The role of stromal cell-derived factor 1 on cartilage development and disease.

Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine ligand 12 (CXCL12), is recognized as a homeostatic cytokine with strong chemotactic potency. It plays an important role in physiological and pathological processes, such as the development of multiple tissues and organs, the regulation of cell distribution, and tumour metastasis. SDF-1 has two receptors, CXC chemokine receptor type 4 (CXCR4) and CXC chemokine receptor type 7 (CXCR7). SDF-1 affects the proliferation, survival, differentiation and maturation of chondrocytes by binding to CXCR4 on chondrocytes. Therefore, SDF-1 has been used as an exogenous regulatory target in many studies to explore the mechanism of cartilage development. SDF-1 is also a potential therapeutic target for osteoarthritis (OA) and rheumatoid arthritis (RA), because of its role in pathological initiation and regulation. In addition, SDF-1 shows potent capacity in the repair of cartilage defects by recruiting endogenous stem cells in a cartilage tissue engineering context. To summarize the specific role of SDF-1 on cartilage development and disease, all articles had been screened out in PubMed by May 30, 2020. The search was limited to studies published in English. Search terms included SDF-1; CXCL12; CXCR4; chondrocyte; cartilage; OA; RA, and forty-seven papers were studied. Besides, we reviewed references in the articles we searched to get additional relevant backgrounds. The review aims to conclude the current knowledge regarding the physiological and pathological role of SDF-1 on the cartilage and chondrocyte. More investigations are required to determine methods targeted SDF-1 to cartilage development and interventions to cartilage diseases.

Comparison of clinically used bilayer collagen membrane and trilayer collagen prototype fixation stability in chondral defects at the talus - An experimental human specimen study.

BACKGROUND: The purpose of this human specimen experimental study was to compare the fixation stability of clinically used bilayer collagen membrane with fibrin glue with trilayer collagen prototype without fibrin glue in chondral defects at the medial or lateral talar shoulder (both matrices from Geistlich Pharma AG, Wollhusen, Switzerland). METHODS: Eleven human specimens were used. The membranes were implanted in standardized chondral defects at the medial and lateral talar shoulder randomized. All tests were performed in load-control 15 kg. Range of motion ROM of each ankle was examined individually before testing. The average ROM was 10° dorsiflexion range 0°-20° and 30° plantarflexion range 20°-45°. 1,000 testing cycles with the defined ROM were performed. Two independent investigators, blinded to membrane and fixation type, visually assessed the membrane fixation integrity for peripheral detachment, area of defect uncovered, membrane constitution and delamination. RESULTS: The clinically used bilayer collagen membrane plus fibrin glue showed higher fixation stability than the trilayer prototype (all p < 0.05). No significant differences occurred between medial and lateral talar shoulder location (all p > 0.05). CONCLUSIONS: The fixation stability of the trilayer collagen prototype without fibrin glue is lower than of the clinically used bilayer membrane with fibrin glue in chondral defects at the medial and lateral talar shoulder in an experimental human specimen test. Clinical use of trilayer collagen prototype without fibrin glue has to be validated by clinical testing to evaluate if the lower stability of fixation is still sufficient.

Degeneration alters the biomechanical properties and structural composition of lateral human menisci.

OBJECTIVE: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration. DESIGN: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content. RESULTS: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements. CONCLUSION: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity.

Return to Sport and Outcomes After Concomitant Lateral Meniscal Allograft Transplant and Distal Femoral Varus Osteotomy.

PURPOSE: To evaluate the time and rate of return to sport (RTS), as well as outcomes, in young and active patients receiving concomitant lateral meniscal allograft transplantation (MAT) and distal femoral varus osteotomy (DFVO) for lateral meniscal deficiency and valgus malalignment. METHODS: This was a retrospective study of consecutive patients who underwent concomitant MAT and DFVO by a single surgeon. The exclusion criteria were any concomitant procedures other than cartilage restoration procedures for focal full-thickness cartilage defects of the lateral femoral condyle and less than 2 years of follow-up. At final follow-up, patients were asked to complete a subjective sports questionnaire, the Marx Activity Rating Scale, a visual analog scale (VAS), the Single Assessment Numeric Evaluation, and a satisfaction questionnaire. Changes in patient-reported outcome measures were assessed using nonparametric statistical testing. RESULTS: A total of 21 patients met the inclusion criteria, of whom 17 were included for analysis at an average follow-up of 7.5 years (range, 2.2-13.3 years). The average age at the time of surgery was 23.3 years (range, 16.9-36.2 years), and 76.5% of patients were female patients. The average VAS score decreased from 5.7 preoperatively to 2.6 postoperatively (P = .02). Of the 15 patients who participated in sports within 3 years prior to their surgical procedure, 14 (82.4%) returned to 1 or more sports at an average of 16.9 months (range, 6-36 months); however, only 46.7% were able to return to their preinjury level of participation or higher. Furthermore, 88.2% of patients reported being satisfied with their sport-related outcomes. Direct rates of sport-specific return were as follows: weightlifting, 100%; skiing, 100%; running, 66.7%; and basketball, 50%. CONCLUSIONS: In our study population, concomitant MAT and DFVO afforded a high rate of RTS at an average of 16.9 months postoperatively, as well as a significant decrease in VAS pain scores. These findings are essential to note when counseling patients receiving these procedures who wish to resume sports and physical activities so that they may expect an extensive recovery process before they can RTS. LEVEL OF EVIDENCE: Level IV, case series.

Cartilage damage at the time of anterior cruciate ligament reconstruction is associated with weaker quadriceps function and lower risk of future ACL injury.

PURPOSE: To determine whether articular cartilage damage noted at the time of primary anterior cruciate ligament reconstruction (ACLR) affects the likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery or risk of recurrent ACL injury. METHODS: Five hundred and eight patients underwent primary ACLR and diagnostic arthroscopy. All identified cartilage lesions were graded using the Outerbridge system. All patients underwent isokinetic strength testing. The association between cartilage Outerbridge grade and a ≥ 90% Limb Symmetry Index (LSI) and recurrent ACL injury risk at mean 38.7 month follow-up (SD 31.8) was evaluated via multivariate regression analysis. RESULTS: Grade 2 or higher damage was present in 394 (77.5%) of patients, grade 3 or higher in 143 (28.1%) and grade 4 in 83 (16.4%) at time of ACLR. Ipsilateral ACLR graft rupture occurred in 31 (6.1%) of patients. Contralateral ACL injury occurred in 19 (3.7%). Patients with grade 2 or higher damage were significantly less likely to meet an LSI goal of ≥ 90% for fast (300°/s) isokinetic extension. There was no association with slow isokinetic extension. Cartilage lesion severity at or beyond grade 2 had a similar effect on isokinetic testing results regardless of compartment involvement or performance of microfracture. Patients with grade 2-4 cartilage damage were less likely to sustain a second ipsilateral ACL injury or a contralateral native ACL injury. CONCLUSIONS: Cartilage damage seen at time of ACL reconstruction is common and associated with lower likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery. However, lower recurrent ACL injury rates are seen in patients with concurrent cartilage damage. These data may inform future clinical decisions regarding operative managment of recurrent ACL injuries. LEVEL OF EVIDENCE: III.

Transtibial fixation for medial meniscus posterior root tear reduces posterior extrusion and physiological translation of the medial meniscus in middle-aged and elderly patients.

PURPOSE: To investigate changes in meniscal extrusion during knee flexion before and after pullout fixation for medial meniscus posterior root tear (MMPRT) and determine whether these changes correlate with articular cartilage degeneration and short-term clinical outcomes. METHODS: Twenty-two patients (mean age 58.4 ± 8.2 years) diagnosed with type II MMPRT underwent open magnetic resonance imaging preoperatively, 3 months after transtibial fixation and at 12 months after surgery, when second-look arthroscopy was also performed. The medial meniscus medial extrusion (MMME) and the medial meniscus posterior extrusion (MMPE) were measured at knee 10° and 90° flexion at which medial meniscus (MM) posterior translation was also calculated. Articular cartilage degeneration was assessed using International Cartilage Research Society grade at primary surgery and second-look arthroscopy. Clinical evaluations included Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective knee evaluation form, Lysholm score, Tegner activity level scale, and pain visual analogue scale. RESULTS: MMPE at 10° knee flexion was higher 12 months postoperatively than preoperatively (4.8 ± 1.5 vs. 3.5 ± 1.2, p = 0.01). MMPE at 90° knee flexion and MM posterior translation were smaller 12 months postoperatively than preoperatively (3.5 ± 1.1 vs. 4.6 ± 1.3, 7.2 ± 1.7 vs. 8.9 ± 2.0, p < 0.01). Articular cartilage degeneration of medial femoral condyle correlated with MMME in knee extension (r = 0.5, p = 0.04). All clinical scores significantly improved 12 months postoperatively. However, correlations of all clinical scores against decreased MMPE and increased MMME were not detected. CONCLUSIONS: MMPRT transtibial fixation suppressed the progression of MMPE and cartilage degeneration and progressed MMME minimally in knee flexion position at 1 year. However, in the knee extension position, MMME progressed and correlated with cartilage degeneration of medial femoral condyle. MMPRT transtibial fixation contributes to the dynamic stability of the MM in the knee flexion position. LEVEL OF EVIDENCE: IV.

Autologous chondrocyte implantation for treatment of focal articular cartilage defects of the humeral head.

BACKGROUND: Autologous chondrocyte implantation (ACI) constitutes an established treatment option for cartilage defects of the knee joint. Experience in the shoulder, however, is limited, and the management of cartilage defects remains a challenge. The purpose of this study was to evaluate the results after ACI with 3-dimensional spheroids of human autologous matrix-associated chondrocytes in the shoulder. METHODS: Seven male patients (median age, 42.8 years [range, 18-55 years]) underwent ACI for symptomatic focal grade IV cartilage lesions of the humeral head by an open or arthroscopic approach. Clinical parameters (range of motion, visual analog scale score, Subjective Shoulder Value, Constant score, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score) and osteoarthritis grades were assessed. Arthroscopic re-evaluation was additionally performed in 5 patients. RESULTS: After a median follow-up period of 32 months (range, 22-58 months), the median Subjective Shoulder Value was 95% (range, 70%-100%) compared with 60% (range, 30%-60%) preoperatively, the visual analog scale score was 0 at rest and was a median of 0 (range, 0-2) during exercise, the median Constant score was 95 points (range, 80-100 points), and the median American Shoulder and Elbow Surgeons score was 97 points (range, 90-100 points). The median preoperative size of the cartilage lesion was 3 cm2 (range, 2.3-4.5 cm2). Arthroscopically, complete coverage of the cartilage defect was observed in 4 cases whereas a circumferential residual defect of 0.25 cm2 was found in 1 patient. Grade I osteoarthritis (Samilson and Prieto classification) was observed in 2 cases. One patient had postoperative adhesive capsulitis and required revision surgery. CONCLUSION: ACI using 3-dimensional spheroids of human autologous matrix-associated chondrocytes for treatment of grade IV articular cartilage lesions of the humeral head achieves satisfactory clinical results during a short- to mid-term follow-up period and leads to successful defect coverage with only minor radiologic degenerative changes. In this case series, ACI proved to constitute a viable treatment in the shoulder joint. However, in consideration of the 2-stage surgical design and the cost intensiveness of this procedure, the indication is restricted to young and active symptomatic patients in our practice.

[What does the clinician expect from the radiologist regarding cartilage-specific imaging?] / Was erwartet der Kliniker vom Radiologen bei der dezidierten Knorpelbildgebung?

CLINICAL ISSUE: Today's advanced MRI imaging allows for a precise diagnosis and thus better treatment planning of cartilage damage. The phrase "depending on intraoperative findings" is therefore slowly becoming a thing of the past. However, this also increases the demand for an exact interpretation of the imaging, from clinicians and patients alike. This article highlights the importance of a radiologist's role in different constellations. PRACTICAL RECOMMENDATIONS: In the case of acute injuries, it is crucial to recognize osteochondral flakes, cartilage delamination, subchondral bone bruising and fractures as well as concomitant injuries. These findings must be instantly communicated to the practitioner. In the case of chronic cartilage damage, grading the extent and size of the damage is decisive in choosing the appropriate therapy method. Possible causes and accompanying injuries must also be analyzed and, if necessary, addressed. Direct communication with the clinical colleague is also useful in correlating the clinical and radiological findings.

[Update: clinical imaging of cartilage-part 1 : Technical aspects]. / Update: Klinische Knorpelbildgebung ­ Teil 1 : Technische Aspekte.

BACKGROUND: In order to answer clinical therapy-oriented questions, reliable and consistent depiction of articular cartilage across technical platforms is necessary. MATERIALS AND METHODS: Technical standards and developments in cartilage imaging are summarized based on current literature and experience from clinical daily routine. RESULTS: Clinical questions that need to be answered relate to cross-sectional extent, depth, differentiating cartilaginous from bony components of a lesion and to the lesion's location within the compartment. If present, displaced fragments, concomitant meniscal, ligamentous and/or degenerative lesions should be identified. To date, magnetic resonance imaging (MRI) is the workhorse of cartilage imaging and is largely based on moderately T2-weighted and also proton-density (PD)-weighted fat-suppressed turbo-spin-echo sequences. Direct MR- and CT-arthrography are the gold standard to evaluate thin cartilage layers. Recent advances in coil and MR sequence design, increased availability of 3T-MR scanners and more and more sophisticated acceleration techniques allow for better spatial resolution and more robust image contrast at acceptable scan times. DISCUSSION: As abundant as current developments in clinical routine cartilage imaging may be, the radiologist must carefully select the approach best suited to answering the clinical questions.

The relationship between patellofemoral arthritis and fat tissue volume, body mass index and popliteal artery intima-media thickness through 3T knee MRI

Background/aim: Evaluating the relationship of patellar chondromalacia with obesity, infrapatellar fat pad (IFP) volume and popliteal artery intima-media thickness (IMT). Materials and methods: A total of203 patients with different degree of patellar chondromalacia (103 male, 100 female) and 52 control subjects (19 male, 33 female) were included and grouped according to sex, age, body surface area (BSA), body mass index (BMI) and patellar chondromalacia classification. All measurements were completed with 3T magnetic resonance imaging (MRI). Articular cartilage and IFP volume were measured in saggital plane using double echo steady state (DESS) and DIXON sequences, respectively. Patellar cartilage damage was graded using modified outerbridge classification, and the relations among cartilage volume and BMI, BSA, IFP, IMT were statistically assessed. Results: Popliteal artery IMT showed an independent association with the prevalence of cartilage defects and IFP volumes (P ˂ 0.001). There was an association between BMI and IFP volumes (P ˂ 0.001). However, no differences were observed between IFP volume and different chondromalacia groups. When IFP measurements were corrected using individual BMI and BSA values, a positive correlation was found between control and advanced chondromalacia groups (P ˂ 0.001). Conclusion: This study demonstrates the relationship among obesity, IMT and chondromalacia and highlights this potential circle to develop effective treatments and inhibit the progression of chondromalacia.

Osteochondral Angiogenesis and Promoted Vascularization: New Therapeutic Target.

The control of the different angiogenic process is an important point in osteochondral regeneration. Angiogenesis is a prerequisite for osteogenesis in vivo; insufficient neovascularization of bone constructs after scaffold implantation resulted in hypoxia and cellular necrosis. Otherwise, angiogenesis must be avoided in chondrogenesis; vascularization of the cartilage contributes to structural damage and pain. Finding a balance between these processes is important to design a successful treatment for osteochondral regeneration. This chapter shows the most important advances in the control of angiogenic process for the treatment of osteochondral diseases focused on the administration of pro- or anti-angiogenic factor and the design of the scaffold.

Good clinical results but moderate osseointegration and defect filling of a cell-free multi-layered nano-composite scaffold for treatment of osteochondral lesions of the knee.

PURPOSE: The aim of this retrospective study was to evaluate the clinical and radiological results of a nano-composite multi-layered three-dimensional biomaterial scaffold for treatment of osteochondral lesions (OCL) of the knee. It was a particular radiological interest to analyse the osseointegration, filling of the defects and the bone tracer uptake (BTU), and it was hypothesised that this scaffold, which was created to mimic the entire osteo-cartilaginous unit, is integrated within the bone 12 months postoperatively and comes along with improved patients symptoms and function. METHODS: Fourteen patients (male:female = 11:3, mean age ± SD 33.1 ± 10.7 years) treated for OCL (size 1.0-3.5 cm2) were clinically and radiologically evaluated at 1 year postoperatively. The data were prospectively collected including SPECT/CT, Tegner and Lysholm scores. BTU was anatomically localised and volumetrically quantified in SPECT/CT. Defect filling was analysed in CT. Spearman's rho and Wilcoxon test were used for correlation of BTU in SPECT/CT and clinical scores (p < 0.05). RESULTS: A significant improvement in Lysholm knee score (p < 0.001) and slight deterioration in Tegner score were found (p < 0.01). A complete filling of the defect was shown in 14%, a partial filling in 14% and only minor filling was seen in 72%. A significant correlation (p < 0.001) was found between location of osteochondral lesions and increased BTU. At the lesion sites pre- and postoperative BTU was markedly increased and did not show any decrease at 12-month follow-up. Median Tegner and mean Lysholm scores did not correlate with BTU at any time. CONCLUSIONS: Treatment of OCL in the knee joint with a nano-composite multi-layered three-dimensional biomaterial scaffold resulted in a significant clinical improvement at 1-year follow-up. However, osseointegration was still ongoing at 12-month follow-up. LEVEL OF EVIDENCE: Case series, Level IV.

Relationship between symptomatic osteochondral lesions of the talus and quality of life, body mass index, age, size and anatomic location.

INTRODUCTION: The aim of the study was to assess the relationship between symptomatic osteochondral lesions of the talus (OLTs) and age, body mass index (BMI), quality of life (QOL), size and anatomic location. METHODS: Fifty-two patients with chronic OLTs were analyzed including BMI, Visual Analogue Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS), Short-Form Health Survey (SF-12 divided into Mental (MCS) and Physical (PCS) score) and the 12-Item General Health Questionnaire (GHQ-12). Every patient underwent magnetic resonance imaging (MRI) and computed tomography (CT) examinations. We carried out a sub-analysis by dividing the talus into 6 areas, 3 vertical (medial, central and lateral group) and 3 horizontal (anterior, middle and posterior group). RESULTS: There were 31 (60%) male and 21 (40%) female patients. Mean MCS and PCS resulted respectively 43.9 and 35.2. OLTs were located as follows: medial 20 (38.50%); central 13 (24.0%); and lateral 19 (36.50%); anterior 24 (46.15%); middle 16 (30.77%); and posterior 12 (23.08%). No significant differences were found among different groups with the exception of the anterior and posterior group for MCS (p=0.021). In the central group we identified a negative correlation (R=-0.672) between aging and AOFAS and a positive correlation between BMI and lesion size. We found a positive correlation between CT and MRI in each group. CONCLUSIONS: OLTs impact patients' quality of life particularly in the physical component. Additionally, in patients with central lesions we found a positive linear correlation between lesion size and BMI and a worsening of the ankle with increasing age.

S100A1 and S100B: Calcium Sensors at the Cross-Roads of Multiple Chondrogenic Pathways.

The S100 protein family comprises more than 20 members of small calcium binding proteins operating as Ca2 +-activated switches that interact and modulate the activity of a large number of targets. S100A1 and S100B, two members of this family, have been recently associated with the differentiation status of human articular chondrocytes. Both proteins are homogeneously expressed in all cartilage zones, their expression decreases during chondrocyte dedifferentiation, and can be induced under conditions promoting redifferentiation. Although S100 proteins have a broad range of extra- and intracellular roles, functional studies of S100 proteins expressed in chondrocytes have focused on their extracellular roles linked to catabolic processes. The intracellular roles of S100A1 and S100B in chondrocytes remain largely unexplored, yet the few studies addressing their intracellular activity point toward potentially important functions in chondrocyte biology. This review summarizes reported intracellular S100A1 and S100B regulatory functions described in other cell types that could be also involved in the regulation of chondrogenic processes in cartilage. Potential roles of S100A1 and S100B in the TGF-ß-SMAD, the cAMP-PKA-CREB, and the PI3K-AKT pathways, Ca2+ homeostasis, cytoskeleton dynamics, the calcineurin-NFAT pathway, interactions with the p53 family, and the Hippo pathway are examined in the context of chondrocyte biology. Based on the plethora of interactions of S100A1 and S100B with different molecular partners playing essential roles in chondrocyte biology, and the staggering complexity and ubiquity of cross-talk among these partners, we hypothesize that these S100 proteins play fundamental roles in the spatial and temporal regulation of chondrogenesis. J. Cell. Physiol. 232: 1979-1987, 2017. © 2016 Wiley Periodicals, Inc.

Differential knee joint loading patterns during gait for individuals with tibiofemoral and patellofemoral articular cartilage defects in the knee.

OBJECTIVE: To determine compartment-specific loading patterns during gait, quantified as joint reaction forces (JRF), of individuals with knee articular cartilage defects (ACD) compared to healthy controls (HC). METHODS: Individuals with ACDs and HC participated. Individuals with ACDs were divided into groups according to ACD location: PF (only a patellofemoral ACD), TF (only a tibiofemoral ACD), and MIX (both PF and TF ACDs). Participants underwent three-dimensional gait analysis at self-selected speed. TF joint reaction force (TF-JRF) was calculated using inverse dynamics. PF joint reaction force (PF-JRF) was derived from estimated quadriceps force (FQUAD) and knee flexion angle. Primary variables of interest were the PF- and TF-JRF peaks (body weight [×BW]). Related secondary variables (gait speed, quadriceps strength, knee function, activity level) were evaluated as covariates. RESULTS: First peak PF-JRF and TF-JRF were similar in the TF and MIX groups (0.75-1.0 ×BW, P = 0.6-0.9). Both peaks were also similar in the PF and HC groups (1.1-1.3 ×BW, P = 0.7-0.8), and higher than the TF and MIX groups (P = 0.004-0.02). For the second peak PF-JRF, only the HC group was higher than the TF group (P = 0.02). The PF group walked at a similar speed as the HC group; both groups walked faster than the TF and MIX groups (P < 0.001). With gait speed and quadriceps strength as covariates, no differences were observed in JRF peaks. CONCLUSIONS: The results suggest the presence of a TF ACD (TF and MIX groups), but not a PF ACD (PF group), may affect joint loading patterns during walking. Walking slower may be a protective gait modification to reduce load.

The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions.

The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA.

Meniscal extrusion and bone marrow lesions are associated with incident and progressive knee osteoarthritis.

OBJECTIVE: Whether meniscal extrusion and bone marrow lesions (BMLs) are independently associated with the risk of knee osteoarthritis (OA) is unknown. METHODS: Data was extracted from the Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren-Lawrence (KL) grade ≤ 1, n = 2120) or presence (KL ≥ 2, n = 2249) of radiographic OA (ROA). Baseline meniscal extrusion and tibial BMLs were assessed. Tibial plateau cartilage volume was assessed at baseline and 72 months, while radiographic disease was assessed at baseline and 48 months. Total knee replacement (TKR) was assessed at 72 months. RESULTS: In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.5%; lateral: -2.6%/annum vs -1.6%; both P < 0.001), progressive ROA and TKR (Odds ratio (OR) range 1.4-1.8; 95% CI range 1.1-2.9). The presence of a baseline BML was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.6%; lateral: -1.9%/annum vs -1.6%; P ≤ 0.02), progressive ROA and joint replacement (OR range 1.5-2.4; 95% CI range 1.1-3.4). In those with no ROA, a baseline medial meniscal extrusion was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.2%, P < 0.001), and a baseline medial BML with incident ROA (OR 1.7, 95% CI 1.1 to 2.9). CONCLUSIONS: The presence of baseline meniscal extrusion and BMLs are associated with incident and progressive knee of each other (OA) and represent important structural targets for the treatment and prevention of knee OA.

Cross-sectional and longitudinal study of the impact of posterior meniscus horn lesions on adjacent cartilage composition, patient-reported outcomes and gait biomechanics in subjects without radiographic osteoarthritis.

OBJECTIVE: The aim of this study was to assess cross-sectional and longitudinal effects of meniscal lesions on adjacent cartilage T1ρ and T2 relaxation times, patient-reported outcomes and gait biomechanics. DESIGN: Thirty patients with no cartilage morphological defects reported by Whole Organ MRI Score (WORMS) magnetic resonance imaging (MRI) grading and no radiographic osteoarthritis (OA) (Kellgren--Lawrence (KL) ≤ 1) were selected, 15 with posterior meniscus horn lesions and 15 matched controls without meniscal lesions. All were imaged on a 3T MR scanner for three consecutive years, except those who dropped from the study. Sagittal and frontal plane kinematic gait data were acquired at baseline. The Knee Injury and Osteoarthritis Outcome Score (KOOS) survey was taken each time. All images were automatically segmented and registered to an atlas for voxel-by-voxel cross-sectional and longitudinal analyses. RESULTS: Relaxation time comparisons between groups showed elevated T1ρ of the lateral tibia (LP) and elevated T2 of the medial tibia (MT) and LT at 1 and 2 years in the lesion group. Longitudinal comparisons within each group revealed greater relaxation time elevations over one and 2 years in the group with lesions. KOOS Quality of Life (QOL) was significantly different between the groups at all time points (P < 0.05), as were other KOOS subcategories. No significant differences in the frontal or sagittal biomechanics were observed between the groups at baseline. CONCLUSIONS: Individuals with healthy cartilage and posterior meniscal horn lesions have increased relaxation times when compared to matched controls, increased relaxation time changes over 2 years, and consistently report a lower KOOS QOL, yet show no difference in gait biomechanics.

Medial femur T2 Z-scores predict the probability of knee structural worsening over 4-8 years: Data from the osteoarthritis initiative.

OBJECTIVE: The purpose of this study was to determine the probability of structural worsening of knee cartilage and whole joint degeneration over 4-8 years based on cartilage T2 Z-scores at baseline. DESIGN: Right knees with Kellgren-Lawrence (KL) grades of 0-2 in 587 participants from the Osteoarthritis Initiative were studied. 3T MR images were used to perform baseline cartilage T2 quantification and assess 4-year changes in cartilage morphology (WORMS scoring) in 5 regions. Changes in joint space narrowing (JSN) and KL were assessed over 8 years. T2 Z-scores were based on a reference database of knees without morphologic cartilage degeneration at baseline. Odds ratios for, and predicted probabilities of any worsening in WORMS cartilage, JSN and KL grade were obtained from logistic regression models. RESULTS: A one-unit increase in the baseline medial femur T2 Z-score was associated with cartilage worsening in the same region (OR = 1.59; P < 0.0001) and in any region (OR = 1.37; P < 0.0001), and with worsening JSN (OR = 1.82; P < 0.0001) and KL grades (OR = 1.69; P < 0.0001). Predicted probabilities of worsening in knees with a medial femur T2 Z-score from 2-4 were 38% for medial femur cartilage WORMS, 70% for any cartilage region, 28% for increasing JSN and 31% for increasing KL grade. CONCLUSION: Knees with elevated cartilage T2 (especially in the medial femur and those that are 2 to 4 SDs above the mean reference values) are significantly more likely to have structural worsening over 4 to 8 years. Knowing cartilage T2 Z-scores may aid in targeting prevention efforts at early stages of osteoarthritis. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1128-1136.

Recovery of lower extremity muscle strength and functional performance in middle-aged patients undergoing arthroscopic partial meniscectomy.

PURPOSE: To investigate lower extremity muscle strength and functional performance before and after arthroscopic partial meniscectomy in middle-aged patients with degenerative meniscal tears. We hypothesized that patients would experience deficiencies in the affected leg at 3 months post-surgery, and that this deficiency would be normalized at 12 months following surgery. METHODS: Twenty-three patients (46 ± 6.5 years) meniscectomized in 2012 and 2013 were examined for knee extension, knee flexion, and hip abduction maximal isometric muscle strength (iMVC), rate of force development (RFD200), and knee function (single-leg hop for distance and single-leg knee bends in 30 s.) before surgery, 3 and 12 months after surgery. RESULTS: Functional performance, knee extension iMVC and RFD200 were impaired in the affected leg compared to the contralateral leg (p < 0.05) prior to surgery. A significant (Knee extension RFD200, p = 0.033) or borderline significant improvement was observed in the affected leg compared to the contralateral leg from before to 12 months after surgery in most variables (leg × time interaction, n.s.). CONCLUSION: Middle-aged patients undergoing surgery for degenerative medial meniscal tears show significant reductions in muscle strength, rapid force production, and functional performance in the leg undergoing surgery compared to the contralateral leg prior to surgery. These deficits in muscle strength and knee function were still present at 3 months post-surgery but were no longer observed at 12 months following surgery. LEVEL OF EVIDENCE: III.