William F. Harvey

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.

Patterns of compartment involvement in tibiofemoral osteoarthritis in men and women and in whites and African Americans.

We conducted a cross‐sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment.

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial

Importance Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone. Objective To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain. Design, Setting, and Participants Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015. Interventions Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years. Main Outcomes and Measures Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94). Results Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm (between-group difference, −0.11 mm; 95% CI, −0.20 to −0.03 mm); and no significant difference in pain (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, −0.2%; 95% CI, −0.5% to −0.007%). Conclusions and Relevance Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis. Trial Registration ClinicalTrials.gov Identifier: NCT01230424

A randomized trial of patellofemoral bracing for treatment of patellofemoral osteoarthritis.

PURPOSE The number of effective knee osteoarthritis (OA) interventions, especially those tailored to specific compartmental involvement, are small. The objective of this study was to determine the efficacy of a realigning patellofemoral (PF) brace in improving pain and function among persons with symptomatic lateral PF OA. METHOD We conducted a double blind, randomized crossover trial of a realigning PF brace for persons with lateral PF OA. Participants had lateral PF OA with anterior knee symptoms on most days of the month, lateral PF joint space narrowing, and radiographic evidence of a definite osteophyte in the PF joint. We compared two treatments: (1) Control treatment consisting of a BioSkin Q Brace with patellar realigning strap removed; and (2) Active treatment consisting of a realigning BioSkin Q Brace with the strap applied. For each participant, the trial lasted 18 weeks, including 6 weeks each of active and control treatment period separated by a 6-week washout period. The order of treatments was randomized. The primary outcome was change in knee pain on the visual analog scale (VAS). Secondary outcomes included WOMAC pain, function, and stiffness. An unstructured correlation matrix for observations within participants was used in generalized estimating equation fitting to derive a linear regression model that expressed the relation between the intervention and change in VAS pain. RESULTS 80 participants (63 F) with a mean age and body mass index of 61 years and 28 kg/m(2), respectively, were randomized by order of treatment. A model examining the main effects for change in VAS knee pain (0-100) demonstrated no significant treatment effect (-0.68 VAS units, 95% CI: -6.2, 4.8 units, P=0.81) and no differential carryover effect. There was also no significant difference between active and control treatments for WOMAC pain, function, or stiffness outcomes. CONCLUSION The effects of a specific realigning PF brace are not of clinical or statistical significance.

High-Energy Extracorporeal Shock-Wave Therapy for Treating Chronic Calcific Tendinitis of the Shoulder: A Systematic Review

Rotator cuff tendinitis is one of the most common causes of shoulder pain. The term noncalcific tendinitis refers to rotator cuff tendinitis without calcium deposits. The term calcific tendinitis indicates the presence of calcium deposits in the rotator cuff tendons, most commonly in the supraspinatus tendon near its insertion site (1). The prevalence of calcium deposits has been reported as 2% to 20% of asymptomatic shoulders, 6.8% of patients with shoulder pain, and up to 17% of patients with chronic periarthritis (24). The calcifications are most commonly classified into 3 types, according to the Grtner criteria; type 3 is characterized by the highest frequency of spontaneous resorption (5). Although calcium deposits cannot be readily identified by history or clinical examination, they may be identified by plain radiography or sonography, with ultrasonography being somewhat more sensitive (6, 7). Magnetic resonance imaging is not needed to diagnose calcific tendinitis. Conventional therapies used in general practice include rest, ice, nonsteroidal anti-inflammatory drugs, physical therapy, and subacromial corticosteroid injections, although strong evidence to support the efficacy of any of these treatment modalities is lacking (3, 8). Treatment-resistant cases, which are more common with calcific tendinitis, may require surgery, such as arthroscopic debridement of calcifications or subacromial decompression (1). Extracorporeal shock-wave therapy (ESWT) has been suggested as an alternative treatment for refractory shoulder pain due to calcific or noncalcific tendinitis and may be an alternative to expensive and risky surgical interventions. This modality uses sound waves of high or low energy that impart rapid fluctuations of pressure to tissues. The degree of energy imparted to the tissues is measured as energy flux density (EFD). There are many manufacturers of ESWT devices. Shock waves are delivered transcutaneously in an office setting with or without local anesthesia for 10 to 30 minutes. The use of ESWT has gained popularity in many countries worldwide for treating numerous musculoskeletal disorders (9, 10), although it is less common in the United States. Initially used for lithotripsy to treat nephrolithiasis, the application of shock waves to soft-tissue structures has demonstrated promising results in treating such conditions as tendinitis, plantar fasciitis, nonunion long-bone fractures, and avascular necrosis of the femoral head (911). In the United States, ESWT devices have been approved by the U.S. Food and Drug Administration for the treatment of lateral epicondylitis and plantar fasciitis refractory to conventional conservative therapies (913). Although ESWT may provide a nonsurgical alternative to treating multiple soft-tissue conditions, its appropriate use, dosage, and efficacy are still uncertain. Many randomized, controlled trials (RCTs) examining the effects of ESWT on calcific and noncalcific tendinitis showed disparate results regarding resolution of pain and effect on shoulder mobility. To provide evidence-based conclusions about the efficacy of ESWT for calcific and noncalcific tendinitis of the shoulder, we aimed to address the following key questions. 1. In patients with rotator cuff tendinitis, what are the benefits and harms of ESWT compared with placebo? 2. In patients with rotator cuff tendinitis, what are the benefits and harms of different energy levels of ESWT? 3. How do outcomes differ among subgroups of patients with calcific versus noncalcific tendinitis treated with ESWT? 4. In patients with rotator cuff tendinitis, what are the benefits and harms of ESWT compared with other treatment modalities? Methods Data Sources and Searches We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Google Scholar from inception to 1 November 2013 by using the following search terms: shoulder joint, shoulder pain, tendinitis, tendonitis, tendinosis, tendinopathy, calcific tendinitis, calcinosis, bursitis, extracorporeal shock wave therapy, extracorporeal shock-wave therapy, extracorporeal shockwave therapy, and lithotripsy. We also hand-searched review articles, manuscripts, and medical journal supplements for additional references. We placed no restrictions on language and translated relevant nonEnglish-language articles. Study Selection Three independent reviewers screened abstracts and the full text of articles and determined eligibility by consensus. We included all RCTs in humans that studied treatment of calcific or noncalcific tendinitis of the shoulder and compared different energy levels of ESWT against each other or placebo or weighed ESWT against other treatments. We included studies that reported clinical, radiologic, or sonographic outcomes. Outcomes of interest included shoulder pain and function measurements and evaluation of calcification resolution (for calcific tendinitis trials only). We excluded nonrandomized comparative studies, single-cohort studies, and case reports. Data Extraction and Quality Assessment After an a priori training exercise, 3 reviewers independently evaluated the included trials and recorded data on a standardized form. Data on participants demographic characteristics, treatment characteristics, outcomes, adverse events, and study design were obtained. We also recorded information on study quality indicators, including randomization, allocation concealment, blinding, and intention-to-treat analysis and assessed the risk of bias (14). Energy Levels Shock-wave therapy is usually classified as high, medium, or low energy, according to the EFD administered. Although there is no consensus on the threshold values, a commonly used grouping defines EFD less than 0.08 mJ/mm2 as low energy, 0.08 to less than 0.28 mJ/mm2 as medium energy, and 0.28 mJ/mm2 to 0.6 mJ/mm2 as high energy (1517). Once a given EFD is selected, it is applied in pulses to the affected area. The number of pulses per dose typically ranges from 1000 to 3000, and several doses may be given in a course of treatment. The EFD applied to patients varied among the trials in our study. Owing to a paucity of studies comparing different energy levels with each other or with placebo, we categorized the trials as high-energy ESWT (EFD 0.28 mJ/mm2) or low-energy ESWT (EFD <0.28 mJ/mm2). Outcome Measurements The included trials evaluated pain predominantly by using a visual analogue scale pain score: a grading tool for subjective measurement of pain, typically ranging from 0 or 1 (no pain) to 10 (worst pain). Shoulder function was most frequently evaluated by using the Constant score (or ConstantMurley score), a standardized tool that assesses clinical shoulder function by using a 100-point scale (on which 0 is the worst score) to evaluate subjective and objective variables (18). The subjective variables evaluate perception of pain and ability to perform normal tasks of daily living, and the objective variables assess the active range of motion and shoulder power (18). Other reported shoulder function measurement instruments were range of motion, the Shoulder Pain and Disability Index, and the function subscale of the UCLA Shoulder Rating Scale. Resolution of calcification resolution was evaluated only in calcific tendinitis trials and was measured radiographically or sonographically. Role of the Funding Source The study did not receive external funding. Results Trial Selection Our literature search yielded 376 articles (Appendix Figure). After we screened the titles and abstracts and removed duplicates, 38 articles were considered potentially relevant. Seven articles were excluded after full-text review because they described 6 nonrandomized comparative studies and thus did not meet our inclusion criteria (1925). In total, we included 28 RCTs that reported results in 31 publications. Of the 28 RCTs used in our analysis, 20 compared different ESWT energy levels with placebo (2645) and 8 (in 11 publications) compared ESWT with other treatment modalities (4656). Appendix Figure. Summary of evidence search and selection. ESWT = extracorporeal shock-wave therapy. * 38 articles describing 34 studies. 7 articles describing 6 studies. 31 articles describing 28 studies. Trial Characteristics Appendix Tables 1 and 2 show the characteristics of the included trials. Overall, there were 1745 participants, with a mean age of 51 years (range, 47 to 56 years), and the average proportion of women was 58% (range, 39% to 76%). The minimum duration of symptoms ranged from 3 to 12 months. Except for 2 trials from Taiwan (37, 51), all studies were conducted in Europe. Among trials that compared different ESWT energy levels with placebo, 16 (in 15 publications) evaluated calcific tendinitis (2640), and 4 (in 5 publications) evaluated noncalcific tendinitis (4145). Appendix Table 1. Characteristics of Studies Comparing Different ESWT Energy Levels and Placebo Appendix Table 2. Characteristics of Studies Comparing ESWT With Other Active Treatments or Applied to Different Shoulder Sites Quality of Included Trials The quality of trials varied in several respects and was generally low (Appendix Tables 3 and 4). All trials reported a parallel-group design. The sample sizes ranged from 20 to 144 participants. Trial duration ranged from 3 to 12 months. Only 6 trials were double-blinded; the rest were either single-blinded (15 trials) or did not report blinding (7 trials). Withdrawal rates ranged from 0% to 33%, with 3 trials reporting a withdrawal rate of more than 20% (27, 29, 30). Intention-to-treat analysis was reported in 14 trials. No trial reported only on resolution of calcifications without accompanying clinical outcomes. Appendix Table 3. Quality of Included Studies Comparing Different ESWT Energy Levels and Placebo Appendix Table 4. Quality of Included Studies Comparing ESWT With Other Treatment Modalities Possible Sources of Heterogeneity and Bias The trials had numerou

Associations of varus thrust and alignment with pain in knee osteoarthritis

OBJECTIVE To investigate associations of varus thrust and varus static alignment with pain in patients with knee osteoarthritis (OA). METHODS This was a cross-sectional study of participants from a randomized controlled trial of vitamin D treatment for knee OA. Participants were video recorded while walking and scored for presence of varus thrust. Static alignment was measured on standard posteroanterior knee radiographs. Pain questions from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire were used to assess symptoms. We calculated means for total WOMAC pain in relation to varus thrust and static varus alignment (i.e., corrected anatomic alignment<178 degrees). Ordinal logistic regressions were performed, with responses on individual WOMAC pain questions as the outcomes and varus thrust and varus alignment as the predictors. RESULTS There were 82 participants, 60% of whom were female. The mean±SD age was 65.1±8.5 years, and the mean±SD body mass index was 30.2±5.4 kg/m2. The mean total WOMAC pain score was 6.3 versus 3.9, respectively, in those with versus without definite varus thrust (P=0.007) and 5.0 versus 4.2 in those with versus without varus alignment (P=0.36). Odds ratios for pain with walking and standing were 4.7 (95% confidence interval 1.8-11.9) and 5.5 (95% confidence interval 2.2-14.2), respectively, in those with and those without definite varus thrust. There were no significant associations between varus alignment and responses to individual WOMAC pain questions. Sensitivity analyses suggested that varus classified using a more stringent definition might have been associated with pain on walking and standing. CONCLUSION In patients with knee OA, varus thrust, and possibly varus static alignment, were associated with pain, specifically during weight-bearing activities. Treatment of varus thrust (e.g., via bracing or gait modification) may lead to improvement of symptoms.

The Role of Analgesics and Intra-articular Injections in Disease Management

The focus of pharmacologic treatment of osteoarthritis (OA) includes targets from the cell and cytokine level to the larger joint components such as cartilage, bone, innervations, and vascular supply. The most important goals of therapy in patients who have OA are pain management, improvement in function and disability, and ultimately disease modification. This article discusses the current pharmacologic regimens available to address these goals. Specific attention is paid to current trends and controversies related to pharmacologic management, including the use of oral, topical, and injectable agents.

Knee alignment differences between Chinese and Caucasian subjects without osteoarthritis

Objective: Despite the lower prevalence of obesity (a known risk factor for osteoarthritis (OA)), the prevalence of lateral tibiofemoral OA is higher in Chinese communities compared with Caucasian communities. One potential explanation is the difference in knee alignment between the two populations. We measured various knee alignment indices among Chinese and Caucasians and assessed whether these indices were different between the two racial groups. Methods: We selected participants from the Framingham Osteoarthritis Study (FOA) and the Beijing Osteoarthritis Study (BOA), all without knee OA (Kellgren & Lawrence grade <2). Bilateral, fully extended anteroposterior knee radiographs were measured for the following angles in both knees: the anatomic axis (AA), the condylar angle (CA), the tibial plateau angle and the condylar–plateau angle (CP). We compared the mean of each measurement between the two racial groups adjusting for age and body mass index using linear regression and stratified by sex. Results: The mean AA, CA and CP were significantly different in the BOA compared with the FOA. For women, the mean AA and CA were significantly more valgus in BOA subjects, while in men, the mean AA and CP were more valgus in BOA subjects. Conclusions: There are significant differences in knee morphology between Chinese and Caucasian cohorts, which result in a more valgus alignment of the distal femur in Chinese. This would serve to shift the mechanical loading towards the lateral compartment, and provide a possible explanation why Chinese have a higher prevalence of lateral tibiofemoral OA.

Realignment treatment for medial tibiofemoral osteoarthritis: randomised trial

Objectives The objective of this 30-week randomised crossover trial was to determine whether a multi-modal realignment treatmentwould be successful in relieving pain and improving function among persons with medial tibiofemoral osteoarthritis (OA). Methods The authors conducted a double-blind randomised crossover trial of a multi-modal realignment treatment for medial tibiofemoral OA. Trial participants met American College of Rheumatology criteria for OA, with knee pain, aching or stiffness on most days of the past month and radiographic evidence of a definite osteophyte with predominant medial tibiofemoral OA. The authors tested two different treatments: (A) control treatment consisting of a neutral knee brace (no valgus angulation), flat unsupportive foot orthoses and shoes with a flexible mid-sole; and (B) active treatment consisting of a valgus knee brace, customised neutral foot orthoses and shoes designed for motion control. For each subject, the trial lasted 30 weeks, including 12 weeks each of active treatment and control treatment separated by a 6-week washout period. The primary outcome of the linear regression model was change in knee pain and function, as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results 80 participants with medial tibiofemoral OA were randomised. Their mean age was 62 years, their mean body mass index was 34 kg/m2 and their mean WOMAC Pain score was 9.2 (0–20 scale). There was no evidence of a carryover effect. The regression model demonstrated that the mean difference in pain between the active treatment and the control treatment was −1.82 units (95% CI −3.05 to −0.60; p=0.004) on the WOMAC Pain scale, indicating a small but statistically significant decrease in pain with the multi-modal active treatment. For WOMAC Function, the realignment intervention had a non-significant effect on function, with a −2.90 unit decrease (95% CI −6.60 to 0.79) compared with the control condition (p=0.12). Conclusion Multi-modal realignment treatment decreases pain in persons with medial tibiofemoral OA.

Injection of Botulinum Toxin for Treatment of Chronic Lateral Epicondylitis: Systematic Review and Meta-Analysis

OBJECTIVES Lateral epicondylitis can be chronic and difficult to manage with conservative measures such as physical therapy and corticosteroid injection. We attempted to determine the efficacy of botulinum toxin for the treatment of chronic lateral epicondylitis. METHODS We searched PubMed, MEDLINE, CINAHL, Google Scholar, EMBASE, PEDro, and ISI web of Science databases from inception until November 2009. Studies were included if they used any formulation of botulinum toxin A for treatment of chronic lateral epicondylitis and reported at least 1 pain outcome. One author extracted the relevant data using a standardized data extraction sheet and a second author checked the data. We performed a meta-analysis by computing effect sizes for each study separately for pain and grip strength at 3 months after injection. Impact of bias was assessed independently by 2 authors. RESULTS The search found 10 studies relevant to the question. Four of these were randomized controlled trials that could be pooled in a meta-analysis. Results showed a moderate effect for pain favoring botulinum toxin (effect size -0.5, 95% CI -0.9, -0.1, I(2) = 56%) at 3 months and a no effect for grip strength. Qualitative analysis of the studies that could not be pooled also showed improvement in pain, but was limited by potential bias. CONCLUSIONS Present literature provides support for use of botulinum toxin A injections into the forearm extensor muscles (60 units) for treatment of chronic treatment-resistant lateral epicondylitis. It is minimally invasive and can be performed in an outpatient setting.