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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11999-015-4349-z) contains supplementary material, which is available to authorized users.

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.

BackgroundGPs have high consultation rates for symptoms related to knee osteoarthritis (OA). Many risk factors for symptomatic knee OA progression remain unknown. AimTo define distinct knee pain trajectories in individuals with early symptomatic knee OA and determine the risk factors for these pain trajectories. Design and settingData were obtained from the multicentre prospective Cohort Hip and Cohort Knee study in the Netherlands. Participants with knee OA, according to the clinical criteria of the American College of Rheumatology, and a completed 5-year follow-up were included. MethodBaseline demographic, anamnestic, and physical examination characteristics were assessed. Outcome was annually assessed by the Numeric Rating Scale for pain. Pain trajectories were retrieved by latent class growth analysis. Multinomial logistic regression was used to calculate relative risk ratios. ResultsIn total, 705 participants were included. Six distinct pain trajectories were identified with favourable and unfavourable courses. Statistically significant differences were found in baseline characteristics, including body mass index (BMI), symptom severity, and pain coping strategies between the different trajectories. Higher BMI, lower level of education, greater comorbidity, higher activity limitation scores, and joint space tenderness were more often associated with trajectories characterised by more pain at first presentation and pain progression -compared with the reference group with a mild pain trajectory. No association was found for baseline radiographic features. ConclusionThese results can help differentiate those patients who require more specific monitoring in the management of early symptomatic knee OA from those for whom a 'wait-and-see' policy seems justifiable. Radiography provided no additional benefit over clinical diagnosis of early symptomatic knee OA in general practice.Keywords disease progression; knee osteoarthritis; knee pain; pain trajectories; primary health care.e32 British Journal of General Practice, January 2016• aged 45-65 years; and• never consulted a physician for these symptoms, or had done so <6 months prior to recruitment to the study.Participants were excluded from the CHECK study if they had:• other pathological conditions that could explain the existing complaints (for example, other rheumatic disease, previous hip or knee joint replacement, congenital dysplasia, osteochondritis dissecans, intraarticular fractures, septic arthritis, Perthes disease, ligament or meniscus injury, plica syndrome, Baker's cyst);• comorbidity that would not allow physical evaluation during 10 years' follow-up;• malignancy in the past 5 years; and• inability to understand Dutch.For the analyses of the current study participants were included if, at baseline, they:• reported knee pain; and• were considered to have knee OA according to the clinical criteria of the American College of Rheumatology. 4,11If a participant had two affected knees, the knee with the worse score based on pain, Kellgren-Lawrenc...

Three trajectories of pain were identified. Participants with a BMI > 25, secondary school as highest education level, having at least 3 comorbidities, additional hip pain, and/or whose coping style is worrying are more likely to develop a moderate or mild pain trajectory compared with those without these characteristics. In the management of knee pain in people with early symptomatic OA, attention should also be given to additional factors such as hip pain, other comorbidities, passive coping strategy, and obesity.

We defined four distinct pain trajectories over 5 years follow-up in individuals with early symptomatic hip OA, suggesting there are differences in symptomatic progression of hip OA. Baseline radiographic severity was not associated with the pain trajectories. Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment.