Exercise for knee osteoarthritis pain: Association or causation?

Exercise is universally recommended as a primary strategy for the management of knee osteoarthritis (OA) pain. The recommendations are based on results from more than 100 randomized controlled trials (RCTs) that compare exercise to no-attention control groups. However, due to the inherent difficulties with adequate placebo control, participant blinding and the use of patient-reported outcomes, the existing RCT evidence is imperfect. To better understand the evidence used to support a causal relationship between exercise and knee OA pain relief, we examined the existing evidence through the Bradford Hill considerations for causation. The Bradford Hill considerations, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework for assessment of possible causal relationships. There are 9 considerations by which the evidence is reviewed: Strength of association, Consistency, Specificity, Temporality, Biological Gradient (Dose-Response), Plausibility, Coherence, Experiment, and Analogy. Viewing the evidence from these 9 viewpoints did neither bring forward indisputable evidence for nor against the causal relationship between exercise and improved knee OA pain. Rather, we conclude that the current evidence is not sufficient to support claims about (lack of) causality. With our review, we hope to advance the continued global conversation about how to improve the evidence-based management of patients with knee OA.

Diagnostic tests recommended for the clinical assessment of patients with wrist complaints, an e-Delphi study.

BACKGROUND: Evidence-based practice for history-taking and physical examination in the evaluation of wrist complaints is limited. PURPOSE: To create a set of recommended diagnostic tests for the clinical assessment of patients with undifferentiated wrist complaints. STUDY DESIGN: An e-Delphi study, following the recommendations on conducting and reporting Delphi studies, was performed. METHODS: In this e-Delphi study, a national multidisciplinary panel of experts was invited to inventory diagnostic tests, based on several case scenarios, for the probability diagnosis in patients (age ≥18 years) with undifferentiated wrist complaints. Four case scenarios were constructed and presented to the expert panel members, which differed in age of the patient (35 vs 65 years), location (radial vs ulnar), and duration (6 vs 10 weeks) of the complaints. In consecutive rounds, the experts were asked to rate the importance of the inventoried diagnostic tests. Finally, experts were asked to rank recommended diagnostic tests for each case scenario. RESULTS: Merging all results, the following diagnostic tests were recommended for all case scenarios: ask whether a trauma has occurred, ask how the complaints can be provoked, ask about the localization of the complaints, assess active ranges of motion, assess the presence of swelling, assess the difference in swelling between the left and right, assess the deformities or changes in position of the wrist, and palpate at the point of greatest pain. CONCLUSIONS: This is the first scientific study where experts clinicians recommended diagnostic tests when assessing patients with undifferentiated wrist complaints, varying in age of the patient (35 vs 65 years), location (radial vs ulnar), and duration (6 vs 10 weeks).

Factors associated with meniscus volume in knees free of degenerative features.

OBJECTIVES: To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA. METHODS: In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements. RESULTS: From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m2. At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss. CONCLUSIONS: Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time.

Cam morphology is strongly and consistently associated with development of radiographic hip osteoarthritis throughout 4 follow-up visits within 10 years.

OBJECTIVE: To determine the association between cam morphology and the development of radiographic hip osteoarthritis (RHOA) at four time points within 10-year follow-up. DESIGN: The nationwide prospective Cohort Hip and Cohort Knee study includes 1002 participants aged 45-65 years with 2-, 5-, 8-, and 10-year follow-ups. The associations of cam morphology (alpha angle >60°) and large cam morphology (alpha angle >78°) in hips free of osteoarthritis at baseline (Kellgren & Lawrence (KL) grade <2) with the development of both incident RHOA (KL grade≥2) and end-stage RHOA (KL grade≥3) were estimated using logistic regression with generalized estimating equation at each follow-up and using Cox regression over 10 years, adjusted for age, sex, and body mass index. RESULTS: Both cam morphology and large cam morphology were associated with the development of incident RHOA at all follow-ups with adjusted Odd Ratios (aORs) ranging from 2.7 (95% Confidence interval 1.8-4.1) to 2.9 (95% CI 2.0-4.4) for cam morphology and ranging from 2.5 (95% CI 1.5-4.3) to 4.2 (95% CI 2.2-8.3) for large cam morphology. For end-stage RHOA, cam morphology resulted in aORs ranging from 4.9 (95% CI 1.8-13.2) to 8.5 (95% CI 1.1-64.4), and aORs for large cam morphology ranged from 6.7 (95% CI 3.1-14.7) to 12.7 (95% CI 1.9-84.4). CONCLUSIONS: Cam morphology poses the hip at 2-13 times increased odds for developing RHOA within a 10-year follow-up. The association was particularly strong for large cam morphology and end-stage RHOA, while the strength of association was consistent over time.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

Determination and characterization of patient subgroups based on pain trajectories in hand osteoarthritis.

OBJECTIVES: To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA). METHODS: Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of consecutive hand OA patients were used. Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain was measured yearly for four years. Patients with complete AUSCAN at ≥2 time points were eligible for longitudinal analysis. Associations between variables of interest and baseline AUSCAN pain were investigated with linear regression. Development of pain over time was modelled using latent class growth analysis (LCGA). Associations of LCGA classes with variables of interest were analysed using multinomial logistic regression adjusted for baseline pain. RESULTS: A total of 484/538 patients [mean (s.d.) age 60.8 (8.5) years, 86% women, mean (s.d.) AUSCAN pain 9.3 (4.3)] were eligible for longitudinal analysis. Sex, marital and working status, education, disease duration and severity, anxiety and depression scores, lower health-related quality of life (HR-QoL), specific illness perceptions and coping styles were associated with baseline pain. LCGA yielded three classes, characterized by average pain levels at baseline; average pain remained stable over time within classes. Classes with more pain were positively associated with BMI, tender joint count, symptom duration, hand function scores and depression scores, negatively with physical HR-QoL, and education level. CONCLUSION: Baseline pain was associated with patient and disease characteristics, and psychosocial factors. LCGA showed three pain trajectories in hand OA patients, with different baseline pain levels and stable pain over time. Classes were distinguished by BMI, education level, disease severity, depression and HR-QoL.

Hip dysplasia as risk factor for clinically relevant and radiographic hip osteoarthritis: 10-year results from the CHECK cohort.

OBJECTIVES: To investigate hip dysplasia as a risk factor for clinically relevant and incident radiographic hip osteoarthritis. METHODS: From a prospective cohort (CHECK) of 1002 middle-aged, new consulters for hip and/or knee pain, 468 hips (251 individuals) were selected based on hip pain, available lateral center edge angle (LCEA) and absence of definite radiographic hip OA (Kellgren and Lawrence grade (KL) <2) at baseline, as well as available follow-up measures. Clinically relevant hip OA was defined by an expert diagnosis based on clinical and radiographic data obtained between year 5-10 from baseline. Incident radiographic hip OA was defined by KL grade ≥2 or a total hip replacement at the 10-year follow-up. Associations between hip dysplasia (LCEA ≤20°) and outcomes were expressed in odds ratios (OR) adjusted for age, sex and BMI. RESULTS: At baseline, participants had a mean age of 55.5 years (SD 5.4), 88% were female and, on hip level, the prevalence of hip dysplasia was 3.6% (n = 17). After 10 years, hip dysplasia was associated with an increased risk for clinically relevant hip OA (OR 2.80 (95% CI 1.15, 6.79), but not for incident radiographic hip OA (OR 0.78 (95% CI 0.26, 2.30)). CONCLUSION: In the long term, baseline hip dysplasia was associated with an increased risk for clinically relevant hip OA, but not for incident radiographic hip OA. With this in mind, we suggest that future research investigating the link between hip dysplasia and OA strive to include a definition for OA that is clinically relevant.

A machine learning approach reveals features related to clinicians' diagnosis of clinically relevant knee osteoarthritis.

OBJECTIVES: To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. METHODS: General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5-10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. RESULTS: Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76-0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. CONCLUSIONS: Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings.

Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.

OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster. METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards. RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]). CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.

Imaging of early-stage osteoarthritis: the needs and challenges for diagnosis and classification.

In an effort to boost the development of new management strategies for OA, there is currently a shift in focus towards the diagnosis and treatment of early-stage OA. It is important to distinguish diagnosis from classification of early-stage OA. Diagnosis takes place in clinical practice, whereas classification is a process to stratify participants with OA in clinical research. For both purposes, there is an important opportunity for imaging, especially with MRI. The needs and challenges differ for early-stage OA diagnosis versus classification. Although it fulfils the need of high sensitivity and specificity for making a correct diagnosis, implementation of MRI in clinical practice is challenged by long acquisition times and high costs. For classification in clinical research, more advanced MRI protocols can be applied, such as quantitative, contrast-enhanced, or hybrid techniques, as well as advanced image analysis methods including 3D morphometric assessments of joint tissues and artificial intelligence approaches. It is necessary to follow a step-wise and structured approach that comprises, technical validation, biological validation, clinical validation, qualification, and cost-effectiveness, before new imaging biomarkers can be implemented in clinical practice or clinical research.

Cross-Cohort Automatic Knee MRI Segmentation With Multi-Planar U-Nets.

BACKGROUND: Segmentation of medical image volumes is a time-consuming manual task. Automatic tools are often tailored toward specific patient cohorts, and it is unclear how they behave in other clinical settings. PURPOSE: To evaluate the performance of the open-source Multi-Planar U-Net (MPUnet), the validated Knee Imaging Quantification (KIQ) framework, and a state-of-the-art two-dimensional (2D) U-Net architecture on three clinical cohorts without extensive adaptation of the algorithms. STUDY TYPE: Retrospective cohort study. SUBJECTS: A total of 253 subjects (146 females, 107 males, ages 57 ± 12 years) from three knee osteoarthritis (OA) studies (Center for Clinical and Basic Research [CCBR], Osteoarthritis Initiative [OAI], and Prevention of OA in Overweight Females [PROOF]) with varying demographics and OA severity (64/37/24/53/2 scans of Kellgren and Lawrence [KL] grades 0-4). FIELD STRENGTH/SEQUENCE: 0.18 T, 1.0 T/1.5 T, and 3 T sagittal three-dimensional fast-spin echo T1w and dual-echo steady-state sequences. ASSESSMENT: All models were fit without tuning to knee magnetic resonance imaging (MRI) scans with manual segmentations from three clinical cohorts. All models were evaluated across KL grades. STATISTICAL TESTS: Segmentation performance differences as measured by Dice coefficients were tested with paired, two-sided Wilcoxon signed-rank statistics with significance threshold α = 0.05. RESULTS: The MPUnet performed superior or equal to KIQ and 2D U-Net on all compartments across three cohorts. Mean Dice overlap was significantly higher for MPUnet compared to KIQ and U-Net on CCBR ( 0.83±0.04 vs. 0.81±0.06 and 0.82±0.05 ), significantly higher than KIQ and U-Net OAI ( 0.86±0.03 vs. 0.84±0.04 and 0.85±0.03) , and not significantly different from KIQ while significantly higher than 2D U-Net on PROOF ( 0.78±0.07 vs. 0.77±0.07 , P=0.10 , and 0.73±0.07) . The MPUnet performed significantly better on N=22 KL grade 3 CCBR scans with 0.78±0.06 vs. 0.75±0.08 for KIQ and 0.76±0.06 for 2D U-Net. DATA CONCLUSION: The MPUnet matched or exceeded the performance of state-of-the-art knee MRI segmentation models across cohorts of variable sequences and patient demographics. The MPUnet required no manual tuning making it both accurate and easy-to-use. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Course of pain and fluctuations in pain related to suspected early hip osteoarthritis: the CHECK study.

OBJECTIVES: To evaluate the prevalence during a 10-year follow-up of clinically relevant fluctuations in pain and the course of hip pain in participants with hip complaints suspected to be early stage hip osteoarthritis (OA). To distinguish between participants with relevant fluctuations in pain and those without based on baseline characteristics. METHODS: Data were collected at baseline and after 2, 5, 8, and 10 years on 495 participants from the Cohort Hip and Cohort Knee Study (CHECK) with hip pain at baseline. Baseline demographic, anamnestic, and physical-examination characteristics were assessed. The primary outcome was levels of pain in the past week (scored using 0-10 Numeric Rating Scale) at follow-up assessments. Relevant fluctuation was defined as average absolute residuals greater than 1 after fitting a straight line to the participant's pain scores over time. RESULTS: The majority of the participants (76%) had stable or decreasing pain. Relevant fluctuations were found in 37% of the participants. The following baseline variables were positively associated with the presence of relevant fluctuations: higher levels of pain in the past week, use of pain transformation as a coping style, higher number of comorbidities, use of pain medication, and higher levels of high-sensitivity C-reactive protein. No associations were found for baseline radiographic hip OA or clinical hip OA. CONCLUSION: During a 10-year follow-up, the majority of participants had stable or decreasing pain levels. In those participants with relevant fluctuation (37%), a limited number of baseline variables were associated with increased odds of having relevant fluctuations in pain.

Pain appears to be an important reason for consulting the general practitioner (GP) for hip osteoarthritis (OA) complaints. We know that hip pain remained quite stable over 10 years. Also is known that there is considerable variety between patients in pain. In this study, we found relevant pain fluctuations in 37% of primary care patients with hip complaints over a period of 10 years. The pain fluctuation was not associated with having osteoarthritis, neither radiographic hip OA (diagnosed based on a X-ray) or clinical hip OA (determined according to the American College of Rheumatology (ACR) criteria) at baseline. More research is needed to discover why some people experience fluctuations in time than others.

10-Year natural course of early hip osteoarthritis in middle-aged persons with hip pain: a CHECK study.

OBJECTIVE: To explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints. METHODS: Data were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features. RESULTS: In total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years. CONCLUSION: One out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.

Diagnostic criteria for early hip osteoarthritis: first steps, based on the CHECK study.

OBJECTIVES: Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care. METHODS: Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts [general practitioners (GPs), rheumatologists and orthopaedic surgeons] evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5-10 years after baseline. Using the expert-based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing. RESULTS: Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained four to eight baseline factors (mainly WOMAC pain items, painful/restricted movements and radiographic features) and obtained area under the curve between 0.62 (0.002) and 0.71 (0.002). CONCLUSION: Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5-10 years was 'poor' to 'fair'.

Factors associated with longitudinal change of meniscal extrusion in overweight women without clinical signs of osteoarthritis.

OBJECTIVES: To identify variables associated with longitudinal change in meniscal extrusion, which might be used as possible targets for knee osteoarthritis (KOA) prevention. METHODS: In a high-risk population of middle-aged overweight women, meniscal extrusion was assessed with magnetic resonance imaging (1.5 T, coronal proton density, in-plane resolution 0.5 mm2, Sante DICOM Editor) at baseline and after 30 months. Outcomes were the absolute change in medial and lateral extrusion (mm) and relative change in extrusion (%). Based upon literature, 11 factors were hypothesized to be associated with longitudinal change. Generalized estimating equations were used to model the effect on meniscal change (P <0.05). RESULTS: In total, 677 knees of 343 women were available for analysis, with a mean age of 55.7 years (+/-3.2) and a mean BMI of 32.3 kg/m2 (+/-4.2). The greatest change in meniscal extrusion appeared medially with incident meniscal tear (4.4%; absolute 0.9 mm (95% CI: 0.3, 1.5; P =0.004); relative 14.5% (4.4, 24.7; 0.005)). Varus malalignment was associated with an increase of medial extrusion of 0.6 mm (37.6%; 0.1, 1.0; 0.009). A 5 kg/m2 higher baseline BMI was associated with absolute and relative increase of medial extrusion of 0.2 mm and 2.96% (0.1, 0.3; <0.001 and 1.3, 4.8; 0.002). Less explicit but significant changes in extrusion appeared with longitudinal change in BMI. CONCLUSION: Meniscal tears, varus malalignment and BMI were significantly associated with change in meniscal extrusion in middle-aged overweight women, providing viable therapeutic targets to prevent or reduce extrusion and thereby decelerate KOA development.

Characteristics associated between the incidence of hip osteoarthritis and early hip complaints (CHECK study) within 10 years.

OBJECTIVE: To determine which baseline characteristics, especially clinically variables like pain, stiffness, physical functioning and disease variables, are associated with incident hip OA within 10 years in first presenters with hip complaints. Rheumatology key messages History taking and not physical exam variables are associated with incident hip osteoarthritis. Specific questions about daily life activities are associated with incident hip OA. These questions are about pain while walking/shopping, difficulties putting socks on/off and rising from bed. METHODS: Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study (n = 1002). Incident hip OA was defined as fulfilling the clinical ACR criteria for hip OA, a Kellgren and Lawrence score ≥2 with hip pain, or received a hip replacement during follow-up. Baseline measurements were used of participants with hip complaints and without hip OA. Principal component analysis (PCA) was used to reduce the number of correlated variables. Associations between baseline characteristics (including PCA components) and incident hip OA were investigated using logistic regression analysis, adjusted for age, sex and BMI. RESULTS: In total, 312 participants (85% female and 98% Caucasian) were included, 181 developed hip OA. PCA resulted in four components. Incident hip OA was associated with (i) component 1 (general presence of pain and symptoms) [odds ratio (OR) = 1.46 (95%CI: 1.08, 1.98)], (ii) component 3 (relatively high levels of pain during shopping/walking combined with less difficulty with putting socks on/off and rising from bed) [OR = 1.58 (95%CI: 1.18, 2.12)] and (iii) knee pain [OR = 0.34 (95% CI: 0.17, 0.66)]. CONCLUSION: In first presenters with hip complaints, use of a few history-taking variables might allow better recognition of those at higher odds for incident hip OA within 10 years.

Association between meniscal volume and development of knee osteoarthritis.

OBJECTIVE: To assess the association between meniscal volume, its change over time and the development of knee OA after 30 months in overweight/obese women. METHODS: Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 women with a BMI ≥ 27 kg/m2, free of OA-related symptoms. The primary outcome measure was incident OA after 30 months, defined by one out of the following criteria: medial or lateral joint space narrowing (JSN) ≥ 1.0 mm, incident radiographic OA [Kellgren and Lawrence (K&L) ≥ 2], or incident clinical OA. The secondary outcomes were either of these items separately. Menisci at both baseline and follow-up were automatically segmented to obtain meniscal volume and delta-volumes. Generalized estimating equations were used to evaluate associations between the volume measures and the outcomes. RESULTS: Medial and lateral baseline and delta-volumes were not significantly associated to the primary outcome. Lateral meniscal baseline volume was significantly associated to lateral JSN [odds ratio (OR) = 0.87; 95% CI: 0.75, 0.99], while other measures were not. Medial and lateral baseline volume were positively associated to K&L incidence (OR = 1.32 and 1.22; 95% CI: 1.15, 1.50 and 1.03, 1.45, respectively), while medial and lateral delta-volume were negatively associated to K&L incidence (OR = 0.998 and 0.997; 95% CI: 0.997, 1.000 and 0.996, 0.999, respectively). None of the meniscal measures were significantly associated to incident clinical OA. CONCLUSION: Larger baseline meniscal volume and the decrease of meniscal volume over time were associated to the development of structural OA after 30 months in overweight and obese women.

Time-saving opportunities in knee osteoarthritis: T2 mapping and structural imaging of the knee using a single 5-min MRI scan.

OBJECTIVES: To assess the discriminative power of a 5-min quantitative double-echo steady-state (qDESS) sequence for simultaneous T2 measurements of cartilage and meniscus, and structural knee osteoarthritis (OA) assessment, in a clinical OA population, using radiographic knee OA as reference standard. METHODS: Fifty-three subjects were included and divided over three groups based on radiographic and clinical knee OA: 20 subjects with no OA (Kellgren-Lawrence grade (KLG) 0), 18 with mild OA (KLG2), and 15 with moderate OA (KLG3). All patients underwent a 5-min qDESS scan. We measured T2 relaxation times in four cartilage and four meniscus regions of interest (ROIs) and performed structural OA evaluation with the MRI Osteoarthritis Knee Score (MOAKS) using qDESS with multiplanar reformatting. Between-group differences in T2 values and MOAKS were calculated using ANOVA. Correlations of the reference standard (i.e., radiographic knee OA) with T2 and MOAKS were assessed with correlation analyses for ordinal variables. RESULTS: In cartilage, mean T2 values were 36.1 ± SD 4.3, 40.6 ± 5.9, and 47.1 ± 4.3 ms for no, mild, and moderate OA, respectively (p < 0.001). In menisci, mean T2 values were 15 ± 3.6, 17.5 ± 3.8, and 20.6 ± 4.7 ms for no, mild, and moderate OA, respectively (p < 0.001). Statistically significant correlations were found between radiographic OA and T2 and between radiographic OA and MOAKS in all ROIs (p < 0.05). CONCLUSION: Quantitative T2 and structural assessment of cartilage and meniscus, using a single 5-min qDESS scan, can distinguish between different grades of radiographic OA, demonstrating the potential of qDESS as an efficient tool for OA imaging. KEY POINTS: • Quantitative T2values of cartilage and meniscus as well as structural assessment of the knee with a single 5-min quantitative double-echo steady-state (qDESS) scan can distinguish between different grades of knee osteoarthritis (OA). • Quantitative and structural qDESS-based measurements correlate significantly with the reference standard, radiographic degree of OA, for all cartilage and meniscus regions. • By providing quantitative measurements and diagnostic image quality in one rapid MRI scan, qDESS has great potential for application in large-scale clinical trials in knee OA.

Diagnostic accuracy of history taking, physical examination and imaging for phalangeal, metacarpal and carpal fractures: a systematic review update.

BACKGROUND: The standard diagnostic work-up for hand and wrist fractures consists of history taking, physical examination and imaging if needed, but the supporting evidence for this work-up is limited. The purpose of this study was to systematically examine the diagnostic accuracy of tests for hand and wrist fractures. METHODS: A systematic search for relevant studies was performed. Methodological quality was assessed and sensitivity (Se), specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were extracted from the eligible studies. RESULTS: Of the 35 eligible studies, two described the diagnostic accuracy of history taking for hand and wrist fractures. Physical examination with or without radiological examination for diagnosing scaphoid fractures (five studies) showed Se, Sp, accuracy, PPV and NPV ranging from 15 to 100%, 13-98%, 55-73%, 14-73% and 75-100%, respectively. Physical examination with radiological examination for diagnosing other carpal bone fractures (one study) showed a Se of 100%, with the exception of the triquetrum (75%). Physical examination for diagnosing phalangeal and metacarpal fractures (one study) showed Se, Sp, accuracy, PPV and NPV ranging from 26 to 55%, 13-89%, 45-76%, 41-77% and 63-75%, respectively. Imaging modalities of scaphoid fractures showed predominantly low values for PPV and the highest values for Sp and NPV (24 studies). Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Ultrasonography (US) and Bone Scintigraphy (BS) were comparable in diagnostic accuracy for diagnosing a scaphoid fracture, with an accuracy ranging from 85 to 100%, 79-100%, 49-100% and 86-97%, respectively. Imaging for metacarpal and finger fractures showed Se, Sp, accuracy, PPV and NPV ranging from 73 to 100%, 78-100%, 70-100%, 79-100% and 70-100%, respectively. CONCLUSIONS: Only two studies were found on the diagnostic accuracy of history taking for hand and wrist fractures in the current review. Physical examination was of moderate use for diagnosing a scaphoid fracture and of limited use for diagnosing phalangeal, metacarpal and remaining carpal fractures. MRI, CT and BS were found to be moderately accurate for the definitive diagnosis of clinically suspected carpal fractures.

Effectiveness of intramuscular gluteal glucocorticoid injection versus intra-articular glucocorticoid injection in knee osteoarthritis: design of a multicenter randomized, 24 weeks comparative parallel-group trial.

BACKGROUND: The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection. METHODS/DESIGN: The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score ≥ 3 on 0-10 numerical rating scale; 0 = no knee pain) will be included. Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area. The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients' reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle. DISCUSSION: This study will evaluate non-inferiority of intramuscular glucocorticoid injection compared to intra-articular glucocorticoid injection for knee osteoarthritis symptoms. TRIAL REGISTRATION: This trial is registered in the Dutch Trial Registry (number NTR6968) at 2018-01-22 (https://www.trialregister.nl/trial/6784). Issue date: 1 October 2019. TRIAL SPONSOR: Erasmus MC University Medical Center Rotterdam. PO-box 2040. 3000 CA Rotterdam. The Netherlands.