Neil A. Segal

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.

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.

Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort

OBJECTIVE Quadriceps weakness has been reported with incident but not progressive knee osteoarthritis (OA) in longitudinal studies. This study examined the relationship between quadriceps strength and worsening of knee joint space narrowing (JSN) over 30 months. METHODS Longitudinal, observational study of adults aged 50-79 years with OARSI JSN score <3 at baseline. Baseline measures included bilateral weight-bearing fixed flexion radiographs, isokinetic concentric quadriceps and hamstring strength, height and weight, and physical activity. Hamstring:quadriceps (H:Q) strength ratios also were evaluated. Worsening was defined as an increase in JSN score in the tibiofemoral and/or patellofemoral compartments on 30-month radiographs or total knee replacement. Knee-based analyses used generalized estimating equations, stratified by sex, to assess relationships between strength and knee JSN while controlling for covariance between knees within subjects as well as age, body mass index (BMI), history of knee injury and/or surgery, physical activity level and alignment. RESULTS 3856 knees (2254 females and 1602 males) with JSN score <3 at baseline and no missing follow-up data were included. Mean+/-SD age was 62.2+/-7.7 in women and 61.6+/-8.1 in men. Women in the lowest tertile of quadriceps strength had an increased risk of whole knee JSN (OR=1.66, 95% CI=1.26, 2.19) and tibiofemoral JSN (OR=1.69, 95% CI=1.26, 2.28). However, no associations were found between strength and JSN in men or H:Q<0.6 and JSN in men or women. CONCLUSIONS In women but not in men, quadriceps weakness was associated with increased risk for tibiofemoral and whole knee JSN.

Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression: Findings from the multicenter osteoarthritis study and the osteoarthritis initiative

OBJECTIVE To study the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression. METHODS We measured the mechanical axis from long limb radiographs from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) to define limbs with valgus malalignment (mechanical axis of ≥1.1° valgus) and examined the effect of valgus alignment versus neutral alignment (neither varus nor valgus) on OA structural outcomes. Posteroanterior radiographs and knee magnetic resonance (MR) images were obtained at the time of the long limb radiograph and at followup examinations. Lateral progression was defined as an increase in joint space narrowing (on a semiquantitative scale) in knees with OA, and incidence was defined as new lateral narrowing in knees without radiographic OA. We defined lateral cartilage damage and progressive meniscal damage as increases in cartilage or meniscus scores at followup on the Whole-Organ Magnetic Resonance Imaging Score scale (for the MOST) or the Boston Leeds Osteoarthritis Knee Score scale (for the OAI). We used logistic regression with adjustment for age, sex, body mass index, and Kellgren/Lawrence grade, as well as generalized estimating equations, to evaluate the effect of valgus alignment versus neutral alignment on disease outcomes. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS We studied 5,053 knees (881 valgus) of subjects in the MOST cohort and 5,953 knees (1,358 valgus) of subjects in the OAI cohort. In both studies, all strata of valgus malalignment, including 1.1° to 3° valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3° was associated with incidence (e.g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3° was also associated with cartilage damage on MR imaging in knees without OA (e.g., in the OAI, adjusted OR 5.9 [95% CI 1.1-30.3]).We found a strong relationship of valgus malalignment with progressive lateral meniscal damage. CONCLUSION Valgus malalignment increases the risk of knee OA radiographic progression and incidence as well as the risk of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.

The role of varus and valgus alignment in the initial development of knee cartilage damage by MRI: the MOST study

Objective Varus and valgus alignment are associated with progression of knee osteoarthritis, but their role in incident disease is less certain. Radiographic measures of incident knee osteoarthritis may be capturing early progression rather than disease development. The authors tested the hypothesis: in knees with normal cartilage morphology by MRI, varus is associated with incident medial cartilage damage and valgus with incident lateral damage. Methods In MOST, a prospective study of persons at risk of or with knee osteoarthritis, baseline full-limb x-rays and baseline and 30-month MRI were acquired. In knees with normal baseline cartilage morphology in all tibiofemoral subregions, logistic regression was used with generalised estimating equations to examine the association between alignment and incident cartilage damage adjusting for age, gender, body mass index, laxity, meniscal tear and extrusion. Results Of 1881 knees, 293 from 256 persons met the criteria. Varus versus non-varus was associated with incident medial damage (adjusted OR 3.59, 95% CI 1.59 to 8.10), as was varus versus neutral, with evidence of a dose effect (adjusted OR 1.38/1° varus, 95% CI 1.19 to 1.59). The findings held even excluding knees with medial meniscal damage. Valgus was not associated with incident lateral damage. Varus and valgus were associated with a reduced risk of incident lateral and medial damage, respectively. Conclusion In knees with normal cartilage morphology, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment. These results support that varus increases the risk of the initial development of knee osteoarthritis.

Home Training, Local Corticosteroid Injection, or Radial Shock Wave Therapy for Greater Trochanter Pain Syndrome

Background There are no controlled studies testing the efficacy of various nonoperative strategies for treatment of greater trochanter pain syndrome. Hypothesis The null hypothesis was that local corticosteroid injection, home training, and repetitive low-energy shock wave therapy produce equivalent outcomes 4 months from baseline. Study Design Randomized controlled clinical trial; Level of evidence, 2. Methods Two hundred twenty-nine patients with refractory unilateral greater trochanter pain syndrome were assigned sequentially to a home training program, a single local corticosteroid injection (25 mg prednisolone), or a repetitive low-energy radial shock wave treatment. Subjects underwent outcome assessments at baseline and at 1, 4, and 15 months. Primary outcome measures were degree of recovery, measured on a 6-point Likert scale (subjects with rating completely recovered or much improved were rated as treatment success), and severity of pain over the past week (0–10 points) at 4-month follow-up. Results One month from baseline, results after corticosteroid injection (success rate, 75%; pain rating, 2.2 points) were significantly better than those after home training (7%; 5.9 points) or shock wave therapy (13%; 5.6 points). Regarding treatment success at 4 months, radial shock wave therapy led to significantly better results (68%; 3.1 points) than did home training (41%; 5.2 points) and corticosteroid injection (51%; 4.5 points). The null hypothesis was rejected. Fifteen months from baseline, radial shock wave therapy (74%; 2.4 points) and home training (80%; 2.7 points) were significantly more successful than was corticosteroid injection (48%; 5.3 points). Conclusion The role of corticosteroid injection for greater trochanter pain syndrome needs to be reconsidered. Subjects should be properly informed about the advantages and disadvantages of the treatment options, including the economic burden. The significant short-term superiority of a single corticosteroid injection over home training and shock wave therapy declined after 1 month. Both corticosteroid injection and home training were significantly less successful than was shock wave therapy at 4-month follow-up. Corticosteroid injection was significantly less successful than was home training or shock wave therapy at 15-month follow-up.

Association of Leg-Length Inequality With Knee Osteoarthritis: A Cohort Study

BACKGROUND Leg-length inequality is common in the general population and may accelerate development of knee osteoarthritis. OBJECTIVE To determine whether leg-length inequality is associated with prevalent, incident, and progressive knee osteoarthritis. DESIGN Prospective observational cohort study. SETTING Population samples from Birmingham, Alabama, and Iowa City, Iowa. PATIENTS 3026 participants aged 50 to 79 years with or at high risk for knee osteoarthritis. MEASUREMENTS The exposure was leg-length inequality, measured by full-limb radiography. The outcomes were prevalent, incident, and progressive knee osteoarthritis. Radiographic osteoarthritis was defined as Kellgren and Lawrence grade 2 or greater, and symptomatic osteoarthritis was defined as radiographic disease in a consistently painful knee. RESULTS Compared with leg-length inequality less than 1 cm, leg-length inequality of 1 cm or more was associated with prevalent radiographic (53% vs. 36%; odds ratio [OR], 1.9 [95% CI, 1.5 to 2.4]) and symptomatic (30% vs. 17%; OR, 2.0 [CI, 1.6 to 2.6]) osteoarthritis in the shorter leg, incident symptomatic osteoarthritis in the shorter leg (15% vs. 9%; OR, 1.7 [CI, 1.2 to 2.4]) and the longer leg (13% vs. 9%; OR, 1.5 [CI, 1.0 to 2.1]), and increased odds of progressive osteoarthritis in the shorter leg (29% vs. 24%; OR, 1.3 [CI, 1.0 to 1.7]). LIMITATIONS Duration of follow-up may not be long enough to adequately identify cases of incidence and progression. Measurements of leg length, including radiography, are subject to measurement error, which could result in misclassification. CONCLUSION Radiographic leg-length inequality was associated with prevalent, incident symptomatic, and progressive knee osteoarthritis. Leg-length inequality is a potentially modifiable risk factor for knee osteoarthritis. PRIMARY FUNDING SOURCE National Institute on Aging.

Effect of quadriceps strength and proprioception on risk for knee osteoarthritis.

PURPOSE Impaired quadriceps strength and joint position sense (JPS) have been linked with knee osteoarthritis (OA) cross-sectionally. Although neither has been independently associated with incident radiographic OA, their combination may mediate risk. The purpose of this study was to determine whether better sensorimotor function protects against the development of incident radiographic or symptomatic knee OA. METHODS The Multicenter Osteoarthritis study is a longitudinal study of adults aged 50–79 yr at high risk for knee OA. Participants underwent bilateral, weight-bearing, fixed-flexion radiographs, JPS acuity tests, and isokinetic quadriceps strength tests. The relationships between combinations of the tertiles of sex-specific baseline peak strength and mean JPS and development of incident radiographic (Kellgren–Lawrence (KL) grade Q2) or symptomatic knee OA (KL grade Q2 and frequent knee pain or stiffness) at a 30-month follow-up were evaluated. Secondary analyses defined JPS as the variance during the 10 JPS trials and also assessed the interaction of strength and JPS in predicting each outcome. RESULTS The study of incident radiographic knee OA included 1390 participants (age = 61.2 ± 7 .9 yr and body mass index = 29.4 ± 5.1 kg·m−²), and the study of incident symptomatic knee OA included 1829 participants (age = 62.2 ± 8.0 yr and body mass index = 30.0 ± 5.4 kg·m−²). Greater strength at baseline protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile. There was no significant relationship between the strength–JPS interaction and the development of radiographic or symptomatic knee OA. CONCLUSIONS The finding that quadriceps strength protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile suggests that strength may be more important than JPS in mediating risk for knee OA.

Baseline articular contact stress levels predict incident symptomatic knee osteoarthritis development in the MOST cohort.

We studied whether contact stress estimates from knee magnetic resonance images (MRI) predict the development of incident symptomatic tibiofemoral osteoarthritis (OA) 15 months later in an at‐risk cohort. This nested case‐control study was conducted within a cohort of 3,026 adults, age 50 to79 years. Thirty cases with incident symptomatic tibiofemoral OA by their 15 month follow‐up visit were randomly selected and matched with 30 control subjects. Symptomatic tibiofemoral OA was defined as daily knee pain/stiffness and Kellgren‐Lawrence Grade ≥2 on weight bearing, fixed‐flexion radiographs. Tibiofemoral geometry was segmented on baseline knee MRI, and contact stresses were estimated using discrete element analysis. Linear mixed models for repeated measures were used to examine the association between articular contact stress and case/control status. No significant intergroup differences were found for age, sex, BMI, weight, height, or limb alignment. However, the maximum articular contact stress was 0.54 ± 0.77 MPa (mean ± SD) higher in incident OA cases compared to that in control knees (p = 0.0007). The interaction between case‐control status and contact stress was significant above 3.20 MPa (p < 0.0001). The presence of differences in estimated contact stress 15 months prior to incidence suggests a biomechanical mechanism for symptomatic tibiofemoral OA and supports the ability to identify risk by subject‐specific biomechanical modeling.

Lateral Wedge Insoles as a Conservative Treatment for Pain in Patients With Medial Knee Osteoarthritis: A Meta-analysis

IMPORTANCE There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. OBJECTIVE To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. DATA SOURCES Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. STUDY SELECTION Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. DATA EXTRACTION AND SYNTHESIS Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. MAIN OUTCOME AND MEASURES Change in self-reported knee pain at follow-up. RESULTS Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, -0.47; 95% CI, -0.80 to -0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of -2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, -1.20 [95% CI, -2.09 to -0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, -0.03 [95% CI, -0.18 to 0.12] on WOMAC; this represents an effect of -0.12 points), and results showed little heterogeneity (I2 = 7.1%). CONCLUSIONS AND RELEVANCE Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication.