Objective. Cam deformity and acetabular dysplasia have been recognized as relevant risk factors for hip osteoarthritis (OA) in a few prospective studies with limited sample sizes. To date, however, no evidence is available from prospective studies regarding whether the magnitude of these associations differs according to sex, body mass index (BMI), and age.Methods. Participants in the Rotterdam Study cohort including men and women ages 55 years or older without OA at baseline (n 5 4,438) and a mean follow-up of 9.2 years were included in the study. Incident radiographic OA was defined as a Kellgren/Lawrence grade of ‡2 or a total hip replacement at follow-up. Alpha and center-edge angles were measured to determine the presence of cam deformity and acetabular dysplasia/pincer deformity, respectively. Odds ratios (ORs) were calculated to assess the associations between both deformities and the development of OA.Results. Subjects with cam deformity (OR 2.11, 95% confidence interval [95% CI] 1.55-2.87) and those with acetabular dysplasia (OR 2.19, 95% CI 1.50-3.21) had a 2-fold increased risk of developing OA compared with subjects without deformity, while pincer deformity did not increase the risk of OA. Stratification analyses showed that the associations of cam deformity and acetabular dysplasia with OA were driven by younger individuals, whereas BMI did not influence the associations. Female sex appears to modify the risk of hip OA related to acetabular dysplasia.Conclusion. Individuals with cam deformity and those with acetabular dysplasia are predisposed to OA; these associations were independent of other well-known risk factors. Interestingly, both deformities predisposed to OA only in relatively young individuals. Therefore, early identification of these conditions is important.Osteoarthritis (OA) of the hip is one of the main causes of musculoskeletal disability with pain and dysfunction in the elderly (1). Epidemiologic studies have identified several risk factors predisposing to hip OA, including increasing age, male sex (after age 55 years, hip OA is more common in women), excess body weight (which has a stronger association with knee OA), trauma, mechanical workload (occupational) and leisure-time physical activity, and gross bony abnormalities (i.e., congenital hip dislocation, Legg-Calve-Perthes disease, or slipped capital femoral epiphysis) (1-3). Moreover, a review study (4) showed an association between bony abnormalities (e.g., acetabular dysplasia and cam deformity) and hip OA, although the conclusions drawn were based on limited prospective evidence (based on 110 individuals in 1 study of cam deformity, and a total of 1,365 individuals in 5 studies of dysplasia) (5-10).Recent prospective epidemiologic studies have supported the notion that mild acetabular dysplasia is associated with an increased risk of incident hip OA

BackgroundWe aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated.MethodsSerum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders.ResultsThe uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP.ConclusionsOur study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0976-3) contains supplementary material, which is available to authorized users.

Background: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population.Methods: Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL.Results: In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-γ (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-α (TNF-α; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-γ (P trend = 0.08).Conclusions: The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-γ, and TNF-α with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines.Impact: Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL. Cancer Epidemiol Biomarkers Prev; 19(6); 1577-84. ©2010 AACR.

Lower socioeconomic position (SEP) has consistently been associated with poorer health. To explore potential biological embedding and the consequences of SEP experiences from early life to adulthood, we investigate how SEP indicators at different points across the life course may be related to a combination of 28 inflammation markers. Using blood-derived inflammation profiles measured by a multiplex array in 268 participants from the Italian component of the European Prospective Investigation into Cancer and Nutrition cohort, we evaluate the association between early life, young adulthood and later adulthood SEP with each inflammatory markers separately, or by combining them into an inflammatory score. We identified an increased inflammatory burden in participants whose father had a manual occupation, through increased plasma levels of CSF3 (G-CSF; β = 0.29; P = 0.002), and an increased inflammatory score (β = 1.96; P = 0.029). Social mobility was subsequently modelled by the interaction between father’s occupation and the highest household occupation, revealing a significant difference between “stable Non-manual” profiles over the life course versus “Manual to Non-manual” profiles (β = 2.38, P = 0.023). Low SEP in childhood is associated with modest increase in adult inflammatory burden; however, the analysis of social mobility suggests a stronger effect of an upward social mobility over the life course.

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The aim of this narrative review is to summarize important findings from biochemical marker studies relevant to osteoarthritis (OA) in the context of new discoveries and clinical and scientific need. Design: We conducted a systematic search of electronic medical databases (Embase, Medline, Web of Science, Cochrane central) between 01-03-2017 and 31-03-2018. The search was restricted to human studies, English language and full text available publications while reviews were excluded. Only papers describing protein based biomarkers measured in human body fluids (blood, urine and synovial fluid (SF)) were included. Of the 992 papers, 86 were reviewed here, with inclusion primarily based on relevance to OA biochemical markers. Results: This review highlights a selection of studies based on their quality and perceived importance to the field mainly including those that 1 evaluate prognostic value of biomarkers for OA progression (i.e., biomarkers reflecting change in composition of joint tissues and biomarkers of inflammation) 2 , help in assessment of intervention efficacy, and 3 are innovative and uncover new candidate biomarkers, or use new approaches in biomarker discovery. Conclusions: Key findings and implications for possible clinical utility of biochemical markers are summarized and discussed. Given the paucity of robust biomarkers within the field, and the heterogeneity of the condition, enormous works are needed for development and validation of novel and clinically applicable biomarkers to reduce the impact of this highly prevalent and debilitating condition.

Background: Elevated circulating soluble CD30 (sCD30) has been previously associated with AIDS-related non-Hodgkin lymphoma (NHL) risk. This finding was recently extended to the general population where elevated levels of sCD30 were reported in prediagnostic serum among subjects that developed NHL later in life.Methods: We carried out a replication study within the Italian European Prospective Investigation into Cancer and Nutrition cohort. Plasma sCD30 concentration was measured by ELISA in prospectively collected blood of 35 B-cell lymphoma cases and 36 matched controls.Results: We observed significantly increased relative risks for lymphoma with increasing sCD30 levels [OR (95% CI) for second and third tertiles vs. first tertile: 5.5 (1.5-20.2), 4.0 (1.1-13.9), respectively]. In addition, spline analyses showed that the dose-response curve of sCD30 and lymphoma risk was monotonic and quite similar to the risks reported in the previous study.Conclusion: This replication study adds to the evidence that sCD30 is related to future lymphoma risk in a concentration-dependent manner in the general population.Impact: The results of this study strengthen the observation that chronic sustained B-cell activation plays an important role in lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 20(9); 1925-7. Ó2011 AACR.

The purpose of this paper is to identify immunologic hallmarks of excessive bodyweight. The analysis is based on 176 adults (106 women, 70 men) who participated in a nested case-control study in Italy. All participants were healthy at the time of blood collection and aged between 36 and 75 years. We employed multivariate analysis of variance and a nonparametric Bayesian additive regression tree approach along with a receiver operating characteristic (ROC) curve analysis to determine the immunologic signature of excessive body weight (i.e., obesity and overweight). Interleukin 8 (IL-8), IL-10, interferon γ, and inducible protein 10 were shown to be predictive of excessive body weight with an area under the ROC curve of 71% (p < 0.0002). We propose that by using this profile-based approach to define immunologic signatures, it might be possible to identify unique immunologic hallmarks of specific types of obesity.