Subject: Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis -- Cicuttini et al. 43 (3): 321 -- Rheumatology

Rheumatology Advance Access originally published online on January 6, 2004 

Rheumatology 2004; 43: 321-324
Rheumatology Vol. 43 No. 3 (c) British Society for Rheumatology 2003; all rights reserved

Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis

F. Cicuttini, A. Wluka, J. Hankin and Y. Wang

Department of Epidemiology and Preventive Medicine, Monash University Medical School, Alfred Hospital, Prahran 3181, Australia.

Correspondence to: F. Cicuttini. E-mail: flavia.cicuttini@med.monash.edu.au

 
Objectives. There is emerging evidence that knee alignment is associated with progression of osteoarthritis (OA). The aim of this study was to examine the relationship between baseline knee angle and the rate of cartilage loss in subjects with knee OA.

Methods. One hundred and seventeen subjects with knee OA had standing radiographs and MRI on their symptomatic knee at baseline and at the 1.9±0.2 yr follow-up. Knee cartilage volume was measured at baseline and follow-up. Knee angle was defined as the angle subtended by a line drawn through the mid-shaft of the femur with respect to one drawn through the mid-shaft of the tibia.

Results. At baseline, in the medial compartment, as the angle decreased (i.e. was less varus) the tibial and femoral cartilage volume increased. In the lateral compartment, as the angle became more valgus, there was a reduction in tibial and femoral cartilage volume. In the longitudinal study, for every 1° increase in baseline varus angulation there was an average annual loss of medial femoral cartilage of 17.7 µl [95% confidence interval (CI) 6.5–28.8]. Although not statistically significant, there was a trend for a similar relationship between loss of medial tibial cartilage volume and baseline knee angle. In the lateral compartment, there was an average loss of tibial cartilage volume of 8.0 µl (95% CI 0.0–16.0) for every 1° increase in valgus angle.

Conclusions. Baseline knee angle is associated with the rate of cartilage loss in the knee. Further work will be needed to determine whether therapies aimed at modifying the knee angle will reduce the progression of knee OA.

KEY WORDS: Osteoarthritis, Tibiofemoral compartments, Angles, Knee cartilage volume, Progression.

 
Osteoarthritis (OA) is a major cause of work-related and long-term disability in people over the age of 50 yr [1]. Despite this, factors influencing progression are poorly understood. One factor that is thought to play a role is knee alignment [2]. Changes in the alignment may redistribute the medial and/or lateral loads at the joint. In the normal state, 60–80% of the compressive load transmitted across the knee is on the medial compartment [3]. Alignment influences the medial-to-lateral-compartment load distribution [2].

Previous studies have examined the association between malalignment at the knee and progression of knee OA by using radiographic outcome [2]. Minimum joint space width, following specific acquisition protocols developed for joint space assessment, has been recommended as the best measure of disease progression in OA for the approximation of articular cartilage [4]. However, the radiological joint space consists of articular cartilage, meniscal cartilage and possibly other structures, including effusions [5]. Mild to moderate joint space loss has also been shown to be brought about by meniscal extrusion, and not by loss of articular cartilage [5]. Thus, although being the currently recommended method, the use of change in minimum joint space width as a surrogate marker of articular cartilage and disease progression in OA may not be entirely accurate. In addition, as it does not allow direct visualization of articular cartilage it cannot be used to examine the femoral and tibial cartilage plates individually or separately.

Magnetic resonance imaging (MRI) visualizes all components of the joint simultaneously. We and others have validated this as a method for measuring articular cartilage volume [6–10]. Using different acquisition protocols and postprocessing techniques, we have shown that articular cartilage volume can be measured accurately and reproducibly in healthy individuals, those with OA, and children [6–10]. Because this method measures cartilage in three dimensions, the results are less likely to be influenced by positioning. This is important in longitudinal studies. Cartilage volume has been shown to correlate with radiological grade of OA [11]. Articular cartilage volume may be a useful measure for disease progression in OA. We examined a cohort of subjects with moderate symptomatic OA for 2 yr to determine the influence of knee angle on change in articular knee cartilage volume during that time.

 
Subjects with moderate symptomatic knee OA were recruited by advertising through local newspapers and the Victorian branch of the Arthritis Foundation of Australia, and in collaboration with general practitioners, rheumatologists and orthopaedic surgeons, as described previously [12]. The study was approved by the ethics committee of the Alfred and Caulfield Hospitals in Melbourne, Australia. All subjects gave informed consent. One hundred and seventeen subjects were included in this study [12]. Of the original population, six were excluded because of missing X-rays. There were no differences between those missing and those included in terms of age, gender distribution and average cartilage volume. Inclusion criteria were age over 40 yr and symptomatic [at least one pain dimension of WOMAC (Western Ontario and McMaster University Osteoarthritis Index) score above 20 mm and osteophytes present] knee OA (American Rheumatism Association clinical and radiographic criteria [13]). Subjects were excluded if any other form of arthritis was present, if they had any contraindication to MRI (e.g. pacemaker, cerebral aneurysm clip, cochlear implant, presence of shrapnel in strategic locations, metal in the eye, claustrophobia), if they were unable to walk 50 feet without the use of assistive devices, if they had hemiparesis of either lower limb, or if total knee replacement was planned. Weight was measured to the nearest 0.1 kg (shoes and bulky clothing removed) using a single pair of electronic scales. Height was measured to the nearest 0.1 cm (shoes removed) using a stadiometer. Body mass index (BMI) [weight (kg)/height (m)²] was calculated.

Each subject had a weight-bearing anteroposterior tibiofemoral radiograph, taken in full extension, at baseline, of the symptomatic knee with the patella facing forwards, as described previously [14]. Where both knees had OA and were symptomatic, the knee with less severe radiographic OA was used. Knees were scored independently by two trained observers, who used a published atlas to classify disease in the tibiofemoral joint. The radiological features of tibiofemoral OA were graded in each compartment, on a four-point scale (0–3), for individual features of osteophytes and joint-space narrowing [15]. Intra-observer reproducibility for agreement on features of OA was 0.93 for osteophytes (grade 0, 1 vs 2, 3) and 0.93 for joint space narrowing (grade 0, 1 vs 2, 3). Interobserver reproducibility was 0.86 for osteophytes and 0.85 for joint space narrowing   statistic) [16].

Knee angles were measured by a single observer, as has been described previously from standing anteroposterior radiographs [14, 17]. Lines were drawn through the middle of the femoral shaft and through the middle of the tibial shaft. The angle subtended at the point at which these two lines met in the centre of the tibial spines was based on a modification of the method of Moreland et al. [17] described recently by Felson et al. [14]. The angle subtended by the lines on the medial side was measured using Osiris software (University of Geneva). Thus, an angle less than 180° was more varus and an angle greater than 180° more valgus. The intra-observer variability was 0.98.

Each subject had an MRI performed on his or her designated knee at baseline and approximately 2 yr later. Knee cartilage volume was determined by means of image processing on an independent workstation using the software program Osiris, as described previously [7, 16]. Knees were imaged in the sagittal plane on the same 1.5-T whole-body magnetic resonance unit (Signa Advantage HiSpeed; GE Medical Systems, Milwaukee, WI, USA) using a commercial receive-only extremity coil, as described previously [7, 16]. Two trained observers read each MRI. The scans were measured by two observers independently. Each subject's baseline and follow-up MRI scans were scored unpaired and blinded to subject identification and timing of MRI. The same two observers measured cartilage volume on each scan once. Their results were compared. If the results were within ±20%, an average of the results was used. If they were outside this range, the measurements were repeated until the independent measures were within ±20%, and the averages were used. Repeat measurements were made blind to the results of the comparison of the previous results. The medial and lateral femoral cartilage volumes were measured from images transformed in the coronal plane, as described previously [18]. The intra-observer reproducibility for repeat measures of cartilage volume from single acquisitions, as measured by coefficients of variation, were as follows: medial tibial cartilage volume, 2.3%; lateral tibia cartilage volume, 2.4%; medial femoral cartilage volume, 2.6%; lateral femoral cartilage volume, 2.8%.

Descriptive statistics for characteristics of the subjects were tabulated. Change in cartilage volume (follow-up cartilage volume subtracted from initial cartilage volume) over the period of time (1.9±0.2 yrs) was divided by time between MRI scans to obtain an annual rate of change. Linear regression techniques were used to examine the relationship between knee angle and cartilage volume at baseline and on the rate of change of cartilage volume in the different compartments. Multiple linear regression techniques were used to adjust for age, gender and BMI. All analyses were performed using the SPSS statistical package, version 10.0.5 (SPSS, Cary, NC, USA).

 
Study subjects had moderate OA (Table 1). Joint cartilage loss varied between 4.7 and 5.2% per annum in the medial and lateral tibial and femoral compartments of the knee. The mean knee angle was 180.8 ± 5.8°.

In the medial compartment, there was a positive association between both tibial and femoral cartilage volumes and knee angle at baseline. Thus, the medial tibial and femoral cartilage volumes increased as the angle decreased (i.e. was less varus). Similarly, in the lateral compartment there was an inverse association at baseline between tibial and femoral cartilage volumes and the measured knee angle (Table 2). Thus, as the angle became more valgus, there was a reduction in lateral tibial and lateral femoral cartilage volume. The correlation of the increase in baseline varus angulation with medial femoral cartilage volume was r = -0.20 (P = 0.04) and the correlation with medial tibial cartilage volume was r = -0.22 (P = 0.07). The correlation of the increase in baseline valgus angulation with lateral tibial cartilage volume was r = 0.12 (P = 0.05) and the correlation with lateral femoral cartilage volume was r = 0.14 (P = 0.08).

When the longitudinal change in cartilage volume was examined, in the medial compartment there was an inverse association between loss of medial femoral cartilage volume and knee angle, after adjusting for age, gender and BMI (Table 3). With increasing varus angulation at the knee at baseline, increased loss of medial femoral cartilage was seen. For every 1° increase in baseline varus angulation, there was an average annual loss of medial femoral cartilage of 17.7 µl [95% confidence interval (CI) 6.5–28.8]. This corresponded to a correlation of r = -0.26 (P = 0.01) between the increase in baseline varus angulation and annual loss of medial femoral cartilage. There was a trend for a similar inverse association between loss of medial tibial cartilage volume and increase in knee angle at baseline. However, this was not statistically significant. In the lateral compartment, there was an increase in loss of tibial cartilage volume when the baseline knee angle was most valgus (Table 3). In the lateral compartment, there was an average loss of tibial cartilage volume of 8.0 µl (95% CI 0.00–16.0) for every 1° increase in valgus angle. This corresponded to a correlation of r = 0.14 (P = 0.02) between the increase in baseline valgus angulation and the annual loss of lateral tibial cartilage. No effect of interaction between severity of radiological OA and knee angle on knee cartilage plates in either the medial or the lateral tibiofemoral compartment was statistically significant at the 25% level.

At baseline, we found that the degree of varus knee angle was inversely associated with both femoral and tibial cartilage volume in the medial tibiofemoral compartment of the knee, although this did not reach statistical significance for the tibial cartilage. Similarly, increase in the degree of valgus knee angle at baseline was inversely associated with both femoral and tibial cartilage volume in the lateral tibiofemoral compartment of the knee. When the study subjects were followed longitudinally, those with a more varus knee angle at baseline had a significantly increased loss of articular femoral cartilage in the medial compartment, with a similar trend affecting the tibial cartilage. Similarly, those with a more valgus knee angle at baseline had an increase in loss of joint cartilage in the tibial cartilage plate in the lateral tibiofemoral compartment. However, no clear association was seen with change in the lateral femoral cartilage.

To our knowledge, this is the first study describing the relationship between the knee angle and knee cartilage volume at baseline and longitudinal change in cartilage volume in subjects with OA. Malalignment has been shown to be a risk factor for progression of OA using radiological outcomes [2]. One previous study showed that a subject's recollection of being bow-legged or knock-kneed in childhood was associated with a 5-fold increase in the risk of progression [19]. Sharma et al. [2] demonstrated that the presence of varus alignment, defined by measurements from full-leg standing radiographs at baseline, increased the risk of subsequent medial progression of disease in subjects with knee OA (odds ratio 4.09, 95% CI 2.20–7.62). Similarly, valgus alignment increased the risk of lateral progression (odds ratio 4.89, 95% CI 2.13–11.20). These findings using radiological joint space grade are consistent with our observations based on the direct measurement of joint cartilage. This group also suggested some effect of malalignment at almost all stages of OA [20]. However, the impact of varus or valgus malalignment on the odds of OA disease progression was greatest in knees with more advanced OA [20]. Although we were able to show an association between varus and valgus knee angle and loss of cartilage across all grades of radiological OA severity, we were not able to show an interaction between grade of radiological OA and knee angle on loss of joint cartilage. This may have been due to our smaller sample size.

An important potential limitation of our work is that we did not obtain full-limb films. Although the anatomical axis of the tibia is supposed to be straight [21], it is possible that bowing curvature of the tibia could lead to differences between anatomical alignment (measured by knee angle) and mechanical alignment using the entire tibia. It is possible that the strength of the relationship between alignment and cartilage volume decrease may have been stronger if a full limb assessment of alignment had been used and mechanical alignment measured directly. For example, this difference in measurement technique may be one explanation for the somewhat stronger correlation between knee angle and radiological change seen in the study by Sharma et al. [2]. We did not take specific steps to ensure that no rotation was present. However, it is most likely that rotation would cause non-differential misclassification and thus underestimate our findings, because it is unlikely that rotation at the knee assessed is more likely in one group of subjects than in another. We also observed complementary findings in the medial and lateral tibiofemoral compartments as the knee angle changed from more varus to more valgus. Furthermore, although we used radiographs to measure knee angle, we used MRI to measure change in cartilage volume, so any rotation would have no role in the outcome measure. In addition, we did not use a cut-off to categorize subjects as valgus or varus. Rather, we measured knee angle as a continuous variable and examined the relationship between increasing valgus and varus knee angle and cartilage loss in the medial and lateral compartments. Using this method, we were able to show a significant association with cartilage loss as the knee angles became progressively more varus or valgus within the population.

A potential strength of our study is that we used a very sensitive, reproducible and validated method for examining joint cartilage [7, 16]. This enabled us to examine both the femoral and the tibial cartilage plate in both the medial and the lateral tibiofemoral joint directly and avoid potential problems associated with radiological assessment of joint-space narrowing, which is an indirect measure of articular cartilage. Potential problems with radiography include the difficulty of reselecting identical locations in follow-up knee radiographs and the concern that mild to moderate joint space loss may reflect change in structures other than articular cartilage; for example, meniscal extrusion rather than joint cartilage erosion [5].

This study provides direct support for an association of varus and valgus alignment with progression of OA. We have shown some differences in the association with femoral and tibial cartilage volume in the two knee compartments. The significance of this is unclear. It may be due in part to our sample size and the duration of follow-up, which may have limited the power of our study to detect changes in all compartments. In support of this is the finding that the direction of change in the respective femoral and tibial cartilage plates was the same within the one compartment. However, further work will be needed to clarify this.

It has been suggested for a number of years that varus and valgus deformities of the knee are important factors in the development of OA in the medial and lateral tibiofemoral compartments [22]. Sharma et al. [23] have argued that varus malalignment increases medial compartment load while valgus malalignment increases lateral compartment load. With increased compartment load, the joint is subjected to greater regional stresses across the articular cartilage, which theoretically predates OA. Our study has shown a direct association with joint cartilage volume. Strategies aimed at modifying the knee angle in subjects with OA, such as the use of orthotics and physiotherapy interventions such as muscle retraining in some individuals, may have a beneficial role in reducing the rate of progression in knee OA [24].

In this study we found that the degree of varus knee angle was associated with a reduction in both femoral and tibial cartilage in the medial tibiofemoral compartment of the knee and an increase in the loss of joint cartilage over time. An increasing valgus knee angle is associated with a reduction in both femoral and tibial cartilage in the lateral tibiofemoral compartment of the knee and an increase in the loss of joint cartilage in the tibial cartilage plate in the lateral tibiofemoral compartment. Further work will be needed to determine whether therapies aimed at modifying the knee angle will reduce the progression of knee OA.

The authors have declared no conflicts of interest.

 
This study was supported by the National Health and Medical Research Council and the Colonial Foundation. AW is the recipient of a National Health and Medical Research Council Scholarship and additional funds from the Alfred Research Trusts. We would like to thank the MRI Unit at the Alfred Hospital for their cooperation and Kevin Morris for technical support. We would especially like to thank the study participants, who made this study possible.

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Submitted 20 May 2003; Accepted 24 July 2003

 
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