biomechanical properties and cartilage thickness of the donor and recipient, to ensure smooth integration with the surrounding tissue. A 7 mm depth achieved a higher Young's modulus, and may represent the ideal length.

Associations between weight change, knee subcutaneous fat and cartilage thickness in overweight and obese individuals: 4-Year data from the osteoarthritis initiative.

OBJECTIVE: To assess (i) the impact of changes in body weight on changes in joint-adjacent subcutaneous fat (SCF) and cartilage thickness over 4 years and (ii) the relation between changes in joint-adjacent SCF and knee cartilage thickness. DESIGN: Individuals from the Osteoarthritis Initiative (total=399) with > 10% weight gain (n=100) and > 10% weight loss (n=100) over 4 years were compared to a matched control cohort with less than 3% change in weight (n=199). 3.0T Magnetic Resonance Imaging (MRI) of the right knee was performed at baseline and after 4 years to quantify joint-adjacent SCF and cartilage thickness. Linear regression models were used to evaluate the associations between the (i) weight change group and 4-year changes in both knee SCF and cartilage thickness, and (ii) 4-year changes in knee SCF and in cartilage thickness. Analyses were adjusted for age, sex, baseline body mass index (BMI), tibial diameter (and weight change group in analysis (ii)). RESULTS: Individuals who lost weight over 4-years had significantly less joint-adjacent SCF (beta range, medial/lateral joint sides: 2.2-4.2 mm, p < 0.001) than controls; individuals who gained weight had significantly greater joint-adjacent SCF than controls (beta range: -1.4 to -3.9 mm, p < 0.001). No statistically significant associations were found between weight change and cartilage thickness change. However, increases in joint-adjacent SCF over 4 years were significantly associated with decreases in cartilage thickness (p = 0.04). CONCLUSIONS: Weight change was associated with joint-adjacent SCF, but not with change in cartilage thickness. However, 4-year increases in joint-adjacent SCF were associated with decreases in cartilage thickness independent of baseline BMI and weight change group.

The effect of ferritin levels on distal femoral cartilage thickness in patients with beta thalassaemia major.

INTRODUCTION: To the best of our knowledge, the present study is the first in the literature to assess distal femoral cartilage thickness and its relationship with ferritin levels in adult patients with beta thalassaemia major (BTM). MATERIALS AND METHODS: 45 patients with BTM and 45 healthy controls were included in the study. Ferritin and haemoglobin levels of the patient and healthy groups were determined by blood analysis and distal femoral cartilage thicknesses were measured via ultrasound. Then, the patient group was divided into subgroups according to whether their ferritin levels were below or above 2500 µg/L. They were then compared among themselves and with the healthy control group using the available data. RESULTS: Distal femoral cartilage thickness values were statistically significantly lower in the BTM group compared to the healthy control group (p values < 0.001). Patients with a ferritin level below 2500 µg/L had statistically significantly higher right and left average distal femoral cartilage thickness values than the patients with a ferritin level above 2500 µg/L (p = 0.029 and p = 0.019, respectively). The right and left average distal femoral cartilage thickness values of the patient subgroup with low ferritin levels were statistically similar to the control group (p = 0.146 and p = 0.164, respectively). CONCLUSION: Our study showed that thalassaemia patients are more likely to develop osteoarthritis (OA) than the normal population and possible OA development can be prevented by keeping the ferritin levels of these patients in the optimum range.

Ultrasonographic Evaluation of the Distal Femoral Cartilage Thickness in Parkinson's Patients.

OBJECTIVES: Both Parkinson's disease (PD) and osteoarthritis (OA) are characterized by chronic inflammation and tissue degeneration. The aim of this study is to investigate the relationship between PD and distal femoral cartilage thickness (DFCT). Our study is the first in the literature to measure DFCT in PD. METHODS: 68 patients with PD and 30 healthy individuals participated. The patient group was divided into three subgroups, according to the Hoehn Yahr stages (HYS): mild, moderate and severe. Patient subgroups and the control group were compared with each other in terms of neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and DFCT. RESULTS: The NLR and CRP levels of the PD patients were higher than the values of the healthy people. The DFCT values of the mild PD subgroup were significantly higher than those of the control group, except for one value. The DFCT values of the moderate PD subgroup and the healthy group were similar. The DFCT values of the severe PD subgroup were lower than the values of the healthy group. CONCLUSIONS: Our study showed the presence of ultrasonographic evidence consistent with early signs of cartilage destruction in early-stage PD disease. As the PD stage progressed, the cartilage thickness decreased accordingly.

The relationship between cartilage thickness and muscle thickness or leg length discrepancy in poliomyelitis sequelae.

OBJECTIVES: To evaluate the relationship between cartilage loss and differences in muscle thickness and/or leg length in poliomyelitis sequelae (PMS). Our study is the first to evaluate the relationship between cartilage loss and both muscle atrophy and leg length discrepancy in the same population. METHODS: 37 patients with PMS and 38 healthy controls were included. Talar and distal femoral cartilage thicknesses and gastrocnemius medialis and quadriceps femoris muscle thicknesses were measured via ultrasound. Leg length differences and manual muscle strength were also evaluated. RESULTS: The mean muscle thicknesses and cartilage thicknesses were thinner in the more affected legs than in the less affected legs in the patient group. All of the ultrasonographic measurements were thinner in the less affected legs of the patient group than in the right legs of the control group, except for the knee cartilage thicknesses. While there was a correlation between the cartilage thickness difference and the muscle thickness difference between the less and more affected legs in the patient group, there was no correlation between the cartilage thickness difference and leg length differences. CONCLUSIONS: Patients with PMS are predisposed to osteoarthritis. Talar and knee cartilage thicknesses may be more associated with the muscle thickness than the leg length discrepancy in PMS.

Exploring the differences between radiographic joint space width and MRI cartilage thickness changes using data from the IMI-APPROACH cohort.

OBJECTIVE: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. METHODS: The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (ΔJSWmed), minimum JSW (ΔJSWmin), and medial femorotibial cartilage thickness (ΔMFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee-specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. RESULT: Correlations between ΔMFTC and ΔJSWmed and ΔJSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations. CONCLUSIONS: While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion.

Evaluation of the effect of high-intensity laser therapy (HILT) on function, muscle strength, range of motion, pain level, and femoral cartilage thickness in knee osteoarthritis: randomized controlled study.

This study was designed as a double-blind randomized placebo-controlled study. The aim of this study was to evaluate the effects of high-intensity laser therapy (HILT) on pain, range of motion, function, muscle strength, and femoral cartilage thickness in patients with knee osteoarthritis. Sixty patients who were admitted between November 2021 and April 2022 and diagnosed with knee osteoarthritis based on anamnesis, physical examination, and imaging methods were included in the study. The patients observed during the research were randomly divided into two groups with 30 patients in each group. Hotpack, transcutaneous electrical nerve stimulation (TENS), exercise (5 days a week for a total of 15 sessions), and HILT (analgesic mode with a power of 10.0 w, energy density of 12 j/cm2, and 2 min for every 25 cm2, biostimulant mode with a power of 5.0 W, energy density of 120 j/cm2, and 10 min for each 25 cm2; total 9 sessions 3 days a week) were applied for 3 weeks for the first group, and hot pack, TENS, exercise (5 days a week for a total of 15 sessions), and sham laser treatment (0 W total 9 sessions 3 days a week) was applied for 3 weeks for the second group. The patients were evaluated with the determined scales before the treatment, at the end of the treatment, and at the third month. A goniometer was used to measure joint range of motion measurement, a visual analog scale (VAS) for pain, WOMAC Osteoarthritis Index to assess pain and function, Biodex System 3 isokinetic device for knee flexion-extension muscle strength measurement, and ultrasonography to measure femoral cartilage thickness. There was no statistically significant difference in VAS, range of motion, WOMAC, muscle strength, and femoral cartilage thickness measurement between the groups, whether before treatment, after treatment or at the third-month follow-up (p > 0.05). There was a statistically significant decrease in pain intensity, an increase in flexion range of motion, WOMAC, and femoral cartilage thickness in both groups (p < 0.005). A statistically significant increase was found in the average peak torque flexion muscle strength measurements at isokinetic 60°/s angular velocities in the post-treatment and third-month checkup compared to the pre-treatment analysis in both groups (p < 0.05). In conclusion, there was no statistically significant difference between HILT + exercise and placebo laser + exercise observed. However, the exercise program performed under the supervision of a physiotherapist has been shown to be effective in improving all parameters.

Application of diffuse optical back reflection spectroscopy for determining articular cartilage thickness in a clinical setting.

PURPOSE: Develop a spectroscopic method to assess cartilage thickness during the arthroscopic examination. METHODS: Currently, arthroscopy assesses cartilage damage visually; outcomes are based on the surgeon's subjective experience. Light reflection spectroscopy is a promising method for measuring cartilage thickness based on the absorption of light by the subchondral bone. In the presented study, in vivo diffuse optical back reflection spectroscopic measurements were acquired by gently placing an optical fibre probe on different locations of the articular cartilage of 50 patients during complete knee replacement surgery. The optical fibre probe consists of two optical fibers with a diameter of 1 mm to deliver the light and detect back-reflected light from the cartilage. Centre to centre distance between the source and the detector fibers was 2.4 mm. Actual thicknesses of the articular cartilage samples were measured under microscopy using histopathological staining. RESULTS: Using half of the samples in the patient data, a linear regression model was formed to estimate cartilage thicknesses from the spectroscopic measurements. The regression model was then used to predict the cartilage thickness in the second half of the data. The cartilage thickness was predicted with a mean error of 8.7% if the actual thickness was less than 2.5 mm (R2 = 0.97). CONCLUSION: The outer diameter of the optical fibre probe was 3 mm, which can fit into the arthroscopy channel and can be used to measure the cartilage thickness in real-time during the arthroscopic examination of the articular cartilage.

ULTRASONOGRAPHIC EVALUATION OF FEMORAL CARTILAGE THICKNESS IN PARTICIPANTS WITH ASYMPTOMATIC HYPERURICEMIA: A CASE-CONTROL STUDY.

The aim was to evaluate the effect, if any, of asymptomatic hyperuricemia on distal femoral cartilage thickness through musculoskeletal ultrasonography. A total of 66 participants were evaluated in this prospective, controlled study, including 33 asymptomatic hyperuricemic patients who presented at our outpatient clinic between January and April 2020, and 33 normouricemic subjects matched for age, gender and body mass index. Participants with systemic diseases affecting uric acid level such as chronic renal failure, psoriasis, gout, etc., participants using drugs that can affect uric acid level, and those with knee complaints were excluded from the study. Cartilage thickness measurements were taken using musculoskeletal ultrasonography from the right medial condyle, right lateral condyle, right intercondylar area, left medial condyle, left lateral condyle and left intercondylar area. Distal femoral cartilage thickness was lower in all measurement areas in the asymptomatic hyperuricemia group than in the normouricemic group (p<0.05 all). No correlation was noted between uric acid levels and cartilage thickness in all measurement areas in either the asymptomatic hyperuricemic or normouricemic group (p>0.05 all). We think that distal femoral cartilages seem to be thinner in participants with asymptomatic hyperuricemia. Longitudinal studies are needed to determine whether asymptomatic hyperuricemia will lead to knee osteoarthritis in individuals, although we believe that people with asymptomatic hyperuricemia should be informed accordingly in order to prevent development of potential knee osteoarthritis.

Knee joint distraction results in MRI cartilage thickness increase up to 10 years after treatment.

OBJECTIVES: Knee joint distraction (KJD) has been shown to result in long-term clinical improvement and short-term cartilage restoration in young OA patients. The objective of the current study was to evaluate MRI cartilage thickness up to 10 years after KJD treatment, using a 3D surface-based approach. METHODS: Twenty end-stage knee OA patients were treated with KJD. MRI scans (1.5 T) were performed before and at 1, 2, 5, 7, and 10 years after treatment. Tibia and femur cartilage segmentation and registration to a canonical surface were performed semi-automatically. Statistical parametric mapping with linear mixed models was used to analyse whole-joint changes. The influence of baseline patient characteristics was analysed with statistical parametric mapping using linear regression. Relevant weight-bearing parts of the femur were selected to obtain the average cartilage thickness in the femur and tibia of the most- (MAC) and least-affected compartment. These compartmental changes over time were analysed using repeated measures ANOVA; missing data was imputed. In all cases, P <0.05 was considered statistically significant. RESULTS: One and 2 years post-treatment, cartilage in the MAC weight-bearing region was significantly thicker than pre-treatment, gradually thinning after 5 years, but still increased at 10 years post-treatment. Long-term results showed that areas in the least-affected compartment were significantly thicker than pre-treatment. Male sex and more severe OA at baseline somewhat predicted shorter-term benefit (P >0.05). Compartmental analyses showed significant short- and long-term thickness increase in the tibia and femur MAC (all P <0.05). CONCLUSION: KJD results in significant short- and long-term cartilage regeneration, up to 10 years post-treatment. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl, NL419.

Device for Assessing Knee Joint Dynamics During Magnetic Resonance Imaging.

BACKGROUND: Knee assessment with and without load using magnetic resonance imaging (MRI) can provide information on knee joint dynamics and improve the diagnosis of knee joint diseases. Performing such studies on a routine MRI-scanner require a load-exerting device during scanning. There is a need for more studies on developing loading devices and evaluating their clinical potential. PURPOSE: Design and develop a portable and easy-to-use axial loading device to evaluate the knee joint dynamics during the MRI study. STUDY TYPE: Prospective study. SUBJECTS: Nine healthy subjects. FIELD STRENGTH/SEQUENCE: A 0.25 T standing-open MRI and 3.0 T MRI. PD-T2 -weighted FSE, 3D-fast-spoiled-gradient-echo, FS-PD, and CartiGram sequences. ASSESSMENT: Design and development of loading device, calibration of loads, MR safety assessment (using projectile angular displacement, torque, and temperature tests). Scoring system for ease of doing. Qualitative (by radiologist) and quantitative (using structural similarity index measure [SSIM]) image-artifact assessment. Evaluation of repeatability, comparison with various standing stances load, and loading effect on knee MR parameters (tibiofemoral bone gap [TFBG], femoral cartilage thickness [FCT], tibial cartilage thickness [TCT], femoral cartilage T2 -value [FCT2], and tibia cartilage T2 -value [TCT2]). The relative percentage change (RPC) in parameters due to the device load was computed. STATISTICAL TEST: Pearson's correlation coefficient (r). RESULTS: The developed device is conditional-MR safe (details in the manuscript and supplementary materials), 15 × 15 × 45 cm3 dimension, and <3 kg. The ease of using the device was 4.9/5. The device introduced no visible image artifacts, and SSIM of 0.9889 ± 0.0153 was observed. The TFBG intraobserver variability (absolute difference) was <0.1 mm. Interobserver variability of all regions of interest was <0.1 mm. The load exerted by the device was close to the load during standing on both legs in 0.25 T scanner with r > 0.9. Loading resulted in RPC of 1.5%-11.0%, 7.9%-8.5%, and -1.5% to 13.0% in the TFBG, FCT, and TCT, respectively. FCT2 and TCT2 were reduced in range of 1.5-2.7 msec and 0.5-2.3 msec due to load. DATA CONCLUSION: The proposed device is conditionally MR safe, low cost (material cost < INR 6000), portable, and effective in loading the knee joint with up to 50% of body weight. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Pathological, Morphometric and Correlation Analysis of the Modified Mankin Score, Tidemark Roughness and Calcified Cartilage Thickness in Rat Knee Osteoarthritis after Extracorporeal Shockwave Therapy.

The paper displayed the pathological changes and relationships of the modified Mankin score, tidemark roughness and calcified cartilage (CC) thickness by extracorporeal shockwave therapy (ESWT) (0.25 mJ/ mm2 with 800 impulses) on different positions of the medial and lateral rat knee OA joint. After the experiments, the articular cartilage was assessed using histomorphometry, image analysis and statistical method. In the micro-CT analysis, ESWT on medial groups were better than lateral groups in the trabecular volume and trabecular number. The data showed a strong negative correlation between the modified Mankin score and tidemark roughness (r = -0.941; P < 0.001). In terms of the relationship of tidemark roughness with CC thickness, the medial and Sham groups showed a significant negative correlation (r = -0.788, P = 0.022). Additionally, the Euclidean distance derived from 3D scatter plot analysis was an indicator of chondropathic conditions, exhibiting a strong correlation with OA stage in the articular cartilage of the femur (r = 0.911, P < 0.001) and tibia (r = 0.890, P < 0.001) after ESWT. Principle component analysis (PCA) further demonstrated that ESWT applied to medial locations had a better outcome than treatment at lateral locations for knee OA by comparing with Sham and OA groups, and CC thickness was the most important factor affecting hyaline cartilage repair after ESWT.

Changes in joint space width over time and risk factors for deterioration of joint space width after medial opening-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to evaluate the changes in joint space width (JSW) over time after medial opening-wedge high tibial osteotomy (MOWHTO) and identify risk factors for deterioration of JSW using anteroposterior (AP) and Rosenberg views. METHODS: We retrospectively analyzed changes in JSW of 104 MOWHTO patients whose preoperative osteoarthritis (OA) grade was K-L grade 3 or less on AP and Rosenberg views. Serial changes in JSW were assessed from preoperatively to at least 3 years postoperatively. Patients were divided into two groups according to JSW change patterns on each of AP and Rosenberg views: non-deterioration group had either unchanged or increased JSW, and deterioration group had decreased JSW. Clinical outcomes were compared using Western Ontario and McMaster Universities OA Index (WOMAC) score between groups. Multivariate logistic regression analysis was performed to identify risk factors for deterioration of JSW. RESULTS: JSW on average for all patients increased 0.5 mm and 0.8 mm on AP and Rosenberg views, respectively (p < 0.05). Non-deterioration group showed significant improvement based on patient-reported outcomes (WOMAC) than deterioration group (all p < 0.05). Undercorrection was an independent risk factor for failure to achieve maintained or increased JSW on both AP (OR 6.885, 95% CI 1.976-23.986, p = 0.002) and Rosenberg (OR 12.756, 95% CI 2.952-55.129, p = 0.001) views. CONCLUSION: JSW increased gradually and continuously on standing AP and Rosenberg views until postoperative 3 years after MOWHTO. Deterioration of JSW following MOWHTO was closely related to the undercorrection and affected clinical outcomes. LEVEL OF EVIDENCE: Level III, case control study.

An exploratory study to investigate the association between age, physical activity, femoral trochlear cartilage thickness and biomarkers of tissue metabolism in adult males.

PURPOSE: To investigate the association between age, physical activity, femoral trochlear cartilage thickness and biomarkers of tissue metabolism in a cross-sectional sample of adult males. This study utilizes several emerging biomarkers that have been associated with early joint degenerative changes; serum COMP (cartilage oligomeric matrix protein), HA (hyaluronan) and lubricin. METHODS: Eighty-one males (age: mean (range): 43(18-70) years; body mass index: 25.2 (21.0-30.6) kg/m2) volunteered. Resting serum COMP, HA and lubricin concentrations were determined via commercially available enzyme-linked immunosorbent assay (ELISA) and femoral trochlear cartilage thickness via supra-patellar ultrasound imaging. Physical activity levels were assessed using questionnaires. Statistical analyses were performed using correlation and regression analyses. RESULTS: Age was correlated with lateral trochlear cartilage thickness (r = - 0.372; p < 0.01) and serum COMP (r = 0.342; p < 0.01). 7-day physical activity was correlated with serum COMP (r = 0.357, p < 0.01), and 12-month physical activity with both lateral trochlear cartilage thickness (r = 0.340, p = 0.01) and serum HA (r = 0.296, p < 0.05). Regression analyses revealed that age significantly accounted for the variability in lateral cartilage thickness and serum COMP, following the adjustment for potential cofounders. However, the association between age and lateral trochlear cartilage thickness was not moderated by physical activity levels (all p > 0.05). CONCLUSION: This study indicates that older age may be associated with thinner lateral trochlear cartilage and higher cartilage turnover. Being physically active may also be positive for lateral trochlear cartilage thickness. However, overall, both age and physical activity level only account for a small amount of the variability in cartilage thickness and serum biomarkers.

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints.

OBJECTIVE: Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up period. METHOD: Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren-Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5 mm; knee pain at worst 4-9 in the past 30 days on an 11-point scale, or 0-3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes. RESULTS: Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively). CONCLUSIONS: 2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.

Three-Dimensional Surface-Based Analysis of Cartilage MRI Data in Knee Osteoarthritis: Validation and Initial Clinical Application.

BACKGROUND: Traditional quantitative analysis of cartilage with MRI averages measurements (eg, thickness) across regions-of-interest (ROIs) which may reduce responsiveness. PURPOSE: To validate and describe clinical application of a semiautomated surface-based method for analyzing cartilage relaxation times ("composition") and morphology on MRI, 3D cartilage surface mapping (3D-CaSM). STUDY TYPE: Validation study in cadaveric knees and prospective observational (cohort) study in human participants. POPULATION: Four cadaveric knees and 14 participants aged 40-60 with mild-moderate knee osteoarthritis (OA) and 6 age-matched healthy volunteers, imaged at baseline, 1, and 6 months. FIELD STRENGTH/SEQUENCE: 3D spoiled gradient echo, T1 rho/T2 magnetization-prepared 3D fast spin echo for mapping of T1 rho/T2 relaxation times and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using variable flip angle T1 relaxation time mapping at 3T. ASSESSMENT: 3D-CaSM was validated against high-resolution peripheral quantitative computed tomography (HRpQCT) in cadaveric knees, with comparison to expert manual segmentation. The clinical study assessed test-retest repeatability and sensitivity to change over 6 months for cartilage thickness and relaxation times. STATISTICAL TESTS: Bland-Altman analysis was performed for the validation study and evaluation of test-retest repeatability. Six-month changes were assessed via calculation of the percentage of each cartilage surface affected by areas of significant change (%SC), defined using thresholds based on area and smallest detectable difference (SDD). RESULTS: Bias and precision (0.06 ± 0.25 mm) of 3D-CaSM against reference HRpQCT data were comparable to expert manual segmentation (-0.13 ± 0.26 mm). 3D-CaSM demonstrated significant (>SDD) 6-month changes in cartilage thickness and relaxation times in both OA participants and healthy controls. The parameter demonstrating the greatest 6-month change was T2 relaxation time (OA median %SC [IQR] = 8.8% [5.5 to 12.6]). DATA CONCLUSION: This study demonstrates the construct validity and potential clinical utility of 3D-CaSM, which may offer advantages to conventional ROI-based methods. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2. J. Magn. Reson. Imaging 2020;52:1139-1151.

Keratoconus: a potential risk factor for osteoarthritis.

PURPOSE: This study was undertaken to compare the distal femoral cartilage thickness in patients with keratoconus (KC) with that of age- and sex-matched healthy controls, in order to identify a potential risk factor for early osteoarthritis in patients with KC and to allow initiation of early rehabilitation. METHODS: Thirty-six KC patients between 18 and 35 years of age and 36 healthy controls were included in this study. Keratometry readings (K1, K2), central corneal thickness (CCT), anterior chamber depth (ACD), iridocorneal angle (ICA), and corneal volumes (CV) were measured using a Sirius imaging system (Costruzioni Strumenti Oftalmici, Italy). Also, the distal femoral cartilage thickness (DFCT) was assessed bilaterally using ultrasound by the same physiatrist. Lateral femoral condyle (LFC), intercondylar area (ICA), medial femoral condyle (MFC), and body mass index (BMI) values were recorded. RESULTS: Patient and control groups were comparable in terms of age, gender, and BMI. On the other hand, patients with KC had a significant reduction in right LFC, MFC thickness and left ICA, MFC as compared to controls (p < 0.05). In the corneal topographic evaluation of the groups, it was observed that K1, K2, CCT, and ACD values differed significantly. CONCLUSIONS: Detection of thinner DFCT in KC patients suggests that these patients may be future candidates of osteoarthritis.

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

OBJECTIVE: To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. METHODS: 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. RESULTS: Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (-858 µm; [95% confidence interval -1016, -701 µm]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (-634 µm; [-673, -596 µm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530 µm, [-631, -428 µm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. CONCLUSIONS: Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.