Longitudinal performance evaluation and validation of fixed‐flexion radiography of the knee for detection of joint space loss

Objective

The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed‐flexion radiography protocol to detect knee joint space loss over 3 years.

Methods

We assessed the same‐day test–retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23–47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70–79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions.

Results

A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean ± SD joint space loss for all knees over 3 years was 0.24 ± 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean ± SD joint space loss over 3 years was 0.43 ± 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 ± 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup.

Conclusion

Radiography of the knee in the fixed‐flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.

     

Detection of radiographic joint space narrowing in subjects with knee osteoarthritis: longitudinal comparison of the metatarsophalangeal and semiflexed anteroposterior views

OBJECTIVE: Although recent protocols for standardized knee radiography afford highly reproducible radioanatomic alignment of the joint and measurement of joint space width (JSW) in repeat radiographs acquired on the same day, the sensitivity of these techniques to joint space narrowing (JSN) over time in subjects with knee osteoarthritis (OA) is unknown. The present study was undertaken to compare the metatarsophalangeal (MTP) view and the semiflexed anteroposterior (AP) view with respect to sensitivity to JSN in knee OA. METHODS: In 49 subjects with definite knee OA, 2 MTP radiographs and 1 semiflexed AP radiograph were obtained at baseline. Each examination was repeated 14 months later. In MTP views, minimum JSW and the distance between the anterior and posterior margins of the medial tibial plateau (intermargin distance [IMD], an indicator of parallel alignment of the tibial plateau and the x-ray beam) were measured with a pair of calipers and a magnifying lens fitted with a graticule. JSW in semiflexed AP views was measured by digital image analysis. RESULTS: The mean of within-knee standard deviations of JSW in the baseline MTP examinations (n = 52 OA knees) was 0.24 mm (coefficient of variation 5.8%). Although IMDs in the 2 baseline MTP views were very highly correlated (+0.88), IMDs in the serial examinations were only moderately correlated (+0.45). Serial MTP views showed a small increase in mean JSW over 14 months that was not significantly greater than zero (mean +/- SD +0.09 +/- 0.66 mm; P not significant). In contrast, concurrent semiflexed AP examinations showed a marginally significant decrease in mean JSW (-0.09 +/- 0.31 mm; P = 0.10). CONCLUSION: These results demonstrate that evidence of the short-term reproducibility of a radiographic protocol is an insufficient basis on which to predict the quality of its longitudinal performance.     

Measurement of radiographic joint space width in the tibiofemoral compartment of the osteoarthritic knee: comparison of standing anteroposterior and Lyon schuss views

OBJECTIVE: To evaluate progression of joint space narrowing in radiographs of osteoarthritic (OA) knees imaged in both the standing anteroposterior (AP) and the Lyon schuss positions, using alternative methods to measure joint space width (JSW). METHODS: Standing AP (extended view) and Lyon schuss (posteroanterior [PA] view, with 20-30 degrees of flexion) radiographic images of 58 OA knees were obtained twice (at baseline and 2 years later). With both methods, fluoroscopy was used to align the anterior and posterior margins of the medial or lateral tibial plateau with the central x-ray beam. Minimum JSW, mean JSW, and joint space area (JSA) of the medial or lateral femorotibial joint space were measured using a new digital image analysis system. The effects of knee flexion versus extension and parallel versus nonparallel tibial plateau alignment were evaluated with respect to the reproducibility of JSW in repeated examinations (intraclass correlation coefficient [ICC]), the mean of within-knee standard deviations of repeated measurements (SD(m)), and the sensitivity to changes in JSW in serial radiographs (standardized response mean [SRM]). RESULTS: The performance of the new software, as assessed by the reproducibility of repeated measurements of minimum JSW on the same image, was excellent in both the standing AP (ICC = 0.98) and Lyon schuss radiographs (2 SD(m) = 0.5 mm, ICC = 0.98). The reproducibility in different radiographs of the same knee was not evaluated. However, over 2 years, the mean (+/- SD) decrease in the minimum JSW of OA knees was 0.17 +/- 0.75 mm in standing AP radiographs (P not significant) and 0.24 +/- 0.50 mm in Lyon schuss views (P = 0.007), with SRMs of 0.23 and 0.48, respectively. The quality of alignment of the tibial plateau was satisfactory (<1 mm between anterior and posterior margins of the medial tibial plateau) in 66% of the pairs of Lyon schuss radiographs and in 57% of the pairs of standing AP radiographs. In the Lyon schuss radiographs, SRM was highly dependent on tibial plateau alignment. Minimum JSW was more sensitive to change than was mean JSW or JSA, in paired Lyon schuss radiographs that exhibited satisfactory alignment. CONCLUSION: Compared with the standing AP radiograph, PA imaging of the knee in 20-30 degrees flexion (the schuss position) increases the reproducibility of radiographic JSW measurements in OA knees and the sensitivity to change in JSW in serial radiographs. Sensitivity to change in minimum JSW is notably increased by aligning the medial tibial plateau with the central x-ray beam in the Lyon schuss radiograph.     

The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial

OBJECTIVE: Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS: The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION: At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.     

Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial

OBJECTIVE: To determine whether chondroitin sulfate (CS) is effective in inhibiting cartilage loss in knee osteoarthritis (OA). METHODS: In this randomized, double-blind, placebo-controlled trial, 300 patients with knee OA were recruited from an outpatient clinic, from private practices, and through advertisements. Study patients were randomly assigned to receive either 800 mg CS or placebo once daily for 2 years. The primary outcome was joint space loss over 2 years as assessed by a posteroanterior radiograph of the knee in flexion; secondary outcomes included pain and function. RESULTS: Of 341 patients screened, 300 entered the study and were included in the intent-to-treat analysis. The 150 patients receiving placebo had progressive joint space narrowing, with a mean +/- SD joint space loss of 0.14 +/- 0.61 mm after 2 years (P = 0.001 compared with baseline). In contrast, there was no change in mean joint space width for the 150 patients receiving CS (0.00 +/- 0.53 mm; P not significant compared with baseline). Similar results were found for minimum joint space narrowing. The differences in loss of joint space between the two groups were significant for mean joint space width (0.14 +/- 0.57 mm; P = 0.04) and for minimum joint space width (0.12 +/- 0.52 mm; P = 0.05). CS was well tolerated, with no significant differences in rates of adverse events between the two groups. CONCLUSION: While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.     

Accuracy and precision of joint space width measurements in standard and macroradiographs of osteoarthritic knees.

OBJECTIVES--To improve the reproducibility and accuracy of joint space width (JSW) measurement as an assessment of cartilage loss in patients with osteoarthritis (OA) of the knee by determining how precision and accuracy of JSW measurement were altered by a computerised method of measurement, correction for radiographic magnification, radiography of the knee in the standing semiflexed view, and high definition macroradiography of the knee in the semiflexed view--taking JSW measurements from standard radiographs of OA knees in the extended view as the standard for comparison. METHODS--Twenty five OA and 10 nonarthritic knees were radiographed in the extended view and minimum JSW was measured manually. Conventional and x5 macroradiographs were taken in the semiflexed view. All radiographs were taken twice on the same day and repeated two weeks later. Automated computerised measurement of minimum JSW was obtained from digitally stored images of all radiographs. RESULTS--For medial compartment JSW measurements, computerised was more accurate than manual, correction for radiographic magnification improved precision and accuracy, measurements in the semiflexed view were more precise and accurate, and macroradiography increased measurement precision. For the lateral compartment JSW measurements, correction for radiographic magnification improved precision and accuracy, and the semiflexed view improved precision only. CONCLUSIONS--Protocols defining radiographic and mensural procedures are essential for quality control of knee radiography in the semiflexed view to permit accurate and reproducible measurement of JSW. Macroradiography provides greater precision of JSW measurement.     

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

OBJECTIVE: The hallmark of osteoarthritis (OA) is the loss of articular cartilage. This loss arises from an imbalance between cartilage synthesis and cartilage degradation over a variable period of time. The aims of this study were to investigate the rates of these processes in patients with knee OA using two new molecular markers and to investigate whether the combined use of these markers could predict the progression of joint damage evaluated by both radiography and arthroscopy of the joints during a period of 1 year. METHODS: Seventy-five patients with medial knee OA (51 women, 24 men; mean +/- SD age 63 +/- 8 years, mean +/- SD disease duration 4.8 +/- 5.2 years) were studied prospectively. At baseline, we measured serum levels of N-propeptide of type IIA procollagen (PIIANP) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) as markers of type II collagen synthesis and degradation, respectively. Joint space width (JSW) on radiography and medial chondropathy at arthroscopy (assessed using a 100-mm visual analog scale [VAS]) were measured in all patients at baseline and in 52 patients at 1 year. Progression of joint destruction was defined as a decrease of > or =0.5 mm in JSW on radiography and as increased chondropathy (an increase in the VAS score of >8.0 units) between the baseline and 1-year evaluations. RESULTS: At baseline, compared with 58 healthy age- and sex-matched controls, patients with knee OA had decreased serum levels of PIIANP (20 ng/ml versus 29 ng/ml; P < 0.001) and increased urinary excretion of CTX-II (618 ng/mmole creatinine [Cr] versus 367 ng/mmole Cr; P < 0.001). The highest discrimination between OA patients and controls was obtained by combining PIIANP and CTX-II in an uncoupling index (Z score CTX-II - Z score PIIANP), which yielded a mean Z score of 2.9 (P < 0.0001). Increased baseline values in the uncoupling index were associated with greater progression of joint damage evaluated either by changes in JSW (r = -0.46, P = 0.0016) or by VAS score (r = 0.36, P = 0.014). Patients with both low levels of PIIANP (less than or equal to the mean - 1 SD in controls) and high levels of CTX-II (greater than or equal to the mean + 1 SD in controls) had an 8-fold more rapid progression of joint damage than other patients (P = 0.012 and P < 0.0001 as assessed by radiography and arthroscopy, respectively) and had relative risks of progression of 2.9 (95% confidence interval [95% CI] 0.80-11.1) and 9.3 (95% CI 2.2-39) by radiography and arthroscopy, respectively. CONCLUSION: Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II. The combination of these two new markers could be useful for identifying knee OA patients at high risk for rapid progression of joint damage.     

Quantification of progressive joint space narrowing in osteoarthritis of the hip: longitudinal analysis of the contralateral hip after total hip arthroplasty

OBJECTIVE: The rate of progressive joint space narrowing in the contralateral hip after total hip arthroplasty (THA) for osteoarthritis (OA) and the factors which may predispose patients to more aggressive joint space narrowing remain undefined. The current study sought to evaluate the rate and pattern of, and risk factors for, progressive joint space narrowing in the contralateral hip after THA for OA. METHODS: Each patient who underwent THA for OA in 1984-1985 was followed up longitudinally, and annual anteroposterior (AP) pelvis radiographs were obtained. The radiographic joint space width (JSW) of each contralateral hip joint was quantified, and the rates of JSW narrowing were determined. Evaluation of potential risk factors for accelerated progression of joint space narrowing included age, sex, side of surgery, weight, height, body mass index (BMI), hip pain, etiology of OA, and Kellgren/Lawrence radiographic grade. RESULTS: Ninety-nine patients and 619 AP pelvis radiographs were evaluated. The median initial JSW was 3.48 mm (interquartile range 1.55). JSW declined in a linear manner at a median rate of 0.10 mm/year. The rate of decline between baseline and followup in 20 months was predictive of the overall slope. Two subpopulations were identified. Eighty-five percent of patients maintained a slow decline in JSW (< or =0.2 mm/year), and 15% exhibited an accelerated decline in JSW (>0.2 mm/year). Kellgren/ Lawrence radiographic grade > or =2 and a diagnosis of primary OA were each associated with a more rapid decline in JSW (P = 0.006 and P = 0.02, respectively). Initial JSW, age, sex, weight, height, BMI, and hip pain were not risk factors for rapid decline in JSW. CONCLUSION: Radiographic hip JSW may be reliably quantified and followed up longitudinally using standard AP radiographs. Progression of JSW narrowing in the contralateral hip after THA for OA proceeds in a linear manner over several years. A subpopulation of patients with accelerated narrowing of contralateral JSW may be identified within 20 months, and may represent a suitable population with which to assess the potential efficacy of new disease-modifying agents.     

Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views

OBJECTIVE: To improve the radiographic assessment of cartilage loss, as measured by joint space width (JSW) in patients with osteoarthritis (OA) of the knees required to detect the effect of structure modifying drugs in OA trials. This was achieved by determining which of 3 nonfluoroscopic radiographic views--standing extended, semiflexed, and schuss--produced the most accurate radioanatomic positioning of the joint and greater reproducibility in joint repositioning and JSW measurement. METHODS: Knees from 74 patients with OA of the knees who had medial tibiofemoral compartment JSW > or =2 mm in all views were studied. For all 3 radiographic views, accuracy in the radioanatomic positioning of the knee was determined for both joint rotation and flexion. Reproducibility in joint repositioning and JSW measurement were determined from the difference between repeat examinations taken within 2 h. RESULTS: About 86% of knees in the 3 views had accurate rotational position of the joint at each visit. Radioanatomically, knees in the semiflexed view were significantly more accurately positioned in regard to knee flexion (p<0.0005) than in the schuss view, which in turn was better (p<0.014) than in the extended knee view. Joint repositioning was significantly more reproducible in the semiflexed (p<0.0001) than in the extended knee, which was better (p<0.013) than in the schuss position. JSW measurement was significantly more reproducible in the semiflexed (p<0.014) than both schuss and extended knee positions, which were not significantly different from each other. CONCLUSION: Protocols defining the nonfluoroscopic radiographic procedures for the semiflexed view provide the most accurate radioanatomic joint positioning, and the most reproducible joint repositioning and JSW measurement. Using this method significantly fewer knees would be required to detect significant JSW changes in a structure modifying drug trial compared to the schuss and the extended knee positions.     

Knee pain reduces joint space width in conventional standing anteroposterior radiographs of osteoarthritic knees

OBJECTIVE: A suspected, but heretofore undemonstrated, limitation of the conventional weight-bearing anteroposterior (AP) knee radiograph, in which the joint is imaged in extension, for studies of progression of osteoarthritis (OA) is that changes in knee pain may affect extension, thereby altering the apparent thickness of the articular cartilage. The present study was undertaken to examine the effect of changes in knee pain of varying magnitudes on radiographic joint space width (JSW) in the weight-bearing extended and the semiflexed AP views, in which radioanatomic positioning of the knee was carefully standardized by fluoroscopy. METHODS: Fifteen patients with knee OA underwent a washout of their analgesic/nonsteroidal antiinflammatory drug (NSAID) agents (duration 5 half-lives), after which standing AP and semiflexed AP knee radiographs of both knees were obtained. Examinations were repeated 1-12 weeks later (median 4.5 weeks, mean 6.0 weeks), after resumption of analgesic/NSAID therapy. Knee pain was measured with the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (Likert scale). JSW was measured with a pair of calipers and a magnifying lens. Mixed model analyses of variance were used to test the significance of changes in pain and JSW within and between 2 groups of knees with mild-to-moderate radiographic severity of OA: (a) "flaring knees," in which the patient rated standing knee pain as severe or extreme after the washout and in which pain decreased to any degree after resumption of analgesics and/or NSAIDs (n = 12) and (b) "nonflaring knees," in which standing knee pain was absent, mild, or moderate after the washout or did not decrease after resumption of treatment (n = 15). RESULTS: After reinstitution of treatment, WOMAC pain scores decreased significantly in both flaring and nonflaring knees (-44%; P < 0.0001 and -18%; P < 0.01, respectively). After adjustment for the within-subject correlation between knees, mean JSW (+/-SEM) in the extended view of the flaring OA knee increased significantly from the first to second examination (0.20 +/- 0.06 mm; P = 0.005). In contrast, the change in adjusted mean JSW in the extended view of the nonflaring OA knee was negligible (-0.04 +/- 0.04 mm) and significantly smaller than that observed in flaring knees (P < 0.01). Mean JSW in the semiflexed AP view was unaffected by the severity or responsiveness of standing knee pain in flaring and nonflaring OA knees. CONCLUSION: JSW in weight-bearing extended-view radiographs of highly symptomatic OA knees can be altered significantly by changes in joint pain. In clinical trials and in epidemiologic studies of OA progression that use this radiographic technique, longitudinal variations in pain may confound changes in the apparent thickness of the articular cartilage.     

Selection of knee radiographs for trials of structure-modifying drugs in patients with knee osteoarthritis: a prospective, longitudinal study of Lyon Schuss knee radiographs with the definition of adequate alignment of the medial tibial plateau

OBJECTIVE: The quality of medial tibial plateau (MTP) alignment, which is assessed by measuring the distance between the anterior and posterior margins (intermargin distance [IMD]) of the tibial plateau, and the reproducibility of alignment in serial radiographs are suggested to be key elements in determining the accuracy and sensitivity to change in knee radiographs in patients with tibiofemoral osteoarthritis (OA). We evaluated the influence of both MTP alignment and radiograph superimposition on the sensitivity to change in radiographic joint space narrowing (JSN) in knee OA. METHODS: The study group comprised 106 patients with knee pain (73 with OA). Lyon schuss radiographic images of the knee were obtained twice (at baseline [month 0] and 12 months later), using a standardized radiographic procedure. Computerized measurement of the IMD for the assessment of MTP alignment was compared with the grading of MTP alignment by 2 observers using a 5-point scale (excellent, good, fair, poor, bad). To obtain the rate of JSN, computerized measurement of the joint space width was performed at month 0 and month 12. The sensitivity of the joint space width to change over 1 year was evaluated by the standardized response mean (SRM). RESULTS: The mean (+/-SD) IMD was 1.2 +/- 0.9 mm. The correlation between scoring and computer measurement of MTP alignment was highly significant. The cutoff value for satisfactory alignment (excellent or good) was an IMD of 1.2 mm at month 0 and/or month 12. CONCLUSION: The quality of MTP alignment at both baseline and the end point highly influences the sensitivity to change in radiographic JSN in knee OA. To obtain relevant data, only radiographs showing an IMD of 相似文献   

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.     

Superiority of the Lyon schuss view over the standing anteroposterior view for detecting joint space narrowing, especially in the lateral tibiofemoral compartment, in early knee osteoarthritis

OBJECTIVE: To evaluate the validity of using the conventional anteroposterior (AP) radiograph of the knee in order to identify joint space narrowing (JSN) at an early stage of osteoarthritis (OA). METHODS: Grading of JSN using a 0-5 score and quantitative measurement of joint space width (JSW) of the medial and lateral compartments of the tibiofemoral joint in AP and fluoroscopically assisted posteroanterior Lyon schuss (LS) radiographs of 202 patients with knee OA. RESULTS: Knees without definite JSN (score <2) were twice as common in AP than in LS radiographs (36.1% vs 18.8%). The number of knees showing definite medial JSN was identical in both views but four knees showing a medial OA in AP view were classified differently in the LS radiographs (three bicompartmental OA and one lateral OA). The frequency of lateral JSN was approximately twice as great in the LS view as in the AP view. JSN score was significantly higher (p<0.001) and JSW was significantly smaller (p<0.01) in the LS view than in the AP view. In knees with definite JSN, JSW of the compartment with no narrowing was significantly (p<0.04) larger than in knees that did not exhibit definite JSN. Medial JSW and lateral JSW were inversely correlated (p<0.001). CONCLUSIONS: The standing AP radiograph performed poorly in identifying both the location of JSN in patients with early tibiofemoral OA (especially, lateral OA) and the severity of JSN. The LS radiographs are preferable to standing AP views for the selection of patients for therapeutic trials of structure-modifying OA drugs.     

Comparison of quantitative and semiquantitative indicators of joint space narrowing in subjects with knee osteoarthritis

OBJECTIVE: To compare quantitative estimates of change in joint space width (JSW) with semiquantitative ratings of the progression of joint space narrowing (JSN) with respect to sensitivity to change over time. METHODS: 431 obese women 45 to 64 years old with unilateral radiographic knee osteoarthritis were randomised to 30 months' treatment with doxycycline 100 mg twice daily or placebo. Quantitative estimates of change in JSW in the medial tibiofemoral compartment from fluoroscopically assisted semiflexed AP radiographs were obtained at baseline and 16 and 30 months after randomisation. Radiographic JSN was rated (0-3 scale) in the same images by two readers using a standard atlas. Changes in overall severity of knee osteoarthritis were derived from gradings of conventional standing AP radiographs at baseline and 30 months, with blinding to treatment group and chronological order of examination. RESULTS: Follow up radiographs were obtained from 381 subjects (88%) at 16 months and from 367 (85%) at 30 months. The treatment groups did not differ in the frequency of significant loss of JSW by dichotomous criteria (> or =0.5 mm, > or =1.0 mm, > or =20%, or > or =50% of baseline JSW). Progressors and non-progressors, as defined by each of the dichotomous outcomes, differed significantly in mean value for quantitative measurement of change in JSW at 30 months (p< or =0.001). CONCLUSIONS: Quantitative and semiquantitative indicators of progression of osteoarthritis in fluoroscopically standardised radiographs of osteoarthritic knees are highly related, but the effect of doxycycline on articular cartilage thickness was more easily detected with quantitative measurements of change in JSW than with semiquantitative ratings of JSN.     

Field test of the reproducibility of automated measurements of medial tibiofemoral joint space width derived from standardized knee radiographs.

OBJECTIVE: To estimate the reproducibility of computerized measurements of minimum joint space width (JSW) in the medial tibiofemoral compartment in knee radiographs (semiflexed AP view) obtained from clinical radiology units. METHODS: Technologists from 5 clinical radiology units were trained in the performance of the fluoroscopically assisted semiflexed AP knee examination. Each of 44 subjects (34 with knee osteoarthritis, OA, 10 with bilaterally normal knees) were examined within 7 days in 2 of the 5 units. The examination in each unit was repeated 1 week later. Minimum JSW was measured on digitized radiographic images with computer software that corrected for radiographic magnification. RESULTS: Despite ongoing quality control by technologists, 11% of radiographs were flawed with respect to the protocol standard for knee rotation and 36% with respect to the standard for knee flexion. The standard error of measurement (SEm) of JSW in 174 knees that were examined twice in the same unit was 0.32 mm (SEm = 0.25 mm for the subset of 76 paired radiographs with uniformly high quality). The overall between-unit SEm was 0.45 mm. Within-unit, but not between-unit, precision was related to the technical quality of the radiographs. Precision was unrelated to subject age, sex, race, weight, and radiographic severity of knee OA. CONCLUSION: The within-unit precision of JSW measurements from all pairs of semiflexed views (irrespective of technical quality) represented a notable improvement over that observed in radiographs with flawed knee rotation or flexion (as would be the case in conventional extended knee views). In future applications of this technique, assurance of technical quality by an independent observer should result in a level of measurement precision that will permit the design of clinical trials of disease modifying OA drugs with fewer subjects and/or shorter duration of treatment than is possible with conventional knee radiography.     

Age and sex differences in hip joint space among asymptomatic subjects without structural change: implications for epidemiologic studies

OBJECTIVE: The prevalence of hip osteoarthritis (OA) increases significantly with age. Although it is not clear whether joint space loss at the hip is a feature of normal aging or a reflection of the OA process, epidemiologic criteria for OA are based on narrowing alone. The aim of this study was to determine whether changes in joint space width occur with age, and whether there are sex differences, in asymptomatic subjects without hip OA. METHODS: We identified a total of 1,806 subjects who had undergone intravenous urography between 1994 and 1996 and sent a questionnaire to the 1,527 of these subjects who were alive in 1998; 1,031 replies (68%) were received. All radiographs were read by an observer blinded to age, sex, and pain status. Individual radiographic features of OA (narrowing, osteophyte, sclerosis, and cysts) were graded, and an overall qualitative grade was allocated, according to a standard atlas. Minimum joint space width (JSW) was measured by metered caliper to within 0.1 mm. A total of 276 women (mean age 63 years) and 257 men (mean age 64 years) were identified who had never had hip pain (defined as having ever had pain on most days for at least 1 month) and who had no evidence of either joint space narrowing or osteophyte (grade 0, no structural changes). The minimum JSW in either hip was tabulated according to age. RESULTS: JSW measurement was reproducible (95% confidence limits of agreement) to within +/-0.5 mm. At all ages, men had larger JSW than women (3.85 mm in women, 4.19 mm in men, mean difference 0.34 mm; 95% confidence interval [95% CI] 0.24, 0.44). A significant decline in JSW with age was seen in women, with a mean difference between ages 45-54 and 75-84 years of 0.36 mm (95% CI 0.15, 0.58; P = 0.001). No significant change in JSW with age was seen in men (mean difference 0.16 mm; 95% CI -0.11, 0.43). Analysis of an additional 64 women and 61 men who were without hip pain and had overall qualitative grade 1-2 changes gave similar results. Implementing these results to alter the threshold for definition of hip OA in women from < or =2.5 mm to < or =2.2 mm reduced the prevalence of hip OA from 10.6% to 5.6%. CONCLUSION: These sex differences in joint space have significant implications in terms of the major emphasis on joint space narrowing in definitions of hip OA. Women also have a significant progressive decline in joint space with age that is not seen in men. This suggests that in women, loss of cartilage may be an age-related phenomenon that is independent of other aspects of structural change. Consideration should be given to the development of sex-specific definitions of hip "OA."     

The lateral view radiograph for assessment of the tibiofemoral joint space in knee osteoarthritis: its reliability, sensitivity to change, and longitudinal validity

OBJECTIVE: To evaluate the reliability, validity, and sensitivity to change of tibiofemoral (TF) narrowing on lateral radiographic views. METHODS: In a natural history study of symptomatic knee osteoarthritis (OA), both lateral view and fluoroscopically positioned posteroanterior (PA) semiflexed view radiographs of the knee in 30 degrees of flexion and with weight bearing were obtained at baseline and at 30 months. Test-retest reliability was evaluated using repeat radiographs, with joint space width measured using electronic calipers. All radiographs were scored on a 0-3 scale, and progression of joint space loss was defined as narrowing of the joint space by 1 grade. We evaluated sensitivity to change compared with the PA view. We evaluated validity by examining whether knees with progression showed expected malalignment on full-limb films. RESULTS: Test-retest reliability of the TF joint space using the lateral view had a root mean square error of 0.303 mm, with 92.5% of repeats within 1 mm. More knees showed progression on the lateral view alone (n = 41) than on the PA view alone (n = 27). Compared with knees without joint space loss, knees with medial compartment loss on the lateral view only were more varus malaligned (P < 0.001), while those with lateral compartment loss were more valgus malaligned (P = 0.008). CONCLUSION: In the assessment of TF joint space loss, lateral view radiographs are reliable, valid, and more sensitive to change than fluoroscopically positioned PA radiographs.     

Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years

OBJECTIVE: In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period. METHODS: Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or > or =2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models. RESULTS: The mean +/- SD ages of the progressors and nonprogressors were 64.2 +/- 7.8 years and 63.3 +/- 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by > or =2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean +/- SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 +/- 3.39 units/liter versus 12.62 +/- 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 +/- 2.71 versus 10.82 +/- 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%. CONCLUSION: The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.     

Radiographic progression of knee osteoarthritis in a Czech cohort

OBJECTIVE: To determine the 5-year radiographic progression of osteoarthritis (OA) of the knee in a Czech cohort. METHODS: 139 patients with idiopathic OA were followed for 5 years, receiving only physical therapy and non-steroidal antiinflammatory drugs as needed. Weight-bearing radiographs of both knees were performed at the initial and final evaluation by a single technician using the same instrument and a standardized procedure. Radiographs were evaluated using the Kellgren-Lawrence scale (KL). Joint space width (JSW) was determined by 2 independent trained readers, and discrepancies re-reviewed. RESULTS: JSW decreased 0.39 +/- 0.95 mm in 5 years, or 0.078 +/- 0.19 annually. The reduction of JSW was greatest in the KL grade III radiographs (0.099 +/- 0.18 mm). The smallest reduction in JSW was seen in those with KL grade I (0.044 +/- 0.14 mm). However, only 25% of those with KL stage II or stage III demonstrated any change in JSW over the 5-year period. The reduction in JSW was not constant, being most rapid in the first year and then much slower. The coefficient of variation (CV) of the method was good (intra- and inter-observer CV 3.6%). CONCLUSION: This 5-year follow up of Czech patients with OA of the knee demonstrated a low rate of radiographic progression of JSW. The most rapid progression appeared in KL stage III. The progression was most rapid in the first year.     

Radiologic assessment of age‐related knee joint space changes in women: A 4‐year longitudinal study

Objective

To analyze a population‐based cohort of women in order to establish normal values of joint space width (JSW) and to evaluate the existence of age‐related joint space loss (JSL).

Methods

Knee radiographs were performed 4 years apart in women from the OFELY (Os des Femmes de Lyon) Cohort. Posteroanterior radiographs of both knees were taken in semiflexion with a standardized fluoroscopically assisted protocol. Radiographs were qualitatively evaluated using a scoring system based on the Altman score that assessed joint space narrowing, osteophytes, and sclerosis for each tibiofemoral compartment and each side. For quantitative assessment, radiographs were digitized using a video camera, and specific software was used to measure JSW in every compartment.

Results

We evaluated the radiographs of 606 women (ages 39–90 years, mean 62 years) and found that in all subjects, JSW significantly decreased with age in every compartment (r = ?0.12 to ?0.16, P < 0.001), including in 358 subjects without any radiographic abnormality related to osteoarthritis (OA) at baseline. The longitudinal analysis confirmed a significant loss over 4 years of ～0.30 mm (6%) for the medial compartment. Multiple regression analysis did not identify significant predictors of JSL among clinical risk factors and biochemical markers of bone and cartilage turnover.

Conclusion

In this first longitudinal study of a population‐based cohort of women, we have established normal values of JSW and shown that JSW decreases with aging, especially at the medial compartment, even in subjects without any radiographic abnormalities related to OA.