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1.  Spiking of the tibial tubercles--a radiological feature of osteoarthritis? 
Annals of the Rheumatic Diseases  1996;55(2):105-108.
OBJECTIVE: To determine whether 'spiking' or angulation of the tibial tubercle is associated with other radiographic markers of osteoarthritis (OA) or pain in the knee joint, and could be taken as a reliable marker for early OA, in a large general population sample. METHODS: A total of 950 women from the Chingford general population survey underwent anteroposterior extended weight bearing radiography of the knees. Angulation of the tip of the medial and lateral tubercles, and height of the tubercles above the tibial plateau were measured. These measures were compared with standard radiographic indices including qualitative Kellgren and Lawrence global score, individual scores of osteophytes and joint space narrowing, and pain score. Intraobserver and interobserver reproducibility for assessment of spiking was tested in a subgroup of 50 films using two observers and two readings. Tibial spiking (angulation and height) was defined for this study as the top 10th centile for the whole population. Patients with normal radiographs (Kellgren and Lawrence grade 0) were allocated to quartile groups on the basis of spiking to define severity. Odds ratios were then calculated for the association of spiking and knee pain. RESULTS: The majority of the measures of tibial spiking were highly reproducible. There was a significant correlation between tibial spike angulation and the presence of osteophytes, but not joint space narrowing. The correlations for spike height with osteophytes and joint space narrowing were poor. There was an association between spike angulation at the lateral tubercle and reported knee pain (odds ratio 1.45 (95% confidence interval 1.03 to 2.03)) after adjustment for age, body mass index, and Kellgren and Lawrence score. There was no association between medial spike angulation or spike height and pain. Among the 950 women, 683 (72%) had normal radiographs (Kellgren and Lawrence = 0); in this group there was a similar association between pain and lateral spike angulation, but not medial spike angulation or spike height. CONCLUSIONS: Tibial spiking is associated with the presence of knee osteophytes and is reproducible, but does not have a strong independent relationship with knee pain. In patients with normal radiographs there is no useful correlation between tibial spiking and pain. Isolated tibial spiking is not a reliable sign of early knee OA, and should not routinely be reported.
PMCID: PMC1010103  PMID: 8712859
2.  Defining osteoarthritis of the hand for epidemiological studies: the Chingford Study. 
Annals of the Rheumatic Diseases  1994;53(4):220-223.
OBJECTIVES--To explore the relative merits of clinical and radiological examination in defining hand osteoarthritis (OA) for epidemiological purposes. METHODS--A total of 976 women aged 45-64 years were selected from the general population and underwent a structured interview, clinical examination of the hand joints and radiography of the hands and knees. The inter-relationship of the clinical and radiological findings was examined, and also the association of each with hand symptoms and the presence of knee OA. RESULTS--Clinical and radiographic signs of hand OA generally correlated with each other, and each was associated with hand symptoms to a similar degree. When analysed in combination, they were only marginally better at predicting symptoms than when tested individually. However, when they were examined in relation to radiographic features of knee OA, there was a significantly stronger association with radiographic features of hand OA than with clinical features. CONCLUSIONS--Hand radiology provides a better overall assessment of osteoarthritis than physical examination of the interphalangeal joints or carpo-metacarpal joint; in situations where radiology is not available clinical examination is a viable substitute.
PMCID: PMC1005298  PMID: 8203948
3.  Osteoarthritis in the elderly: clinical and radiological findings in 79 and 85 year olds. 
Annals of the Rheumatic Diseases  1991;50(8):535-539.
The prevalence of joint complaints and clinical and radiological findings of osteoarthritis in wrist, hand, and knee joints was studied in representative population subsamples of 79 and 85 year olds. Joint complaints, clinical findings of osteoarthritis, and radiographic osteoarthritis were more common in women. Age related differences in the prevalence of osteoarthritis were not found. Although there was a correlation between clinical signs of osteoarthritis and radiographic osteoarthritis, clinical signs were often present without radiographic evidence and moderate and severe radiographic osteoarthritis was often present without clinical signs.
PMCID: PMC1004482  PMID: 1888194
4.  Radiographic assessment of patellofemoral osteoarthritis. 
Annals of the Rheumatic Diseases  1993;52(9):655-658.
OBJECTIVES--To determine the feasibility of assessing patellofemoral osteoarthritis using the 'skyline' view and to compare its reproducibility with the standard lateral view. METHODS--Fifty patients attending a rheumatology outpatient department with osteoarthritis of the knee had standard radiographs taken of both knees: standing weightbearing anteroposterior; lateral supine radiograph in 30 degrees of flexion; and a skyline view of the patellofemoral joint. After an initial training period using 20 sets of films the remaining 30 sets were read blind by five observers. Intraobserver and interobserver variability was assessed using the kappa statistic. The minimum joint space in each compartment was measured using a ruler. Two views of a single normal subject were measured to determine the effect of knee flexion. RESULTS--The final 30 study films were from 20 women and 10 men, median age 72.5, range 18-91 years. A grading system comprising assessment of osteophytosis, joint space narrowing, sclerosis, cysts, and attrition could easily be applied to the skyline patellofemoral view. Intraobserver reproducibility was better than the interobserver reproducibility for all features. The skyline view performed more reproducibly and over a wider range of categorisation for joint space narrowing than the lateral radiograph. Measurement using a ruler was easy to perform and precise to within 1 mm for the medial tibiofemoral and lateral facet of the patellofemoral joint. In normal knees the degree of flexion significantly affected the measurement. CONCLUSIONS--Radiographic grading of the skyline patellofemoral view is readily achieved, is more reproducible than assessment of the lateral view, and allows more precise localisation of change. Such views should be considered in radiological surveys of osteoarthritis of the knee.
PMCID: PMC1005142  PMID: 8239760
5.  CHECK (Cohort Hip and Cohort Knee): similarities and differences with the Osteoarthritis Initiative 
Annals of the rheumatic diseases  2008;68(9):1413-1419.
To describe the osteoarthritis study population of CHECK (Cohort Hip and Cohort Knee) in comparison with relevant selections of the study population of the Osteoarthritis Initiative (OAI) based on clinical status and radiographic parameters.
In The Netherlands a prospective 10-year follow-up study was initiated by the Dutch Arthritis Association on participants with early osteoarthritis-related complaints of hip and/or knee: CHECK. In parallel in the USA an observational 4-year follow-up study, the OAI, was started by the National Institutes of Health, on patients with or at risk of symptomatic knee osteoarthritis. For comparison with CHECK, the entire cohort and a subgroup of individuals excluding those with exclusively hip pain were compared with relevant subpopulations of the OAI.
At baseline, CHECK included 1002 participants with in general similar characteristics as described for the OAI. However, significantly fewer individuals in CHECK had radiographic knee osteoarthritis at baseline when compared with the OAI (p<0.001). In contrast, at baseline, the CHECK cohort reported higher scores on pain, stiffness and functional disability (Western Ontario and McMaster osteoarthritis index) when compared with the OAI (all p<0.001). These differences were supported by physical health status in contrast to mental health (Short Form 36/12) was at baseline significantly worse for the CHECK participants (p<0.001).
Although both cohorts focus on the early phase of osteoarthritis, they differ significantly with respect to structural (radiographic) and clinical (health status) characteristics, CHECK expectedly representing participants in an even earlier phase of disease.
PMCID: PMC3134276  PMID: 18772189
6.  Definition of osteoarthritis of the knee for epidemiological studies. 
Annals of the Rheumatic Diseases  1993;52(11):790-794.
OBJECTIVES--There are no agreed criteria for osteoarthritis (OA) of the knee in population studies. The radiographic scoring system of Kellgren and Lawrence has been the system most used in the past and although other methods have been developed, comparisons have not been performed. Therefore these grading systems were compared in radiographs from a general population sample. METHODS--Anteroposterior weightbearing radiographs of 1954 knees from 977 women aged 45-64 years from the Chingford population study were read by a variety of methods, including quantitative measures of minimum joint space, qualitative measures of osteophytes and of joint space, and a qualitative Kellgren and Lawrence global score. All qualitative methods used standardised atlases. Intra-observer and interobserver reproducibility was tested on a subgroup of 100 films using three observers and two readings. Variables were dichotomised at the tenth and second centiles to define OA. Odds ratios were calculated for each method for the association of OA with knee pain, obesity, and with each of the other methods. RESULTS--Most methods had high intraobserver and interobserver reproducibility, except for measurements of lateral joint space. The best predictors of knee pain were the presence of osteophytes and the Kellgren and Lawrence grade. Methods measuring narrowing performed less well, with measurements of lateral joint space being particularly poor. Similar results were achieved in the comparison with obesity and in the comparisons between methods. CONCLUSIONS--These data suggest that the presence or absence of a definite osteophyte read by a single observer with an atlas is the best method of defining OA of the knee for epidemiological studies in women. Assessment of narrowing may be better used in evaluating severity.
PMCID: PMC1005190  PMID: 8250610
7.  Isometric Quadriceps Strength in Women with Mild, Moderate, and Severe Knee Osteoarthritis 
Quadriceps weakness is a common clinical sign in persons with moderate-to-severe osteoarthritis and results in physical disability; however, minimal data exist to establish whether quadriceps weakness is present in early stages of the disease. Therefore, our purpose was to determine whether quadriceps weakness was present in persons with early radiographic and cartilaginous evidence of osteoarthritis. Further, we sought to determine whether quadriceps strength decreases as osteoarthritis severity increases.
Three hundred forty-eight women completed radiologic and magnetic resonance imaging evaluation, in addition to strength testing. Anterior-posterior radiographs were graded for tibiofemoral osteoarthritis severity using the Kellgren-Lawrence scale. Scans from magnetic resonance imaging were used to assess medial tibiofemoral and patellar cartilage based on a modification of the Noyes scale. The peak knee extension torque recorded was used to represent strength.
Quadriceps strength (Nm/kg) was 22% greater in women without radiographic osteoarthritis than in women with osteoarthritis (P < 0.05). Quadriceps strength was also greater in women with Noyes’ medial tibial and femoral cartilage scores of 0 when compared in women with Noyes’ grades 2 and 3–5 (P ≤ 0.05).
Women with early evidence of osteoarthritis had less quadriceps strength than women without osteoarthritis as defined by imaging.
PMCID: PMC3294452  PMID: 20463561
Knee Extensors; Muscle; Joint Disease
8.  Choosing the best method for radiological assessment of patellofemoral osteoarthritis. 
Annals of the Rheumatic Diseases  1996;55(2):134-136.
OBJECTIVE: To assess the reproducibility of different methods of radiological assessment of patellofemoral osteoarthritis (OA) and to determine which is the best view as a research tool in epidemiological studies of knee OA requiring explicit diagnostic criteria to classify the disease in the general population. METHODS: A population based study of 252 unrelated, normal individuals (504 knees) was performed. Lateral and skyline radiographs from each individual were graded for joint space narrowing and osteophytes using a standard atlas. Reproducibility was assessed by two observers on 50 knees. Radiographic features were assessed on their ability to predict knee pain. RESULTS: The skyline views performed better than the lateral views in the assessment of patellofemoral joint OA. The reproducibility for osteophytes was high (kappa > 0.8) and that for joint space narrowing moderate (kappa > 0.6) for both lateral and skyline views. Although the specificity for detecting knee pain was similar in both views, the sensitivity of skyline views in the assessment of knee pain was greater (52.8% versus 30%). The odds ratio for skyline osteophytes as a predictor of knee pain was 7.66 (95% confidence interval (CI) 3.68 to 15.90); that for osteophytes seen on lateral view was 1.83 (95% CI 0.96 to 3.49). Narrowing on both views was a poor predictor of pain. There was frequent disagreement between the lateral and skyline views for detecting osteophytes. CONCLUSION: In a community based study, skyline views performed better than lateral views in terms of reproducibility and for identifying symptomatic patellofemoral joint OA. Skyline radiographs should be the preferred method for examining the patellofemoral joint in such studies.
PMCID: PMC1010108  PMID: 8712864
9.  The Effects of Bariatric Surgery Weight Loss on Knee Pain in Patients with Osteoarthritis of the Knee 
Arthritis  2012;2012:504189.
Studies have shown that osteoarthritis (OA) is highly associated with obesity, and individuals clinically defined as obese (BMI > 30.0 kg/m2) are four times more likely to have knee OA over the general population. The purpose of this research was to examine if isolated weight loss improved knee symptoms in patients with osteoarthritis. Adult patients (n = 24; age 18–70; BMI > 35 kg/m2) with clinical and radiographic evidence of knee OA participated in a one-year trial in which WOMAC and KOOS surveys were administered at a presurgery baseline and six and twelve months postsurgery. Statistical analysis was performed using Student's t and Wilcoxon Signed Rank tests. Weight loss six and twelve months following bariatric surgery was statistically significant (P < 0.05) compared to presurgery measurements. All variables from both KOOS and WOMAC assessments were significantly improved (P < 0.05) when compared to baseline. Isolated weight loss occurring via bariatric surgery resulted in statistically significant improvement in patient's knee arthritis symptoms at both six and twelve months. Further research will need to be done to determine if symptom relief continues over time, and if the benefits are also applicable to individuals with symptomatic knee arthritis that are overweight but not obese.
PMCID: PMC3518076  PMID: 23243506
10.  The knee skyline radiograph: its usefulness in the diagnosis of patello-femoral osteoarthritis 
International Orthopaedics  2006;31(2):247-252.
The aim of this study was to determine the usefulness of the skyline radiograph in the diagnosis of patellofemoral osteoarthritis. Additionally, we wanted to assess the usefulness of patello-femoral crepitus as a clinical sign of this condition. Seventy-seven patients scheduled to undergo knee surgery had standard antero-posterior, lateral and skyline X-rays of their affected knee. The presence of clinical patello-femoral crepitus was also documented preoperatively. At the operation, their patellofemoral joints were graded into two groups according to the presence or absence of osteoarthritis. The lateral and skyline view X-rays as well as patello-femoral crepitus were compared individually against the operative findings. The skyline view had a sensitivity of 79% and a specificity of 80%. The lateral view had a sensitivity of 82% and specificity of 65%. Patello-femoral crepitus as a sign had a sensitivity of 89% and a specificity of 82%. There was no statistically significant difference between the two radiological views in terms of sensitivity and specificity in the diagnosis of patellofemoral osteoarthritis. Hence, we cannot recommend the skyline view as a routine radiological investigation in all cases of suspected patellofemoral osteoarthritis.
PMCID: PMC2267568  PMID: 16783548
11.  Gender difference in symptomatic radiographic knee osteoarthritis in the Knee Clinical Assessment – CAS(K): A prospective study in the general population 
A recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis (knee ROA) in symptomatic males compared to females. This was independent of age, BMI and other clinical signs and symptoms. Since this finding contradicts many previous studies, our objective was to explore four possible explanations for this gender difference: X-ray views, selection, occupation and non-articular conditions.
A community-based prospective study. 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal questionnaires to a research clinic involving plain radiography (weight-bearing posteroanterior semiflexed, supine skyline and lateral views), clinical interview and physical examination. Any knee ROA, ROA severity, tibiofemoral joint osteoarthritis (TJOA) and patellofemoral joint osteoarthritis (PJOA) were defined using all three radiographic views. Occupational class was derived from current or last job title. Proportions of each gender with symptomatic knee ROA were expressed as percentages, stratified by age; differences between genders were expressed as percentage differences with 95% confidence intervals.
745 symptomatic participants were eligible and had complete X-ray data. Males had a higher occurrence (77%) of any knee ROA than females (61%). In 50–64 year olds, the excess in men was mild knee OA (particularly PJOA); in ≥65 year olds, the excess was both mild and moderate/severe knee OA (particularly combined TJOA/PJOA). This male excess persisted when using the posteroanterior view only (64% vs. 52%). The lowest level of participation in the clinic was symptomatic females aged 65+. Within each occupational class there were more males with symptomatic knee ROA than females. In those aged 50–64 years, non-articular conditions were equally common in both genders although, in those aged 65+, they occurred more frequently in symptomatic females (41%) than males (31%).
The excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views. Although prior occupational exposures and the presence of non-articular conditions cannot be fully excluded, selective non-participation bias seems the most likely explanation. This has implications for future study design.
PMCID: PMC2443794  PMID: 18547403
12.  Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study 
For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.
Two sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5° angulation and 15° angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (κ). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.
Observer reproducibility (κ) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (κ 0.73) and foot (κ 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (ptrend <0.001).
The two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.
PMCID: PMC2896354  PMID: 20565825
13.  Direct Comparison of Fixed Flexion Radiography and MRI in Knee Osteoarthritis: Responsiveness Data from the Osteoarthritis Initiative 
Minimum radiographic joint space width (mJSW) represents the FDA standard for demonstrating structural therapeutic benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness (sensitivity to change). We directly compare the responsiveness of MRI-based cartilage thickness and JSW measures from fixed-flexion radiography (FFR) and explore the correlation of region-matched changes between both methods.
967 knees of Osteoarthritis Initiative participants with radiographic KOA were studied: 445 over one year with coronal FLASH MRI and FFR, and 375/522 over one/two years with sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage thickness and mJSW were compared using the sign-test.
With FLASH MRI, SRM was −0.28 for medial compartment (MFTC) cartilage loss vs. −0.15 for mJSW, and −0.32 vs. −0.22 for the most sensitive MRI subregion (central MFTC) vs. the most sensitive fixed location JSW(X=0.25). With DESS MRI, one-year SRM was −0.34 for MFTC vs. −0.22 for mJSW and −0.44 vs. −0.28 for central MFTC vs. JSW(X=0.225). Over two years, the SRM was significantly greater for MFTC than for mJSW (−0.43 vs. −0.31, p=0.017) and for central MFTC than for JSW(X=0.225) (−0.51 vs. −0.44, p<0.001). Correlations between changes in spatially matched MRI subregions and fixed location JSW were not consistently higher (r=0.10–0.51) than those between non-matched locations (r=0.15–0.50).
MRI displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest SRM observed in the central medial femorotibial compartment. Fixed-location radiographic measures appear not capable of determining the spatial distribution of femorotibial cartilage loss.
PMCID: PMC3569717  PMID: 23128183
Sensitivity to change; Radiography; Fixed Flexion; Magnetic resonance imaging; Knee osteoarthritis
14.  Reliability and Agreement of Measures Used in Radiographic Evaluation of the Adult Hip 
Several mechanical derangements reportedly contribute to the development of noninflammatory arthritis of the hip. Diagnosis of these derangements involves the use of specific radiographic measures (eg, alpha angle, lateral center edge angle, cross-over sign). The reliability of some of these measures is not known, whereas others have not been confirmed.
We examined the reproducibility of 20 radiographic parameters of the hip used in clinical practice.
Twenty radiographic parameters on standardized digital AP and cross-table lateral radiographs were evaluated by two observers on two different occasions. The parameters were evaluated from the standpoint of reproducibility (reliability and agreement). The intraclass correlation coefficient (ICC), kappa coefficient, and standard error of measurement were calculated. The minimal detectable change was calculated where possible.
Interrater reliability ranged from 0.45 to 0.90 for ICC depending on the measure. Intrarater reliability ranged from 0.55 to 0.99. Measurements that could be measured directly (femoral head diameter) were more reliable than measurements requiring estimation on the part of the observer (Tönnis angle, neck-shaft angle). Categorical parameters had interrater and intrarater reliability kappa values greater than 0.90 for all parameters measured. Agreement between repeated measurements, as given by the minimal detectable change, showed many parameters with low absolute reliability have clinical use in the context of the large changes seen in clinical practice.
Radiographic hip measures show clinical utility when evaluated from the perspective of agreement and reliability.
Clinical Relevance
All measures investigated show clinical utility when evaluated from the perspective of reliability and agreement.
Level of Evidence
Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3008883  PMID: 20596806
15.  Clinical classification criteria for knee osteoarthritis: performance in the general population and primary care 
Annals of the Rheumatic Diseases  2006;65(10):1363-1367.
Doubts have been expressed about the performance of the American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis when applied in the general population.
To investigate whether the distribution of population subgroups and underlying disease severity might explain the performance of these criteria in the population setting.
Population‐based cross‐sectional study. 819 adults aged ⩾50 years reporting knee pain in the last 12 months were clinically assessed by research therapists using standardised protocols and blinded to radiographic status. All participants underwent plain radiography of the knees, scored by a single reader blinded to clinical status. The relationship between fulfilling the ACR clinical classification criteria for knee osteoarthritis and the presence of symptomatic radiographic knee osteoarthritis was summarised for the sample as a whole and within subgroups.
Radiographic osteoarthritis was present in 539 participants (68%) and symptomatic radiographic knee osteoarthritis in 259 (33%). 238 participants (30%) fulfilled the ACR clinical criteria for knee osteoarthritis. Agreement between the ACR clinical criteria and symptomatic radiographic knee osteoarthritis was low (sensitivity 41%; specificity 75%; positive predictive value 44%; negative predictive value 72%). Sensitivity and specificity did not vary markedly between population subgroups, although they were influenced by the underlying severity of radiographic osteoarthritis.
The ACR clinical criteria seem to reflect later signs in advanced disease. Other approaches may be needed to identify early, mild osteoarthritis in the general population and primary care.
PMCID: PMC1798313  PMID: 16627539
16.  The inter-observer agreement of examining pre-school children with acute cough: a nested study 
The presence of clinical signs have implications for diagnosis, prognosis and treatment. Therefore, the aim of this study was to examine the inter-observer agreement of clinical signs in pre-school children presenting to primary care.
A nested study comparing two clinical assessments within a prospective cohort of 256 pre-school children with acute cough recruited from eight general practices in Leicestershire, UK. We examined agreement (using kappa statistics) between unstandardised and standardised clinical assessments of tachypnoea, chest signs and fever.
Kappa values were poor or fair for all clinical signs (range 0.12 to 0.39) with chest signs the most reliable.
Primary care clinicians should be aware that clinical signs may be unreliable when making diagnosis, prognosis and treatment decisions in pre-school children with cough. Future research should aim to further our understanding of how best to identify abnormal clinical signs.
PMCID: PMC387826  PMID: 15102326
17.  Imaging modalities in hand osteoarthritis - status and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography 
Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought.
PMCID: PMC3334630  PMID: 22189142
18.  Pre-radiographic MRI findings are associated with onset of knee symptoms: the most study 
Magnetic resonance imaging (MRI) has greater sensitivity to detect osteoarthritis (OA) damage than radiographs but it is uncertain which MRI findings in early OA are clinically important. We examined MRI abnormalities detected in knees without radiographic OA and their association with incident knee symptoms.
Participants from the Multicenter Osteoarthritis Study (MOST) without frequent knee symptoms (FKS) at baseline were eligible if they also lacked radiographic features of OA at baseline. At 15 months, knees that developed FKS were defined as cases while control knees were drawn from those that remained without FKS. Baseline MRIs were scored at each subregion for cartilage lesions (CARTs); osteophytes (OST); bone marrow lesions (BML) and cysts. We compared cases and controls using marginal logistic regression models, adjusting for age, gender, race, body mass index (BMI), previous injury and clinic site.
36 case knees and 128 control knees were analyzed. MRI damage was common in both cases and controls. The presence of a severe CART (P = 0.03), BML (P = 0.02) or OST (P = 0.02) in the whole knee joint was more common in cases while subchondral cysts did not differ significantly between cases and controls (P > 0.1). Case status at 15 months was predicted by baseline damage at only two locations; a BML in the lateral patella (P = 0.047) and at the tibial subspinous subregions (P = 0.01).
In knees without significant symptoms or radiographic features of OA, MRI lesions of OA in only a few specific locations preceded onset of clinical symptoms and suggest that changes in bone play a role in the early development of knee pain. Confirmation of these findings in other prospective studies of knee OA is warranted.
PMCID: PMC2990960  PMID: 19919856
MRI; Knee osteoarthritis; BML; Epidemiology
19.  Assessing progression of patellofemoral osteoarthritis: a comparison between two radiographic methods. 
Annals of the Rheumatic Diseases  1996;55(12):875-879.
OBJECTIVE: To compare two plain radiographic methods for sensitivity to detect progression of patellofemoral osteoarthritis. METHODS: Two sets of paired skyline and lateral knee radiographs from 54 hospital referred patients (108 knees) with knee osteoarthritis were taken an average of 31 months apart (range 12-40). Films were examined separately in random order by a single observer blind to patient identity and time order. Minimum joint space was measured by metered caliper; individual features of osteoarthritis were graded 0-3 using an atlas. RESULTS: Intraobserver reproducibility assessed on 40 knees was to within +/- 0.5 mm for skyline lateral facet and +/- 0.7 mm for medial facet and lateral views. On the lateral view measured joint space decreased in 51% of knees but increased in 43%, with overall no significant mean group change with time (-0.2 mm, 95% confidence interval, 0.1 to -0.5). By contrast on the skyline view joint space decreased in at least one facet in 71% of knees, with significant decrease in mean joint space for both lateral facets (-0.4 mm, 95% CI, -0.2 to -0.6) and medial facets (-0.5 mm, 95% CI, -0.1 to -0.8). CONCLUSIONS: It is possible to detect significant joint space loss with time on the skyline view that is not apparent on the lateral view. The skyline view should be the method of choice to detect progression of patellofemoral osteoarthritis.
PMCID: PMC1010337  PMID: 9014580
20.  BMI vs. body composition and radiographically-defined osteoarthritis of the knee in women: a 4-year follow-up study 
To elucidate the role of body mass index (BMI) and knee osteoarthritis (OAK) by evaluating measures of body composition including fat mass and skeletal muscle mass (SMM).
Data is from 541 women enrolled in the Michigan Bone Health Study, a longitudinal, population-based study. At visits in 1998 and 2002, radiographs were taken of both knees and were evaluated for the presence of OAK (≥ 2 on the Kellgren and Lawrence (K-L) scale). Joint space width (JSW) was measured with electronic calipers. Fat mass and SMM were determined using bioelectrical impedance analysis.
In 2002, the prevalence of OAK was 11% in this population of women, whose mean age was 47 years. Fat mass, lean mass, SMM, waist circumference and BMI was greater in women with OAK compared to those without OAK. In multiple variable analyses adjusted for age, fat mass and SMM explained OAK prevalence and increasing OAK severity better than models with BMI; further SMM explained more variation than did fat mass. SMM was positively associated with level of left and right medial JSW while there was no consistent association of JSW and BMI or fat mass.
Fat mass and SMM were associated with K-L OAK score and the amount of joint space, with more variation explained by SMM. SMM was highly associated with JSW. Therefore, though obesity, frequently characterized with BMI, is a frequently reported risk factor for OAK, this mis-attribution may mean that interventions that focus on weight loss as treatment for OA should be aware that this may negatively impact muscle mass.
PMCID: PMC2311420  PMID: 17884608
osteoarthritis; body mass index; body composition; fat mass; skeletal muscle mass
21.  Association of a BMP5 microsatellite with knee osteoarthritis: case-control study 
Arthritis Research & Therapy  2012;14(6):R257.
We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.
OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls.
Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10-4 to 4.1 x10-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with those previously reported for hip OA.
We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joints. This result also shows the interest of analysing other multiallelic polymorphisms.
PMCID: PMC3674626  PMID: 23186552
22.  The discordance between clinical and radiographic knee osteoarthritis: A systematic search and summary of the literature 
Studies have suggested that the symptoms of knee osteoarthritis (OA) are rather weakly associated with radiographic findings and vice versa. Our objectives were to identify estimates of the prevalence of radiographic knee OA in adults with knee pain and of knee pain in adults with radiographic knee OA, and determine if the definitions of x ray osteoarthritis and symptoms, and variation in demographic factors influence these estimates.
A systematic literature search identifying population studies which combined x rays, diagnosis, clinical signs and symptoms in knee OA. Estimates of the prevalence of radiographic OA in people with knee pain were determined and vice versa. In addition the effects of influencing factors were scrutinised.
The proportion of those with knee pain found to have radiographic osteoarthritis ranged from 15–76%, and in those with radiographic knee OA the proportion with pain ranged from 15% – 81%. Considerable variation occurred with x ray view, pain definition, OA grading and demographic factors
Knee pain is an imprecise marker of radiographic knee osteoarthritis but this depends on the extent of radiographic views used. Radiographic knee osteoarthritis is likewise an imprecise guide to the likelihood that knee pain or disability will be present. Both associations are affected by the definition of pain used and the nature of the study group. The results of knee x rays should not be used in isolation when assessing individual patients with knee pain.
PMCID: PMC2542996  PMID: 18764949
23.  Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement 
Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.
This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis.
Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale.
Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.
PMCID: PMC3228720  PMID: 22074728
24.  Revision 1 Size and position of the healthy meniscus, and its Correlation with sex, height, weight, and bone area- a cross-sectional study 
Meniscus extrusion or hypertrophy may occur in knee osteoarthritis (OA). However, currently no data are available on the position and size of the meniscus in asymptomatic men and women with normal meniscus integrity.
Three-dimensional coronal DESSwe MRIs were used to segment and quantitatively measure the size and position of the medial and lateral menisci, and their correlation with sex, height, weight, and tibial plateau area. 102 knees (40 male and 62 female) were drawn from the Osteoarthritis Initiative "non-exposed" reference cohort, including subjects without symptoms, radiographic signs, or risk factors for knee OA. Knees with MRI signs of meniscus lesions were excluded.
The tibial plateau area was significantly larger (p < 0.001) in male knees than in female ones (+23% medially; +28% laterally), as was total meniscus surface area (p < 0.001, +20% medially; +26% laterally). Ipsi-compartimental tibial plateau area was more strongly correlated with total meniscus surface area in men (r = .72 medially; r = .62 laterally) and women (r = .67; r = .75) than contra-compartimental or total tibial plateau area, body height or weight. The ratio of meniscus versus tibial plateau area was similar between men and women (p = 0.22 medially; p = 0.72 laterally). Tibial coverage by the meniscus was similar between men and women (50% medially; 58% laterally), but "physiological" medial meniscal extrusion was greater in women (1.83 ± 1.06mm) than in men (1.24mm ± 1.18mm; p = 0.011).
These data suggest that meniscus surface area strongly scales with (ipsilateral) tibial plateau area across both sexes, and that tibial coverage by the meniscus is similar between men and women.
PMCID: PMC3215228  PMID: 22035074
25.  The inter-observer reproducibility of Lasègue's sign in patients with low back pain in general practice. 
BACKGROUND: The spectrum of low back pain patients in general practice differs significantly from that in an orthopaedic clinic. The most frequent specific cause of low back pain is nerve-root irritation or compression caused by intervertebral protrusion, and the diagnosis is still problematic. Testing for Lasègue's sign could be a useful way of detecting high-risk patients, but so far the reproducibility of the test has been measured only in hospital-based studies. AIM: To assess the inter-observer reproducibility of Lasègue's sign in general practice. METHOD: Fifteen General practitioners from Amsterdam and the surrounding areas tested all consecutive low back pain patients who visited them during a period of two years for Lasègue's sign. The test was repeated within two weeks in two samples: sample I consisted of 50 consecutive low back pain patients; sample II consisted of all patients who had pelvic tilt, scoliosis, or positive Lasègue's sign. RESULTS: In sample I, the observation was repeated in 49 patients. The Kappa coefficient was 0.33, and the proportions of positive and negative agreement were 33% and 96%, respectively. In sample II, the observation was repeated in 48 patients. The Kappa coefficient was 0.56, whereas the proportion of positive agreement was 67% and the proportion of negative agreement was 91%. CONCLUSIONS: The reproducibility of Lasègue's sign in routine general practice seems to be low, but may be similar to the reproducibility observed in hospital settings in selected patients who have a high chance of low back pain owing to a specific disease.
PMCID: PMC1239862  PMID: 8995852

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