Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4C(short) or C1,2C), type II cleavage only with Col2:3/4C(longmono) (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels.     

The effects of walking speed on obstacle crossing in healthy young and healthy older adults

The effects of walking speed and age on the peak external moments generated about the joints of the trailing limb during stance just prior to stepping over an obstacle and on the kinematics of the trailing limb when crossing the obstacle were investigated in 10 healthy young adults (YA) and 10 healthy older adults (OA). The peak hip and knee adduction moments in OA were 21-43% greater than those in YA (p相似文献   

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

Hip joint moments in symptomatic vs. asymptomatic people with mild radiographic hip osteoarthritis

Our primary objective was to examine external hip joint moments during walking in people with mild radiographic hip osteoarthritis (OA) with and without symptoms and disease-free controls. Three groups were compared (symptomatic with mild radiographic hip OA, n = 12; asymptomatic with mild radiographic hip OA, n = 13; OA-free controls, n = 20). Measures of the external moment (peak and impulse) in the sagittal, frontal and transverse plane during walking were determined. Variables were compared according to group allocation using mixed linear regression models that included individual gait trials, with group allocation as fixed effect and walking speed as a random effect. Participants with evidence of radiographic disease irrespective of symptoms walked 14–16% slower compared to disease-free controls (p = 0.002). Radiographic disease without symptoms was not associated with any altered measures of hip joint moment compared to asymptomatic OA-free controls once speed was taken into account (p ≥ 0.099). People with both mild radiographic disease and symptoms had lower external peak hip adduction moment (p = 0.005) and lower external peak internal rotation moment (p < 0.001) accounting for walking speed. Among angular impulses, only the presence of symptoms was associated with a reduced hip internal rotation impulse (p = 0.002) in the symptomatic group. Collectively, our observations suggest that symptoms have additional mechanical associations from radiographic disease alone, and provide insight into potential early markers of hip OA. Future research is required to understand the implications of modifying walking speed and/or the external hip adduction and internal rotation moment in people with mild hip OA.     

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

Does Isolated Unilateral Hip or Knee Osteoarthritis Lead to Adverse Changes in Extremity Composition?

BackgroundWhile muscle atrophy is a function of normal aging, loss of muscle in the setting of hip and knee osteoarthritis (OA) has been observed using radiographic studies. There is limited data available regarding changes in extremity composition using bioimpedance (BIA). The purpose of this study was to assess the changes in extremity composition in patients with isolated, unilateral hip or knee OA using BIA.MethodsPatients presenting to our institution’s adult reconstruction clinic from February 2020 to April 2021 were retrospectively reviewed to identify those with isolated, unilateral hip and knee OA. The InBody 770 Body Composition Analyzer (InBody USA, Cerritos, California) was used to perform a complete body composition assessment, per protocol. Lean extremity mass (LEM), fat mass (FM), intracellular water (ICW), extremity body water (EBW = ICW + extracellular water (ECW)) and phase angle (PA) were determined. Differences between the affected (OA) and unaffected (no OA) extremities were compared using t-tests.Results38 patients had isolated hip OA. The mean age was 60.8 (±11.7) years, mean BMI was 31.7 (±6.8) kg/m2, and 39.5% were female. LEM, FM, EBW, ICW, and PA were significantly decreased in the hip OA extremity (LEM: 20.0 vs. 20.4 kg, p=0.0008, FM: 8.8 vs. 8.9 kg, p=0.0049, EBW: 15.7 vs 16.0, p=0.0011, ICW: 9.5 vs. 9.7 L, p=0.0004, PA: 4.5 vs 4.9º, p<0.0001). There were 25 patients with isolated knee OA. Mean age was 62.8 (±11.3) years, mean BMI was 33.6 (±6.9) kg/m2, and 52.0% were female. FM and PA were significantly lower in the knee OA extremity (11.3 vs 11.4 kg, p=0.0291, 4.5 vs 4.9º, p<0.0001). There were no significant differences in LEM, EBW, and ICW between the knee OA extremity and the unaffected extremity.ConclusionPatients with isolated, unilateral hip OA had decreased LEM, FM, EBW, and ICW in the affected extremity. Both unilateral hip and knee OA was associated with decreased PA, suggestive of greater underlying dysfunction in muscle or cellular performance. Further study is needed to better define when these abnormalities develop, how they progress over time, and the impact of targeted interventions in reversing these changes. Level of Evidence: III     

Outcome of Arthroscopy in Patients with Advanced Osteoarthritis of the Hip

Hip arthroscopy has continued to expand its horizons in treating many conditions other than femoroacetabular impingement (FAI). However, the results of hip arthroscopy are known to be poor if the degree of articular cartilage damage is significant. We wanted to assess, whether the procedure might have a role in the management of young and active patients with advanced osteoarthritis (OA) and whether it should be offered as a treatment modality. 77 consecutive patients with Tönnis grade 2 and 3 osteoarthritis of the hip who had undergone hip arthroscopy were included in the study. Patients'' medical notes, plain radiographs and outcome scores (modified Harris hip score (mHHS), non-arthritic hip score (NAHS)) preoperatively and postoperatively at six weeks, six months, one year and annually thereafter, were analysed. 77 patients consisted of 63 men and 14 women with mean follow-up of 2.8 years (2.2 to 4.2) and mean age at surgery of 43 years (19 to 64). The mean preoperative mHHS and NAHS scores were 58 (28 to 87) and 64 (27 to 93) respectively. The mean improvements in both the mHHS and NAHS scores were significant (p = 0.003 and p = 0.0001 for mHHS at one and two years, p = 0.002 and p = 0.0003 for NAHS at one and two years, respectively). There were 34 patients (44%) who required a total hip replacement at mean of 18 months (6 to 48) after hip arthroscopy. We conclude that hip arthroscopy improves outcome scores in 56% of patients with severe OA of the hip (Tönnis grade 2 and 3) for at least two years after surgery. We thus consider the procedure to be a reasonable option for patients with hip OA, although success of the procedure will be less than if undertaken for certain other conditions.     

Lack of association of a variable number of aspartic acid residues in the asporin gene with osteoarthritis susceptibility: case-control studies in Spanish Caucasians

A recent genetic association study has identified a microsatellite in the coding sequence of the asporin gene as a susceptibility factor for osteoarthritis (OA). Alleles of this microsatellite determine the variable number of aspartic acid residues in the amino-terminal end of the asporin protein. Asporin binds directly to the growth factor transforming growth factor beta and inhibits its anabolic effects in cartilage, which include stimulation of collagen and aggrecan synthesis. The OA-associated allele, with 14 aspartic acid residues, inhibits the anabolic effects of transforming growth factor beta more strongly than other asporin alleles, leading to increased OA liability. We have explored whether the association found in several cohorts of Japanese hip OA and knee OA patients was also present in Spanish Caucasians. We studied patients that had undergone total joint replacement for primary OA in the hip (n = 303) or the knee (n = 188) and patients with hand OA (n = 233), and we compared their results with controls (n = 294) lacking overt OA clinical symptoms. No significant differences were observed in any of the multiple comparisons performed, which included global tests of allele frequency distributions and specific comparisons as well as stratification by affected joint and by sex. Our results, together with reports from the United Kingdom and Greece, indicate that the stretch of aspartic acid residues in asporin is not an important factor in OA susceptibility among European Caucasians. It remains possible that lifestyle, environmental or genetic differences allow for an important effect of asporin variants in other ethnic groups as has been reported in the Japanese, but this should be supported by additional studies.     

Bone and cartilage characteristics in postmenopausal women with mild knee radiographic osteoarthritis and those without radiographic osteoarthritis

Objectives:

To evaluate the association between radiographically-assessed knee osteoarthritis and femoral neck bone characteristics in women with mild knee radiographic osteoarthritis and those without radiographic osteoarthritis.

Methods:

Ninety postmenopausal women (mean age [SD], 58 [4] years; height, 163 [6] cm; weight, 71 [11] kg) participated in this cross-sectional study. The severity of radiographic knee osteoarthritis was defined using Kellgren-Lawrence grades 0=normal (n=12), 1=doubtful (n=25) or 2=minimal (n=53). Femoral neck bone mineral content (BMC), section modulus (Z), and cross-sectional area (CSA) were measured with DXA. The biochemical composition of ipsilateral knee cartilage was estimated using quantitative MRI measures, T2 mapping and dGEMRIC. The associations between radiographic knee osteoarthritis grades and bone and cartilage characteristics were analyzed using generalized linear models.

Results:

Age-, height-, and weight-adjusted femoral neck BMC (p for linearity=0.019), Z (p for linearity=0.033), and CSA (p for linearity=0.019) increased significantly with higher knee osteoarthritis grades. There was no linear relationship between osteoarthritis grades and knee cartilage indices.

Conclusions:

Increased DXA assessed hip bone strength is related to knee osteoarthritis severity. These results are hypothesis driven that there is an inverse relationship between osteoarthritis and osteoporosis. However, MRI assessed measures of cartilage do not discriminate mild radiographic osteoarthritis severity.     

Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

IntroductionWe performed a systematic review of prognostic factors for the progression of symptomatic knee osteoarthritis (OA), defined as increase in pain, decline in physical function or total joint replacement.MethodWe searched for available observational studies up to January 2015 in Medline and Embase according to a specified search strategy. Studies that fulfilled our initial inclusion criteria were assessed for methodological quality. Data were extracted and the results were pooled, or if necessary summarized according to a best evidence synthesis.ResultsOf 1,392 articles identified, 30 met the inclusion criteria and 38 determinants were investigated. Pooling was not possible due to large heterogeneity between studies. The best evidence synthesis showed strong evidence that age, ethnicity, body mass index, co-morbidity count, magnetic resonance imaging (MRI)-detected infrapatellar synovitis, joint effusion and baseline OA severity (both radiographic and clinical) are associated with clinical knee OA progression. There was moderate evidence showing that education level, vitality, pain-coping subscale resting, MRI-detected medial femorotibial cartilage loss and general bone marrow lesions are associated with clinical knee OA progression. However, evidence for the majority of determinants was limited (including knee range of motion or markers) or conflicting (including age, gender and joint line tenderness).ConclusionStrong evidence was found for multiple prognostic factors for progression of clinical knee OA. A large variety in definitions of clinical knee OA (progression) remains, which makes it impossible to summarize the evidence through meta-analyses. More research on prognostic factors for knee OA is needed using symptom progression as an outcome measure. Remarkably, only few studies have been performed using pain progression as an outcome measure. The pathophysiology of radiographic factors and their relation with symptoms should be further explored.     

Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis.

The synthesis and contents of extracellular non-collagenous matrix macromolecules was studied in early and late human osteoarthritic (OA) cartilage obtained at surgery for sarcomas in the lower extremities (normal and early OA) or for total knee replacement (late stage OA). The early OA samples were those that had some fibrillation in the joint by visual examination. One group had fibrillation in the area sampled and the other group had no fibrillation. Cartilage was taken from the same topographical area on the medial femoral condyle in all the samples, labeled with [3H]leucine and [35S]sulfate for 4 h at 37 degrees C and extracted with 4 M guanidine-HCl. Analysis of the extracts showed that the total amount of proteoglycans relative to hydroxyproline content was higher in the early and late OA than in the normal cartilage. These proteoglycans showed a relatively lower [35S]sulfate incorporation into GAG chains and a higher [3H]leucine incorporation. The pattern of newly synthesized proteins was altered similarly in early and late OA. Notably, synthesis of cartilage oligomeric matrix protein (COMP), fibronectin, and cartilage intermediate layer protein (CILP) was increased, also reflected in their abundance as determined by enzyme-linked immunosorbent assay (ELISA). Collagen synthesis appeared significantly increased only in the late stage OA. The observed altered composition and pattern of biosynthesis indicate that the joint undergoes metabolic alterations early in the disease process, even before there is overt fibrillation of the tissue. The early OA samples studied appear to represent two distinct groups of early lesions in different stages of the process of cartilage deterioration as shown by their differences in relative rates of synthesis and abundance of proteins.     

Gait and neuromuscular pattern changes are associated with differences in knee osteoarthritis severity levels

Knee osteoarthritis (OA) is a multifactoral, progressive disease process of the musculoskeletal system. Mechanical factors have been implicated in the progression of knee OA, but the role of altered joint mechanics and neuromuscular control strategies in progressive mechanisms of the disease have not been fully explored. Previous biomechanical studies of knee OA have characterized changes in joint kinematics and kinetics with the disease, but it has been difficult to determine if these biomechanical changes are involved in the development of disease, are in response to degenerative changes in the joint, or are compensatory mechanisms in response to these degenerative changes or other related factors as joint pain. The goal of this study was to explore the association between biomechanical changes and knee OA severity in an effort to understand the changing role of biomechanical factors in the progression of knee OA. A three-group cross-sectional model was used that included asymptomatic subjects, subjects clinically diagnosed with moderate knee OA and severe knee OA subjects just prior to total joint replacement surgery. Principal component analysis and discriminant analysis were used to determine the combinations of electromyography, kinematic and kinetic waveform pattern changes at the knee, hip and ankle joints during gait that optimally separated the three levels of severity. Different biomechanical mechanisms were important in discriminating between severity levels. Changes in knee and hip kinetic patterns and rectus femoris activation were important in separating the asymptomatic and moderate OA gait patterns. In contrast, changes in knee kinematics, hip and ankle kinetics and medial gastrocnemius activity were important in discriminating between the moderate and severe OA gait patterns.     

Cartilage oligomeric matrix protein and hyaluronic acid are sensitive serum biomarkers for early cartilage lesions in the knee joint

The purpose of this study was to evaluate the relationship between five previously established serum osteoarthritis biomarkers and the severity of cartilage lesions in the knee. Cartilage damage (classified according to the Outerbridge scoring system) and serum concentrations of cartilage oligomeric matrix protein (COMP), collagen type II C-telopeptide (CTX-II), matrix metalloproteinase-3 (MMP-3), collagen type III N-propeptide, (PIIINP), and hyaluronic acid (HA) were determined in 79 patients who underwent knee arthroscopy or total knee replacement. HA and COMP concentrations were significantly higher in the Outerbridge score 1 and 2 groups, respectively. These results suggest that serum COMP and HA concentrations can be used to predict early cartilage lesions in the knee.     

Animal models of osteoarthritis

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA - and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease - is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.     

Comparative diagnostic accuracy of knee adduction moments in knee osteoarthritis: a case for not normalizing to body size

Previous authors have questioned the practice of normalizing the external knee adduction moment during gait to body size when investigating dynamic joint loading in knee osteoarthritis (OA). The purpose of this study was to compare the abilities of non-normalized and normalized external knee adduction moments during gait in discriminating between patients with least and greatest severity of radiographic medial compartment knee OA. Subjects with mild (n=118) and severe (n=115) medial compartment knee OA underwent three-dimensional gait analysis. The peak external knee adduction moment was calculated and kept in its original units (Nm), normalized to body mass (Nm/kg) and normalized to body weight and height (%BW × Ht). Receiver Operating Characteristic (ROC) curve analysis indicated that non-normalized values better discriminated between patients with mild and severe knee OA. The area under the ROC curve for non-normalized peak knee adduction moments (0.63) was significantly (p<0.05) greater than when normalized to body mass (0.58), or to body weight times height (0.57). Post-hoc analysis of covariance indicated the mean difference in peak knee adduction moment between OA severity groups (7.23 Nm, p=0.003) was reduced by approximately 50% (3.60 Nm, p=0.09) when adjusted for mass. These findings are consistent with the suggestion that non-normalized values are more sensitive to radiographic disease progression. We suggest including knee adduction moment values that are not normalized to body size when investigating knee OA.     

Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis

The aim of this study was to investigate the relationship between the biochemical markers of arthritis and the radiographic grading of osteoarthritis (OA) in knees. Seventy-one women aged 49-85 years with knee OA were studied. Anterior-posterior knee radiographs and hand radiographs were taken in all patients. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria and the joint space width. The 71 patients with knee OA were divided into two groups: 37 patients exhibiting generalized osteoarthritis (GOA) and 34 non-GOA patients, according to the grading of their hand radiograph. C-reactive protein (CRP), urinary pyridinoline, YKL-40, plasma matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were measured as the biochemical markers of arthritis. The radiographic grading with the Kellgren-Lawrence scale revealed a significant relationship to the joint space width (P = 0.003): the joint space width decreased with increasing Kellgren-Lawrence grade. All biochemical markers had negative correlations with the joint space width, but only urinary pyridinoline had a significant correlation (P = 0.039). Pyridinoline (P = 0.034) and TIMP-1 (P = 0.017) also exhibited a significant relationship to the Kellgren-Lawrence grade. In GOA evaluations, the joint space width did not differ between GOA and non-GOA patients. CRP, pyridinoline, YKL-40 and MMP-3 levels were significantly greater in GOA patients than in non-GOA patients. CRP, pyridinoline, YKL-40, MMP-3 and TIMP-1 levels each related to at least one of the radiographic gradings. Furthermore, pyridinoline related to every type of radiographic grading examined in the present study.     

Biomarkers in osteoarthritis

Biomarkers aid the study of osteoarthritis (OA) in a number of different ways. In this article we summarise briefly their multiple uses and reflect on how the study reported in a previous edition of Arthritis Research & Therapy should promote further investigation of cartilage oligomeric matrix protein (COMP). COMP is foremost among hitherto investigated biomarkers and is most consistently shown to predict knee OA progression. Precisely what role it plays in OA pathogenesis remains unclear and elucidating this may be key to defining, and then targeting, the cellular pathways involved in OA.     

Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis

Introduction

The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA).

Methods

We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined.

Results

2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥25 kg/m²) individuals with the variant allele of single-nucleotide polymorphism (SNP) rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P <0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P <0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013).

Conclusion

TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.     

Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 +/- 3.0% for global cartilage and -5.5 +/- 4.3% for the medial compartment at 12 months, and -5.7 +/- 4.4% and -8.3 +/- 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.