Leena Sharma

Knee adduction moment, serum hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis

OBJECTIVE The adduction moment at the knee during gait is the primary determinant of medial-to-lateral load distribution. If the adduction moment contributes to progression of osteoarthritis (OA), then patients with advanced medial tibiofemoral OA should have higher adduction moments. The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age, sex, and pain level, and to examine the correlation of serum hyaluronan (HA) level with disease severity and with the adduction moment in a subset of patients. METHODS Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation. Disease severity was assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In a subset of 23 patients with available sera, HA was quantified by sandwich enzyme-linked immunosorbent assay. Pearson correlations, a random effects model, and multivariate regression models were used. RESULTS The adduction moment correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60, respectively), and with joint space width in the left and right knees (r = -0.45 and r = -0.47, respectively). The relationship persisted after controlling for age, sex, and severity of pain. The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees. For every 1.0-unit increase in adduction moment, there was a 0.63-mm decrease in joint space width. In the subset of patients in whom serum HA levels were measured, HA levels correlated with medial joint space width (r = -0.55), but not with the adduction moment. CONCLUSION There is a significant relationship between the adduction moment and OA disease severity. Serum HA levels correlate with joint space width but not with the adduction moment. Longitudinal studies will be necessary to determine the contribution of the adduction moment, and its contribution in conjunction with metabolic markers, to progression of medial tibiofemoral OA.

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

Laxity in healthy and osteoarthritic knees

OBJECTIVE Although it is a cause of osteoarthritis (OA) in animal models, laxity in human knee OA has been minimally evaluated. Ligaments become more compliant with age; whether this results in clinical laxity is not clear. In theory, laxity may predispose to OA and/or result from OA. Our goals were to examine the correlation of age and sex with knee laxity in control subjects without OA, compare laxity in uninvolved knees of OA patients with that in older control knees, and examine the relationship between specific features of OA and knee laxity. METHODS We assessed varus-valgus and anteroposterior laxity in 25 young control subjects, 24 older control subjects without clinical OA, radiographic OA, or a history of knee injury, and 164 patients with knee OA as determined by the presence of definite osteophytes. A device was designed to assess varus-valgus laxity under a constant varus or valgus load while maintaining a fixed knee flexion angle and thigh and ankle immobilization. Radiographic evaluations utilized protocols addressing position, beam alignment, magnification, and landmark definition; the semiflexed position was used, with fluoroscopic confirmation. RESULTS In the controls, women had greater varus-valgus laxity than did men (3.6 degrees versus 2.7 degrees; 95% confidence interval [95% CI] of difference 0.38, 1.56; P = 0.004), and laxity correlated modestly with age (r = 0.29, P = 0.04). Varus-valgus laxity was greater in the uninvolved knees of OA patients than in older control knees (4.9 degrees versus 3.4 degrees; 95% CI of difference 0.60, 2.24; P = 0.0006). In OA patients, varus-valgus laxity increased as joint space decreased (slope -0.34; 95% CI -0.48, -0.19; P < 0.0001) and was greater in knees with than in knees without bony attrition (5.3 degrees versus 4.5 degrees; 95% CI of difference 0.32, 1.27; P = 0.001). CONCLUSION Greater varus-valgus laxity in the uninvolved knees of OA patients versus older control knees and an age-related increase in varus-valgus laxity support the concept that some portion of the increased laxity of OA may predate disease. Loss of cartilage/bone height is associated with greater varus-valgus laxity. These results raise the possibility that varus-valgus laxity may increase the risk of knee OA and cyclically contribute to progression.

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.

Statin Use and Leg Functioning in Patients With and Without Lower-Extremity Peripheral Arterial Disease

Background—We determined whether statin use (versus nonuse) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease. Methods and Results—Participants included 392 men and women with an ankle brachial index (ABI) <0.90 and 249 with ABI 0.90 to 1.50. Functional outcomes included 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ABI, comorbidities, education level, medical insurance status, cholesterol, and other confounders, participants taking statins had better 6-minute walk performance (1276 versus 1218 feet, P =0.045), faster walking velocity (0.93 versus 0.89 m/s, P =0.006), and a higher summary performance score (10.2 versus 9.4, P <0.001) than participants not taking statins. Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score. We did not find significant associations between lower-extremity functioning and aspirin, ACE inhibitors, vasodilators, or &bgr;-blockers. Conclusions—Statin use is associated with superior leg functioning compared with no statin use, independent of cholesterol levels and other potential confounders. These data suggest that non–cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease.

Is Obesity a Risk Factor for Progressive Radiographic Knee Osteoarthritis

OBJECTIVE To examine whether obesity increases the risk of progression of knee osteoarthritis (OA). METHODS We used data from the Multicenter Osteoarthritis Study, a longitudinal study of persons with or at high risk of knee OA. OA was characterized at baseline and 30 months using posteroanterior fixed-flexion radiographs and Kellgren/Lawrence (K/L) grading, with alignment assessed on full-extremity films. In knees with OA at baseline (K/L grade 2 or 3), progression was defined as tibiofemoral joint space narrowing on the 30-month radiograph. In knees without OA at baseline (K/L grade 0 or 1), incident OA was defined as the development of radiographic OA at 30 months. Body mass index (BMI) at baseline was classified as normal (<25 kg/m(2)), overweight (25-<30 kg/m(2)), obese (30-<35 kg/m(2)), and very obese (>or=35 kg/m(2)). The risk of progression was tested in all knees and in subgroups categorized according to alignment. Analyses were adjusted for age, sex, knee injury, and bone density. RESULTS Among the 2,623 subjects (5,159 knees), 60% were women, and the mean +/- SD age was 62.4 +/- 8.0 years. More than 80% of subjects were overweight or obese. At baseline, 36.4% of knees had tibiofemoral OA, and of those, only one-third were neutrally aligned. Compared with subjects with a normal BMI, those who were obese or very obese were at an increased risk of incident OA (relative risk 2.4 and 3.2, respectively [P for trend < 0.001]); this risk extended to knees from all alignment groups. Among knees with OA at baseline, there was no overall association between a high BMI and the risk of OA progression; however, an increased risk of progression was observed among knees with neutral but not varus alignment. The effect of obesity was intermediate in those with valgus alignment. CONCLUSION Although obesity was a risk factor for incident knee OA, we observed no overall relationship between obesity and the progression of knee OA. Obesity was not associated with OA progression in knees with varus alignment; however, it did increase the risk of progression in knees with neutral or valgus alignment. Therefore, weight loss may not be effective in preventing progression of structural damage in OA knees with varus alignment.

Varus and valgus alignment and incident and progressive knee osteoarthritis

Objective Varus and valgus alignment increase medial and lateral tibiofemoral load. Alignment was associated with tibiofemoral osteoarthritis progression in previous studies; an effect on incident osteoarthritis risk is less certain. This study tested whether alignment influences the risk of incident and progressive radiographic tibiofemoral osteoarthritis. Methods In an observational, longitudinal study of the Multicenter Osteoarthritis Study cohort, full-limb x-rays to measure alignment were acquired at baseline and knee x-rays were acquired at baseline and knee x-rays at baseline and 30 months. Varus alignment was defined as ≤178° and valgus ≥182°. Using logistic regression and generalised estimating equations, the associations of baseline alignment and incident osteoarthritis at 30 months (in knees without baseline osteoarthritis) and alignment and osteoarthritis progression (in knees with osteoarthritis) were examined, adjusting. For age, gender, body mass index, injury, laxity and strength, with neutral knees as referent. Results 2958 knees (1752 participants) were without osteoarthritis at baseline. Varus (adjusted OR 1.49, 95% CI 1.06 to 2.10) but not valgus alignment was associated with incident osteoarthritis. 1307 knees (950 participants) had osteoarthritis at baseline. Varus alignment was associated with a greater risk of medial osteoarthritis progression (adjusted OR 3.59, 95% CI 2.62 to 4.92) and a reduced risk of lateral progression, and valgus with a greater risk of lateral progression (adjusted OR 4.85, 95% CI 3.17 to 7.42) and a reduced risk of medial progression. Conclusion Varus but not valgus alignment increased the risk of incident tibiofemoral osteoarthritis. In knees with osteoarthritis, varus and valgus alignment each increased the risk of progression in the biomechanically stressed compartment.

Does knee malalignment mediate the effects of quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? A randomized controlled trial

OBJECTIVE To examine whether the effects of 12 weeks of quadriceps strengthening on the knee adduction moment, pain, and function in people with medial knee osteoarthritis (OA) differ in those with and without varus malalignment. METHODS A single-blind, randomized controlled trial of 107 community volunteers with medial knee OA was conducted. Participants were stratified according to knee malalignment (more varus or more neutral) and then randomized into either a 12-week supervised home-based quadriceps strengthening group or a control group with no intervention. The primary outcome was the knee adduction moment, measured using 3-dimensional gait analysis. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index scores (measuring pain and physical function), step test score, stair climb test score, and maximum quadriceps isometric strength. Analyses of covariance were carried out based on intent-to-treat principles. RESULTS Quadriceps strengthening did not significantly alter the knee adduction moment in either the more malaligned or the more neutral group (unadjusted knee adduction moment 0.12 and 0.05% Nm/BWxHT, respectively). Function did not improve significantly following quadriceps strengthening in either alignment group, but there was a significant improvement in knee pain in the more neutrally aligned group (P < 0.001). CONCLUSION Quadriceps strengthening did not have any significant effect on the knee adduction moment in participants with either more varus or more neutral alignment. The benefits of quadriceps strengthening on pain were more evident in those with more neutral alignment. Knee alignment thus represents a local mechanical factor that can mediate symptomatic outcome from exercise interventions in knee OA.

Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort

OBJECTIVE To assess whether knee extensor strength or hamstring:quadriceps (H:Q) ratio predicts risk for incident radiographic tibiofemoral and incident symptomatic whole knee osteoarthritis (OA) in adults ages 50-79 years. METHODS We followed 1,617 participants (2,519 knees) who, at the baseline visit of the Multicenter Osteoarthritis (MOST) Study, did not have radiographic tibiofemoral OA and 2,078 participants (3,392 knees) who did not have symptomatic whole knee OA (i.e., did not have the combination of radiographic OA and frequent knee symptoms). Isokinetic strength was measured at baseline, and participants were followed for development of incident radiographic tibiofemoral OA, or incident symptomatic whole knee OA at 30 months. Generalized estimating equations accounted for 2 knees per subject, and multivariable models adjusted for age, body mass index (BMI), hip bone mineral density, knee surgery or pain, and physical activity score. RESULTS In the studies of incident radiographic and incident symptomatic knee OA, mean +/- SD ages were 62.4 +/- 8.0 years and 62.3 +/- 8.0 years, respectively, and mean +/- SD BMI scores were 30.6 +/- 5.8 kg/m(2) and 30.2 +/- 5.5 kg/m(2), respectively. Knee extensor strength and H:Q ratio at baseline significantly differed between men and women. Neither knee extensor strength nor the H:Q ratio was predictive of incident radiographic tibiofemoral OA. Compared with the lowest tertile, the highest tertile of knee extensor strength protected against development of incident symptomatic whole knee OA in both sexes (adjusted odds ratio 0.5-0.6). H:Q ratio was not predictive of incident symptomatic whole knee OA in either sex. CONCLUSION Thigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.