September Cahue

The mechanism of the effect of obesity in knee osteoarthritis: the mediating role of malalignment.

OBJECTIVE Obesity is most strongly linked to osteoarthritis (OA) at the knee. Varus malalignment was examined as a possible local mediator that may increase the impact of body weight at the knee, versus the hip or ankle. Compartment load distribution is more equitable in valgus than in varus knees, and valgus knees may better tolerate obesity. We therefore tested whether 1) body mass index (BMI) is correlated with OA severity in varus knees, 2) the BMI-OA severity correlation is weaker in valgus than in varus knees, 3) BMI is correlated with the severity of varus malalignment, and 4) the BMI-medial tibiofemoral OA severity relationship is reduced after controlling for varus malalignment. METHODS In 300 community-recruited patients with knee OA, 2 groups (varus and valgus) were identified based on dominant knee alignment on a full-limb radiograph, i.e., the angle formed by the intersection of the femoral and tibial mechanical axes. Severity of knee OA was assessed by measurement of the narrowest joint space width on radiographs of knees in a fluoroscopy-confirmed semiflexed position. RESULTS Alignment direction was symmetric (or neutral in 1 limb) in 87% of patients. One hundred fifty-four patients had varus knees and 115 had valgus knees. BMI correlated with OA severity in the varus group (r = -0.29, P = 0.0009) but not in the valgus group (r = -0.13, P = 0.17). BMI correlated with malalignment in those with varus knees (r = 0.26) but not in those with valgus knees (r = 0.16). The partial correlation of BMI and OA severity, controlling for sex, was reduced from 0.24 (P = 0.002) to 0.04 (P = 0.42) when varus malalignment was added to the model. CONCLUSION BMI was related to OA severity in those with varus knees but not in those with valgus knees. Much of the effect of BMI on the severity of medial tibiofemoral OA was explained by varus malalignment, after controlling for sex. Whether it precedes or follows the onset of disease, varus malalignment is one local factor that may contribute to rendering the knee most vulnerable to the effects of obesity.

Quadriceps strength and osteoarthritis progression in malaligned and lax knees

Context Experts routinely recommend that adults with knee osteoarthritis strengthen leg muscles. Contribution This 18-month cohort study of 237 adults with primary knee osteoarthritis found that greater baseline quadriceps strength was associated with greater risk for progressive tibiofemoral joint space narrowing among adults with malaligned or very lax knees. Implications Maximization of quadriceps strength in osteoarthritic patients with malaligned or very lax knees may not be joint protective and should be studied in trials that include joint structure outcomes. Cautions These results do not imply that physical activity in adults with knee osteoarthritis is harmful. The Editors Knee osteoarthritis is responsible for more chronic disability in elderly persons than any other medical condition (1). Quadriceps strengthening is widely recommended for knee osteoarthritis (2, 3), based on cross-sectional studies identifying strength (maximal voluntary muscle force generation) as a correlate of physical function (4-8) and on trials, predominantly short term, suggesting that quadriceps strengthening reduces pain and improves function (9, 10). The impact of quadriceps strength on the course of osteoarthritic disease itself is not well understood. A longitudinal study has shown that, in healthy knees, strong quadriceps offer some protection against new osteoarthritis development (11). However, whether quadriceps strength protects against progression or advancement of osteoarthritis in already arthritic knees has not been demonstrated. Brandt and colleagues (12) found no difference in baseline quadriceps strength between those with and those without disease progression. The effect of quadriceps strength on osteoarthritis disease progression is particularly important given the frequency with which quadriceps strengthening exercises are prescribed for persons with knee osteoarthritis. Muscle effects are less predictable in arthritic knees than in healthy knees. On the positive side, muscle activity promotes cartilage health and stabilizes the joint. During activity, muscles contract at different levels and protective reflexes are applied to shield knee tissues from injury (13). Coactivation, the dual drive of agonist and antagonist muscles, provides control for the stop and start of motion as well as compensation for gravity. Implicit in the recommendation of quadriceps strengthening for knee osteoarthritis is the assumption that greater strength will enhance these positive effects. If this enhancement comes without cost, greater strength may indeed protect arthritic joints from osteoarthritis progression. On the negative side, greater quadriceps strength may be associated with forces that could damage the vulnerable articular cartilage of osteoarthritis. The compensatory increase in muscle forces in osteoarthritis may increase the joint reaction force (14). A higher coactivation level in the agonist versus antagonist muscles can impair motion regulation and reduce ligament-protecting actions (13). The net impact of quadriceps strength on osteoarthritis progression depends on which effectspositive or negativeare greater. Which muscle effects prevail is likely to depend on the local mechanical environment. Local factors that alter load distribution, such as laxity and malalignment, influence how well the joint copes with muscle forces. Woo and associates (15) liken this situation to a hammer (muscle) driving a nail (the joint), while a hand (ligaments and, more broadly, local environment) holds the nail in place. The stabilizing hand allows greater force from the hammer. In other words, a healthy environment contributes to safe muscle force distribution over the menisci, articular cartilage, and other tissues. However, with laxity or malalignment, muscle forces may increase stress on localized areas of cartilage. Similarly, Marks and colleagues (16) theorized that local joint abnormalities can render muscle forces pathogenic. Malalignment and laxity are key local abnormalities. Any shift from a neutral hipkneeankle alignment alters load distribution; varus and valgus alignments increase medial and lateral compartment forces, respectively (17). Alignment influences the outcome of most knee surgeries, as well as natural disease progression and functional decline in osteoarthritis (18). Knee laxityabnormal displacement of the tibia with respect to the femur (19)shifts opposing surfaces of tibiofemoral contact so that congruence is reduced and increases shear and compression forces. Varusvalgus laxity has been linked to greater likelihood of osteoarthritis after ligament injury (20, 21). In other studies, laxity was present in patients with osteoarthritis before full-blown disease and was worsened by aspects of disease (22), was associated with worse function, and altered the strengthfunction relationship (23). If greater quadriceps strength improves the load imbalance created by malalignment or attenuated load in malaligned knees, it might protect against osteoarthritis progression in patients with maligned knees. Alternatively, malalignment may alter the line of action of quadriceps forces, distributing them inequitably across the joint surface (16); in this case, strength might increase the likelihood of osteoarthritis progression. In the lax knee, strength might be protective if greater quadriceps strength enhances dynamic stabilization. However, if the cost of this compensationthat is, greater joint reaction forceexceeds the stabilization benefit, the likelihood of osteoarthritis progression might increase. Our objective was to determine whether greater quadriceps strength was associated with greater probability of tibiofemoral osteoarthritis progression among all knees in persons with osteoarthritis and in two subsets, malaligned knees and high-laxity knees. Methods Participants Mechanical Factors in Arthritis of the Knee (MAK) is a natural history study of knee osteoarthritis at Northwestern University in Chicago, Illinois. Participants in MAK were recruited through periodicals targeting senior citizens, 67 neighborhood organizations, the registry of the Northwestern University Buehler Center on Aging, and medical center referrals. Inclusion and exclusion criteria were based on those developed for osteoarthritis progression studies at a workshop sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging (24). Inclusion criteria were definite osteophyte presence (Kellgren and Lawrence radiographic grade 2) in one or both knees and at least a little difficulty (Likert category) with at least two items in the Western Ontario and McMaster University osteoarthritis index physical function scale. Exclusion criteria were corticosteroid injection within 3 months, avascular necrosis, rheumatoid or other inflammatory arthritis, periarticular fracture, Paget disease, villonodular synovitis, joint infection, ochronosis, neuropathic arthropathy, acromegaly, hemochromatosis, Wilson disease, osteochondromatosis, gout, pseudogout, osteopetrosis, bilateral total knee replacement, or plan for knee replacement within the next year. Persons with past unilateral knee replacement were eligible if they had osteoarthritis in the nonreplaced knee. The institutional review board of Northwestern University approved the study, and all participants gave informed consent. Measurement of Key Factors All measurements were obtained in both knees. Isokinetic quadriceps strength was tested by using a computer-driven isokinetic dynamometer (Cybex, Avocent, Huntsville, Alabama) to assess maximal torque during movement. One tester assessed all participants by following a previously described protocol (23). The computer recorded data in foot-pounds (ft-lbs) and corrected for gravity effects. Reliability, determined by using test repetitions, was high (intraclass correlation coefficients > 0.98) (23). To assess alignment, a single anteroposterior radiograph of both lower extremities was obtained by using a graduated grid cassette (51 14 inches), adhering to a protocol we have described elsewhere (18). Alignment was defined as the measure of the angle formed by the intersection of the line connecting the centers of the femoral head and intercondylar notch and the line connecting the centers of the ankle talus and tibial spines (17, 25, 26). Knees were considered more neutral if the angle was less than 5 degrees in a varus or valgus direction and malaligned if the angle was 5 degrees or more. One experienced reader made all measurements. Reliability, based on a set of radiographs from patients with osteoarthritis (18), was high for varus and valgus alignment (intraclass correlation coefficients, 0.99 and 0.98, respectively). Varus-valgus laxity was measured with a device designed for the MAK study by Dr. Thomas Buchanan (22, 23). The measurement protocol has been described elsewhere (22, 23). Angular deviation was measured at the foot with application of varus or valgus load. Varusvalgus laxity was analyzed as the sum of varus and valgus rotation for each knee (27-29). Because a definition of high and low laxity is not available, knees in the highest laxity tertile ( 5.75 degrees) were designated as high laxity. Laxity measurements were performed by the same examiner and assistant, and reliability was very good in participants with osteoarthritis (within-session intraclass correlation coefficients, 0.85 to 0.96; between-sessions intraclass correlation coefficients, 0.84 to 0.90) (22). Measurement of Outcome Knee radiographs were obtained at baseline and at 18 months, following the semi-flexed, fluoroscopically confirmed protocol developed by Buckland-Wright (24, 30, 31). Knee position, beam alignment, markers to account for magnification, and measurement landmarks were specified. The standing semi-flexed position superimposes anterior and posterior medial tibial margins. Knee position was confir

Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees.

OBJECTIVE Progressive knee osteoarthritis (OA) is believed to result from local factors acting in a systemic environment. Previous studies have not examined these factors concomitantly or compared quantitative and qualitative cartilage loss outcomes. The aim of this study was to test whether meniscal damage, meniscal extrusion, malalignment, and laxity each predicted tibiofemoral cartilage loss after controlling for the other factors. METHODS Laxity and alignment were measured at baseline in individuals with knee OA. Magnetic resonance imaging included spin-echo coronal and sagittal imaging for meniscal scoring and axial and coronal spoiled gradient echo sequences with water excitation for cartilage quantification. Tibial and weight-bearing femoral condylar subchondral bone area and cartilage surface were segmented. Cartilage volume, denuded bone area, and cartilage thickness were quantified in each plate, with progression defined as cartilage loss >2 times the coefficient of variation for each plate. Qualitative outcome was assessed as worsening of the cartilage score. Logistic regression analysis with generalized estimating equations yielded odds ratios for each factor, adjusting for age, sex, body mass index, and the other factors. RESULTS We studied 251 knees in 153 persons. After full adjustment, medial meniscal damage predicted medial tibial cartilage volume loss and tibial and femoral denuded bone increase, while varus malalignment predicted medial tibial cartilage volume and thickness loss and tibial and femoral denuded bone increase. Lateral meniscal damage predicted every lateral outcome. Laxity and meniscal extrusion had inconsistent effects. After full adjustment, no factor except medial laxity predicted qualitative outcome. CONCLUSION Using quantitative cartilage loss assessment, local factors that independently predicted tibial and femoral loss included medial meniscal damage and varus malalignment (medially) and lateral meniscal damage (laterally). A measurement of quantitative outcome was more sensitive at revealing these relationships than a qualitative approach.

The association between varus-valgus alignment and patellofemoral osteoarthritis

OBJECTIVE Little is known about risk factors for patellofemoral (PF) osteoarthritis (OA). The lateral vector at the PF joint increases the likelihood of lateral PF versus medial PF pathology. Both valgus and varus malalignments affect forces at the PF joint and may predispose to PF OA. We examined whether lateral PF OA is more common than medial PF OA, whether valgus malalignment is more frequent in lateral PF OA than in medial PF OA, and whether knees with PF OA are more often valgus than knees with isolated tibiofemoral (TF) OA. METHODS In 292 knee OA patients, we obtained semiflexed, fluoroscopy-confirmed radiographs of the TF joint and weight-bearing, 30 degrees flexion, axial views of the PF joint. Varus-valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full-limb radiograph. RESULTS Lateral PF OA was more common than medial PF OA (P<0.0001). Forty-three of 75 knees with lateral PF OA had valgus malalignment compared with only 5 of 21 patients with medial PF OA (P = 0.0066). Conversely, varus malalignment was more likely in the medial PF OA group. Knees with isolated PF OA were more likely to have valgus malalignment than those with isolated TF OA (P = 0.0002), as were knees with mixed PF-TF OA (P = 0.0006). CONCLUSION Varus-valgus alignment may influence the risk of PF OA and, in particular, which compartment is affected.

Patterns of femorotibial cartilage loss in knees with neutral, varus, and valgus alignment

OBJECTIVE Malalignment is known to alter medial-to-lateral femorotibial load distribution and to affect osteoarthritis (OA) progression in the mechanically stressed compartment. We investigated the pattern of cartilage loss in neutral, varus, and valgus knees. METHODS Alignment was measured from full-limb radiographs in 174 participants with symptomatic knee OA. Coronal magnetic resonance images were acquired at baseline and a mean +/- SD of 26.6 +/- 5.4 months later. The weight-bearing femorotibial cartilages were segmented from paired images. Cartilage volume, surface area, and thickness were determined in total cartilage plates and defined subregions using proprietary software. RESULTS The medial-to-lateral ratio of femorotibial cartilage loss was 1.4:1 in neutral knees (n = 74), 3.7:1 in varus knees (n = 57), and 1:6.0 in valgus knees (n = 43). The relative contribution of cartilage thickness change tended to be greater in knees with mild cartilage loss, whereas the increase of denuded area was greater in knees with accelerated cartilage loss. In both varus and neutral knees, the greatest changes were observed in the same subregions of the medial femorotibial compartment (central and external medial tibia, and central medial femur). In valgus and neutral knees, the subregions with the greatest changes in the lateral femorotibial compartment were also similar (internal and central lateral tibia, external lateral femur). CONCLUSION The medial-to-lateral rate of femorotibial cartilage loss strongly depended on alignment. Subregions of greater-than-average cartilage loss within the stressed compartment were, however, similar in neutral, varus, and valgus knees. This indicates that the medial-to-lateral loading pattern is different, but that the (sub)regional loading pattern may not differ substantially between neutral and malaligned knees.

Within-Subregion Relationship Between Bone Marrow Lesions and Subsequent Cartilage Loss in Knee Osteoarthritis

Bone marrow lesions are believed to increase risk of knee osteoarthritis (OA) progression. Whether their effect is local and whether it can be explained by other types of bone lesions concomitantly present in the same subregion is unclear. We evaluated bone lesion frequency in subregions without cartilage lesions and cartilage lesion frequency in subregions without bone lesions, and investigated the within‐subregion bone marrow lesion/subsequent cartilage loss relationship after adjusting for other types of bone lesions at baseline.

Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis

Objectives Meniscal tears have been linked to knee osteoarthritis progression, presumably by impaired load attenuation. How meniscal tears affect osteoarthritis is unclear; subregional examination may help to elucidate whether the impact is local. This study examined the association between a tear within a specific meniscal segment and subsequent 2-year cartilage loss in subregions that the torn segment overlies. Methods Participants with knee osteoarthritis underwent bilateral knee MRI at baseline and 2 years. Mean cartilage thickness within each subregion was quantified. Logistic regression with generalised estimating equations were used to analyse the relationship between baseline meniscal tear in each segment and baseline to 2-year cartilage loss in each subregion, adjusting for age, gender, body mass index, tear in the other two segments and extrusion. Results 261 knees were studied in 159 individuals. Medial meniscal body tear was associated with cartilage loss in external subregions and in central and anterior tibial subregions, and posterior horn tear specifically with posterior tibial subregion loss; these relationships were independent of tears in the other segments and persisted in tibial subregions after adjustment for extrusion. Lateral meniscal body and posterior horn tear were also associated with cartilage loss in underlying subregions but not after adjustment for extrusion. Cartilage loss in the internal subregions, not covered by the menisci, was not associated with meniscal tear in any segment. Conclusion These results suggest that the detrimental effect of meniscal tears is not spatially uniform across the tibial and femoral cartilage surfaces and that some of the effect is experienced locally.

Knee confidence as it relates to physical function outcome in persons with or at high risk of knee osteoarthritis in the osteoarthritis initiative.

OBJECTIVE To evaluate whether low knee confidence at baseline is associated with poor baseline-to-3-year physical function outcome in the Osteoarthritis Initiative. METHODS Knee confidence was assessed using an item from the Knee Injury and Osteoarthritis Outcome Score instrument. Physical function was assessed using self-report measures (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function score and Short Form 12 physical component scale) and performance-based measures (20-meter walk and chair stand test). Poor function outcome was defined as moving into a worse function group or remaining in the 2 worst function groups between baseline and 3 years. Logistic regression was used to evaluate the relationship between baseline knee confidence level and poor baseline-to-3-year function outcome, adjusting for potential confounders. RESULTS The sample included 3,975 men and women with or at high risk of developing osteoarthritis of the knee, of whom 37-53% had poor baseline-to-3-year function outcome. For both self-report measures, increasingly worse knee confidence was associated with a greater risk of poor function outcome, and trend tests supported a graded response (e.g., the adjusted odds ratios [95% confidence intervals] for the WOMAC function score for worsening confidence categories were 1.26 [1.07-1.49], 1.43 [1.16-1.77], and 2.05 [1.49-2.82], P for trend <0.0001). Similar associations between confidence and performance-based function outcome were observed, but statistical significance did not persist in adjusted analyses. Factors independently associated with poor function outcome for all 4 outcome measures were depressive symptoms, comorbidity, body mass index, and joint space narrowing. CONCLUSION These findings indicate that worse knee confidence at baseline is independently associated with greater risk of poor function outcome by self-report measures, with evidence of a graded response; the relationship with performance measures is not significant in fully adjusted models.

Varus-valgus alignment: reduced risk of subsequent cartilage loss in the less loaded compartment.

OBJECTIVE Varus-valgus alignment has been linked to subsequent progression of osteoarthritis (OA) within the mechanically stressed (medial for varus, lateral for valgus) tibiofemoral compartment. Cartilage data from the off-loaded compartment are sparse. The purpose of this study was to examine our hypotheses that neutral and valgus (versus varus) knees each have reduced odds of cartilage loss in the medial subregions and that neutral and varus (versus valgus) knees each have reduced odds of cartilage loss in the lateral subregions. METHODS Patients with knee OA underwent knee magnetic resonance imaging at baseline and 2 years. The mean cartilage thickness was quantified within 5 tibial and 3 femoral subregions. We used logistic regression with generalized estimating equations to analyze the relationship between baseline alignment and subregional cartilage loss at 2 years, adjusting for age, sex, body mass index, and disease severity. RESULTS A reduced risk of cartilage loss in the medial subregions was associated with neutral (versus varus) alignment (external tibial, central femoral, external femoral) and with valgus (versus varus) alignment (central tibial, external tibial, central femoral, external femoral). A reduced risk of cartilage loss in the lateral subregions was associated with neutral (versus valgus) alignment (central tibial, internal tibial, posterior tibial) and with varus (versus valgus) alignment (central tibial, external tibial, posterior tibial, external femoral). CONCLUSION Neutral and valgus alignment were each associated with a reduction in the risk of subsequent cartilage loss in certain medial subregions and neutral and varus alignment with a reduction in the risk of cartilage loss in certain lateral subregions. These results support load redistribution as an in vivo mechanism of the long-term alignment effects on cartilage loss in knee OA.

421 SIDE-DIFFERENCES OF FEMOROTIBIAL CARTILAGE LOSS IN KNEE OA

affected and contralateral hip are the most important predictors of hip osteoarthritis progression (p< 0.01). (Figure 1, area a and b). Similarly, there are size differences between progressors and non-progressors in the superior part of the femoral head and trochanter major. However the KL score of the affected side was still the most relevant variable in the prediction of OA progression. Conclusions: DXA parameters can significantly contribute to predict future progression of joint space narrowing or total hip replacement in patients with (beginning) hip osteoarthritis. The analysis of the DXA differences between two hips of the patient represents a small but significant contribution to this prediction. These analyses show the importance of bone density changes in the etiology of OA. Accurate measurements of bone density and bone shape can help to diagnose OA and predict its chances of fast progression.