Cartilage Volume Research Articles

Histological Grade and Magnetic Resonance Imaging Quantitative T1rho/T2 Mapping in Osteoarthritis of the Knee: A Study in 20 Patients.

BackgroundMagnetic resonance imaging (MRI) of osteoarthritis (OA) of the knee is a preoperative method of joint assessment. Histology of the joint is invasive and performed after surgery. T1rho/T2 MRI mapping is a new preoperative method of quantifying joint changes. This study aimed to analyze and compare the histological changes in the joint cartilage with the use of quantitative T1rho/T2 MRI mapping in patients with OA of the knee.Material/MethodsTwenty patients with OA of the knee (20 knees) underwent preoperative MRI with T1rho mapping, T2 mapping, T1-weighted, and T2-weighted fat-suppressed MRI sequences. The degree of OA of the knee on MRI was graded according to the Osteoarthritis Research Society International (OARSI) criteria and the Kellgren-Lawrence grading system. Histological grading of OA used the OARSI criteria. Four tibiofemoral condyles were assessed histologically, and the degree of cartilage destruction was determined using the OARSI criteria. Two investigators performed cartilage segmentation for T1rho/T2 values.ResultsHistology of the four knee joint condyles confirmed mild to severe OA. The histology of the cartilage thickness (P<0.001) and the MRI findings of the distal medial condyle (P<0.00) were significantly different from the other three knee joint condyles. The T2 and T1rho values of each condyle were significantly correlated with the histological grade (II–IV) of the joint condyles, including the cartilage volume, cartilage defects, thickness, and bone lesions (P<0.05).ConclusionsIn 20 patients with OA of the knee, preoperative T2/T1rho MRI identified Grade II–IV OA changes in the joint.

Association of age, sex and BMI with the rate of change in tibial cartilage volume: a 10.7-year longitudinal cohort study

BackgroundTo describe the association of age, sex and body mass index with the rate of change of tibial knee cartilage volume over 10.7 years in a community-based sample of older adults.MethodsFour hundred and eighty-one participants (49% female, mean age 60.8 years [range 51.1–79.7], 49% had knee pain and 58% radiographic osteoarthritis) were included. Tibial cartilage volume of the right knee was assessed on T1-weighted fat-suppressed 1.5 T MRI at baseline and 10.7 years. Data analyses were performed using linear regression models.ResultsThe average rate of loss of cartilage volume was 1.2%/year (range 0.2–3.9%) with all participants losing cartilage volume over the study period. There was a significant association between age and loss of tibial cartilage volume in the medial (0.023%/year, 95% confidence interval [CI] 0.010 to 0.036%, p < 0.001), lateral (0.013%/year, 95% CI 0.003 to 0.023%, p = 0.012) and total tibia (0.018%/year, 95% CI 0.009 to 0.026%, p < 0.001). Higher body mass index at baseline and increases in body mass index over time were associated with a greater tibial cartilage loss at the medial (body mass index at baseline 0.040%/year, 95% CI 0.022 to 0.058%, p < 0.001; increases in body mass index 0.055%/year, 95% CI 0.018 to 0.093%, p = 0.004) but not lateral compartment. No evidence of non-linear relationships was observed. Compared to males, females lost more lateral tibial cartilage with increasing age (0.023%/year, 95% CI 0.003 to 0.043%, p = 0.024 for interaction).ConclusionsTibial cartilage volume declines at a faster rate with increasing age and body mass index in both males and females, particularly in the medial compartment. In contrast to the low rate of change in radiographs, our findings suggest that cartilage loss at the tibia is universal in this age group.

Classification of the concha-type microtia and their new suitable treatment strategies without autogenous costal cartilage grafting

ObjectiveNumerous corrective methods have been successfully applied in concha-type microtia reconstruction over the past several decades, and autogenous rib cartilage grafting has become a routine technique in a two or three-stage operation. However, it still remains a challenge due to the effective use of the large volume of the remnant cartilage and skin involved. The objective of this study was to clarify how this remnant cartilage and skin could be manipulated for new suitable treatment strategies without autogenous costal cartilage grafting. MethodsA total of 424 patients with concha-type microtia operated at our Center from January of 2012 to June of 2019 have been reviewed and analyzed cases. At the same time, a classification system for grading the severity of concha-type microtia was created on the basis of anatomical findings and ear size. ResultsA total of 436 ear cases (involving 424 patients), showing concha-type microtia, were included in our study and reviewed through medical records, photographs, analysis of surgical methods, and postoperative outcomes. The concha-type microtia were classified into four graded types: Grade I (n = 151), Grade II (n = 101), Grade III (n = 93), and Grade IV (n = 79). A total of 352 ears in 345 patients with Grade I to III concha-type microtia were followed up for 1 month to 7 years (average, 14.7 months). 329 patients (95.4%) were satisfied with the aesthetic outcomes of the corrected ear. ConclusionsIndividual corrective methods and aesthetic outcomes for patients with Grade I to III of deformity were described in this study. The authors present new suitable approaches according to a progressive classification system which provide conservative and individualized methods of treatment in early stages of life.

Does footwear affect articular cartilage volume change after a prolonged run?

The aim of this study was to investigate knee intra-articular cartilage volume changes after a prolonged running bout in three footwear conditions. Twelve participants performed 75-minute running bouts in the three footwear conditions. Before and after each running bout, magnetic resonance imaging (MRI) scans were obtained using a high-resolution 3.0 Tesla MRI. Three-dimensional reconstruction of the cartilage plates of the patella, the femur, and the tibia was created to quantify cartilage volume change due to the 75-minute running bout. Three-dimensional biomechanical data were also collected using an integrated motion capture and force treadmill system. There were no statistically significant differences among shoe conditions for all anatomical regions. However, significant cartilage volume reductions at all anatomical sites were observed after the 75-minute running bout in each footwear condition. These data suggest that the intra-articular knee cartilage undergoes a significant reduction in cartilage volume during a prolonged run that may indicate an increase in joint loading. There was a considerable variation in cartilage volume between participants across footwear conditions indicating an individual cartilage volume response to footwear. An individualistic approach to footwear recommendations may help in minimizing this change in cartilage.

Association of glucose homeostasis and metabolic syndrome with knee cartilage defects and cartilage volume in young adults

ObjectiveTo describe the associations of glucose homeostasis and metabolic syndrome (MetS) measures with knee cartilage defects and cartilage volume in young adults. MethodsFasting blood biochemistry, waist circumference and blood pressure measures were collected 4–5 years prior to knee magnetic resonance imaging (MRI) scans. Blood measures included levels of glucose, insulin, triglyceride and high-density lipoprotein cholesterol (HDL-C). Homeostatic model assessment 2-insulin resistance (HOMA2-IR), HOMA2-beta cell function (HOMA2-β), HOMA2-insulin sensitivity (HOMA-S) and MetS were calculated or defined. Knee cartilage defects and cartilage volume were measured from MRI scans. Data were analysed using log binomial or linear regressions. ResultsAmong 328 participants (47.3% were females, aged 26–36 years at baseline), 40 (12.7%) had hyperglycaemia and 21 (6.7%) had MetS. Glucose homeostasis measures (except fasting glucose) were associated with tibiofemoral cartilage defects (fasting insulin: relative risk (RR) 1.05, 95% confidence interval (CI) 1.01 to 1.08; HOMA2-IR: 1.44, 1.08 to 1.92; HOMA2-β: 2.59, 1.33 to 5.07; HOMA2-S: 0.36, 0.18 to 0.72), but not patellar cartilage defects. There were no associations between glucose homeostasis measures and knee cartilage volume. High waist circumference (RR 2.32, 95% CI 1.18 to 4.54) and low HDL-C (RR 1.99, 95% CI 1.08 to 3.69) were associated with tibiofemoral cartilage defects, but no other associations were observed between MetS or its components and cartilage defects or volume. ConclusionInsulin resistance, high waist circumference and low HDL-C were associated with higher risk of tibiofemoral cartilage defects, suggesting glucose homeostasis and some MetS components may affect early cartilage damage in young adults.

The Effect of Prenatal Exposure to 2.4 GHz Radio Frequency on the Histology and Expression of the osteocalcin and RUNX2 Gene of the Forelimb in an NMRI Mouse.

Introduction: Today the use of electromagnetic waves has dramatically increased in modern industrial societies. This study aimed to investigate the effect of prenatal exposure to 2.4 GHz wireless frequency on forelimb development in an NMRI mouse in vivo. Methods: A total of 21 female mice weighing 25-30 g were included in the present study. They were randomly assigned to 3 groups, namely control (n=7), sham (n=7), and experimental (n=7). After mating, the experimental group was exposed to 2.4 GHz radio frequency at a distance of 20-30 cm from the device, 4 h/d until the delivery. The sham group was placed at a distance of 20-30 cm from the device every day without exposure to electromagnetic waves, and the control group had a pregnancy period without any stress and electromagnetic wave exposure. After giving birth, the forelimbs were isolated from the infants and examined by stereological studies and RT-PCR for the evaluation of osteocalcin and RUNX2 gene expression. Results: Although, at first glance, there was no macroscopic teratogen effect in forelimbs in all groups, via a stereological method, we showed that bone and cartilage volume decreased in the experimental group compared to the other groups. We also found that the experimental group had lower expression of the osteocalcin and RUNX2 gene than the control and sham groups did. However, there were no significant differences between the control and sham groups in terms of bone and cartilage volume and gene expression. Conclusion: Although teratogen effect of prenatal exposure to 2.4 GHz radio frequency on forelimbs was not demonstrated macroscopically, further studies showed negative effects on the forelimb bone, cartilage volume, and gene expression.

Reduced Size Profile of Amniotic Membrane Particles Decreases Osteoarthritis Therapeutic Efficacy.

Osteoarthritis (OA) is a widespread disease that continues to lack approved and efficacious treatments that modify disease progression. Micronized dehydrated human amnion/chorion membrane (μ-dHACM) has been shown to be effective in reducing OA progression, but many of the engineering design parameters have not been explored. The objectives of this study were to characterize the particle size distributions of two μ-dHACM formulations and to investigate the influence of these distributions on the in vivo therapeutic efficacy of μ-dHACM. Male Lewis rats underwent medial meniscus transection (MMT) or sham surgery, and intra-articular injections of saline, μ-dHACM, or reduced particle size μ-dHACM (RPS μ-dHACM) were administered at 24 hours postsurgery (n = 9 per treatment group). After 3 weeks, the animals were euthanized, and left legs harvested for equilibrium partitioning of an ionic contrast agent microcomputed tomography and histological analysis. μ-dHACM and RPS μ-dHACM particles were fluorescently tagged and particle clearance was tracked in vivo for up to 42 days postsurgery. Protein elution from both formulations was quantified in vitro. Treatment with μ-HACM, but not RPS μ-dHACM, reduced lesion volume in the MMT model 3 weeks postsurgery. In contrast, RPS μ-dHACM increased cartilage surface roughness and osteophyte cartilage thickness and volume compared to saline treatment. There was no difference of in vivo fluorescently tagged particle clearance between the two μ-dHACM sizes. RPS μ-dHACM showed significantly greater protein elution in vitro over 21 days. Overall, delivery of RPS μ-dHACM did result in an increase of in vivo joint degeneration and in vitro protein elution compared to μ-dHACM, but did not result in differences in joint clearance in vivo. These results suggest that particle size and factor elution may be tailorable factors that are important to optimize for particulate amniotic membrane treatment to be an effective therapy for OA. Impact Statement Osteoarthritis (OA) is a widespread disease that continues to lack treatments that modify the progression of the disease. Micronized dehydrated human amnion/chorion membrane (μ-dHACM) has been shown to be effective in reducing OA progression, but many of the engineering design parameters have not been explored. This work investigates the effects of particle size profile of the μ-dHACM particles and lays out the methods used in these studies. The results of this work will guide engineers in designing μ-dHACM treatments specifically and disease-modifying OA therapeutics generally, and it demonstrates the utility of novel therapeutic evaluation methods such as contrast-enhanced microcomputed tomography.

The effect of alignment on knee osteoarthritis initiation and progression differs based on anterior cruciate ligament status: data from the Osteoarthritis Initiative.

Knee alignment and anterior cruciate ligament (ACL) injury are risk factors for knee osteoarthritis (OA). The objective was to examine interactions between knee alignment and ACL status on cartilage volume loss in participants with or at risk of knee OA. Participants were from the Osteoarthritis Initiative, a longitudinal cohort study. Data were from baseline and 24- and 72-month follow-up visits. Participants with knee OA (progression subcohort) or at risk of knee OA (incidence subcohort) that had partial or full ACL tears (OA-ACL group; n=66) or an intact ACL (OA-only group, n=367) were selected. Femur-tibia angles from radiographs quantified knee alignment. Changes in tibial and femoral cartilage volumes were measured using magnetic resonance imaging. Hierarchical linear models examined if knee alignment, presence of ACL, and their interaction were related to cartilage volume loss after accounting for other variables. Interactions between alignment and ACL status were significantly related to cartilage volume loss in the lateral plateau (β=-20.19, 95% confidence interval [CI]=-34.65 to -5.73) and lateral condyle (β=-23.64, 95%CI=-43.06 to -4.23). Valgus alignment was related to lateral compartment cartilage loss in the OA-ACL group, but not in the OA-only group. Varus alignment was related to cartilage loss in the medial plateau (β=7.49, 95%CI=0.17 to 14.80) and medial condyle (β=19.70, 95%CI=5.96 to 33.44) in both groups. The impact of knee alignment on knee OA initiation and progression varies based on ACL status. Initial lateral compartment damage or changes in joint kinematics after ACL rupture might account for these findings.Key Points• The relationship between knee alignment and lateral compartment cartilage loss depended on the status of the anterior cruciate ligament in participants with knee osteoarthritis or at risk for knee osteoarthritis.• Valgus alignment was related to lateral compartment cartilage loss in participants with a deficient anterior cruciate ligament.• Varus alignment was related to medial compartment cartilage loss regardless of the status of the anterior cruciate ligament.

Short Nose Correction: Septal Cartilage Combined With Ethmoid Bone Graft.

Multiple methods are employed to correct short nose deformities, with septal extension graft representing the first choice for Asians. However, the volume of the septal cartilage in many Asian patients is not sufficient to be used alone for such operation. The present work developed a new method combining the septal cartilage with ethmoid bone graft to overcome this issue in Asian patients with short noses. Thirty-five women with short noses underwent septal extension graft from February 2015 to March 2017. The endoscopic technique was utilized to harvest the ethmoid bone to enhance the L-strut structure. An L-strut, comprising 0.8 cm segments of the caudal and dorsal cartilaginous septa, is left altered in order to harvest more cartilage for septal extension. The harvested the septal cartilage, approximately 1.0 mm thick and 16 to 20 mm long, underwent grafting on one side of the caudal septum. This was followed by alar cartilage fixation at the septal cartilage graft end. Finally, nose length, nasal tip projection and nasolabial angle were assessed before and after the surgery. Septal cartilage combined with ethmoid bone graft yielded an adequate nose lengthening and reduced nostril show, also in individuals showing extremely little septal cartilage. This new method is effective for short nose deformity correction in Asian patients. Combining the septal cartilage with ethmoid bone graft yields ideal outcome without overt complications, achieving commendable patient satisfaction.

Higher Serum Levels of Resistin Are Associated With Knee Synovitis and Structural Abnormalities in Patients With Symptomatic Knee Osteoarthritis

ObjectiveResistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. DesignA prospective cohort study. Setting and participantsPatients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated. MeasuresAll measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. ResultsSerum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Conclusion and implicationsHigher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways.

Effects of treadmill running and limb immobilization on knee cartilage degeneration and locomotor joint kinematics in rats following knee meniscal transection

This study examined the effects of reduced and elevated weight bearing on post-traumatic osteoarthritis (PTOA) development, locomotor joint kinematics, and degree of voluntary activity in rats following medial meniscal transection (MMT). Twenty-one adult rats were subjected to MMT surgery of the left hindlimb and then assigned to one of three groups: (1) regular (i.e., no intervention), (2) hindlimb immobilization, or (3) treadmill running. Sham surgery was performed in four additional rats. Voluntary wheel run time/distance was measured, and 3D hindlimb kinematics were quantified during treadmill locomotion using biplanar radiography. Rats were euthanized 8weeks after MMT or sham surgery, and the microstructure of the tibial cartilage and subchondral bone was quantified using contrast enhanced micro-CT. All three MMT groups showed signs of PTOA (full-thickness lesions and/or increased cartilage volume) compared to the sham group, however the regular and treadmill-running groups had greater osteophyte formation than the immobilization group. For the immobilization group, increased volume was only observed in the anterior region of the cartilage. The treadmill-running group demonstrated a greater knee varus angle at mid-stance than the sham group, while the immobilization group demonstrated greater reduction in voluntary running than all the other groups at 2 weeks post-surgery. Elevated weight-bearing via treadmill running at a slow/moderate speed did not accelerate PTOA in MMT rats when compared to regular weight-bearing. Reduced weight-bearing via immobilization may attenuate overall PTOA but still resulted in regional cartilage degeneration. Overall, there were minimal differences in hindlimb kinematics and voluntary running between MMT and sham rats.

Age-related histological changes in calcified cartilage and subchondral bone in femoral heads from healthy humans.

Age is the most important risk factor for osteoarthritis (OA). It is suggested that changes in subchondral bone and calcified cartilage may occur in early OA. Therefore, the aim was to investigate age-related changes in the femoral head composition. We hypothesise that the thickness of the subchondral bone plate decreases with age, while the thickness of the calcified cartilage increases with age as seen in early-stage OA. Femoral heads from 29 women (20-74 years) and 32 men (23-78 years), who had died suddenly and unexpectedly, were obtained at autopsy. Individuals with bone or joint diseases or macroscopic abnormal cartilage were excluded. Using design-based stereology, femoral head volume as well as thickness and volume of the calcified cartilage and subchondral bone plate were estimated and correlated to sex and age. The thickness and volume of the subchondral bone plate were not correlated with age. Calcified cartilage thickness and volume correlated positively with age in women, while the femoral head volume was correlated positively with age in men. In human femoral heads obtained from a cross-sectional population without macroscopic OA changes, the thickness of the subchondral bone plate did not change with age, which differs from the thinning seen in early OA. Surprisingly, the age-related changes of the volume and thickness of the calcified cartilage and of the volume of the femoral head were different for women and men. This indicate that cartilage and bone metabolism is sex-specific, which may influence ageing of the hip joint.

Association between metabolic syndrome and knee structural change on MRI.

To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change. Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program-Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing. Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = -0.30%; central obesity, β = -0.26%; and low HDL, β = -0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment. MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change.

Visualization of Cartilage from Knee Joint Magnetic Resonance Images and Quantitative Assessment to Study the Effect of Age, Gender and Body Mass Index (BMI) in Progressive Osteoarthritis (OA).

Osteoarthritis (OA) is a degenerative disease of joint cartilage affecting the elderly people around the world. Visualization and quantification of cartilage is very much essential for the assessment of OA and rehabilitation of the affected people. Magnetic Resonance Imaging (MRI) is the most widely used imaging modality in the treatment of knee joint diseases. But there are many challenges in proper visualization and quantification of articular cartilage using MRI. Volume rendering and 3D visualization can provide an overview of anatomy and disease condition of knee joint. In this work, cartilage is segmented from knee joint MRI, visualized in 3D using Volume of Interest (VOI) approach. Visualization of cartilage helps in the assessment of cartilage degradation in diseased knee joints. Cartilage thickness and volume were quantified using image processing techniques in OA affected knee joints. Statistical analysis is carried out on processed data set consisting of 110 of knee joints which include male (56) and female (54) of normal (22) and different stages of OA (88). The differences in thickness and volume of cartilage were observed in cartilage in groups based on age, gender and BMI in normal and progressive OA knee joints. The results show that size and volume of cartilage are found to be significantly low in OA as compared to normal knee joints. The cartilage thickness and volume is significantly low for people with age 50 years and above and Body Mass Index (BMI) equal and greater than 25. Cartilage volume correlates with the progression of the disease and can be used for the evaluation of the response to therapies. The developed methods can be used as helping tool in the assessment of cartilage degradation in OA affected knee joint patients and treatment planning.

Tibiofemoral joint structural change from 2.5 to 4.5\u2009years following ACL reconstruction with and without combined meniscal pathology

BackgroundPeople who have had anterior cruciate ligament reconstruction (ACLR) are at a high risk of developing tibiofemoral joint (TFJ) osteoarthritis (OA), with concomitant meniscal injury elevating this risk. This study aimed to investigate OA-related morphological change over 2 years in the TFJ among individuals who have undergone ACLR with or without concomitant meniscal pathology and in healthy controls. A secondary aim was to examine associations of baseline TFJ cartilage defects and bone marrow lesions (BML) scores with tibial cartilage volume change in ACLR groups.MethodsFifty seven ACLR participants aged 18–40 years (32 isolated ACLR, 25 combined meniscal pathology) underwent knee magnetic resonance imaging (MRI) 2.5 and 4.5 years post-surgery. Nine healthy controls underwent knee MRI at the ~ 2-year intervals. Tibial cartilage volume, TFJ cartilage defects and BMLs were assessed from MRI.ResultsFor both ACLR groups, medial and lateral tibial cartilage volume increased over 2 years (P < 0.05). Isolated ACLR group had greater annual percentage increase in lateral tibial cartilage volume compared with controls and with the combined group (P = 0.03). Cartilage defects remained unchanged across groups. Both ACLR groups showed more lateral tibia BML regression compared with controls (P = 0.04). Baseline cartilage defects score was positively associated with cartilage volume increase at lateral tibia (P = 0.002) while baseline BMLs score was inversely related to medial tibia cartilage volume increase (P = 0.001) in the pooled ACLR group.ConclusionsTibial cartilage hypertrophy was apparent in ACLR knees from 2.5 to 4.5 years post-surgery and was partly dependent upon meniscal status together with the nature and location of the underlying pathology at baseline. Magnitude and direction of change in joint pathologies (i.e., cartilage defects, BMLs) were less predictable and either remained stable or improved over follow-up.

Activation of The Phosphatidylcholine to Lysophosphatidylcholine Pathway Is Associated with Osteoarthritis Knee Cartilage Volume Loss Over Time

To identify serum biomarker(s) for predicting knee cartilage volume loss over time, we studied 139 knee osteoarthritis (OA) patients from a previous 24-month clinical trial cohort. Targeted metabolomic profiling was performed on serum collected at baseline. The pairwise metabolite ratios as proxies for enzymatic reaction were calculated and used in the analysis. Cartilage volume loss between baseline and 24 months was assessed quantitatively by magnetic resonance imaging (MRI). Data revealed an association between the serum ratio of lysophosphatidylcholine 18:2 (lysoPC 18:2) to phosphatidylcholine 44:3 (PC44:3) and the cartilage volume loss in the lateral compartment (β = −0.21 ± 0.04, p = 8.53*10−7) and with joint degradation markers, COMP (r = 0.32, p = 0.0002) and MMP1 (r = 0.26, p = 0.002). The significance remained after adjustment for age, sex, BMI, diabetes, hypertension, dyslipidemia, and the treatment taken in the original study. As the ratio indicated the over activation of the conversion pathway of PC to lysoPC catalyzed by phospholipase A2 (PLA2), we assessed and found that a specific PLA2, PLA2G5, was significantly increased in human OA cartilage and synovial membrane (85% and 19% respectively, both p < 0.04) compared to controls, and its overexpression correlated with IL-6 (r = 0.63, p = 0.0008). Our data suggest that the serum lysoPC 18:2 to PC44:3 ratio is highly associated with a greater risk of cartilage volume loss of the knee and warrants further investigation in an independent cohort.

The habitual motion path: evidence from an MRI study on cartilage volume changes after 75 minutes of running in different footwear conditions

The habitual motion path: evidence from an MRI study on cartilage volume changes after 75 minutes of running in different footwear conditions

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

Background/aimEvaluating the relationship of patellar chondromalacia with obesity, infrapatellar fat pad (IFP) volume and popliteal artery intima-media thickness (IMT).Materials and methodsA total of 203 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.ResultsPopliteal 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).ConclusionThis study demonstrates the relationship among obesity, IMT and chondromalacia and highlights this potential circle to develop effective treatments and inhibit the progression of chondromalacia.

Hyaluronan derivative HYMOVIS\xae increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

BackgroundThe objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger placebo-controlled clinical trial studying the disease-modifying activity of this treatment.MethodsForty six patients with symptomatic knee Osteoarthritis (OA) were enrolled in this open-label, prospective, multicenter, pilot study. Patients received two treatment cycles of intra-articular injections (3 mL) of HYMOVIS® (8 mg/mL of hyaluronic acid hexadecylamide) at 6 months interval. Each treatment cycle involved two intra-articular injections 1 week apart. All patients had Magnetic Resonance Imaging (MRI) of the target knee at baseline and 1 year, and blood samples to assess joint biomarkers. The primary outcome was the change in type II collagen-specific biomarkers (Coll2–1, Coll2–1NO2 and CTX-II) after HYMOVIS® treatment versus baseline. Secondary endpoints included levels changes in aggrecan chondroitin sulfate 846 epitope (CS-846), Cartilage Oligomeric Matrix Protein (COMP), procollagen type II N-terminal propeptide (PIIANP), Matrix Metalloprotease (MMP)-3, Myeloperoxidase (MPO) and Interleukin (IL)-6 serum biomarkers, the ratio Coll2–1/PIIANP, CTX-II/PIIANP, variation of MRI cartilage volume, and Knee injury and Osteoarthritis Outcome Score (KOOS) index.ResultsColl2–1 serum levels significantly increased overtime while Coll2–1NO2 levels were only increased at D360. Serum PIIANP levels also progressively and significantly enhanced with time. In contrast, other serum biomarker levels including CTX-II, CS-846, COMP, MMP-3, MPO or IL-6 did not change significantly overtime. Interestingly, the ratios Coll2–1/PIIANP and CTX-II/PIIANP decreased, indicating a decrease of cartilage catabolism. Compared to baseline value, MRI cartilage volume and thickness increased in lateral femoral and lateral trochlea compartments and not in medial compartment. These results, in addition to an improvement of T2 mapping score suggest a positive structural effect of the product. Interestingly, WORMS effusion score, an indicator of synovitis, significantly decreased. Finally, global KOOS score and subscales significantly increased overtime while pain at rest, walking pain and patients or investigators global assessment of disease activity decreased. The safety profile was favorable with a low incidence of injection-site pain.ConclusionHYMOVIS®, a well-tolerated intra-articular treatment, significantly enhanced type II collagen turnover as suggested by the increase in Coll2–1 and PIIANP levels and cartilage volume observed by MRI in lateral knee compartment. Importantly, this study provides critical information for the design of a larger phase III clinical trial investigating Disease Modifying effect of HYMOVIS®.Trial registrationhttp://www.isrctn.com/ISRCTN12227846 11/02/2015.

Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative\u2014a prospective cohort study

ObjectiveTo examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis.MethodsThis study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses.ResultsThe rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of − 0.86% per annum (95% CI − 1.58% to − 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07–1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes.ConclusionsThese data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.