Reading radiographs in pairs or in chronological order influences radiological progression in osteoarthritis

S. Botha-Scheepers, I. Watt1, F. C. Breedveld and M. Kloppenburg

Departments of Rheumatology and 1 Radiology, Leiden University Medical Centre, The Netherlands.

Correspondence to: S. Botha-Scheepers, Leiden University Medical Centre, Department of Rheumatology, C4-R, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: S.A.Scheepers{at}lumc.nl


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To determine the influence of the order in which a series of radiographs were read on the sensitivity to change over a 2-yr follow-up period in patients with osteoarthritis (OA) at multiple sites.

Methods. Radiographs of 20 patients with OA in at least two joint sites were obtained at baseline and after 2 yr, and scored according to the consensus of two readers. Joint space narrowing (JSN) and osteophytes were graded (0–3) in the hand, hip and tibiofemoral joints. The cervical (C2–7) and lumbar spine disc spaces (L1–S1) were graded (0–3) for disc space narrowing (DSN) and anterior osteophytes. Films were read by two different procedures: in pairs, with an unknown time sequence and in chronological order. Radiological progression was defined as an increase of at least one grade in JSN, DSN or osteophyte total scores. The two procedures were compared using standardized response means (SRM).

Results. The SRM for changes in JSN or DSN progression scores in the hands, hips, knees and spine were, respectively, 0.00, 0.00, 0.32, 0.13 and 0.38, 0.32, 0.56, 0.18 for the paired and chronological readings. The SRM for changes in osteophyte progression scores in the hands, hips, knees and spine were, respectively, 0.39, 0.20, 0.32, 0.38 and 0.41, 0.37, 0.56, 0.66 for the paired and chronological readings.

Conclusion. When assessing radiological progression in OA, reading a series of radiographs in chronological order tended to be more sensitive to change over a 2-yr follow-up period than reading in pairs with an unknown time sequence.

KEY WORDS: Osteoarthritis, Radiological progression, Reading procedure, Chronological order, Paired radiographs


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Osteoarthritis (OA) is defined as gradual loss of articular cartilage, combined with thickening of the subchondral bone and bony outgrowths at joint margins. At present, conventional radiography remains the best validated, most widely available and most economical imaging technique for the assessment of the structural characteristics of OA. Dependent on the individual joint group, several published methodologies exist to assess the degree of radiological severity of OA. These include scoring systems such as Kellgren–Lawrence global scores and semiquantitative scoring systems based on individual radiographic features, as well as quantitative measurements of joint space width (JSW).

Comparison of the radiological OA severity of a joint using at least two different time points can assess progression of OA in longitudinal studies. When assessing radiological progression, the order in which radiographs are read depends upon the reading procedure used. Many possibilities exist, for example (1) randomized: radiographs read individually in random order with regard to both patient and time sequence; (2) paired radiographs of the same patient read without information about their chronological sequence; (3) chronologically, all radiographs of the same patient being read in chronological sequence. Different reading procedures have been used in longitudinal studies of OA progression [1–6]. It is unclear which is the most appropriate. Moreover, the choice of reading procedure may depend on the study design and joint group under investigation.

Buckland-Wright et al. [7] recommended that in epidemiological and genetic studies in hand OA, films should be read randomly, and that in clinical trials films should be read in chronological order, but blinded to treatment group. For assessment of radiological progression in knee and hip OA, Dieppe and Altman [8, 9] recommended that films should be read in pairs. One study compared random, paired and chronological reading procedures in hip OA and concluded that paired reading with landmarks for JSW measurements is preferable in longitudinal studies of hip OA [10].

The different reading procedures have not been compared to date in the assessment of OA progression in the hands, knees or spine. Hence, in the present study, the paired and chronological procedures were compared to determine the influence of reading procedure on sensitivity to change over a 2-yr follow-up period in patients with OA at multiple sites. These procedures were chosen in order to evaluate the effect of knowledge of chronology.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Study population
Patients are participants in the Genetics, Arthrosis and Progression (GARP) Study that is aimed primarily at identification of the genetic determinants of OA susceptibility and progression in a population comprising Caucasian sibships of Dutch ancestry. Details of recruitment, selection procedures and inclusion into the GARP study have been published elsewhere [11]. Probands (aged 40–70 yr) and their siblings, with symptomatic OA at multiple sites in the hands or at two or more of the following joints sites, hand, spine (cervical or lumbar), knee or hip, were included after giving informed consent. Sibling pairs with at least one subject with symptomatic hip or knee OA (but not radiological end-stage disease) were followed for 2 yr. The GARP study was approved by the Medical Ethics Committee of the Leiden University Medical Centre.

Diagnosis of OA
Symptomatic hand OA was defined according to the American College of Rheumatology (ACR) criteria [12]. Symptomatic knee OA was defined as pain or stiffness for most days of the prior month and osteophytes at joint margins [13]. Symptomatic hip OA was defined as pain or stiffness in the groin and hip region on most days of the prior month in addition to femoral or acetabular osteophytes or axial joint space narrowing on radiographs [14]. Hips or knee joint prostheses inserted as a result of end-stage OA were included as OA in that particular joint. Symptomatic spine OA (cervical and lumbar) was defined as pain or stiffness on most days of the prior month in the spine in addition to a Kellgren–Lawrence score of two in at least one disc or one facet joint.

Radiographs
Standardized conventional radiographs of the hands (antero-posterior, AP), knees [posterior–anterior (PA) weight bearing/semiflexed], hips (PA/weight bearing), lumbar (PA and lateral) and cervical spine (anterior-posterior, lateral and transoral) were obtained at baseline and after 2 yr. A single experienced radiographer took the radiographs employing a standard protocol with a fixed film–focus distance.

Radiological assessment
All radiographs were scored by consensus opinion of two experienced readers (S.B., I.W.) for individual radiographic OA features. In case of disagreement, the lower, more conservative score was recorded. Radiographs were graded on a scale of 0–3 for joint space narrowing (JSN) and for osteophytes. The joints that were scored with the help of the Altman atlas [15] comprised the eight distal interphalangeal (DIP) joints, the eight proximal interphalangeal (PIP) joints, the 10 metacarpophalangeal (MCP) joints, the two interphalangeal (IP) joints of the thumbs, the right and left first carpometacarpal (CMC) joints, the right and left scaphotrapezial (STT) joints, right and left medial and lateral compartments of the tibiofemoral joints, and right and left hip joints. The cervical (C2–7) and lumbar (L1–S1) spine was graded for disc space narrowing (DSN) and anterior osteophytes using the Lane atlas [16].

Reading procedures
Films were blinded for patient characteristics and read by two different reading procedures. First, all films were read in pairs with the radiographs of the same patient at both time points being assessed together but with unknown time sequence. Approximately 2 weeks later the radiographs of the same patient were assessed again, but in known chronological order.

Statistical analyses
The JSN, DSN and osteophyte scores of the following groups of joints were analysed in combination: hands (DIPs, PIPs, MCPs, IPs, CMC1s, STTs), knees (medial and lateral compartments of the tibiofemoral joints), hips and spine (cervical and lumbar). Total scores for JSN and osteophytes in the hands, hips and knees were calculated by adding the scores of left and right sides. Total scores for DSN and anterior osteophytes in the spine were calculated by adding the scores of cervical and lumbar spine. The maximum scores for JSN or DSN were, respectively, 96 in the hands, 12 in the knees, 6 in the hips and 30 in the cervical and lumbar spine. The maximum scores for osteophytes were, respectively, 96 in the hands, 24 in the knees, 6 in the hips and 30 in the cervical and lumbar spine. The radiological outcomes were the change in total JSN, DSN or osteophyte scores in each joint group after 2 yr. Radiological progression was defined as an increase of at least one grade in JSN, DSN or osteophyte total scores of the different joint groups. The non-parametric Wilcoxon signed rank test was used to detect statistically significant differences in progression scores between the paired and chronological reading procedures.

To evaluate the sensitivity to change, independent of sample size, the two procedures were compared by using the standardized response mean (SRM), calculated as the mean change between 2 yr and baseline divided by the standard deviation of the change [17]. A higher SRM indicates a higher sensitivity to change. The JSN, DSN and osteophyte total scores were analysed as continuous variables.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
At baseline, the 18 women and two men included in the study had a median age of 61.6 yr. Hand, knee, hip and spine OA were present in, respectively, 75, 45, 30 and 60% of the patients. The radiographic severity of OA at baseline in the hands, hips, knees and spine is depicted in Table 1.


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TABLE 1. Characteristics of patients at baseline (n = 20)

 
Hands
Progression in JSN and osteophytes was observed for the paired readings in, respectively, 5 and 15% of the patients compared with 15 and 15% when read chronologically (Table 2). The mean changes and the standard deviation (S.D.) of the changes observed after 2 yr are shown in Table 3. No significant differences were found between the progression scores obtained with the two procedures (Wilcoxon signed rank test; P>0.05). The SRMs for changes in JSN and osteophyte progression scores in the hands were smaller for the paired (0.00 and 0.39) than for the chronological (0.38 and 0.41) readings (Table 3).


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TABLE 2. Distribution of changes in JSN, DSN and osteophyte scores after 2 yr follow-up using the paired and chronological reading procedures

 

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TABLE 3. Mean changes in JSN, DSN and osteophyte scores after 2 yr and SRMs for paired and chronological reading procedures

 
Knees
Progression in JSN and osteophytes was observed for the paired readings in, respectively, 20 and 10% of the patients compared with 25 and 25% when read chronologically (Table 2). No significant differences were found between the progression scores obtained with the two procedures (Wilcoxon signed rank test; P>0.05). The SRMs for changes in JSN and osteophyte progression scores in the knees were smaller for the paired (0.32 and 0.32) than for the chronological (0.56 and 0.56) readings (Table 3).

Hips
Progression in JSN and osteophytes was observed for the paired readings in, respectively, 5 and 10% of the patients compared with 10 and 10% when read chronologically (Table 2). No significant differences were found between the progression scores obtained with the two procedures (Wilcoxon signed rank test; P>0.05). The SRMs for changes in JSN and osteophyte progression scores in the hips were also smaller for the paired (0.00 and 0.20) than for the chronological (0.32 and 0.37) readings (Table 3).

Spine
Progression in DSN and osteophytes was observed for the paired readings in, respectively, 20 and 20% of the patients compared with 25 and 35% when read chronologically (Table 2). No significant differences were found between the progression scores obtained with the two procedures (Wilcoxon signed rank test; P>0.05). The SRMs for changes in DSN and osteophyte progression scores in the spine were also smaller for the paired (0.13 and 0.38) than for the chronological (0.18 and 0.66) readings (Table 3).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Radiological progression of OA was assessed during a follow-up period of 2 yr in multiple joint sites, including hands, hips, knees, and the cervical and lumbar spine. Paired and chronological reading procedures were compared with regard to their sensitivity to change. Progression, defined by an increase of at least one grade for JSN, DSN or osteophytes, in general was observed more often with the chronological than with the paired reading procedure. Reading radiographs with the chronological reading procedure tended to be more sensitive to changes in JSN, DSN and osteophyte scores than with the paired reading procedure.

It is difficult to compare the accuracy of the scores on radiological change obtained with the two reading procedures as no ‘gold standard’ exists in OA to determine the ‘true’ scores for radiological progression. Therefore, one cannot be certain which procedure is more precise. It is possible that the results from the films read without knowledge of sequence are more accurate, and that reading in chronological order leads to an overestimation of change as the observer may expect progression over time. On the other hand, it could be that results from the films read without knowledge of sequence are less accurate and give an underestimation of the real change.

However, the present study is not a comparison of the accuracy of these two procedures using a ‘gold standard’, but a comparison of the internal responsiveness of the two procedures to detect changes in JSN, DSN or osteophytes in serial hand, knee, hip and spine radiographs. Internal responsiveness can be calculated by using the distribution of the scores. For this, two statistics were used. With the Wilcoxon test, no significant differences were observed in JSN, DSN or osteophyte progression scores from baseline to 2 yr between the paired or the chronological reading procedures. One needs to interpret these results carefully, because this test is not independent of the sample size. The reason for the non-significant result may be insufficient power, rather than no real difference between the procedures.

Hence, the two reading procedures were compared also with regard to the SRM, relating the mean change over 2 yr to the S.D. of the change. The SRM provides an indication of the actual size of the change in scores, expressed in terms of a standardized score, independent of sample size. The SRM estimates for the JSN, DSN and osteophyte progression scores in the hands, hips, knees and spine were higher for the chronological than for the paired procedure, suggesting a greater responsiveness to change.

One previous study compared reading procedures for hip OA longitudinal studies [10]. In that study, radiographs of the hip joints at baseline and after 3 yr were assessed using Kellgren–Lawrence grades, JSN scores (0–3) and JSW measurements with and without landmarks. Random, paired and chronological reading procedures were used. Kellgren–Lawrence and JSN grading scores seemed to be influenced by the reading procedure. In contrast to the present study, with both scoring systems, the random procedure resulted more often in changes in grades. Furthermore, Auleley et al. [10] compared the SRM estimates for JSW measurements using four different procedures and recommended the use of paired reading with landmarks for longitudinal studies of hip OA due to a higher SRM estimates of 0.71 compared with SRM estimates of, respectively, 0.68, 0.65 and 0.70 for random with and without landmarks and chronological with landmarks reading procedures. From the frequency distributions given in that article, the SRM estimates of the Kellgren–Lawrence and JSN grades could be calculated for the three reading procedures. The chronological reading procedure with Kellgren–Lawrence grades, as well as JSN grades, had higher SRM estimates than the random and paired reading procedures, as was the case in the present study.

This study was performed with data from a relatively small number of patients. Therefore one has to be careful to use these results for recommendations for future OA studies. However, we obtained radiographs of not only one but of multiple joint sites from all of the patients. In this way, we confirmed the results four times in the different joint groups. In addition to that, progression scores with regard to JSN, DSN as well as osteophytes were obtained, again resulting in a confirmation of the observed trend.

In conclusion, our data demonstrate a trend that when assessing radiological progression in OA, reading series of radiographs in chronological order tends to be more sensitive to change over a 2-yr follow-up period rather than reading in pairs with unknown time sequence. These findings suggest that further studies comparing paired and chronological reading procedures are required. If these results are confirmed, it might have implications for the choice of reading procedures in OA trials.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Submitted 24 June 2005; Accepted 12 July 2005





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