Knee osteoarthritis (OA) is a leading cause of chronic disability (1). Few factors that contribute to the progression or advancement of OA disease at the knee have been identified. One factor that has been found to play an important role is knee alignment (i.e., hip–knee–ankle angle). Varus and valgus malalignment were shown to increase the risk of subsequent medial and lateral knee OA progression, respectively (2). The effect of malalignment potentially extends beyond its direct effect in at least two ways: malalignment is part of a vicious circle with progressive OA, and it may have effects on knee tissues other than cartilage that could further propagate OA disease.
The primary mechanism of the alignment effect is biomechanical. In the normal state, 60–80% of the total intrinsic compressive load transmitted across the knee is on the medial compartment (3). Alignment influences medial to lateral compartment load distribution. In a varus knee, the load-bearing axis is shifted so that the medial compartment experiences greater stress. In a valgus knee, stress is increased in the lateral compartment (4).
The impact of a mechanical factor depends not only on the factor itself, but also on the state of vulnerability of the knee to insult, including its OA disease stage. This state of vulnerability may change during the evolution of OA from mild to moderate stages. The less-damaged joint of mild OA may be less vulnerable to the biomechanical effects of malalignment than the more-damaged joint of moderate OA. Rarely have progression studies stratified examination of the effect of a given risk factor according to the baseline stage of OA.
The goal of this study was to examine whether the influence of alignment on subsequent progression of knee OA differs according to the baseline stage of disease. We examined the alignment/progression relationship in patients with knee OA separately in their knees without radiographic OA, with mild OA, and with moderate OA.
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- PATIENTS AND METHODS
There were 237 MAK subjects with at least 1 knee that could progress (i.e., without the most severe grade of joint space narrowing at baseline). Seven of these 237 subjects (3%) did not return at 18 months (5 had died; 2 could not be reached) (2). The mean ± SD age of the 230 subjects constituting the study sample was 64.0 ± 10.8 years and their mean ± SD BMI was 30.4 ± 6.0 kg/m2. There were 173 women and 57 men. There were 45 K/L grade 0–1 knees (in 39 patients with a mean age of 64.0 years and a mean BMI of 28.0 kg/m2, 82% of whom were women), 241 K/L grade 2 knees (in 162 patients with a mean age of 63.4 years and a mean BMI of 29.6 kg/m2, 73% of whom were women), and 91 K/L grade 3 knees (in 75 patients with a mean age of 65.1 years and a mean BMI of 32.9 kg/m2, 70% of whom were women).
As shown in Table 1, there was a >2-fold increase in the odds of medial progression in the K/L grade 0–1 knees conferred by varus alignment, but this was not statistically significant. In the K/L grade 2 knees, the OR for medial progression associated with varus alignment rose to 4.12 and was significant. In the K/L grade 3 knees, the OR was even greater, at 10.96, and continued to be significant. The direction of change in the OR from K/L grade 0–1 to grade 2 and from grade 2 to grade 3 was consistent; the risk of medial progression related to varus alignment was greater in grade 3 knees (OR 10.96) compared with grade 0–1 knees (OR 2.50), although not significantly so (P = 0.11), which may have been due to low power related to small subgroup sizes. We recognized that a difference in the severity of malalignment between K/L grades might contribute to this difference in the odds of progression. Among varus knees, the mean ± SD severity of varus was 3.13 ± 1.25° (range 1.00–5.00) in K/L grade 0–1 knees, 3.04 ± 1.95° (range 1.00–8.00) in grade 2 knees, and 4.34 ± 2.66° (range 1.00–10.00) in grade 3 knees (P not significant for grade 0–1 versus grade 2 knees; P = 0.03 for grade 2 versus grade 3 knees).
Table 1. Risk of medial compartment progression conferred by varus alignment, stratified by baseline radiographic (K/L) grade of osteoarthritis*
|Baseline K/L grade||No. of knees (no. of subjects)||OR for medial progression (95% CI)|
|0–1||45 (39)||2.50 (0.67–9.39)|
|2||241 (162)||4.12 (1.92–8.82)|
|3||91 (75)||10.96 (3.10–38.77)|
It was not possible to examine the valgus effect in K/L grade 0–1 knees because of the small number of knees with lateral progression within this subgroup (i.e., 0 of 24 nonvalgus, K/L grade 0–1 knees and 1 of 24 valgus, K/L grade 0–1 knees progressed in the lateral compartment). As shown in Table 2, in K/L grade 2 knees, there was a >2-fold increase in the risk of lateral progression associated with valgus alignment, and this difference approached significance. In K/L grade 3 knees, there was a >10-fold increase in the odds of lateral progression, and this difference was significant. The risk of lateral progression related to valgus alignment in grade 3 knees (OR 10.44) was statistically significantly greater (P = 0.02) than the associated risk in grade 2 knees (OR 2.46). Among valgus knees, the mean ± SD severity of valgus was 3.13 ± 2.18° (range 1.00–10.00) in K/L grade 2 knees and 5.45 ± 3.07° (range 1.00–12.00) in grade 3 knees (P = 0.002 for grade 2 versus grade 3 knees).
Table 2. Risk of lateral compartment progression conferred by valgus alignment, stratified by baseline radiographic (K/L) grade of osteoarthritis*
|Baseline K/L grade||No. of knees (no. of subjects)||OR for lateral progression (95% CI)†|
|2||241 (162)||2.46 (0.95–6.34)|
|3||91 (75)||10.44 (2.76–39.49)|
Potential covariates considered included age, sex, and BMI. Of these factors, only BMI had a bivariate relationship to disease progression. After adjusting for BMI, the magnitude of the ORs was minimally altered.
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- PATIENTS AND METHODS
In the present study, we found that in knees with mild OA (K/L grade 2), the odds of 18-month progression in the medial compartment were increased 4-fold by varus alignment at baseline. In K/L grade 2 knees, the odds of lateral progression were increased 2-fold by valgus alignment (approaching significance). In knees with moderate OA (K/L grade 3), the impact of malalignment in either the varus or valgus direction on subsequent 18-month progression was substantial (>10-fold increase).
Varus and valgus alignment are associated with increased force across the medial and lateral compartments, respectively. Joint pathology present at moderate stages of OA, including cartilage loss or meniscal degeneration, may render the joint less able to handle the forces imposed by a given alignment. In keeping with the concept that malalignment and OA progression are in a vicious circle, malalignment appeared somewhat more severe in K/L grade 3 knees than in K/L grade 2 knees (i.e., by 1.3° in varus knees and by 2.3° in valgus knees). The individual contributions of knee joint vulnerability and malalignment severity to the current results cannot be segregated; it is likely that both factors come into play.
In the K/L grade 2 knees, the effect of valgus alignment on lateral progression appeared weaker than the effect of varus alignment on medial progression (despite comparable absolute severity of malalignment). A biomechanical rationale exists for a smaller impact of valgus than varus in these mildly diseased knees. In the normally aligned, ambulating knee, load is disproportionately transmitted to the medial compartment (18). Varus further increases the total load passing medially during gait (9). Although valgus is associated with an increase in lateral compartment peak pressures, the medial compartment often continues to bear more load than the lateral compartment until more severe valgus is present (19, 20). Therefore, compartment load distribution in the mildly diseased valgus knee is likely to be more equitable than in the comparably diseased varus knee. A difference between the impact of varus and valgus alignment on subsequent progression was less apparent in the more vulnerable K/L grade 3 knees.
Numerous studies in the orthopedic literature demonstrate that knee alignment is associated with surgical outcome. Of particular relevance, tibial osteotomy, developed with the view that transferring load away from the stressed area of the knee would be beneficial, improves relevant outcomes in subsets of patients (21–24). That malalignment is a risk factor for the natural progression of knee OA has also been demonstrated. We previously found that the presence of varus alignment at baseline in all knees at risk of progression in subjects with knee OA increased the risk of subsequent medial progression (OR 4.09, 95% CI 2.20–7.62) (2). Valgus alignment increased the risk of lateral progression (OR 4.89, 95% CI 2.13–11.20). In a previous natural history study, a patient's recollection of having had “bow-legs or knock-knees in childhood” was associated with a 5-fold increase in the risk of OA progression (25). To our knowledge, no previous study has examined the malalignment effect according to baseline stage of disease severity.
Limitations of this study include the small number of knees in certain subsets, including the K/L grade 3 group (contributing to the wide 95% CI for the OR) and the K/L grade 0–1 group (precluding analysis of the valgus impact), which limits the power to detect statistically significant relationships. However, in spite of the size of certain subsets, with progressively worse baseline stage of disease severity, there was a clear trend toward an increase in the magnitude of the varus-associated OR and a significant increase in the valgus-associated OR.
These results have several implications. First, they add support to the concept that (among knees without end-stage OA) the influence of alignment is more pronounced as disease stage advances. This is possibly due to greater joint vulnerability, with some contribution from more severe malalignment. The alignment effect on a relatively healthy knee (the target of the epidemiologic investigation of the new development of OA) cannot be assumed to be the same as the alignment effect on a diseased knee (the target of progression studies), and needs to be separately examined. While the issue of vulnerability is directly relevant to mechanical factors, perhaps it should also be considered for risk factors in general. Second, the response to interventions for malalignment needs to be stratified according to baseline stage of disease. Interventions which reduce the stresses that malalignment places on a knee are in various phases of development and investigation (e.g., wedge insoles, “unloading” braces). The current results imply that such interventions, if they can improve compartment load distribution, may delay disease progression in varus K/L grade 2 knees and in varus or valgus K/L grade 3 knees—this warrants further study. The role of such interventions in K/L grade 0–1 knees (varus or valgus) or in valgus K/L grade 2 knees is less clear. It is important to note that the current study assessed progression during the ensuing 18 months; the effect of malalignment in knees without OA or with mild OA may take years to be fully evident. In contrast, the impact of malalignment on progression in the K/L grade 3 knees was evident within 18 months.
In summary, some effect of malalignment was suggested at almost all stages of OA examined. However, the impact of varus or valgus malalignment on the odds of OA disease progression during the ensuing 18 months was greater in knees with more advanced OA at baseline.