A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: A cross sectional study comparing Osgood Schlatter disease with controls.

BACKGROUND: Osgood-Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. PURPOSE: This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. STUDY DESIGN: Cross-sectional study. METHODS: Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). RESULTS: Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the  tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2).  Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, -0.05, 95% CI: -0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, -0.09, 95% CI: -0.4 to 0.2, p = 0.04; distal mean difference, -0.6, 95% CI: -0.9 to -0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = -2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. CONCLUSION: Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. CLINICAL RELEVANCE: Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD.

Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis.

OBJECTIVE: To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence. DESIGN: Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined. RESULTS: Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.

3D patellar shape is associated with radiological and clinical signs of patellofemoral osteoarthritis.

OBJECTIVE: To examine the association between 3D patellar shape and 1) isolated magnetic resonance imaging (MRI)-based patellofemoral osteoarthritis (PFOA), 2) the morphological features of PFOA, and 3) the clinical symptoms of PFOA. DESIGN: MRI data from 66 women with isolated MRI-based PFOA and 66 age- and BMI-matched healthy women were selected from a cohort study. The patellae were manually segmented from MRI scans and used to create a 3D statistical shape model (SSM) of the patella. Structural abnormalities were semi-standardized scored on MRI using MRI osteoarthritis knee score (MOAKS). Regression analyses were applied to determine the associations between the shape parameters retrieved from the SSM, group status, clinical symptoms, and structural abnormalities. RESULTS: Four shape variants showed a statistically significant (<0.05) association with the group status. The mode responsible for most of the shape variations showed participants with PFOA possess a relatively thicker dorsal bump on the articular part of the patella, compared to patellae of control participants. Three of these variants showed an association with the presence of osteophytes and cartilage loss on the patella. Multiple associations were found between patellar shape and the clinical symptoms of PFOA. CONCLUSIONS: Patellar shape is associated with the prevalence of MRI-based PFOA in women. Some shape variants were also associated with clinical symptoms. Interestingly, one particular shape variant associated with the presence of MRI-based PFOA was earlier shown to be associated with structural abnormalities associated with OA in a population aged under 40. This may suggest that patellar shape may be an early detectable risk factor for PFOA.

Metabolic syndrome and the progression of knee osteoarthritis on MRI.

OBJECTIVE: Metabolic osteoarthritis (OA) is one of the proposed clinical phenotypes defined by the existence of metabolic syndrome (MetS). This study aimed to (1) investigate whether MetS and its components are associated with progression of knee OA magnetic resonance imaging (MRI) features, and (2) to evaluate the interaction of MetS with menopause and progression of MRI features. METHOD: 682 women from the Rotterdam Study who participated in a sub-study with knee MRI data available and 5-year follow-up were included. Tibiofemoral (TF) and patellofemoral (PF) OA features were assessed with the MRI Osteoarthritis Knee Score. MetS was quantified by the MetS severity Z-score. Generalized estimating equations were used to evaluate associations between MetS and menopausal transition and progression of MRI features. RESULTS: MetS severity at baseline was associated with progression of osteophytes in all compartments, bone marrow lesions (BMLs) in the PF compartment, and cartilage defects in the medial TF compartment. Waist circumference was associated with progression of osteophytes in all compartments and cartilage defects in the medial TF compartment. High-density lipoprotein (HDL)-cholesterol levels were associated with progression of osteophytes in the medial and lateral TF compartment and glucose levels with osteophytes in the PF and medial TF compartment. No interactions were found between MetS with menopausal transition and MRI features. CONCLUSION: Women with higher MetS severity at baseline showed progression of osteophytes, BMLs, and cartilage defects, indicating more structural knee OA progression after 5 years. Further studies are required to understand whether targeting MetS components may prevent the progression of structural knee OA in women.

The KNee OsteoArthritis Prediction (KNOAP2020) challenge: An image analysis challenge to predict incident symptomatic radiographic knee osteoarthritis from MRI and X-ray images.

OBJECTIVES: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. DESIGN: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). RESULTS: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. CONCLUSION: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.

Osteoarthritis year in review 2021: imaging.

PURPOSE: To provide a narrative review of original articles on imaging of osteoarthritis (OA) published between January 1, 2020 and March 31, 2021, with a special focus on imaging of inflammation, imaging of bone, cartilage and bone-cartilage interactions, imaging of peri-articular tissues, imaging scoring methods for OA, and artificial intelligence (AI) applied to OA imaging. METHODS: The Embase, Pubmed, Medline, Cochrane databases were searched for original research articles in the English language on human, in vivo, imaging of OA published between January 1, 2020 and March 31, 2021. Search terms related to osteoarthritis combined with all imaging modalities and artificial intelligence were applied. A selection of articles reporting on one of the focus topics was discussed further. RESULTS: The search resulted in 651 articles, of which 214 were deemed relevant to human OA imaging. Among the articles included, the knee joint (69%) and magnetic resonance imaging (MRI) (52%) were the predominant anatomical area and imaging modality studied. There were also a substantial number of papers (n = 46) reporting on AI applications in the field of OA imaging. CONCLUSION: Imaging continues to play an important role in the assessment of OA. Recent advances in OA imaging include quantitative, non-contrast, and hybrid imaging techniques for improved characterization of multiple tissue processes in OA. In addition, an increasing effort in AI techniques is undertaken to enhance OA imaging acquisition and analysis.

Are changes in meniscus volume and extrusion associated to knee osteoarthritis development? A structural equation model.

OBJECTIVE: To explore the interplay between (changes in) medial meniscus volume, meniscus extrusion and radiographic knee osteoarthritis (OA) development over 30 months follow-up (FU). METHODS: Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 middle-aged women with a body mass index ≥27 kg/m2, who were free of knee OA at baseline. Demographics were collected by questionnaires at baseline. All menisci at both baseline and FU were automatically segmented from MRI scans to obtain the meniscus volume and the change over time (delta volume). Baseline and FU meniscus body extrusion was quantitatively measured on mid-coronal proton density MR images. A structural equation model was created to assess the interplay between both medial meniscus volume and central extrusion at baseline, delta volume, delta extrusion, and incident radiographic knee OA at FU. RESULTS: The structural equation modeling yielded a fair to good fit of the data. The direct effects of both medial meniscus volume and extrusion at baseline on incident OA were statistically significant (Estimate = 0.124, p = 0.029, and Estimate = 0.194, p < 0.001, respectively). Additional indirect effects on incident radiographic OA through delta meniscus volume or delta meniscus extrusion were not statistically significant. CONCLUSION: Baseline medial meniscus volume and extrusion were associated to incidence of radiographic knee OA at FU in middle-aged overweight and obese women, while their changes were not involved in these effects. To prevent knee OA, interventions might need to target the onset of meniscal pathologies rather than their progression.

Development of a prediction model for future risk of radiographic hip osteoarthritis.

OBJECTIVE: To develop and validate a prognostic model for incident radiologic hip osteoarthritis (HOA) and determine the value of previously identified predictive factors. DESIGN: We first validated previously reported predictive factors for HOA by performing univariate and multivariate analyses for all predictors in three large prospective cohorts (total sample size of 4548 with 653 incident cases). The prognostic model was developed in 2327 individuals followed for 10 years from the Rotterdam Study-I (RS-I) cohort. External validation of the model was tested on discrimination in two other cohorts: RS-II (n = 1435) and the Cohort Hip and Cohort Knee (CHECK) study (n = 786). RESULTS: From the total number of 28 previously reported predictive factors, we were able to replicate 13 factors, while 15 factors were not significantly predictive in a meta-analysis of the three cohorts. The basic model including the demographic, questionnaire, and clinical examination variables (area under the receiver-operating characteristic curve (AUC) = 0.67) or genetic markers (AUC = 0.55) or urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) levels (AUC = 0.67) alone were poor predictors of HOA in all cohorts. Imaging factors showed the highest predictive value for the development of HOA (AUC = 0.74). Addition of imaging variables to the basic model led to substantial improvement in the discriminative ability of the model (AUC = 0.78) compared with uCTX-II (AUC = 0.74) or genetic markers (AUC = 0.68). Applying external validation, similar results were observed in the RS-II and the CHECK cohort. CONCLUSIONS: The developed prediction model included demographic, a limited number of questionnaire, and imaging risk factors seems promising for prediction of HOA.

Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women.

OBJECTIVE: To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA. DESIGN: 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n = 260; +0.1 ± 4.0 kg, +0.2 ± 4.4%), weight gain (n = 43; +8.6 ± 4.0 kg, +9.8 ± 4.1%) or weight loss (n = 44; -9.0 ± 7.2 kg, -9.8 ± 7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations. RESULTS: 687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2 kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39-5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92-2.84) and 53% (OR 1.53; 95%CI 0.92-2.56) in the weight gain vs the stable weight subgroup. CONCLUSIONS: In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.

Factors associated with meniscal body extrusion on knee MRI in overweight and obese women.

OBJECTIVE: To determine factors associated with higher degree of meniscal body extrusion in overweight and obese women at high risk of knee osteoarthritis (OA). DESIGN: We used baseline data of the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study, Netherlands, comprising overweight or obese women aged 50-60 years, free of clinical knee OA. All subjects completed a questionnaire on knee complaints and physical activity, underwent physical examination, radiography, and 1.5 T magnetic resonance imaging (MRI) of both knees. Using the mid-coronal MRI slice, one blinded observer measured tibial plateau width and meniscal body extrusion of both menisci in both knees. The association between baseline factors and meniscal extrusion, were analyzed with a random effects regression model. In addition, we used a fixed effect regression model for evaluation of knee-specific factors. RESULTS: Mean age of the included women (n = 395) was 55.7 years and mean body mass index (BMI) 32.4 kg/m2. Of all knees, 23% had an absolute medial meniscus body extrusion ≥3.0 mm and 4% had lateral meniscus body extrusion ≥3.0 mm. In the multivariable model, the medial meniscus extrusion was increased by 0.44 mm (95% confidence interval [CI] 0.11, 0.77) when a medial meniscus tear was present, by 0.20 mm per 5 kg/m2 (95% CI 0.05, 0.35) increase in BMI and by 0.25 in the presence of mild knee symptoms (95% CI 0.05 to 0.44). Kellgren-Lawrence (KL) grade ≥1 and tibia width were associated with increased both medial and lateral extrusion. CONCLUSION: In women, ipsilateral meniscus tear and high BMI are factors associated with medial meniscus body extrusion.

Incidence, prevalence, natural course and prognosis of patellofemoral osteoarthritis: the Cohort Hip and Cohort Knee study.

OBJECTIVE: To examine the proportion of isolated patellofemoral osteoarthritis (PFOA) compared to tibiofemoral osteoarthritis (TFOA) in middle-aged participants with early osteoarthritis (OA) symptoms of the knee; to describe the natural course of PFOA compared with that of TFOA and to identify whether patients with PFOA have a different phenotype compared to patients with TFOA, or with combined PFOA and TFOA (combined osteoarthritis (COA)). DESIGN: Participants with early OA symptoms of the knee were selected, completed questionnaires, underwent physical examination, and had knee radiographs at baseline, and at 2 and 5 years follow-up. Based on radiographs, participants were classified as having isolated TFOA, isolated PFOA, COA, or no radiographic OA. Multivariate logistic regression was used to identify participant characteristics associated with a specific group of OA at 2 years follow-up. RESULTS: The cohort comprised 845 participants (mean age 55.9 years). At baseline, 116 had PFOA, none had TFOA or COA. Of these 116 participants, 66.3% had developed COA at 5 years follow-up. At 2 years follow-up, PFOA, TFOA and COA were present in 77 (10.8%), 39 (5.5%) and 83 (11.6%) participants, respectively. Multivariate regression analyses at 2 years follow-up showed that participants with radiographic PFOA or TFOA were not significantly different from each other with respect to signs and symptoms. CONCLUSIONS: These results suggest that OA is more likely to start in the patellofemoral joint and then progress to COA in individuals with symptoms of early knee OA. No differences in TFOA and PFOA phenotypes were determined with respect to signs and symptoms.

Baseline meniscal extrusion associated with incident knee osteoarthritis after 30 months in overweight and obese women.

OBJECTIVE: To investigate the association between baseline meniscal extrusion and the incidence of knee osteoarthritis (KOA) after 30 months in a high-risk population of overweight and obese women, free of clinical and radiological KOA at baseline. METHODS: 407 middle-aged overweight women (body mass index - BMI ≥ 27 kg/m2) were evaluated at baseline and after 30 months of follow-up. Meniscal extrusion was defined as grade ≥2 on MRI according to MRI Osteoarthritis Knee Score (MOAKS). The primary outcome measure was KOA after 30 months follow-up, defined using the following criteria: either incidence of radiographic KOA (Kellgren & Lawrence grade 2 or higher), or clinical osteoarthritis (OA) according to the American College of Radiology (ACR) criteria, or medial or lateral joint space narrowing (JSN) of ≥1.0 mm. Using generalized estimating equations (GEE), we determined the association between knees with and without meniscal extrusion and both outcomes, corrected for the baseline differences. RESULTS: 640 knees were available at baseline of which 24% (153) had meniscal extrusion. There was a significantly higher incidence of KOA according to the primary outcome measure in women with meniscal extrusion compared to those without extrusion (28.8%, odds ratio - OR 2.39, 95% CI 1.53, 3.73). A significantly higher incidence was found for the development of radiographic KOA (12.4%, OR 2.61, 95% CI 1.11, 6.13) and medial JSN (11.8%, OR 3.19, 95% CI 1.59, 6.41). Meniscal extrusion was not significantly associated with clinical KOA and lateral JSN. CONCLUSION: Meniscal extrusion was associated with a significantly higher incidence of KOA, providing an interesting target for early detection of individuals at risk for developing KOA.

Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on T2-mapping: is it possible to comprehensively assess knee cartilage composition in one post-contrast MR examination at 3 Tesla?

OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T.

Differences in MRI features between two different osteoarthritis subpopulations: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate differences in MRI features between two etiologically distinct subtypes of knee osteoarthritis (OA): one group with metabolic syndrome and one lean group with frequent physical activity. METHODS: We included two groups of 50 subjects of the Osteoarthritis Initiative (OAI) incidence subcohort, with KL ≥ 2 in at least one knee at 48 months follow-up. Inclusion criteria for the metabolic syndrome group were a body mass index (BMI) ≥ 30 kg/m(2) and two out of three of the following criteria: hypertension (RR > 130/85 mm Hg or hypertension medication), insulin resistance (high blood sugar or diabetic medication) or dyslipidemia (lipid lowering medication). Inclusion criteria for the active lean group were a BMI < 25 kg/m(2) and a Physical Activity Scale for the Elderly (PASE) score ≥ 2. MRI scans were scored using MR Imaging Osteoarthritis Knee Score (MOAKS). Differences in MOAKS items between groups were tested using generalized linear models adjusted for sex and age. RESULTS: Scores for cartilage damage were significantly higher in the patella, trochlea and lateral femur in the metabolic syndrome group. Osteophyte scores were higher for all compartments in the metabolic syndrome group, though only significant for the patella, trochlea and medial tibia. Hoffa synovitis was significantly more prevalent in the active lean group while prepatellar bursa signal was more prevalent in the metabolic syndrome group. CONCLUSION: Metabolic OA and OA related to physical activity showed differences in MRI features, depending on knee compartment. These results show that different etiological processes in knee OA can lead to differences in structural degradation.

Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: correlation with ex-vivo reference standards.

OBJECTIVE: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. DESIGN: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-µCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-µCT X-ray attenuation, sGAG content and collagen content was assessed. RESULTS: CTa X-ray attenuation correlated well with EPIC-µCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). CONCLUSIONS: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research.

Reducing progression of knee OA features assessed by MRI in overweight and obese women: secondary outcomes of a preventive RCT.

OBJECTIVE: To evaluate the preventive effects of a randomized controlled trial on progression of Magnetic Resonance Imaging (MRI) features of knee osteoarthritis (OA) in overweight and obese women. DESIGN: In a 2 × 2 factorial design, 2.5 years effects of a diet and exercise program and of glucosamine sulphate (double-blind, placebo-controlled) were evaluated in 407 middle-aged women with body mass index (BMI) ≥ 27 kg/m(2) without clinical signs of knee OA at baseline (ISRCTN 42823086). MRIs were scored with the MRI Osteoarthritis Knee Score (MOAKS). Progression was defined for bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities and meniscal extrusion. Analyses on knee level were performed over the four intervention groups using adjusted Generalized Estimating Equations (GEE). RESULTS: 687 knees of 347 women with mean age 55.7 years (±3.2 SD) and mean BMI 32.3 kg/m(2) (±4.2 SD) were analyzed. Baseline prevalence was 64% for BMLs, 70% for cartilage defects, 24% for osteophytes, 66% for meniscal abnormalities and 52% for meniscal extrusions. The diet and exercise program + placebo intervention showed significantly less progression of meniscal extrusion compared to placebo only (12% vs 22%, OR 0.50, 95% CI [0.27-0.92]). The interventions did not result in significant differences on other OA MRI features. CONCLUSIONS: In subjects at high risk for future knee OA development, a diet and exercise program, glucosamine sulphate and their combination showed small and mainly non-significant effects on the progression of OA MRI features. Only progression of meniscal extrusion was significantly diminished by the diet and exercise program.

Factors that predict a poor outcome 5-8†years after the diagnosis of patellofemoral pain: a multicentre observational analysis.

BACKGROUND: Patellofemoral pain (PFP) has traditionally been viewed as self-limiting, but recent studies show that a large proportion of patients report chronic knee pain at long-term follow-up. We identified those patients with an unfavourable recovery ('moderate improvement' to 'worse than ever' measured on a Likert scale) and examined whether there is an association between PFP and osteoarthritis (OA) at 5-8-year follow-up. METHODS: Long-term follow-up data were derived from 2 randomised controlled trials (n=179, n=131). Patient-reported measures were obtained at baseline. Pain severity (100 mm visual analogue scale (VAS)), function (Anterior Knee Pain Scale (AKPS)) and self-reported recovery were measured 5-8 years later, along with knee radiographs. Multivariate backward stepwise linear regression analyses were used to evaluate the prognostic ability of baseline pain duration, pain VAS and AKPS on outcomes of pain VAS and AKPS at 5-8 years. RESULTS: 60 (19.3%) participants completed the questionnaires at 5-8-year follow-up (45 women, mean age at baseline 26 years) and 50 underwent knee radiographs. No differences were observed between responders and non-responders regarding baseline demographics, and 3-month and 12-month pain severity and recovery. 34 (57%) reported unfavourable recovery at 5-8 years. 48 out of 50 participants (98%) had no signs of radiographic knee OA. Multivariate models revealed that baseline PFP duration (>12 months; R(2)=0.22) and lower AKPS (R(2)=0.196) were significant predictors of poor prognosis at 5-8 years on measures of worst pain VAS and AKPS, respectively. SUMMARY AND CONCLUSION: More than half of participants with PFP reported an unfavourable recovery 5-8 years after recruitment, but did not have radiographic knee OA. Longer PFP duration and worse AKPS score at baseline predict poor PFP prognosis. Education of health practitioners and the general public will provide patients with more realistic expectations regarding prognosis.

Association of urinary biomarker COLL2-1NO2 with incident clinical and radiographic knee OA in overweight and obese women.

OBJECTIVE: To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA). DESIGN: Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m(2) without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses. RESULTS: 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome. CONCLUSIONS: In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted.

Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors.

OBJECTIVE: To develop and validate a prognostic model for incident knee osteoarthritis (KOA) in a general population and determine the value of different risk factor groups to prediction. METHODS: The prognostic model was developed in 2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate analyses were performed for questionnaire/easily obtainable variables, imaging variables, genetic and biochemical markers. The extended multivariate model was tested on discrimination (receiver operating characteristic curve and area under the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and Chingford Study. RESULTS: In RS-I, there was moderate predictive value for incident KOA based on the genetic score alone in subjects aged <65 years (AUC 0.65), while it was only 0.55 for subjects aged ≥65 years. The AUC for gender, age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the questionnaire variables, genetic score or biochemical marker urinary C-terminal cross-linked telopeptide of type II collagen to the model did not change the AUC. However, when adding the knee baseline KL score to the model the AUC increased to 0.79. Applying external validation, similar results were observed in the Rotterdam Study-II and the Chingford Study. CONCLUSIONS: Easy obtainable 'Questionnaire' variables, genetic markers, OA at other joint sites and biochemical markers add only modestly to the prediction of KOA incidence using age, gender and BMI in an elderly population. Doubtful minor radiographic degenerative features in the knee, however, are a very strong predictor of future KOA. This is an important finding, as many radiologists do not report minor degenerative changes in the knee.