Infrapatellar fat pad in the knee: is local fat good or bad for knee osteoarthritis?

Introduction

Recent studies regarding the infrapatellar fat pad (IPFP) mainly focus on the roles of the cells derived from the IPFP. There have been few clinical or epidemiological studies reporting on the association between the IPFP and knee osteoarthritis (OA). Our objective is to generate hypotheses regarding the associations between IPFP maximum area and knee OA measures in older adults.

Methods

A total of 977 subjects between 50 and 80 years of age (mean, 62.4 years) participated in the study. Radiographic knee osteophyte and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was utilized to assess IPFP maximum area, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire.

Results

After adjustment for potential confounders, IPFP maximum area was significantly associated with joint space narrowing (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.62 to 0.91 (medial), 0.77, 95% CI: 0.62 to 0.96 (lateral)) and medial osteophytes (OR: 0.52, 95% CI: 0.35 to 0.76), knee tibial and patellar cartilage volume (β: 56.9 to 164.9 mm³/cm², all P <0.001), tibial cartilage defects (OR: 0.58, 95% CI: 0.41 to 0.81 (medial), 0.53, 95% CI: 0.40-0.71 (lateral)), any BMLs (OR: 0.77, 95% CI: 0.63 to 0.94), and knee pain on a flat surface (OR: 0.79, 95% CI: 0.63 to 0.98). IPFP maximum area was negatively, but not significantly, associated with femoral cartilage defects, lateral tibiofemoral BMLs, and total knee pain or other knee pain subscales.

Conclusion

IPFP maximum area is beneficially associated with radiographic OA, MRI structural pathology and knee pain on a flat surface suggesting a protective role for IPFP possibly through shock absorption. Consequently, we must pay special attention to IPFP in the clinical settings, avoiding resection of normal IPFP in knee surgery.     

Can a finite set of knee extension in supine position be used for a knee functional examination?

The kinematic magnetic resonance imaging technique has been developed to provide a functional examination of the knee. Technical limitations require this examination to be performed in supine position, and the knee motion is represented by an assembly of static positions at different knee angles. However, the main knee function is to support the body weight and perform continuous motion, e.g. parallel squat. Our study quantified the knee kinematics of 20 healthy subjects in different motion conditions (finite and continuous) and in different mechanical conditions (continuous unloaded and continuous loaded). We evaluated the angular and localisation difference of a finite helical axis of the knee motion for parallel squat, continuous knee extension in supine position and the finite set of knee extension in supine position. We found large inter-individual dispersion. The majority of subjects had equivalent knee kinematics between continuous knee extension and the finite set of knee extension in supine position, but not between continuous knee extension in supine position and the parallel squat. Therefore, results from a functional examination of a finite set of knee extensions in supine position do not represent the knee motion in a parallel squat. Our results suggest that functional examination of the knee from magnetic resonance imaging do not necessarily reflect the physiological kinematics of the knee. Further investigation should focus on a new magnetic resonance imaging acquisition protocol that allows image acquisition during weight bearing or includes a special device which reproduces the loaded condition.     

In-silico wear prediction for knee replacements—methodology and corroboration

The capability to predict in-vivo wear of knee replacements is a valuable pre-clinical analysis tool for implant designers. Traditionally, time-consuming experimental tests provided the principal means of investigating wear. Today, computational models offer an alternative. However, the validity of these models has not been demonstrated across a range of designs and test conditions, and several different formulas are in contention for estimating wear rates, limiting confidence in the predictive power of these in-silico models.This study collates and retrospectively simulates a wide range of experimental wear tests using fast rigid-body computational models with extant wear prediction algorithms, to assess the performance of current in-silico wear prediction tools.The number of tests corroborated gives a broader, more general assessment of the performance of these wear-prediction tools, and provides better estimates of the wear ‘constants’ used in computational models. High-speed rigid-body modelling allows a range of alternative algorithms to be evaluated. Whilst most cross-shear (CS)-based models perform comparably, the ‘A/A+B’ wear model appears to offer the best predictive power amongst existing wear algorithms. However, the range and variability of experimental data leaves considerable uncertainty in the results. More experimental data with reduced variability and more detailed reporting of studies will be necessary to corroborate these models with greater confidence. With simulation times reduced to only a few minutes, these models are ideally suited to large-volume ‘design of experiment’ or probabilistic studies (which are essential if pre-clinical assessment tools are to begin addressing the degree of variation observed clinically and in explanted components).     

Is the meniscus of the knee joint a fibrocartilage?

A histological analysis of the structure of intact knee joint menisci was carried out in adult dogs. By means of specific histochemical methods for the connective tissue and cartilage, it was found that the meniscus as a whole does not have a unique structure. The anterior and posterior horns are populated by round chondroid cells encircled by abundant interstitial substance and branched wavy connective fibers; blood vessels are present. The outer third of the meniscus is constituted of cross bundles of connective fibers, fibrocytes and spindle-like areas of loose connective tissue with blood vessels. The inner avascular two thirds of the meniscus are filled with parallel circumferentially oriented fascicles of connective fibers, ovally elongated chondroid cells, and a small quantity of chondroid interstitial substance. In some menisci, in the inner two thirds of the body, there are isles of typical cartilage, which show metachromasia of the beta type and rarely of the gamma type. The occurrence and way of the manifestation of cartilage are of an individual character. The structural duality of the knee meniscus is accounted for by its functional duality manifested in offering resistance to the forces of traction and pressure, the latter ones favoring the process of evolution of tissue from connective, through chondroid, to cartilaginous.     

Does gender influence neuromotor control of the knee and hip?

Patellofemoral pain (PFP) is a common condition that occurs more frequently in females. Anatomical, hormonal and neuromuscular factors have been proposed to contribute to the increased incidence of PFP in females, with neuromuscular factors considered to be of particular importance. This cross-sectional study aimed to evaluate differences in the neuromotor control of the knee and hip muscles between genders and to investigate whether clinical measures of hip rotation range and strength were associated with EMG measures of hip and thigh motor control. Twenty-nine (16 female and 13 male) asymptomatic participants completed a visual choice reaction-time stair stepping task. EMG activity was recorded from vastus medialis oblique, vastus lateralis, anterior and posterior gluteus medius muscles. In addition hip rotation range of motion and hip external rotation, abduction and trunk strength were assessed. There were no differences in the timing or peak of EMG activation of the vasti or gluteus medius muscle between genders during the stepping task. There were however significant associations between EMG measures of motor control of the vasti and hip strength in both females and males. These findings are suggestive of a link between hip muscle control and vasti neuromotor control.     

Impaired varus–valgus proprioception and neuromuscular stabilization in medial knee osteoarthritis

Impaired proprioception and poor muscular stabilization in the frontal plane may lead to knee instability during functional activities, a common complaint in persons with knee osteoarthritis (KOA). Understanding these frontal plane neuromechanical properties in KOA will help elucidate the factors contributing to knee instability and aid in the development of targeted intervention strategies. The objectives of the study were to compare knee varus–valgus proprioception, isometric muscle strength, and active muscular contribution to stability between persons with medial KOA and healthy controls. We evaluated knee frontal plane neuromechanical parameters in 14 participants with medial KOA and 14 age- and gender-matched controls, using a joint driving device (JDD) with a customized motor and a 6-axis force sensor. Analysis of covariance with BMI as a covariate was used to test the differences in varus–valgus neuromechanical parameters between these two groups. The KOA group had impaired varus proprioception acuity (1.08±0.59° vs. 0.69±0.49°, p<0.05), decreased normalized varus muscle strength (1.31±0.75% vs. 1.79±0.84% body weight, p<0.05), a trend toward decreased valgus strength (1.29±0.67% vs. 1.88±0.99%, p=0.054), and impaired ability to actively stabilize the knee in the frontal plane during external perturbation (4.67±2.86 vs. 8.26±5.95 Nm/degree, p<0.05). The knee frontal plane sensorimotor control system is compromised in persons with medial KOA. Our findings suggest varus–valgus control deficits in both the afferent input (proprioceptive acuity) and muscular effectors (muscle strength and capacity to stabilize the joint).     

Wolff’s law in action: a mechanism for early knee osteoarthritis

There is growing interest in the role of bone in knee osteoarthritis. Bone is a dynamic organ, tightly regulated by a multitude of homeostatic controls, including genetic and environmental factors. One such key environmental regulator of periarticular bone is mechanical stimulation, which, according to Wolff’s law, is a key determinant of bone properties. Wolff’s law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads. Despite being an adaptive response of bone, the remodeling process may inadvertently trigger maladaptive responses in other articular structures. Accumulating evidence at the knee suggests that expanding articular bone surface area is driven by mechanical stimulation and is a strong predictor of articular cartilage loss. Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health. This review hypothesizes that adaptations of periarticular bone in response to mechanical stimulation cause maladaptive responses in other articular structures that mediate the development of knee osteoarthritis. A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.     

Chronic oral or intraarticular administration of docosahexaenoic acid reduces nociception and knee edema and improves functional outcomes in a mouse model of Complete Freund’s Adjuvant–induced knee arthritis

Introduction

Clinical and preclinical studies have shown that supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ω-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ω-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis.

Methods

Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 μg/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection.

Results

The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA.

Conclusions

To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and anti-inflammatory effects as individual ω-3 PUFAs following sustained systemic and intraarticular administration in a mouse model of CFA-induced knee arthritis. The results suggest that DHA treatment may offer a new therapeutic approach to alleviate inflammation as well as a beneficial effect on pain-related functional disabilities in RA patients.     

Test–retest reliability of quadriceps muscle function outcomes in patients with knee osteoarthritis

Quadriceps muscle weakness and the underlying neuromuscular deficits have been increasingly studied over the last few years in patients with knee osteoarthritis, but the applied methodologies have never been validated for this specific population. The aim of this study was to investigate test–retest reliability of several quadriceps muscle function outcomes in patients with knee osteoarthritis both before and after knee arthroplasty surgery. Ten preoperative and 20 postoperative patients participated in two identical testing sessions. A series of voluntary and/or electrically stimulated contractions of the involved quadriceps with concomitant torque and electromyographic recordings were used to characterize muscle strength, muscle activation and muscle contraction properties. Vastus lateralis morphology (thickness and fascicle pennation angle) was also assessed using ultrasonography. Overall, good reliability scores were observed for the majority of the 13 assessed variables (nine variables with intraclass correlation coefficients >0.75, 12 variables with coefficients of variation <15%). The most reliable testing protocol for patients with knee osteoarthritis would entail the assessment of (1) isometric maximal voluntary torque for evaluating muscle strength, with (2) simultaneous vastus lateralis electromyographic activity for evaluating muscle activation, (3) potentiated (resting) doublet peak torque for evaluating muscle contractility, and (4) vastus lateralis thickness for evaluating muscle size.     

Gene–gene interactions of the Wnt/β-catenin signaling pathway in knee osteoarthritis

Molecular Biology Reports - This study was designed to investigate whether genetic polymorphisms of the Wnt/β-catenin signaling pathway and its interactions are involved in the development of...     

Taping the patella medially: a new treatment for osteoarthritis of the knee joint?

OBJECTIVE--To test the hypothesis that medial taping of the patella reduces the symptoms of osteoarthritis of the knee when the patellofemoral joint is affected. DESIGN--Randomised, single blind, crossover trial of three different forms of taping of the knee joint. Each tape (medial, lateral, or neutral) was applied for four days, with three days of no treatment between tape positions. SUBJECTS--14 patients with established, symptomatic osteoarthritis of the knee and both clinical and radiographic evidence of patellofemoral compartment disease. MAIN OUTCOME MEASURES--Daily visual analogue scale ratings for pain; patients'' rating of change with each treatment; and tape preference. RESULTS--Medial taping of the patella was significantly better than the neutral or lateral taping for pain scores, symptom change, and patient preference. The medial tape resulted in a 25% reduction in knee pain. CONCLUSION--Patella taping is a simple, safe, cheap way of providing short term pain relief in patients with osteoarthritis of the patellofemoral joint.     

Automated hexahedral meshing of knee cartilage structures – application to data from the osteoarthritis initiative

We propose a fully automated methodology for hexahedral meshing of patient-specific structures of the human knee obtained from magnetic resonance images, i.e. femoral/tibial cartilages and menisci. We select eight patients from the Osteoarthritis Initiative and validate our methodology using MATLAB on a laptop computer. We obtain the patient-specific meshes in an average of three minutes, while faithfully representing the geometries with well-shaped elements. We hope to provide a fundamentally different means to test hypotheses on the mechanisms of disease progression by integrating our patient-specific FE meshes with data from individual patients. Download both our meshes and software at http://im.engr.uconn.edu/downloads.php.     

Does medio-lateral motion occur in the normal knee? An in-vitro study in passive motion

Medio-lateral translation during knee flexion continues to raise controversy. Small population sizes, small joint flexion ranges, less-reliable measurement techniques and disparate experimental conditions led to inconsistent reports in the past. To study this subject with more accurate and reliable measurements, we carried out femur and tibia tracking in 22 intact cadaver knees during passive joint motion using a state-of-the-art surgical navigation system. Trackers with active light-emitting diodes were fixed onto the femur and tibia, and an instrumented pointer was used to digitize a number of anatomical landmarks. International recommendations were adopted for anatomical-based reference frame definitions and joint kinematic analysis. For the first time, knee joint translations were reported in both the femoral and tibial reference frames, and over a flexion/extension arc as large as 140°. During flexion, in the femoral reference frame, the center of the tibial plateau moved 4.8 ± 2.8mm medially when averaged over the specimens. In the tibial frame, the knee center moved 13.3 ± 5.7 mm laterally. The relative femoral-to-tibial medio-lateral translation was, on average over the specimens, nearly 20% of the width of the tibial plateau, and can be as large as 35%. Medio-lateral translation occurs in the natural normal knee joint.     

What is the clinical and ethical importance of incidental abnormalities found by knee MRI?

Introduction

Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown.

Methods

We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities.

Results

These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study.

Conclusion

As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice.     

Does acute whole-body vibration training improve the physical performance of people with knee osteoarthritis?

ABSTRACT: Salmon, JR, Roper, JA, and Tillman, MD. Does acute whole-body vibration training improve the physical performance of people with knee osteoarthritis? J Strength Cond Res 26(11): 2983-2989, 2012-The purpose of this study was to determine the effects of a single session of whole-body vibration training (WBVT) on the physical performance of individuals with knee osteoarthritis (OA) in 3 tests designed to simulate activities of daily living (ADLs). Fifteen individuals with symptomatic knee OA completed the Timed-Up-and-Go Test, step test, 20-m walk test, and visual analog scale (VAS) recordings of knee pain intensity. A main effect was detected for time to complete the step test (F[2,28] = 6.243, p = 0.006, (Equation is included in full-text article.)). Post hoc analyses revealed that the time to complete the step test at 5 minutes after WBVT improved significantly (p = 0.042) from that of the pretest. A moderate correlation (r = 0.465, p = 0.001) was found between the VAS scores and the time to complete the step test across all trials. A main effect was found for time to complete the walk test (F[2,28] = 4.370, p = 0.022, (Equation is included in full-text article.)). Post hoc analyses did not indicate significant improvements from pretest seen at 5 minutes after WBVT (p = 0.110) and 1 hour after WBVT (p = 0.224). The WBVT was well tolerated in nearly all the participants, and we observed that an acute bout of WBVT was effective in improving the ability of individuals with knee OA to perform a step test and 20-m walk test. Our findings suggest that WBVT may be an effective nonpharmacologic modality to treat some knee OA symptoms and improve ADLs.     

Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized,triple-blind,placebo-controlled phase 1/2 clinical trial

Background

In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.

Are hamstrings activated to counteract shear forces during isometric knee extension efforts in healthy subjects?

The hamstring muscles have the potential to counteract anterior shear forces at the knee joint by co-contracting during knee extension efforts. Such a muscle recruitment pattern might protect the anterior cruciate ligament (ACL) by reducing its strain. In this study we investigated to what extent co-activation of the knee flexors during extension efforts is compatible with the hypothesis that this co-activation serves to counteract anterior tibial shear forces during isometric knee extension efforts in healthy subjects. To this aim, it is investigated whether co-activation varies with the required knee extension moment, with the knee joint angle, and with the position of the external flexing force relative to the knee joint. With unaltered moment and muscle activation, distal positioning of the flexing force on the tibia causes higher resultant (muscular plus external) forward shear forces at the knee as compared to proximal positioning. In ten subjects, knee flexor and extensor EMG was measured during a quasi-isometric positioning task for a range (5-50 degrees) of knee flexion angles. It was found that the co-activation of the knee flexors increased with the extension moment, but this increase was less than proportional (p<0.001). The extension moment increased 2.7 to 3.4 times, whereas the activation of Biceps Femoris and Semitendinosus increased only a factor 1.3 to 2.0 (joint angle dependent). Furthermore, a strong increase in co-activation was seen near full extension of the knee joint. The position of the external extension load on the tibia did not affect the level of co-contraction. It is argued that these results do not suggest a recruitment pattern that is directed at reduction of anterior shear forces in the knee joint during sub-maximal isometric knee extension efforts in healthy subjects.     

AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.