J. Runhaar

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review

INTRODUCTION Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. METHODS A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. RESULTS The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. CONCLUSION These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

A systematic review on changed biomechanics of lower extremities in obese individuals: A possible role in development of osteoarthritis

Obesity has been identified as a risk factor for osteoarthritis. For the weight‐bearing joints, the combination of increased load and changed joint biomechanics could be regarded as underlying principle for this relation. This systematic review of the literature focused on the differences between obese and normal‐weight subjects in biomechanics of the hip, knee and ankle joint during every day movements to summarize differences in joint load due to both higher body weight and differences in movement patterns. A systematic search, up to November 2010, was performed in the Pubmed and Embase databases. This review showed that obese individuals adjust their movement strategy of every day movements. At self‐selected speed, obese individuals walked slower, with shorter and wider steps, had longer stance duration and had a greater toe‐out angle compared with normal‐weight individuals. Obese sit‐to‐stand movement was characterized by less hip flexion and greater foot displacement. Obese individuals showed altered biomechanics during every day movements. These altered biomechanics could be related to the initiation of osteoarthritis by a change in the load‐bearing regions of the articular cartilage in the weight‐bearing joints.

Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

IntroductionWe performed a systematic review of prognostic factors for the progression of symptomatic knee osteoarthritis (OA), defined as increase in pain, decline in physical function or total joint replacement.MethodWe searched for available observational studies up to January 2015 in Medline and Embase according to a specified search strategy. Studies that fulfilled our initial inclusion criteria were assessed for methodological quality. Data were extracted and the results were pooled, or if necessary summarized according to a best evidence synthesis.ResultsOf 1,392 articles identified, 30 met the inclusion criteria and 38 determinants were investigated. Pooling was not possible due to large heterogeneity between studies. The best evidence synthesis showed strong evidence that age, ethnicity, body mass index, co-morbidity count, magnetic resonance imaging (MRI)-detected infrapatellar synovitis, joint effusion and baseline OA severity (both radiographic and clinical) are associated with clinical knee OA progression. There was moderate evidence showing that education level, vitality, pain-coping subscale resting, MRI-detected medial femorotibial cartilage loss and general bone marrow lesions are associated with clinical knee OA progression. However, evidence for the majority of determinants was limited (including knee range of motion or markers) or conflicting (including age, gender and joint line tenderness).ConclusionStrong evidence was found for multiple prognostic factors for progression of clinical knee OA. A large variety in definitions of clinical knee OA (progression) remains, which makes it impossible to summarize the evidence through meta-analyses. More research on prognostic factors for knee OA is needed using symptom progression as an outcome measure. Remarkably, only few studies have been performed using pain progression as an outcome measure. The pathophysiology of radiographic factors and their relation with symptoms should be further explored.

What Are the Prognostic Factors for Radiographic Progression of Knee Osteoarthritis? A Meta-analysis

BackgroundA previous systematic review on prognostic factors for knee osteoarthritis (OA) progression showed associations for generalized OA and hyaluronic acid levels. Knee pain, radiographic severity, sex, quadriceps strength, knee injury, and regular sport activities were not associated. It has been a decade since the literature search of that review and many studies have been performed since then investigating prognostic factors for radiographic knee OA progression.Questions/purposesThe purpose of this study is to provide an updated systematic review of available evidence regarding prognostic factors for radiographic knee OA progression.MethodsWe searched for observational studies in MEDLINE and EMBASE. Key words were: knee, osteoarthritis (or arthritis, or arthrosis, or degenerative joint disease), progression (or prognosis, or precipitate, or predictive), and case-control (or cohort, or longitudinal, or follow-up). Studies fulfilling the inclusion criteria were assessed for methodologic quality according to established criteria for reviews on prognostic factors in musculoskeletal disorders. Data were extracted and results were pooled if possible or summarized according to a best-evidence synthesis. A total of 1912 additional articles were identified; 43 met our inclusion criteria. The previous review contained 36 articles, thus providing a new total of 79 articles. Seventy-two of the included articles were scored high quality, the remaining seven were low quality.ResultsThe pooled odds ratio (OR) of two determinants showed associations with knee OA progression: baseline knee pain (OR, 2.38 [95% CI, 1.74–3.27) and Heberden nodes (OR, 2.66 [95% CI, 1.46–8.84]). Our best-evidence synthesis showed strong evidence that varus alignment, serum hyaluronic acid, and tumor necrosis factor-α are associated with knee OA progression. There is strong evidence that sex, former knee injury, quadriceps strength, smoking, running, and regular performance of sports are not associated with knee OA progression. Evidence for the majority of determined associations, however, was limited, conflicting, or inconclusive.ConclusionsBaseline knee pain, presence of Heberden nodes, varus alignment, and high levels of serum markers hyaluronic acid and tumor necrosis factor-α predict knee OA progression. Sex, knee injury, and quadriceps strength, among others, did not predict knee OA progression. Large variation remains in definitions of knee OA and knee OA progression. Clinical studies should use more consistent definitions of these factors to facilitate data pooling by future meta-analyses.

Identifying potential working mechanisms behind the positive effects of exercise therapy on pain and function in osteoarthritis; a systematic review

OBJECTIVE Although physical exercise is the commonly recommended for osteoarthritis (OA) patients, the working mechanism behind the positive effects of physical exercise on pain and function is a black box phenomenon. In the present study we aimed to identify possible mediators in the relation between physical exercise and improvements of pain and function in OA patients. DESIGN A systematic search for all studies evaluating the effects of physical exercise in OA patients and select those that additionally reported the change in any physiological factor from pre-to post-exercise. RESULTS In total, 94 studies evaluating 112 intervention groups were included. Most included studies evaluated subjects with solely knee OA (96 out of 112 groups). Based on the measured physiological factors within the included studies, 12 categories of possible mediators were formed. Muscle strength and ROM/flexibility were the most measured categories of possible mediators with 61 and 21 intervention groups measuring one or more physiological factors within these categories, respectively. 60% (31 out of 52) of the studies showed a significant increase in knee extensor muscle strength and 71% (22 out of 31) in knee flexor muscle strength over the intervention period. All 5 studies evaluating extension impairments and 10 out of 12 studies (83%) measuring proprioception found a significant change from pre-to post-intervention. CONCLUSION An increase of upper leg strength, a decrease of extension impairments and improvement in proprioception were identified as possible mediators in the positive association between physical exercise and OA symptoms.

Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review

The identification of early biochemical predictors of osteoarthritis (OA) has been the focus of much research over the past few years. However, it still is unclear whether current biochemical markers can be used in prognostic risk assessment of OA. The aim of this systematic review is to evaluate the possible prognostic application of blood and urinary biochemical markers of knee and hip OA. Abstract and full text selection was done by two independent reviewers. A total of 25 relevant publications including 37 biochemical markers of bone and cartilage turnover and inflammation associated with some aspects of OA were reviewed. Most of those biomarkers were studied only once or twice. Due to heterogeneity of both OA-phenotype and determinant among the publications, meta-analysis of the studied biochemical markers was not possible. There was strong evidence for urinary C-terminal telopeptide of collagen type II (uCTX-II) as a prognostic marker for knee OA progression and serum cartilage oligomeric protein (COMP) level as prognostic marker for incidence of knee and hip OA. Evidence for prognostic value of C-reactive protein is still inconclusive. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.

How to define subregional osteoarthritis progression using semi-quantitative MRI Osteoarthritis Knee Score (MOAKS)

OBJECTIVE Recently, the MRI Osteoarthritis Knee Score (MOAKS), a new semi-quantitative magnetic resonance imaging (MRI) scoring tool, was introduced by a panel of experienced researchers in osteoarthritis (OA). The MOAKS is primarily applicable to quantify OA status, since the interpretation of change in the MOAKS features was not described. In order to enable longitudinal evaluation, we propose definitions for progression and improvement of the main MOAKS features. METHOD Clear definitions for progression and improvement of the main MOAKS features are given in this brief report. 687 baseline and 30 months follow-up MRIs of the knees of 348 overweight and obese middle-aged women, free of OA at baseline, were scored using the MOAKS. Baseline prevalence and the change of MOAKS features after 30 months follow-up, based on our definitions for progression and improvement, are presented. RESULTS The proposed definitions showed 3% to 23% progression and 0% to 11% improvement in the MOAKS features during the 30 months follow-up. Overall, progression rates were higher in the medial than in the lateral tibiofemoral (TF) joint. Progression of bone marrow lesions (BMLs) and cartilage defects was highest in the patellofemoral (PF) joint. Inter-rater reliability of the MOAKS scores was moderate to nearly perfect (PABAK 0.77-0.88), with high percentage of agreement overall (89-94%). CONCLUSION This brief report presents definitions for progression and improvement of the main MOAKS features for the longitudinal evaluation of knee OA features on MRI. We advocate uniform usage of the proposed definitions across studies, but welcome suggestions for optimization.

Malalignment: a possible target for prevention of incident knee osteoarthritis in overweight and obese women

OBJECTIVES The present study aims to investigate the associations between malalignment and incident knee OA after 2.5 years in a high-risk group of 333 middle-aged overweight women (BMI ≥ 27 kg/m(2)) free of clinical and radiological knee OA at baseline. METHODS The primary outcome measure was the incidence of knee OA, defined as the incidence of radiographic knee OA (Kellgren and Lawrence grade ≥2), clinical knee OA (ACR criteria) or medial or lateral joint space narrowing (≥1.0 mm). Using generalized estimating equations, associations between valgus and varus alignment (compared with neutrally aligned knees) and the primary outcome measure and all its items separately were studied. RESULTS Neither varus- nor valgus-aligned knees had a significantly increased risk for incident knee OA according to the primary outcome measure. A significantly increased risk for the development of radiographic knee OA was found for varus-aligned knees [odds ratio (OR) 3.3, 95% CI 1.5, 7.3]. Valgus-aligned knees showed a borderline increased OR (2.8, 95% CI 1.0, 8.0) for the development of radiographic knee OA. No statistically significant effects were found for varus and valgus alignment on the incidence of clinical knee OA or medial or lateral joint space narrowing. CONCLUSION Since this study was performed in a true target population, current data suggest that malalignment might be a target for the prevention of radiographic knee OA in overweight and obese women.

Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank.

Objective To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data. Methods After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted. As a minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed to be assessed. Results Of 21 eligible studies, six (n=1663) shared their trial data with the OA Trial Bank. Five trials (all independent of industry, n=1625) compared glucosamine with placebo, representing 55% of the total number of participants in all published placebo-controlled RCTs. Glucosamine was no better than placebo for pain or function at short (3 months) and long-term (24 months) follow-up. Glucosamine was also no better than placebo among the predefined subgroups. Stratification for knee OA and type of glucosamine did not alter these results. Conclusions Although proposed and debated for several years, open trial data are not widely made available for studies of glucosamine for OA, especially those sponsored by industry. Currently, there is no good evidence to support the use of glucosamine for hip or knee OA and an absence of evidence to support specific consideration of glucosamine for any clinically relevant OA subgroup according to baseline pain severity, BMI, sex, structural abnormalities or presence of inflammation.

Prevention of Incident Knee Osteoarthritis by Moderate Weight Loss in Overweight and Obese Females.

This study evaluated the effect of moderate weight loss on the incidence of knee osteoarthritis (OA) in middle‐aged overweight and obese women, without clinical and radiologic knee OA at baseline.