Objective: The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x-ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views.
Methods: At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated.
Results: In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and −0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001).
Conclusions: LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.
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Progression of structural damage in the knee with osteoarthritis (OA) is inferred from the reduction in joint space width (JSW), which is considered a surrogate for the thickness of articular cartilage on the femur and tibia,1 although meniscal pathology may contribute to joint space narrowing (JSN).2 Protocols for radioanatomic positioning of the knee have been developed to optimise reproducibility of JSW measurements in trials of structure-modifying drugs for OA (SMOADs), in which the less the variability in JSN due to measurement error in the placebo group, the smaller the sample size and/or treatment duration required to demonstrate a drug effect.3
The importance of alignment of the medial tibial plateau (MTP) and x-ray beam (ie, superimposition ±1 mm of anterior and posterior margins of the plateau) was emphasised by demonstration that JSN was twice as rapid, and only one-quarter as variable, when alignment was present in paired standing anteroposterior (AP) films as when alignment was unsatisfactory.4
The fixed flexion (FF)5 and Lyon Schuss (LS)6 7 radiographic protocols offer greater reliability for measurement of tibiofemoral JSW and greater sensitivity to change in JSW than a conventional standing AP view. Both employ 20–30° of knee flexion, providing contact at the site on the femoral condyle at which cartilage damage in OA is usually greatest.8 The FF protocol, however, does not utilise fluoroscopy and the beam angle is uniformly fixed at 10° caudally. In contrast, the beam angle is adjusted fluoroscopically for each LS examination, to align the margins of the MTP.
Recently,9 MTP alignment was found to be much less frequent with the FF view than with a fluoroscopically assisted semiflexed AP view, in which alignment is a quality control criterion.10 However, that comparison was based on data from separate cohorts that differed in age, disease severity, duration of follow-up and other features. No study has directly compared the FF and LS view with respect to long-term reproducibility of JSW measurements in normal knees and sensitivity to change in JSW in OA. This report provides such head-to-head comparison.
SUBJECTS AND METHODS
The 161 individuals in this analysis included 62 with radiographic OA at baseline (Kellgren and Lawrence grade (KLG) 2–311 in a standing AP view of the study knee and grade 0–3 in the contralateral knee). These subjects, recruited in seven academic medical centres, were enrolled in a multicentre study to evaluate the progression of OA based, in part, on changes in medial compartment JSW. The remaining 99 subjects were age- and sex-matched non-arthritic controls in the observational study.
All subjects were women at least 40 years old and in good general health. In the hope of increasing the likelihood of progression of JSN, all patients with OA had a body mass index (BMI) ⩾30, and all controls a BMI <28, with no x-ray or clinical evidence of OA.
In patients who had bilateral radiographic knee OA the study knee was defined as the more symptomatic knee. If pain scores were identical in both OA knees, the knee with more advanced radiographic changes was selected. If pain scores and radiographic severity of OA in the two knees were identical, the knee in the dominant leg was chosen as the study knee, as it was for all control subjects. Detailed characterisation of the subjects, risk factors for OA, and inclusion and exclusion criteria for the observational study will be presented elsewhere.
A standing AP view of both knees in extension was used to determine eligibility for the study on the basis of the KLG assigned by the clinical centre directors. An experienced central reader (SAM), who was blinded to the grade assigned in the clinical centre, re-read each radiograph for standardisation of KLG. If the grade assigned in the clinical centre differed from that of the central reader, the difference was adjudicated by a third reader (KDB). Intra-reader reproducibility, determined using 30 radiographs with KLGs from 0 to 3, showed an intraclass correlation coefficient (ICC) of 0.91 and κ of 0.66. After ascertaining that the subject qualified for the study, an LS view of the study knee was obtained to assure the medial tibiofemoral JSW was >2 mm. If it was not, the patient was deemed ineligible for the study. If JSW was >2 mm, a FF view was obtained and the patient was scheduled to return in 12 months for follow-up radiographs.
The posteroanterior (PA) views for the LS and FF images were obtained as in fig 1. For both views, a V-shaped angulation support on the base of a SynaFlexer frame (Synarc, Inc., San Francisco, California, USA) was used to fix the foot in 10° external rotation.5
Semi-automated measurement of minimum joint space width
mJSW in the medial tibiofemoral compartment was measured by an experienced observer using digitised image analysis software (Holy’s Software, UCLB, Lyon, France).12 Intra-observer reproducibility of mJSW measurements was determined by blinded re-measurement of 36 randomly selected LS radiographs and 18 FF radiographs. To determine interobserver reproducibility, a second experienced observer measured mJSW in the 36 LS radiographs. Both observers were blinded to the chronology of the films and mode of image acquisition.
Measurement of intermargin distance
Using the above software, the degree of alignment of the MTP with the x-ray beam, based on the distance, in mm, between the anterior and posterior margins at the centre of the plateau (inter-margin distance, IMD), was evaluated. Intra-observer reliability was assessed by repeating the IMD reading on the subsets of 36 LS and 18 FF radiographs.
Reproducibility of measurements was evaluated by the SD of the difference between measurements, the ICC and by the method of Bland and Altman.13 Comparisons of medial compartment mJSW and 12-month JSN in FF and LS radiographs of the same knee were made with a paired Student’s t test. Comparisons of medial JSW in relation to KLG were made by ANOVA. Correlation between medial JSW and IMD was made with a simple regression analysis. Sensitivity to change in JSW was assessed by the standardised response mean, the mean difference in JSW between baseline and 12 months divided by the SD of the difference.
Controls and patients with OA were similar in age (56.0 (8.8) years vs 57.2 (8.0) years), but differed markedly with respect to BMI (25.1 (5.2) vs 36.9 (5.3)) and WOMAC pain score (1.0 (2.7) vs 6.3 (3.7), possible range = 0–20)).14
Reproducibility of measurements of minimum joint space width and intermargin distance
Minimum joint space width
The SD of the mean difference between the two measurements of mJSW in the 36 LS images on which assessment of intra-observer reproducibility was based was 0.04 mm and the intraclass correlation coefficient (ICC), 0.99. Among the 18 FF images, the mean (SD) of the difference in mJSW was 0.003 (0.039) mm and the ICC, 0.99. The SD of the mean difference between mJSW measurements of the same LS images by the two observers was 0.04 mm and the inter-observer ICC was 0.99, ie, identical to the intra-observer ICC.
Figure 2 shows the reproducibility of JSW measurements in LS radiographs in relation to the magnitude of JSW in 36 randomly selected radiographs of the knee. The data indicate that error in measurement of mJSW was unrelated to the magnitude of JSW.
The SD of the mean difference between the two measurements of IMD in the 36 LS radiographs was 0.36 mm and the ICC was 0.86. Among the 18 FF knees, the difference between the two measurements of IMD was 0.01 (0.26) mm and the ICC was 0.93. Figure 3 shows intra-observer reliability of IMD measurement in LS radiographs according to the Bland and Altman method.13 The error in measurement of the IMD was unrelated to the magnitude of the IMD.
Relation of Kellgren and Lawrence grade to minimum joint space width and joint space narrowing
Ninety-five subjects had KLG 0, four had KLG 1, and 31 each had KLG 2 or 3 changes of OA (table 1). Among all 161 subjects, mean mJSW at baseline was significantly larger in the FF view than the LS view (4.01 (0.84) mm vs 3.89 (0.77) mm; p = 0.0011) and follow-up (4.01 (0.90) mm vs 3.79 (0.86) mm; p<0.0001). In the 12-month films, the difference between the two views was twice as great as in the baseline exam (mean difference = 0.11 mm at baseline and 0.22 mm at 12 months, p = 0.0011 and p<0.0001, respectively).
With both protocols, baseline mJSW varied with radiographic severity of OA (ANOVA, p<0.0001). In the LS view, mJSW was larger in KLG 2 knees than in KLG 0 knees (p = 0.0015) and smaller in KLG 3 knees than in grade 0–2 knees (p<0.0001) (table 1). Similarly, in the FF view mJSW was larger in KLG 2 knees than KLG 0 knees (p = 0.012) and smaller in KLG 3 knees than in those with a lower KLG (p<0.0001). The FF view of KLG 1 knees showed a significant increase in JSW, relative to KLG 0 (p = 0.016). In the LS view, a similar trend was seen, but was not significant. However, only four subjects exhibited KLG 1 changes (table 1).
Among normal knees (KLG 0), mean mJSW did not vary over 12 months with either the LS or FF view (table 2). In both views, the correlation between baseline and 12-month mJSW was excellent (r = 0.87 p<0.0001 for LS and r = 0.88 p<0.0001 for FF).
Although knees with definite radiographic OA (KLG 2–3) showed marked JSN in the LS views, JSN was not apparent in FF views of these knees (table 2). In the LS films, loss of JSW, relative to baseline, was highly significant in KLG 3 knees and approached significance in KLG 2 knees (p = 0.06).
Joint space narrowing and intermargin distance
LS and FF protocols differed markedly in achieving MTP alignment. In both the baseline and 12-month examinations, IMD was approximately twice as large in the FF view (table 3). Among baseline exams of the 161 study knees, IMD ⩽1.5 mm was seen in 92% of the LS views but only 51% of the FF views. IMD ⩽1 mm was achieved in 57% of baseline LS views but only 29% of baseline FF views.
Not only were absolute values for IMD smaller in the LS view than the FF view, reproducibility of alignment, based upon the difference between IMD in the baseline and follow-up radiograph (IMDBL and IMD12 mo) was much better in paired LS films than in paired FF films (0.46 (0.40) mm vs 0.87 (0.74) mm, p<0.0001). Among 49% of paired LS radiographs, but only 14% of paired FF views, IMD was ⩽1 mm in both exams. Similarly, in 88% of paired LS exams, but only 35% of paired FF films, IMD was ⩽1.5 mm in both exams.
In FF views of all 161 knees, the 12-month change in JSW correlated with the change in IMD (r = 0.27, p = 0.0005). However, no such correlation was apparent among the 55 FF exams in which IMDBL and IMD12 mo were both <1.5 mm and the paired LS views showed a much weaker correlation between change in JSN and change in IMD (r = 0.03, p = 0.39).
Based on the regression curve, a 1 mm difference between IMDBL and IMD12 mo in FF views resulted in a 0.10 mm change in JSW. When IMD12 mo was ⩾1 mm larger than IMDBL, mean JSN was –0.17 (0.51) mm (n = 24), ie, JSW increased. In contrast, when IMD12 mo was at least 1 mm smaller than IMDBL, JSN was 0.15 (0.42) mm (n = 25), p = 0.017, ie, JSW decreased.
The 12-month change in JSW in paired FF views of the 62 OA knees correlated even more strongly with differences in IMD between the two exams (r = 0.4, p = 0.0011) than it did for all 161 knees (r = 0.27, p = 0.0005, fig 4), whereas no such correlation was apparent in the paired LS views (r = 0.009, p = 0.94).
This report provides the first head-to-head comparison of the LS and FF views, which, although essentially identical with respect to positioning of the knee (fig 1), differ in one important respect: in the LS view, the x-ray beam angle is adjusted to achieve optimal alignment of the MTP for each examination; in the FF view, no specific attention is paid to alignment and the beam angle is fixed at 10°.
Our results show the following: mean JSW was significantly smaller in the LS than FF view; in both views, JSW was significantly smaller in knees with KLG 3 changes than in knees with grade 0–2 changes; in the LS, but not FF, view, JSW was significantly greater in grade 2 knees than in those with grade 0–1 OA (table 1); at 12 months, JSW had narrowed significantly in the LS, but not the FF views, of OA knees (table 2); and MTP alignment was achieved twice as often with the LS as with the FF view (table 3). The findings are consistent with the possibility that the smaller JSW and greater JSN with the LS view were related to the lower frequency of MTP alignment with the FF protocol.
Even though the observer was blinded to the mode of acquisition of the image, large IMDs occurred only with the FF view. In such cases, the reader may have suspected that the image had been obtained with the FF protocol. None the less, because JSW measurements were fully automated, it is highly unlikely that the above results were due to inadequate blinding.
The significantly greater JSW in grade 2 knees, relative to grade 0 or 1 knees, in both the LS and FF views is consistent with the hypertrophic repair of cartilage that occurs in the earlier stages of OA.15 16 It can not be attributed to anthropomorphic differences between these patients with OA, because the BMI of patients with KLG 2 was lower than that of those with KLG 3 OA (table 1). Furthermore, among healthy young women, Duren et al17 found JSW did not correlate with body size.
With neither imaging protocol was JSN observed among KLG 0–1 knees. The strong correlation between mJSW at baseline and at 12 months indicates that LS and FF views offer similar reproducibility in measurement of JSW in such knees. However, the two views differed strikingly with respect to the detection of JSN in OA knees, in which mean 12-month JSN in the LS views was 0.22 mm (p = 0.0002), but was negligible in the FF views (−0.01 mm, p = 0.92) (table 2).
Given that the FF view does not include specific alignment measures, it is not surprising that IMD was twice as great in FF films, and the difference between IMDBL and IMD12 mo only half as great, with the LS protocol (p<0.001).
Finally, our results indicate that the difficulty in achieving MTP alignment in the FF view influences measurements of JSN. Among paired FF films, in which an IMD ⩽1.5 mm in both exams was achieved in only about 36%, when alignment was better in the second radiograph than in the first, JSW decreased. Notably, when alignment was better in the baseline exam than at follow-up, JSW increased. This correlation was not observed when IMD was ⩽1.5 mm in both FF exams or with the LS view, in which good alignment was sufficiently common that differences in IMD between exams did not affect JSN. That IMD12 mo was larger than IMDBL in FF exams of 55% of the subjects may help account for the absence of mean JSN in OA knees imaged with the FF protocol.
These results indicate the LS view is more sensitive than the FF view knee OA in measuring change in JSW in OA. Because of the disadvantages of fluoroscopy (eg, training of radiology technicians, limitations in the number of clinical centres in which the exam can be performed, cost, additional radiation exposure), non-fluoroscopic approaches that achieve MTP alignment should be developed.
These findings have practical implications: an interval of only 12 months was sufficient to detect JSN with the LS, but not FF, view of OA knees. In an observational study, increasing the duration of follow-up or the sample size may overcome the limitations of the FF technique. However, in a clinical trial attempting to demonstrate slowing of JSN by an SMOAD, those limitations would require exposure of a larger number of subjects to possible adverse effects of the test drug than use of the LS protocol.
We are grateful to the dedicated group of site x-ray technologists and study co-ordinators whose skills were essential in assuring the successful conduct of this study: Emily Brown, Sandra Chapman, Eugene Dunkle, Kristen Fredley, Donna Gilmore, Joyce Goggins, Mohsen Haddad-Kaveh, Norine Hall, Thelma Munoz and Kim Tally. We also would like to thank Sharmila Majumdar, Julia Crim, Maureen Ainslie, the Duke Image Analysis Laboratory staff, Charles Packard and Mark Tengowski for their invaluable efforts in conducting this study.
Funding: Pfizer Global Research & Development.
Competing interests: None of the authors has a competing interest with regard to publication of the study, because no organisation may gain or lose financially from the results of conclusions published here. M-PHLeG is employed by Pfizer Inc. EV receives grant support from Pfizer. KDB provides consulting services to Pfizer. MP receives grant support from Pfizer. RJB is employed by Pfizer Inc. HCC receives contract support from Pfizer. DH receives grant support from Pfizer, Merck and DonJoy. CJ receives research grants from Pfizer. VBK receives research grants from Pfizer. TML receives research grants from Pfizer, GlaxoSmithKline and Merck. SAM receives grant support from, and provides consulting services to Pfizer. TJS receives research grants from Pfizer. AV receives research grants from Pfizer. BW is employed by Pfizer Inc.
Ethics approval: The study was conducted in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with local Institutional Review Board, informed consent regulations, and International Conference on Harmonisation Good Clinical Practices Guidelines.
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