The Impact of Exercise Training and Supplemental Oxygen on Peripheral Muscles in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

OBJECTIVE: Exercise training is a cornerstone of the treatment of chronic obstructive pulmonary disease, whereas the related interindividual heterogeneity in skeletal muscle dysfunction and adaptations are not yet fully understood. We set out to investigate the effects of exercise training and supplemental oxygen on functional and structural peripheral muscle adaptation. METHODS: In this prospective, randomized, controlled, double-blind study, 28 patients with nonhypoxemic chronic obstructive pulmonary disease (forced expiratory volume in 1 second, 45.92% ± 9.06%) performed 6 wk of combined endurance and strength training, three times a week while breathing either supplemental oxygen or medical air. The impact on exercise capacity, muscle strength, and quadriceps femoris muscle cross-sectional area (CSA) was assessed by maximal cardiopulmonary exercise testing, 10-repetition maximum strength test of knee extension, and magnetic resonance imaging, respectively. RESULTS: After exercise training, patients demonstrated a significant increase in functional capacity, aerobic capacity, exercise tolerance, quadriceps muscle strength, and bilateral CSA. Supplemental oxygen affected significantly the training impact on peak work rate when compared with medical air (+0.20 ± 0.03 vs +0.12 ± 0.03 W·kg -1 , P = 0.047); a significant increase in CSA (+3.9 ± 1.3 cm 2 , P = 0.013) was only observed in the training group using oxygen. Supplemental oxygen and exercise-induced peripheral desaturation were identified as significant opposing determinants of muscle gain during this exercise training intervention, which led to different adaptations of CSA between the respective subgroups. CONCLUSIONS: The heterogenous functional and structural muscle adaptations seem determined by supplemental oxygen and exercise-induced hypoxia. Indeed, supplemental oxygen may facilitate muscular training adaptations, particularly in limb muscle dysfunction, thereby contributing to the enhanced training responses on maximal aerobic and functional capacity.

Fate of the lateral femoral notch following early anterior cruciate ligament reconstruction.

BACKGROUND: The goal of this longitudinal study was to investigate the fate of the lateral femoral notch (LFN), which is frequently seen as an impaction fracture of the lateral femoral condyle in patients with anterior cruciate ligament (ACL) tears. METHODS: Patients who underwent early ACL reconstruction between 2006 and 2010 were reviewed. If post-injury magnetic resonance images showed an LFN greater than 1.5 mm in depth, patients with untreated LFN were followed. Two blinded observers performed quantitative and qualitative imaging analysis. RESULTS: Sixteen patients (five women, 11 men) were available for follow-up nine years (six to 10 years) post-injury. The median defect area of the LFN significantly decreased from 2.3 cm2 (range: 0.9-3.8 cm2) to 1.6 cm2 (range: 0.4-3.2 cm2) (P < .001). The defect depth did not significantly change from 2.3 mm (range: 2.0-3.6 mm) to 2.5 mm (range: 1.3-3.6 mm) (P > .05). The International Cartilage Repair Society (ICRS) score increased from 1.5 (range: 0-3) post-injury to 2.0 (range: 0-4) at follow-up (P < .01). The Lysholm score was 93 (72-100), the Tegner activity level was 6 (3-9) and the knee injury and osteoarthritis outcome score (KOOS) score was 97 (91-100). CONCLUSIONS: The defect area of the LFN decreased overtime, whereas the depth of the impression remained. Focal cartilage lesions were found in all except two patients post-injury and progressed during follow-up. However, patient-reported outcome scores were satisfying.

Cartilage Morphological and Histological Findings After Reconstruction of the Glenoid With an Iliac Crest Bone Graft.

BACKGROUND: The J-bone graft is presumably representative of iliac crest bone grafts in general and allows anatomic glenoid reconstruction in cases of bone defects due to recurrent traumatic anterior shoulder dislocations. As a side effect, these grafts have been observed to be covered by some soft, cartilage-like tissue when arthroscopy has been indicated after such procedures. PURPOSE: To evaluate the soft tissue covering of J-bone grafts by use of magnetic resonance imaging (MRI) and histological analysis. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients underwent MRI at 1 year after the J-bone graft procedures. Radiological data were digitally processed and evaluated by segmentation of axial images. Independent from the MRI analysis, 2 biopsy specimens of J-bone grafts were harvested for descriptive histological analysis. RESULTS: Segmentation of the images revealed that all grafts were covered by soft tissue. This layer had an average thickness of 0.87 mm compared with 1.96 mm at the adjacent native glenoid. Of the 2 biopsy specimens, one exhibited evident hyaline-like cartilage and the other presented patches of chondrocytes embedded in a glycosaminoglycan-rich extracellular matrix. CONCLUSION: J-bone grafts are covered by soft tissue that can differentiate into fibrous and potentially hyaline cartilage. This feature may prove beneficial for delaying the onset of dislocation arthropathy of the shoulder.

Segmentation of the lateral femoral notch sign with MRI using a new measurement technique.

BACKGROUND: The goal of this present study was to precisely determine the dimension and location of the impaction fracture on the lateral femoral condyle in patients with an ACL rupture. METHODS: All patients with post-injury bi-plane radiographs and MRI images after sustaining a tear to the anterior cruciate ligament were included. Lateral radiographs of the affected knee were inspected for a lateral femoral notch sign. MRIs of patients with a lateral condylopatellar sulcus ≥1.5 mm were used to segment and measure the lateral condylopatellar sulcus. The MRI examination was interpreted by an expert in musculoskeletal radiology. The study was approved by the ethics committee of the state of Salzburg. RESULTS: A "lateral femoral notch sign"was seen in 50 patients. The average total surface area of the lateral femoral condyle was 3271.7 mm(2) (SD 739.5 mm(2)). The defect had a mean surface area of 266.1 mm(2) (SD 125.5 mm(2)), a mean volume of 456.5 mm(3) (SD 278.5 mm(3)), a mean depth of 3.0 mm (SD 0.8 mm). On average 169 mm(2) (SD 99.6 mm(2)) of the surface of the condyle were affected by the impaction fracture which corresponds to 5.2% (SD 2.8%) of the surface of the lateral femoral condyle. In 51 % the impaction fracture was located in the central-external area of the femoral condyle. CONCLUSIONS: In cases of a clinically suspected ACL rupture lateral radiographs of the knee should be checked for a lateral femoral notch sign further MRI for confirmation should be performed. Knowing of the precise defect on the lateral femoral condyle is an additionally valuable information, as concomitant injuries to a rupture of the anterior cruciate ligament increase the risk for early-onset osteoarthritis in the future.

Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes.

Little is known about changes in human cartilage thickness and subchondral bone plate area (tAB) during growth. The objective of this study was to explore longitudinal change in femorotibial cartilage thickness and tAB in adolescent athletes, and to compare these data with those of mature former athletes. Twenty young (baseline age 16.0 ± 0.6 years) and 20 mature (46.3 ± 4.7 years) volleyball athletes were studied (10 men and 10 women in each group). Magnetic resonance images were acquired at baseline and at year 2-follow-up, and longitudinal changes in cartilage thickness and tAB were determined quantitatively after segmentation. The yearly increase in total femorotibial cartilage thickness was 0.8% (95% confidence interval [CI]: -0.5; 2.1%) in young men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95% CI: -0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant difference between sexes). The cartilage thickness increase was greatest in the medial femur, and was not significantly associated with the variability in tAB growth (r=-0.19). Mature athletes showed smaller gains in tAB, and lost >1% of femorotibial cartilage per annum, with the greatest loss observed in the lateral tibia. In conclusion, we find an increase in cartilage thickness (and some in tAB) in young athletes toward the end of adolescence. This increase appeared somewhat greater in women than men, but the differences between both sexes did not reach statistical significance. Mature (former) athletes displayed high rates of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of knee injuries.

Meniscus body position, size, and shape in persons with and persons without radiographic knee osteoarthritis: quantitative analyses of knee magnetic resonance images from the osteoarthritis initiative.

OBJECTIVE: To quantitatively evaluate the position, size, and shape of the menisci in subjects with radiographic knee osteoarthritis (OA) compared to subjects without OA, using magnetic resonance imaging (MRI). METHODS: We studied the right knees of 39 Osteoarthritis Initiative participants (24 women and 15 men with a mean age of 59.6 ± 8.7 years) with medial compartment radiographic tibiofemoral OA (Kellgren/Lawrence grade of 2 or 3). Subjects were matched individually for age, sex, and height to controls without knee OA and without risk factors for knee OA. The right knees of the controls were used as references. One observer performed manual segmentation of the tibial plateau and the medial and lateral meniscus based on a coronally reconstructed double-echo steady-state sequence with water excitation, focusing on 5 central 3T MRIs. RESULTS: In OA knees, there was less meniscal coverage of the medial tibial plateau (435 mm(2) versus 515 mm(2) ; P = 0.0004), the medial meniscus body showed more extrusion (2.64 mm versus 0.53 mm; P < 0.0001), and the peripheral margin had a more convex shape, i.e., bulged more (mean 0.61 mm versus 0.27 mm; P < 0.0001). The thickness or volume of the medial meniscus body of OA knees did not differ substantially from reference knees. In contrast, in OA knees the lateral meniscus body had a larger volume (mean 266 mm(3) versus 224 mm(3) ; P = 0.0005) and extruded more (mean 1.16 mm versus -1.01 mm; P < 0.0001), and the external margin bulged more (mean 0.53 mm versus 0.35 mm; P < 0.0001), than in reference knees. CONCLUSION: Our findings indicate altered meniscal position and shape (i.e., more bulging) in both compartments in medial compartment knee OA. These changes may be important features of OA pathogenesis and/or disease consequences.

Quantitative MRI measures of cartilage predict knee replacement: a case-control study from the Osteoarthritis Initiative.

OBJECTIVE: Knee osteoarthritis commonly requires joint replacement, substantially reduces quality of life and increases healthcare utilisation and costs. This study aimed to identify whether quantitative measures of articular cartilage structure predict knee replacement, and to establish their utility as outcomes in clinical trials of disease-modifying therapy. METHODS: A nested case-control study was performed in Osteoarthritis Initiative participants, a multicentre observational cohort of 4796 participants with or at risk of knee osteoarthritis. 127 knees were replaced between baseline and 4 years follow-up, and one control knee per case matched for baseline radiographic disease stage (Kellgren-Lawrence grade; KLG), gender and age. Quantitative cartilage measures were obtained from 3 T magnetic resonance images at the exam before knee replacement, and longitudinal change during the previous 12 months when available (n=110). RESULTS: Cartilage thickness loss in the central and total medial femorotibial compartment (primary and secondary predictor variables) was significantly greater in case than control knees (AUC=0.59/0.58). Differences in cartilage loss were greater at earlier than later radiographic disease stages (p<0.01 for interaction with KLG). Cartilage thickness loss in the central tibia was the most predictive longitudinal measure (AUC=0.64). Denuded bone areas in the medial femur were the most predictive and discriminatory cross-sectional measure between case and control knees (AUC=0.66). CONCLUSIONS: This study demonstrates the predictive value of quantitative, MRI-based measures of cartilage for the clinically relevant endpoint of knee replacement, providing support for their utility in clinical trials to evaluate the effectiveness of structure-modifying intervention.

Bilateral loss of neural function after interscalene plexus blockade may be caused by epidural spread of local anesthetics: a cadaveric study.

BACKGROUND AND OBJECTIVES: Interscalene brachial plexus blockade is widely used in surgical procedures of the upper limb. Recently, we experienced the complication of a contralateral blockade after ultrasound-guided interscalene block. The clinical appearance was a blockade of both the ipsilateral and the contralateral cervical segments 6 to 8. We hypothesized that epidural spread of local anesthetics could be cause for this phenomenon. METHODS: We conducted a cadaveric study using ultrasound for needle guidance of interscalene blocks in 5 cadavers by a single investigator using contrast agent. Injections were made either ventral (extrafascial) or dorsal (subfascial) to the prevertebral lamina of the deep cervical fascia. Computed tomography was obtained following each injection with contrast agent immediately after incremental injections of progressively higher volumes. Subsequently, contrast spread to anatomic landmarks was investigated by a radiologist. RESULTS: After ultrasound-controlled injection of contrast agent beneath the prevertebral layer of the deep cervical fascia, 4 of the 5 investigated specimens showed contrast enhancement in the epidural space in the consecutive computed tomography scans. After extrafascial injection, none of the investigated specimens showed contrast enhancement in the epidural space. CONCLUSIONS: Contralateral blockade after ultrasound-guided interscalene injection of local anesthetics is very likely to be the effect of epidural spread. Future in vivo studies are needed to understand the implications of needle location and volume on epidural spread in interscalene blockade.

Relationship of 3D meniscal morphology and position with knee pain in subjects with knee osteoarthritis: a pilot study.

OBJECTIVES: To explore whether quantitative, three-dimensional measurements of meniscal position and size are associated with knee pain using a within-person, between-knee study design. METHODS: We studied 53 subjects (19 men, 34 women) from the Osteoarthritis Initiative, with identical radiographic OA grades in both knees, but frequent pain in one and no pain in the other knee. The tibial plateau and menisci were analyzed using coronally reconstructed double echo steady-state sequence with water excitation (DESSwe) MRI. RESULTS: The medial meniscus covered a smaller proportion of the tibial plateau (-5%) and displayed greater extrusion of the body (+15%) in painful than in painless knees (paired t-test; p < 0.05). The external margin of the lateral meniscus showed greater extrusion of the body in painful knees (+22%; p = 0.03), but no significant difference in the position of its internal margin or tibial coverage. Medial or lateral extrusion ≥3 mm was more frequent in painful (n = 23) than in painless knees (n = 12; McNemar's test; p = 0.02). No significant association was observed between meniscal size and knee pain. CONCLUSIONS: These data suggest a relationship between extrusion of the meniscal body, as measured with quantitative MRI, and knee pain in subjects with knee OA. Further studies need to confirm these findings and their clinical relevance.

Comparison between different implementations of the 3D FLASH sequence for knee cartilage quantification.

OBJECTIVE: To compare several sequence implementations of the 3D FLASH sequence in the context of quantitative cartilage imaging. MATERIALS AND METHODS: Test-retest coronal fast low angle shot (FLASH) sequences with water excitation were acquired in knees of 12 healthy participants, using two 1.5 T scanners from the same manufacturer. On one of the scanners, the FLASH was additionally compared with a FLASH VIBE, 75% with 100% slice resolution, a non-selective with a conventional spatial pulse, and "asymmetric echo allowed" with "not allowed". RESULTS: Implementations of the FLASH showed systematic differences of up to 3.3%, but these were not statistically significant. Precision errors were similar between protocols, but tended to be smallest for the FLASH VIBE with 100% slice resolution (0.6-6.7%). In the medial tibia cartilage volume and thickness differed significantly (P < 0.01; 6.2 and 5.9%) between the two scanners. CONCLUSION: Using a validated FLASH sequence, one can reduce slice resolution to 75% and allow asymmetric echo without sacrificing precision, in order to reduce the total acquisition time. However, in longitudinal studies, the scanner and the specific sequence implementation should be kept constant between baseline and follow-up, in order to avoid systematic off-sets in the measurements.

Interobserver reproducibility of quantitative meniscus analysis using coronal multiplanar DESS and IWTSE MR imaging.

The objective of this study was to determine the interobserver reproducibility of quantitative measures of meniscus size and position, and to compare the interobserver reproducibility and agreement between a double echo steady state water excitation and an intermediately-weighted turbo spin-echo sequence. Eight knees (four healthy, four with radiographic knee osteoarthritis) from the Osteoarthritis Initiative cohort were studied. Manual segmentation of the menisci was performed by three observers and quantitative measures of meniscus size and position (i.e., extrusion) computed using image analysis software. The root mean square interobserver reproducibility error (e.g., 5.4% for medial meniscus volume with double echo steady state and 8.4% with intermediately-weighted turbo spin-echo) was found considerably smaller than the intersubject variability (average ratio ~1:3). The lowest interobserver reproducibility error for meniscus extrusion was obtained for the central five coronal slices across the tibial surface. Quantitative meniscus measures from double echo steady state and intermediately-weighted turbo spin-echo were highly correlated (r = 0.71 to 0.99 for the medial meniscus).

Revision 1 size and position of the healthy meniscus, and its correlation with sex, height, weight, and bone area- a cross-sectional study.

BACKGROUND: Meniscus extrusion or hypertrophy may occur in knee osteoarthritis (OA). However, currently no data are available on the position and size of the meniscus in asymptomatic men and women with normal meniscus integrity. METHODS: Three-dimensional coronal DESSwe MRIs were used to segment and quantitatively measure the size and position of the medial and lateral menisci, and their correlation with sex, height, weight, and tibial plateau area. 102 knees (40 male and 62 female) were drawn from the Osteoarthritis Initiative "non-exposed" reference cohort, including subjects without symptoms, radiographic signs, or risk factors for knee OA. Knees with MRI signs of meniscus lesions were excluded. RESULTS: The tibial plateau area was significantly larger (p < 0.001) in male knees than in female ones (+23% medially; +28% laterally), as was total meniscus surface area (p < 0.001, +20% medially; +26% laterally). Ipsi-compartimental tibial plateau area was more strongly correlated with total meniscus surface area in men (r = .72 medially; r = .62 laterally) and women (r = .67; r = .75) than contra-compartimental or total tibial plateau area, body height or weight. The ratio of meniscus versus tibial plateau area was similar between men and women (p = 0.22 medially; p = 0.72 laterally). Tibial coverage by the meniscus was similar between men and women (50% medially; 58% laterally), but "physiological" medial meniscal extrusion was greater in women (1.83 ± 1.06mm) than in men (1.24mm ± 1.18mm; p = 0.011). CONCLUSIONS: These data suggest that meniscus surface area strongly scales with (ipsilateral) tibial plateau area across both sexes, and that tibial coverage by the meniscus is similar between men and women.

Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the Osteoarthritis Initiative.

OBJECTIVE: To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end-stage radiographic OA. METHODS: One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight-bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status. RESULTS: Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (<1%; minimal SRM -0.22) and not significantly different from healthy knees. Knees with calculated K/L grade 3 showed substantial loss of cartilage thickness (up to -2.5%; minimal SRM -0.35), with OV1 changes being significantly (P < 0.05) greater than those in healthy knees. Calculated K/L grade 4 knees displayed the largest rate of loss across radiographic OA grades (up to -3.9%; minimal SRM -0.51), with OV1 changes also significantly (P < 0.05) greater than in healthy knees. CONCLUSION: MRI-based cartilage thickness showed high rates of loss in knees with moderate and end-stage radiographic OA, and small rates (indistinguishable from healthy knees) in mild radiographic OA. From the perspective of sensitivity to change, end-stage radiographic OA knees need not be excluded from longitudinal studies using MRI cartilage morphology as an end point.

Effect of exercise intervention on thigh muscle volume and anatomical cross-sectional areas--quantitative assessment using MRI.

The objective of this study was to evaluate the location-specific magnitudes of an exercise intervention on thigh muscle volume and anatomical cross-sectional area, using MRI. Forty one untrained women participated in strength, endurance, or autogenic training for 12 weeks. Axial MR images of the thigh were acquired before and after the intervention, using a T1-weighted turbo-spin-echo sequence (10 mm sections, 0.78 mm in-plane resolution). The extensor, flexor, adductor, and sartorius muscles were segmented between the femoral neck and the rectus femoris tendon. Muscle volumes were determined, and anatomical cross-sectional areas were derived from 3D reconstructions at 10% (proximal-to-distal) intervals. With strength training, the volume of the extensors (+3.1%), flexors (+3.5%), and adductors (+3.9%) increased significantly (P < 0.05) between baseline and follow-up, and with endurance training, the volume of the extensor (+3.7%) and sartorius (+5.1%) increased significantly (P < 0.05). No relevant or statistically significant change was observed with autogenic training. The greatest standardized response means were observed for the anatomical cross-sectional area in the proximal aspect (10-30%) of the thigh and generally exceeded those for muscle volumes. The study shows that MRI can be used to monitor location-specific effects of exercise intervention on muscle cross-sectional areas, with the proximal aspect of the thigh muscles being most responsive.

Femorotibial subchondral bone area and regional cartilage thickness: a cross-sectional description in healthy reference cases and various radiographic stages of osteoarthritis in 1,003 knees from the Osteoarthritis Initiative.

OBJECTIVE: To identify structural differences in total subchondral bone area (tAB) and cartilage thickness between healthy reference knees and knees with radiographic osteoarthritis (OA). METHODS: Baseline magnetic resonance images from 1 knee of 1,003 Osteoarthritis Initiative participants were studied: 112 healthy reference knees without radiographic OA, symptoms, or risk factors; 70 preradiographic OA knees (calculated Kellgren/Lawrence [K/L] grade 0/1); and 821 radiographic OA knees (calculated K/L grade ≥2). Means and standard (Z) scores (SD unit differences compared with normal subjects) of the tAB and regional cartilage thickness were assessed in the weight-bearing femorotibial joint and compared between groups. RESULTS: In men, tAB was 8.2% larger in preradiographic OA knees and 6.6%, 8.1%, and 8.5% larger in calculated K/L grade 2, 3, and 4 radiographic OA knees, respectively, than in reference knees. In women, the differences were +6.8%, +7.3%, +9.9%, and +8.1%, respectively. The external medial tibia showed the greatest reduction in cartilage thickness (Z scores -5.1/-5.6 in men/women) with Osteoarthritis Research Society International medial joint space narrowing (JSN) grade 3, and the external lateral tibia (Z scores -6.0 for both sexes) showed the greatest reduction with lateral JSN grade 3. In all subregions of end-stage radiographic OA knees, ≥25% of the average normal cartilage thickness was maintained. An overall trend toward thicker cartilage was found in preradiographic OA and calculated K/L grade 2 knees, especially in the external central medial femur. CONCLUSION: tABs were larger in preradiographic OA and radiographic OA knees than in healthy reference knees, and the difference did not become larger with higher calculated K/L grades. Specific subregions with substantial cartilage thickening or thinning were identified in pre-, early, and late radiographic OA.

Denuded subchondral bone and knee pain in persons with knee osteoarthritis.

OBJECTIVE: It is unclear how articular cartilage loss contributes to pain in patients with knee osteoarthritis (OA). Full-thickness cartilage defects expose the subchondral bone plate. The relationship between denuded bone and pain has not been examined. The aim of this study was to investigate whether the percent of denuded bone is associated with moderate-to-severe knee pain or frequent knee pain and longitudinally with frequent knee pain 2 years after the baseline evaluation. METHODS: We studied 182 persons with knee OA (305 knees). Applying specialized magnetic resonance imaging techniques, manual segmentation was used to compute cartilage-covered and denuded bone areas for each surface. Moderate-to-severe knee pain was defined as a score of >or=40 mm on a knee-specific 100-mm visual analog scale, and frequent knee pain was defined as pain on most days during the past month. Logistic regression and generalized estimating equations were used in analyses, adjusting for age, sex, body mass index, and bone marrow lesions. RESULTS: Cross-sectional analyses revealed that moderate-to-severe knee pain was associated with percent denuded bone in the medial compartment (adjusted odds ratio [OR] 3.90, 95% confidence interval [95% CI] 1.33-11.47), in the medial and patellar surfaces together, and in the lateral and patellar surfaces. Frequent knee pain was associated with percent denuded bone in the patellar surface (adjusted OR 3.11, 95% CI 1.24-7.81), in the medial and patellar surfaces, and in the lateral and patellar surfaces. Longitudinal analyses (in 168 knees without frequent knee pain at baseline) revealed that percent denuded bone in the medial and patellar surfaces was associated with frequent incident knee pain (adjusted OR 4.19, 95% CI 1.56-11.22). CONCLUSION: These results support a relationship between subchondral bone plate exposure and prevalent and incident knee pain in patients with knee OA.

Magnetic resonance imaging-based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: Data from the Osteoarthritis Initiative.

OBJECTIVE: To determine by magnetic resonance imaging (MRI), whether knees with advanced radiographic disease (medial joint space narrowing [mJSN]) encounter greater longitudinal cartilage loss than contralateral knees with earlier disease (no or less mJSN). METHODS: Participants were selected from 2,678 cases in the Osteoarthritis Initiative, based on exhibition of bilateral pain, body mass index >25 (kg/m(2)), mJSN in 1 knee, no or less mJSN in the contralateral knee, and no lateral JSN in both knees. Eighty participants (mean +/- SD age 60.6 +/- 9.1 years) fulfilled these criteria. Medial tibial and femoral cartilage morphology was analyzed from the baseline and the 1-year followup MRI (sagittal double echo at steady state by 3.0T) of both knees by experienced readers blinded to the time point and mJSN status. RESULTS: Knees with more radiographic mJSN displayed greater medial cartilage loss (-80 mum) assessed by MRI than contralateral knees with less mJSN (-57 mum). The difference reached statistical significance in participants with an mJSN grade of 2 or 3 (P = 0.005-0.08), but not in participants with an mJSN grade of 1 (P = 0.28-0.98). In knees with more mJSN, cartilage loss increased with higher grades of mJSN (P = 0.003 in the medial femur). Knees with an mJSN grade of 2 or 3 displayed greater cartilage loss in the weight-bearing medial femur than in the posterior femur or in the medial tibia (P = 0.048). CONCLUSION: Knees with advanced mJSN displayed greater cartilage loss than contralateral knees with less mJSN. These data suggest that radiography can be used to stratify fast structural progressors, and that MRI cartilage thickness loss is more pronounced at advanced radiographic disease stage.

Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis?

OBJECTIVE: To propose a novel strategy for more efficiently measuring changes in cartilage thickness in osteoarthritis (OA) using magnetic resonance imaging, and to hypothesize that determining the magnitude of thickness change independent of the anatomic location provides improved discrimination between healthy subjects and OA participants longitudinally. METHODS: A total of 148 women were imaged; 90 were Kellgren/Lawrence (K/L) grade 0, 30 were K/L grade 2, and 28 were K/L grade 3. Magnetic resonance images (3T) were acquired at baseline and at 24 months. Changes in femorotibial cartilage thickness were determined in 5 tibial and 3 femoral medial and lateral subregions, respectively (conventional approach). The new strategy provided ordered values of subregional change in each compartment, ranked according to the direction and magnitude of change. RESULTS: Using the new ordered values approach, the minimal P value for the differences in 2-year change in medial cartilage thickness of K/L grade 3 and K/L grade 0 participants was 0.001 (Wilcoxon test), with 4 ordered medial subregions differing significantly between both groups. With the conventional approach, only 1 medial subregion differed significantly between K/L grade 3 and K/L grade 0 (P = 0.037). Cartilage thickening was significantly greater in K/L grade 2 versus K/L grade 0 participants in 1 medial subregion using the conventional approach (P = 0.016), and in 2 medial subregions (minimal P = 0.007) using the ordered values approach. CONCLUSION: The novel ordered values approach is more sensitive in detecting cartilage thinning in K/L grade 3 and cartilage thickening in K/L grade 2 versus K/L grade 0 participants. The new method may be particularly useful in the context of other comparisons, e.g., a group treated with a disease-modifying OA drug versus one treated with a placebo.

Relationship of compartment-specific structural knee status at baseline with change in cartilage morphology: a prospective observational study using data from the osteoarthritis initiative.

INTRODUCTION: The aim was to investigate the relationship of cartilage loss (change in medial femorotibial cartilage thickness measured with magnetic resonance imaging (MRI)) with compartment-specific baseline radiographic findings and MRI cartilage morphometry features, and to identify which baseline features can be used for stratification of fast progressors. METHODS: An age and gender stratified subsample of the osteoarthritis (OA) initiative progression subcohort (79 women; 77 men; age 60.9 +/- 9.9 years; body mass index (BMI) 30.3 +/- 4.7) with symptomatic, radiographic OA in at least one knee was studied. Baseline fixed flexion radiographs were read centrally and adjudicated, and cartilage morphometry was performed at baseline and at one year follow-up from coronal FLASH 3 Tesla MR images of the right knee. RESULTS: Osteophyte status at baseline was not associated with medial cartilage loss. Knees with medial joint space narrowing tended to show higher rates of change than those without, but the relationship was not statistically significant. Knees with medial femoral subchondral bone sclerosis (radiography), medial denuded subchondral bone areas (MRI), and low cartilage thickness (MRI) at baseline displayed significantly higher cartilage loss than those without, both with and without adjusting for age, sex, and BMI. Participants with denuded subchondral bone showed a standardized response mean of up to -0.64 versus -0.33 for the entire subcohort. CONCLUSIONS: The results indicate that radiographic and MRI cartilage morphometry features suggestive of advanced disease appear to be associated with greater cartilage loss. These features may be suited for selecting patients with a higher likelihood of fast progression in studies that attempt to demonstrate the cartilage-preserving effect of disease-modifying osteoarthritis drugs.

Longitudinal quantitative MR imaging of cartilage morphology in the presence of gadopentetate dimeglumine (Gd-DTPA).

MRI-based cartilage morphometry can monitor cartilage loss in osteoarthritis. Intravenous Gd-DTPA injection is needed for compositional (proteoglycan) cartilage imaging with delayed gadolinium enhanced MRI (dGEMRIC). However, longitudinal changes of cartilage morphology have not been compared in the presence and absence of Gd-DTPA. Baseline and 2-year follow-up images were acquired in 41 female participants with definite medial radiographic osteoarthritis, both before and 2 h after Gd-DTPA injection, and cartilage thickness was measured. In the absence of Gd-DTPA, a 2.6% reduction in cartilage thickness was observed between baseline and follow-up in the central subregion of the medial femorotibial compartment (standardized response mean [SRM]= -0.33; P<0.05), but only a 0.7% reduction (SRM= -0.10; P=0.51) in the presence of Gd-DTPA. The findings suggest that morphometric cartilage measurement in the presence of Gd-DTPA needs to undergo further validation, before one can recommend longitudinal dGEMRIC and morphological cartilage imaging to be performed in a single session.