Tibiofemoral Cartilage Thickness Research Articles

Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis

Osteoarthritis (OA) is a major cause of disability in the US, with no approved treatments to slow progression, but animal models suggest that pulsed low-intensity ultrasonography (PLIUS) may promote cartilage growth. To evaluate the efficacy of PLIUS in providing symptom reduction and decreased loss of tibiofemoral cartilage thickness in patients with knee OA. A phase 2A, sham-controlled, parallel, double-blind randomized clinical trial was conducted at 2 Veterans Affairs hospitals in Salt Lake City, Utah, and San Diego, California, from May 22, 2015, to January 31, 2019. Data were analyzed from June 27, 2020, to October 20, 2020. Participants recruited through the US Department of Veterans Affairs (N = 132) with clinical and radiographic evidence of early knee OA were randomly assigned to receive PLIUS or a sham device, self-administered for 20 minutes daily over the medial compartment of the knee. All enrollees participated in a 4-week prerandomization sham run-in period, followed by a 48-week treatment period. Randomization was stratified by study site and Kellgren-Lawrence grades 1 (n = 15), 2 (n = 51), and 3 (n = 66). Participants either received 48 weeks of PLIUS or sham ultrasonography. The trial incorporated 2 coprimary outcomes: symptomatic improvement assessed by Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International Responder Criteria (ie, met if either >50% improvement in pain and function with at least a 20% absolute improvement of at least 2 of the following 3 factors: improvement by at least 20% [pain, function, and patient global assessment] with at least a 10-mm absolute improvement), and cartilage preservation assessed as change in central medial femoral condyle cartilage thickness by magnetic resonance imaging. Intention-to-treat analysis was used. The mean (SD) participant age was 63.6 (10.7) years and 119 were men (90.2%). The mean (SD) duration of OA symptoms was 13.4 (12.3) years. In the PLIUS group, 70.4% (95% CI, 58.2%-82.6%) of the participants experienced symptomatic improvement, compared with 67.3% (95% CI, 54.9%-79.7%) of participants in the sham group (P = .84); there was no statistically significant difference in response rates between the treatment groups, and the between-group rate difference of 3.1% (95% CI, -14.3% to 20.5%) did not meet the predefined 10% threshold for clinically significant symptomatic improvement from application of PLIUS. At 48 weeks of treatment, central medial femoral condyle cartilage thickness decreased by a mean (SD) of 73.8 (168.1) μm in the PLIUS group and by 42.2 (297.0) μm in the sham group. This 48-week mean change between the 2 groups did not reach statistical significance (P = .44), and the between-group 48-week difference of -31.7 μm (95% CI, -129.0 μm to 65.7 μm) did not meet the predefined threshold. There were 99 nonserious adverse events in the PLIUS group and 89 in the sham group during the trial. No serious adverse events were deemed related to the study device. PLIUS, as implemented in this study, demonstrated neither symptomatic benefit nor a decrease in loss of tibiofemoral cartilage thickness in knee OA. ClinicalTrials.gov Identifier: NCT02034409.

The relationship between knee loading during gait and cartilage thickness in nontraumatic and posttraumatic knee osteoarthritis.

The relationship between knee moments and markers of knee osteoarthritis progression has not been examined in different knee osteoarthritis subtypes. The objective was to examine relationships between external knee moments during gait and tibiofemoral cartilage thickness in patients with nontraumatic and posttraumatic knee osteoarthritis. For this cross-sectional study, participants with knee osteoarthritis were classified into two groups: nontraumatic (n = 22; mean age 60 years) and posttraumatic (n = 19; mean age 56 years, history of anterior cruciate ligament rupture). Gait data were collected with a three-dimensional motion capture system sampled at 100 Hz and force plates sampled at 2000 Hz. External knee moments were calculated using inverse dynamics. Cartilage thickness was determined with magnetic resonance imaging (T1-weighted, 3D sagittal gradient-echo sequence). Linear regression analyses examined relationships between cartilage thickness with knee moments, group, and their interaction. A higher knee adduction moment impulse was negatively associated with medial to lateral cartilage thickness ratio (B = -1.97). This relationship differed between participants in the nontraumatic osteoarthritis group (r = -0.56) and posttraumatic osteoarthritis group (r = -0.30). A higher late stance knee extension moment was associated with greater medial femoral condyle cartilage thickness (B = -0.86) and medial to lateral cartilage thickness (B = -0.73). These relationships also differed between participants in the nontraumatic osteoarthritis group (r = -0.61 and r = -0.51, respectively) and posttraumatic osteoarthritis group (r = 0.10 and r = 0.25, respectively). Clinical Significance: The relationship between knee moments with tibiofemoral cartilage thickness differs between patients with nontraumatic and posttraumatic knee osteoarthritis. The potential influence of mechanical knee loading on articular cartilage may also differ between these subtypes.

Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA

BackgroundTPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months.MethodsOne hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject’s contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data.ResultsTPX-100-treated knees (n = 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. − 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P = 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P < 0.01).ConclusionsThis is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA.Trial registrationNIH ClinicalTrials.gov, NCT01925261. Registered 15 August 2013

Linking physical activity with knee osteoarthritis outcomes: an evidence map using the osteoarthritis initiative

Linking physical activity with knee osteoarthritis outcomes: an evidence map using the osteoarthritis initiative

A new technique to evaluate the impact of running on knee cartilage deformation by region

When measuring changes in knee cartilage thickness in vivo after loading, mean values may not reflect local changes. The objectives of this investigation were: (1) use statistical parametric mapping (SPM) to determine regional deformation patterns of tibiofemoral cartilage in response to running; (2) quantify regional differences in cartilage thickness between males and females; and (3) explore the influence of sex on deformation. Asymptomatic males (n = 15) and females (n = 15) had MRI imaging of their right knee before and after 15 min of treadmill running. Medial and lateral tibial, and medial and lateral weight-bearing femoral cartilage were segmented. SPM was completed on cartilage thickness maps to test the main effects of Running and Sex, and their interaction. F-statistic maps were thresholded; clusters above this threshold indicated significant differences. Deformation was observed in all four compartments; the lateral tibia had the largest area of deformation (p < 0.0001). Thickness differences between sexes were observed in all four compartments, showing females have thinner cartilage (p ≤ 0.009). The lateral tibia had small clusters indicating an interaction of sex on deformation (p ≤ 0.012). SPM identified detailed spatial information on tibiofemoral cartilage thickness differences observed after running, and between sexes and their interaction.

Influence of sex on tibiofemoral cartilage response to running in young healthy men and women

Purpose: Women are more likely to experience greater degeneration and more severe symptoms related to osteoarthritis (OA) than men. It is unknown whether sex influences the acute response of cartilage in the knee to loading. Identifying sex-differences, if present, may improve our understanding of the differences in OA experienced between men and women at a tissue level. The purpose of this study was to determine if there is an influence of sex on loading-induced changes in regional tibiofemoral cartilage thickness as measured by magnetic resonance imaging (MRI) following running in young men and women. Methods: Young healthy men (N=15, 25.6±4.1 y, 23.7±2.7 kg/m2) and women (N=15, 26.1±3.4 y, 23.1±3.1 kg/m2) were recruited. Participants were excluded if they were unfit to participate in physical activity as captured by the Get Active! Questionnaire, scored below 74 on the Lower-Extremity Functional Scale, self-reported lower-limb injuries in the last 3 months, had orthopaedic surgery in the limb of interest (right), or had contraindications to MRI. Participants were asked to attend one MRI imaging session in the morning. Participants then rested supine for 30 minutes to mitigate effects of morning loading activities (i.e., walking) on the cartilage. Pre-activity scans were acquired with a 3.0T MR750 Discovery MRI scanner. Specifically, sagittal 3D fat-saturated fast-spoiled gradient recalled (FSPGR) scans were obtained to clearly delineate articular cartilage from surrounding tissues (FOV: 160 mm, Matrix: 512 x 512, In-Plane Resolution: 0.3125 x 0.3125 mm, Slice Spacing: 1 mm, TR: 17.388 ms, TE: 5.832 ms, Frequency: 127.78 MHz, Flip Angle: 18 degrees). Following pre-activity scans, participants ran on a treadmill adjacent to the MRI scanning room for 15 minutes. Then, participants immediately completed post-activity imaging (FSPGR). Tibiofemoral cartilage were segmented from pre- and post-activity FSPGR scans using a convolutional neural network (NeuralSeg). Medial and lateral tibial, and medial and lateral weight-bearing femoral cartilage were extracted and analyzed separately. Thickness maps were created by finding the minimum Euclidean distance from each bone-cartilage interface voxel to the articular surface. These maps were then flattened and warped to the same dimensions for further analyses. Pixelwise statistical parametric mapping using F-statistics was completed to examine the influence of sex on cartilage response to exercise. First, maps were smoothed using a Gaussian kernel filter with a full-width half maximum of 4 mm. Next, pixelwise F-statistic maps were generated for the factors of Sex, Exercise, and the interaction of Sex and Exercise (Sex#Exercise). F-maps were thresholded at a corresponding alpha level of p=0.01. Finally, the significance of thresholded clusters was determined using Gaussian random field (GRF) theory at an alpha level of p=0.001. Results: A minimum cluster size of 20 pixels was determined as a significant change. For the factor of Sex, significant clusters were identified for all four tissues, indicating that female sex was associated with overall thinner cartilage. These clusters of thinner cartilage in women in the medial and lateral tibia were located centrally, aligning approximately with the location of articulation of the femur with the tibia (Fig 1). Similarly, significant medial and lateral weight-bearing femoral clusters were located at the approximate location of the articulation with the tibia. The effect of exercise caused significant clusters for the lateral tibia only, suggesting cartilage thinning following exercise. This cluster was located centrally. The interaction Sex#Exercise did not contain significant clusters. Conclusions: This study compared cartilage thickness changes in young healthy men and women. Consistent with previous literature, women had thinner cartilage; the clustering analysis emphasizes that this thinner cartilage appears in the weight-bearing regions of the knee among women. Running produced systematic deformation patterns in cartilage of the lateral tibia. Finally, no interaction of sex and exercise was found, suggesting that sex does not cause distinct cartilage deformation patterns in response to running. Future work should aim to include other factors that may affect cartilage response to loading, such as age or disease.

Radiographic evaluation of knee joint space width using fixed flexion view in knees of Indian adults

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The objective of this study is to evaluate the tibiofemoral joint space width in the medial and lateral compartments of the knee using digital radiograph. The measurement of knee joint space width (JSW), in between the femur and the tibia is a way of evaluating the tibio-femoral cartilage thickness. This study is aimed at establishing normal references of joint space width for use in diagnosis and follows up of knee cartilage diseases.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This study is prospective and carried on 50 subjects at SAMC &amp;amp; PGI, Indore, M.P. One patient refused to sign the consent and was excluded. All subjects were healthy adults with sedentary lifestyle. All subjects underwent x-ray of bilateral knee joints. The joint space width of both medial and lateral compartments of each knee was measured using the scale in the computerized software.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The average age in the study group was 44.59 years with male preponderance.The mean left medial and lateral joint space width was 5.34 mm±1.26 mm and 5.21 mm±1.04 mm and on right side was 5.26±1.11 mm and 5.57±1.57 mm, respectively. No statistically significant difference was found between right and left knee joint space width compartments.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The values obtained after observing the radiographic references showed no significant gender variation in knee joint space width. But, it is seen that there is a decrease in joint space width with increasing age, which progresses towards osteoarthritis of knee.&lt;/p&gt;

Effects of Anterior Cruciate Ligament Deficiency on Tibiofemoral Cartilage Thickness and Strains in Response to Hopping

Background: Changes in knee kinematics after anterior cruciate ligament (ACL) injury may alter loading of the cartilage and thus affect its homeostasis, potentially leading to the development of posttraumatic osteoarthritis. However, there are limited in vivo data to characterize local changes in cartilage thickness and strain in response to dynamic activity among patients with ACL deficiency. Purpose/Hypothesis: The purpose was to compare in vivo tibiofemoral cartilage thickness and cartilage strain resulting from dynamic activity between ACL-deficient and intact contralateral knees. It was hypothesized that ACL-deficient knees would show localized reductions in cartilage thickness and elevated cartilage strains. Study Design: Controlled laboratory study. Methods: Magnetic resonance images were obtained before and after single-legged hopping on injured and uninjured knees among 8 patients with unilateral ACL rupture. Three-dimensional models of the bones and articular surfaces were created from the pre- and postactivity scans. The pre- and postactivity models were registered to each other, and cartilage strain (defined as the normalized difference in cartilage thickness pre- and postactivity) was calculated in regions across the tibial plateau, femoral condyles, and femoral cartilage adjacent to the medial intercondylar notch. These measurements were compared between ACL-deficient and intact knees. Differences in cartilage thickness and strain between knees were tested with multiple analysis of variance models with alpha set at P < .05. Results: Compressive strain in the intercondylar notch was elevated in the ACL-deficient knee relative to the uninjured knee. Furthermore, cartilage in the intercondylar notch and adjacent medial tibia was significantly thinner before activity in the ACL-deficient knee versus the intact knee. In these 2 regions, thinning was significantly influenced by time since injury, with patients with more chronic ACL deficiency (>1 year since injury) experiencing greater thinning. Conclusion: Among patients with ACL deficiency, the medial femoral condyle adjacent to the intercondylar notch in the ACL-deficient knee exhibited elevated cartilage strain and loss of cartilage thickness, particularly with longer time from injury. It is hypothesized that these changes may be related to posttraumatic osteoarthritis development. Clinical Relevance: This study suggests that altered mechanical loading is related to localized cartilage thinning after ACL injury.

Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial.

BackgroundA recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period.Methods1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann–Whitney − Wilcoxon tests assessed differences between groups.ResultsFifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (−0.04, 0.08) vs. placebo 0.22, 95 % CI (−0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (−0.14, 95 % CI (−0.48, 0.19) vs. placebo 0.44, 95 % CI (−0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes.ConclusionsIn this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee.Trial registrationClinicalTrials.gov identifier: NCT01033994.

Validation of porcine knee as a sex-specific model to study human anterior cruciate ligament disorders.

Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated. We asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury. Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90° flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees. Female pigs had smaller bicondylar widths (2.9 mm, ratio=0.93, effect size=-1.5) and intercondylar notches (width: 2.0 mm, ratio=0.79, effect size=-2.8; area: 30.8 mm2, ratio=0.76, effect size=-2.1; index: 0.4, ratio=0.84, effect size=-2.0), steeper lateral tibial slope (4.3°, ratio=1.13, effect size=1.1), smaller ACL (length: 2.7 mm, ratio=0.91, effect size=-1.1; area: 6.8 mm2, ratio=0.74, effect size=-1.5; volume: 266.2 mm3, ratio=0.68, effect size=-1.5), thinner medial femoral cartilage (0.4 mm, ratio=0.8, effect size=-1.1), lower ACL yield load (275 N, ratio=0.81, effect size=-1.1), and greater AP knee laxity at 30° (0.7 mm, ratio=1.32, effect size=1.1) and 90° (0.5 mm, ratio=1.24, effect size=1.1) flexion compared with their male counterparts. These differences were significant for all parameters (p≤0.04). Observed sex-related differences were similar to those reported for the human knee. Significant differences exist between knees of male and female pigs with respect to prominent anatomic and biomechanical factors. Our findings strongly agreed with published data regarding human knees. The findings highlight the use of the porcine large animal model to study the role of sex on ACL injuries and surgical outcome. This validated preclinical model may facilitate the development of novel, sex-specific interventions to prevent and treat ACL injuries for male and female patients.

Digital radiographic measurement of normal knee joint space in adults at Kano, Nigeria

ObjectiveThe measurement of knee joint space width (JSW), between the distal femur and the proximal tibia is an indirect way of measuring the tibio-femoral cartilage thickness, which is considered a valuable parameter, in assessing knee cartilage disease. This study is aimed at establishing normal references of JSW for use in diagnosis and follow up of knee cartilage diseases. MethodsThis prospective study was conducted on 30° fixed-flexion erect knee computed radiographs of 160 adults. The JSW of both medial and lateral compartments of each knee was measured using in-built electronic calipers. ResultsThe mean right medial and lateral JSW measured 4.74mm±0.75 and 5.63mm±0.86, respectively. The mean left medial and lateral JSW measured 4.74mm±0.76 and 5.66mm±0.87. No statistically significant difference was found between right and left knee JSW compartments. DiscussionsThe radiographic reference values of the knee JSW were obtained, showing no significant gender variation in knee JSW. However, there is a decrease in JSW with increasing age.

Correlation of WOMAC and KOOS scores to tibiofemoral cartilage loss on plain radiography and 3 Tesla MRI: data from the osteoarthritis initiative

The purpose of this study was to determine the correlation between the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) and Knee Injury Osteoarthritis Outcomes scores (KOOS) and the degree of tibiofemoral cartilage loss on plain radiography and 3T magnetic resonance imaging (MRI). We hypothesize that these subjective outcome scores will have a significant correlation to quantitative joint space loss. Data used in the preparation of this article were obtained from the osteoarthritis initiative (OAI) database (OAI public use data sets kMRI_QCart_Eckstein18 and kXR_QJSW_Duryea16). Four hundred and forty-five patients had WOMAC/KOOS scores, quantitative tibiofemoral joints space width on plain radiographs and quantitative tibiofemoral cartilage thickness and per cent full thickness cartilage loss on 3T MRI. Joint space width on plain radiographs was correlated to cartilage thickness on MRI, and WOMAC/KOOS scores were correlated to the degree of cartilage loss using Pearson correlation coefficients. There was a statistically significant correlation between medial and lateral compartment cartilage thickness on MRI and medial and lateral joint space width on plain radiography (r = 0.86, r = 0.80) (p < 0.001). KOOS knee pain score was significantly correlated to increasing per cent full thickness cartilage loss in the medial femoral compartment (r = 0.34) (p < 0.001). KOOS symptom score was significantly correlated to decreasing joint space width in the medial (r = 0.16) and lateral (r = 0.15) compartment and increasing per cent full thickness cartilage loss in the medial femoral compartment (r = 0.36) (p < 0.001). No WOMAC score was correlated to degree of joint space width, cartilage thickness or per cent full thickness cartilage loss (n.s). The WOMAC and KOOS scores are poor indicators of tibiofemoral cartilage loss, with only the KOOS symptom and knee pain score being weakly correlated. Osteoarthritis is a multifactorial process and the need to treat patients based off their symptoms and rely on radiographs as confirmatory modalities, and not diagnostic modalities, when talking about OA and medical intervention.

Tibiofemoral cartilage thickness distribution and its correlation with anthropometric variables

The objective of this study was to determine tibiofemoral cartilage thickness distribution, and to investigate the relationship between cartilage geometry and anthropometric variables. In this study, 20 magnetic resonance examinations of the knee from normal individuals were reconstructed to provide three-dimensional models of the knee joint, including bony and cartilage surfaces. Three regions were defined on the articular surface, and the cartilage thickness distribution along each of these was determined. Statistically significant differences between femoral and tibial regions were examined using the paired Student t test in Microsoft Excel. Correlations were investigated using the correlation tool in Microsoft Excel. The average tibial cartilage thickness was found to be 2.76 mm and the average femoral cartilage thickness was 2.75 mm. Significant correlations exist between the tibia cartilage thickness and body height (R = 0.60; P < 0.05) and weight (R = 0.64; P < 0.05). Significant correlations exist between the femoral cartilage volume and the body height (R = 0.736; P < 0.01) and weight (R = 0.855; P < 0.01). It is suggested that the distribution and correlations of cartilage distribution indicate adaptation in response to mechanical loading. Information regarding cartilage thickness and volume distribution as found in this study may be useful in diagnosing and monitoring cartilage loss in patients with degenerative joint disease.