K. Kwoh

OARSI guidelines for the non-surgical management of knee osteoarthritis

OBJECTIVE To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. METHOD Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). CONCLUSION These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.

Location specific radiographic joint space width for osteoarthritis progression

OBJECTIVE To establish the performance of location specific computer measures of radiographic joint space width (JSW) compared to measurements of minimum joint space width (mJSW) for the assessment of medial compartment knee osteoarthritis (OA). The study also investigated the most disease-responsive location for measuring medial compartment JSW. METHODS Serial bilateral Posterior Anterior (PA) conventional radiographs acquired with a fixed flexion protocol were obtained 36 months apart in 118 persons with knee OA participating in the Health, Aging and Body Composition (Health ABC) Study. Measurements of medial compartment mJSW and JSW at seven fixed locations were facilitated by the use of semi-automated software that delineated the femoral and tibial margins of the joint. A human reader operated custom software to verify and correct the software-drawn margins where necessary. Paired images were displayed with the reader blinded to the chronological order. The amount of joint space narrowing was measured and the standardized response mean (SRM) was used as a metric to quantify performance. RESULTS For all subjects, the mJSW SRM value was 0.42 while, for the most responsive location specific measure of JSW, it was SRM=0.46. For subjects with a Kellgren-Lawrence (KL) score less than or equal to 1, mJSW (SRM=0.40) was more responsive than the new measures (Maximum SRM=0.30). For KL=2or3, SRM=0.49 for mJSW, and SRM=0.74 for the most responsive location specific measure of JSW. Improved responsiveness was observed in the more central portion of the joint on the more diseased knees. CONCLUSIONS Location specific computer measures of JSW are feasible and potentially provide a superior method to assess radiographic OA for more diseased subjects. This new measure has the potential to improve the power of clinical studies that use a fixed flexion protocol.

Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews: Recommendations from an OMERACT 12 Workshop

Objective. Pain is a patient-important outcome, but current reporting in randomized controlled trials and systematic reviews is often suboptimal, impeding clinical interpretation and decision making. Methods. A working group at the 2014 Outcome Measures in Rheumatology (OMERACT 12) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic reviews. Results For individual trials, authors should report, in addition to mean change, the proportion of patients achieving 1 or more thresholds of improvement from baseline pain (e.g., ≥ 20%, ≥ 30%, ≥ 50%), achievement of a desirable pain state (e.g., no worse than mild pain), and/or a combination of change and state. Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation. When pooling data for metaanalysis, authors should consider converting all continuous measures for pain to a 100 mm visual analog scale (VAS) for pain and use the established, minimally important difference (MID) of 10 mm, and the conventionally used, appreciably important differences of 20 mm, 30 mm, and 50 mm, to facilitate interpretation. Effects ≤ 0.5 units suggest a small or very small effect. To further increase interpretability, the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference. This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups. Conclusion. Presentation of relative effects regarding pain will facilitate interpretation of treatment effects.

One-Year Change in Radiographic Joint Space Width in Patients With Unilateral Joint Space Narrowing: Data From The Osteoarthritis Initiative

To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline.

Vitamin D Deficiency Is Associated with Progression of Knee Osteoarthritis

BACKGROUND Knee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH). OBJECTIVE The objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis. METHODS Serum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits. RESULTS The mean concentrations of serum 25(OH)D and PTH were 26.2 μg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 μg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 μg/L] had >2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 μg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4). CONCLUSION Our results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Relationship of meeting physical activity guidelines with quality-adjusted life-years

OBJECTIVE The quality-adjusted life-year (QALY) is a standard outcome measure used in cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines is associated with higher QALY estimates among adults with or at an increased risk for knee osteoarthritis. METHODS This is a prospective study of 1794 Osteoarthritis Initiative participants. Physical activity was measured using accelerometers at baseline. Participants were classified as (1) Meeting Guidelines [≥150min of moderate-to-vigorous (MV) activity per week acquired in sessions ≥10min], (2) Insufficiently Active (≥1 MV session[s]/week but below the guideline), or (3) Inactive (zero MV sessions/week). A health-related utility score was derived from participant responses to the 12-item Short-Form Health Survey at baseline and 2 years later. The QALY was calculated as the area under utility curve over 2 years. The relationship of physical activity level to median QALY adjusted for socioeconomic and health factors was estimated using quantile regression. RESULTS Relative to the Inactive group, median QALYs over 2 years were significantly higher for the Meeting Guidelines (0.112, 95% CI: 0.067-0.157) and Insufficiently Active (0.058, 95% CI: 0.028-0.088) groups, controlling for socioeconomic and health factors. CONCLUSION We found a significant graded relationship between greater physical activity level and higher QALYs. Using the more conservative estimate of 0.058, if an intervention could move someone out of the Inactive group and costs <

Clinical significance of worsening versus stable preradiographic MRI lesions in a cohort study of persons at higher risk for knee osteoarthritis

2900 over 2 years, it would be considered cost effective. Our analysis supports interventions to promote physical activity even if recommended levels are not fully attained.

Relationship of meeting physical activity guidelines with health-related utility.

Background Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12–48 month MRI lesion status worsening is associated with 12–48 month incident radiographic osteoarthritis (objective component of clinical definition of knee osteoarthritis) and 48–84 month persistent symptoms. Methods In 849 Osteoarthritis Initiative participants Kellgren/Lawrence (KL) 0 in both knees, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci on 12 month (baseline) and 48 month MRIs. Multivariable logistic regression was used to evaluate associations between 12–48 month worsening versus stable status and outcome (12–48 month incident KL ≥1 and KL ≥2, and 48–84 month persistent symptoms defined as frequent symptoms or medication use most days of ≥1 month in past 12 month, at consecutive visits 48–84 months), adjusting for age, gender, body mass index (BMI), injury and surgery. Results Mean age was 59.6 (8.8), BMI 26.7 (4.2) and 55.9% were women. 12–48 month status worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs was associated with 12–48 month incident radiographic outcomes, and worsening of cartilage damage and BMLs with 48–84 month persistent symptoms. There was a dose-response association for magnitude of worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs and radiographic outcomes, and cartilage damage and BMLs and persistent symptoms. Conclusions In persons at higher risk, worsening MRI lesion status was associated with concurrent incident radiographic osteoarthritis and subsequent persistent symptoms. These findings suggest that such lesions represent early osteoarthritis, and add support for a paradigm shift towards investigation of intervention effectiveness at this stage.

Sex differences in osteoarthritis of the knee.

Health‐related utility measures overall health status and quality of life and is commonly incorporated into cost‐effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines translates into better health‐related utility in adults with or at risk for knee osteoarthritis (OA).

Assistive walking device use and knee osteoarthritis: results from the Health, Aging and Body Composition Study (Health ABC Study).

Osteoarthritis (OA) is a leading cause of disability in the United States. It is the most common form of arthritis and afflicts 13.9% of adults aged ≥25 years and 33.6% (12.4 million) of those aged >65 years—an estimated 26.9 million persons in the United States. Studies sponsored by the Centers for Disease Control and Prevention and the National Institutes of Health have identified differences in the incidence and severity of OA between men and women, as well as between racial and ethnic groups. The burden of OA is highest among women and African-Americans, who disproportionately develop knee and hand but not hip OA. The disproportionate number of women in the aging US population is of clinical concern because of the more severe knee OA and its impact on quality of life and independence. Based on these factors, there is a need for research focused on the effect sex differences have in the development and progression of OA as well as the impact on prevention and treatment strategies. However, most studies on the mechanisms underlying OA have not taken sex differences into account, whether in vitro cell culture or animal models were used. Although little is known about the mechanisms that contribute to disparities between men and women in disease incidence and severity, they likely involve mechanical and molecular events in the affected joint. Diagnosis of knee OA is based on evidence of joint pain and/or reduced space between articulating bone surfaces as a result of thinning of the opposing articular cartilages. However, multiple tissues that compose the knee joint appear to be compromised by the disease, including subchondral bone, articular cartilage, the meniscus, the anterior cruciate ligament, the synovium, and synovial fluid. A change in any of these tissues can influence the distribution of load across the joint, with corresponding adaptations in the other tissues and, ultimately, the cartilages. Such pathophysiologic changes may exacerbate age-related physiologic changes in joint function attributable to genetic characteristics, age, sex, and health status, leading to greater cartilage damage. To understand the expression of knee OA in males and females, it is important to view the knee as an organ rather than focusing only on the articular cartilage. Knee tissues are modulated by sex hormones during tissue development and throughout the life cycle in both males and females. Although menopause is associated with an increase in OA severity in women, systemic estrogen alone cannot explain the observed sex differences. Recent data, for example, show that sex-specific variations in the responses of chondrocytes to sex steroids are the result of differences in receptor number as well as mechanisms of hormone action. In addition to increased prevalence of knee OA, women often have greater pain and more substantial reduction in function and quality of life than do men. OA pain can be related to the sensory information that emerges from the knee joint. The pain does not always match the degree of injury, however, and can continue even after total joint arthroplasty. The neural and other mechanisms underlying these differences in pain between men and Barbara D. Boyan, PhD