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.

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.

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.

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.

Genicular artery embolization as a novel treatment for mild to moderate knee osteoarthritis: protocol design of a randomized sham-controlled clinical trial.

INTRODUCTION: Knee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis. METHODS AND ANALYSIS: Fifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions. ETHICS AND DISSEMINATION: This trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03884049. Registered on 21 March 2019.

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.

Prevalence of small osteophytes on knee MRI in several large clinical and population-based studies of various age groups and OA risk factors.

Objective: Osteophytes, also small ones, are an important imaging feature of OA. However, due to their high prevalence on MR, the question has arisen whether these are truly pathophysiologic features of early OA, a result of physiologic aging, or rather a merely transient phenomenon. The aim of this study was to explore the prevalence of osteophytes on MR in various locations of the knee, with special emphasis on small osteophytes, across multiple large studies conducted in our institution comprising a wide range of subjects at different ages. Method: Retrospective explorative study of the prevalence of osteophytes, particularly grade 1 according to MOAKS, among four studies with a wide variety in age and OA risk factors. Results: A large number of grade 1 osteophytes were found in all four studies. The largest number of osteophytes were present in the youngest age group of <30 years (69.6%) compared to 36.8% in the age group of ≥30 â€‹< â€‹50 years and 54,3% when aged ≥50 years, of which most were grade 1 osteophytes. Conclusion: Small osteophytes are highly prevalent among populations with varying age and OA risk factors, in particular among young subjects without other OA features. This might suggest that these "osteophytes" do not necessarily represent early OA, but rather indicate a transient physiologic phenomenon.

Fractional order vs. exponential fitting in UTE MR imaging of the patellar tendon.

PURPOSE: Quantification of the T2∗ relaxation time constant is relevant in various magnetic resonance imaging applications. Mono- or bi-exponential models are typically used to determine these parameters. However, in case of complex, heterogeneous tissues these models could lead to inaccurate results. We compared a model, provided by the fractional-order extension of the Bloch equation with the conventional models. METHODS: Axial 3D ultra-short echo time (UTE) scans were acquired using a 3.0 T MRI and a 16-channel surface coil. After image registration, voxel-wise T2∗ was quantified with mono-exponential, bi-exponential and fractional-order fitting. We evaluated all three models repeatability and the bias of their derived parameters by fitting at various noise levels. To investigate the effect of the SNR for the different models, a Monte-Carlo experiment with 1000 repeats was performed for different noise levels for one subject. For a cross-sectional investigation, we used the mean fitted values of the ROIs in five volunteers. RESULTS: Comparing the mono-exponential and the fractional order T2∗ maps, the fractional order fitting method yielded enhanced contrast and an improved delineation of the different tissues. In the case of the bi-exponential method, the long T2∗ component map demonstrated the anatomy clearly with high contrast. Simulations showed a nonzero bias of the parameters for all three mathematical models. ROI based fitting showed that the T2∗ values were different depending on the applied method, and they differed most for the patellar tendon in all subjects. CONCLUSIONS: In high SNR cases, the fractional order and bi-exponential models are both performing well with low bias. However, in all observed cases, one of the bi-exponential components has high standard deviation in T2∗. The bi-exponential model is suitable for T2∗ mapping, but we recommend using the fractional order model for cases of low SNR.

Is patellofemoral pain a precursor to osteoarthritis?: Patellofemoral osteoarthritis and patellofemoral pain patients share aberrant patellar shape compared with healthy controls.

OBJECTIVES: It has been hypothesized that patellofemoral pain, a common knee condition in adolescents and young adults, may be a precursor of degenerative joint changes and may ultimately lead to patellofemoral osteoarthritis. Since both conditions share several mechanical disease characteristics, such as altered contact area between the femur and patella and increased joint stress, we investigated whether these conditions share similar and different shape characteristics of the patella compared with normal controls. METHODS: This cross-sectional study compared three different study populations: 32 patellofemoral pain subjects (mean age, 32 years (22 to 45); 72% female); 56 isolated radiological patellofemoral osteoarthritis subjects (mean age, 54 years (44 to 58); 89% female); and 80 healthy control subjects (mean age, 52 years (44 to 58); 74% female). Measurements included questionnaires, and lateral and skyline radiographs of the knee. Two separate 30-point 2D statistical shape models of the patella were created from the lateral and skyline radiographs. A general linear model was used to test for differences in standardized shape modes (a specific shape variant of the patella) between patellofemoral osteoarthritis, patellofemoral pain, and controls, using Bonferroni correction and adjustment for body mass index and gender. RESULTS: Five shape modes showed statistically significant differences between groups: skyline modes 1 (p < 0.001), 8 (p = 0.004), and 10 (p < 0.001); and lateral modes 5 (p = 0.002) and 7 (p = 0.002). Skyline mode 8 and lateral mode 5 were similar for patellofemoral osteoarthritis and patellofemoral pain populations, while being statistically significant different from the control group. CONCLUSION: Our results indicate that patellofemoral pain and patellofemoral osteoarthritis share similar shape characteristics, which are different from control subjects. These findings support the proposed continuum disease model of patellofemoral pain predisposing to the development of patellofemoral osteoarthritis.Cite this article: J. F. A. Eijkenboom, J. H. Waarsing, E. H. G. Oei, S. M. A. Bierma-Zeinstra, M. van Middelkoop. Is patellofemoral pain a precursor to osteoarthritis? Patellofemoral osteoarthritis and patellofemoral pain patients share aberrant patellar shape compared with healthy controls. Bone Joint Res 2018;7:541-547. DOI: 10.1302/2046-3758.79.BJR-2018-0112.R1.

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.

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.

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.

Value of quantitative MRI parameters in predicting and evaluating clinical outcome in conservatively treated patients with chronic midportion Achilles tendinopathy: A prospective study.

OBJECTIVES: To evaluate whether baseline MRI parameters provide prognostic value for clinical outcome, and to study correlation between MRI parameters and clinical outcome. DESIGN: Observational prospective cohort study. METHODS: Patients with chronic midportion Achilles tendinopathy were included and performed a 16-week eccentric calf-muscle exercise program. Outcome measurements were the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and MRI parameters at baseline and after 24 weeks. The following MRI parameters were assessed: tendon volume (Volume), tendon maximum cross-sectional area (CSA), tendon maximum anterior-posterior diameter (AP), and signal intensity (SI). Intra-class correlation coefficients (ICCs) and minimum detectable changes (MDCs) for each parameter were established in a reliability analysis. RESULTS: Twenty-five patients were included and complete follow-up was achieved in 20 patients. The average VISA-A scores increased significantly with 12.3 points (27.6%). The reliability was fair-good for all MRI-parameters with ICCs>0.50. Average tendon volume and CSA decreased significantly with 0.28cm3 (5.2%) and 4.52mm2 (4.6%) respectively. Other MRI parameters did not change significantly. None of the baseline MRI parameters were univariately associated with VISA-A change after 24 weeks. MRI SI increase over 24 weeks was positively correlated with the VISA-A score improvement (B=0.7, R2=0.490, p=0.02). CONCLUSIONS: Tendon volume and CSA decreased significantly after 24 weeks of conservative treatment. As these differences were within the MDC limits, they could be a result of a measurement error. Furthermore, MRI parameters at baseline did not predict the change in symptoms, and therefore have no added value in providing a prognosis in daily clinical practice.

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.

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.