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In previous work, relationships between muscle and bone size and strength have been demonstrated and were stronger in females, suggesting possible sexual dimorphism. Here we examine sex-specific associations between individual muscle sarcopenia components with clinical outcomes (falls and fractures). 641 participants were recruited. Muscle mass was assessed as cross-sectional area (CSA) by peripheral quantitative computed tomography of the calf, grip strength (GpS) by Jamar dynamometry and function by gait speed (GtS). Falls and fractures were self-reported. Ordinal and logistic regression were used to examine the associations between muscle measurements and outcomes with and without adjustment for confounders. Mean (SD) age was 69.3 (2.6) years. CSA, GpS, and GtS were greater among males (p p p = 0.053); and reported a previous fracture since age 45 (21.8% vs 18.5%, p = 0.302), than males. Among females, greater CSA was related to reduced risk of falling and fewer falls in the previous year in fully adjusted analysis only (p p = 0.045) and lower risk of fracture since age 45 in both unadjusted and fully adjusted analysis (p

Introduction: Survivin (SVN) is a member of the inhibitor of apoptosis (IAP) protein family that promotes cellular proliferation and inhibits apoptosis. Overexpression of SVN is associated with autoimmune disease, hyperplasia, and tumors and can be used as a biomarker in these diseases. SVN is widely recognized as a tumor-associated antigen (TAA) and has become an important target for cancer diagnosis and treatment. Areas covered: We reviewed SVN research progress from the PubMed and clinical trials focused on SVN from https://clinicaltrials.gov since 2000 and anticipate future developments in the field. The trials reviewed cover various modalities including diagnostics for early detection and disease progression, small molecule inhibitors of the SVN pathway and immunotherapy targeting SVN epitopes. Expert opinion: The most promising developments involve anti-SVN immunotherapy, with several therapeutic SVN vaccines under evaluation in phase I/II trials. SVN is an important new immune-oncology target that expands the repertoire of individualized combination treatments for cancer.

Objectives Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. Design Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). Setting The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. Participants We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. Intervention Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. Measurements The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. Results The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. Conclusion The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Summary Tumour necrosis factor (TNF) is a multi-functional cytokine with profound and diverse effects on physiology and pathology. Identifying the molecular determinants underlying the functions and pathogenic effects of TNF is key to understanding its mechanisms of action and identifying new therapeutic opportunities based on this important molecule. Previously, we showed that some evolutionarily conserved peptides derived from TNF could induce cell death (e.g. apoptosis and/or necrosis), a feature of immune defence mechanisms shared by many vertebrates. In this study, we demonstrated that necrosis-inducing peptide P16 kills human glioblastoma cancer cells and primary human hepatoma or renal cancer cells isolated from patients who had not responded to standard treatments. Importantly, we show that the necrosis-inducing peptide P1516 significantly improves survival by inhibiting tumour metastasis in a 4T1 breast cancer syngeneic graft mouse model. Because the lymphatic system is an important metastatic route in many cancers, we also tested the effect of TNF-derived peptides on monolayers of primary human lymphatic endothelial cells (hDLEC) and found that they increased junctional permeability by inducing cytoskeletal reorganization, gap junction formation and cell death. Transmission electron microscopy imaging evidence, structural analysis and in-vitro liposome leakage experiments strongly suggest that this killing is due to the cytolytic nature of these peptides. P1516 provides another example of a pro-cytotoxic TNF peptide that probably functions as a cryptic necrotic factor released by TNF degradation. Its ability to inhibit tumour metastasis and improve survival may form the basis of a novel approach to cancer therapy.

Background: we consider the relationships between a clinical and radiological diagnosis of knee or hip OA and activities of daily-living (ADL) in older adults. Methods: data were available for 222 men and 221 women from the Hertfordshire Cohort Study (HCS) who also participated in the UK component of the European Project on Osteoarthritis (EPOSA). Participants completed the EuroQoL survey where they reported if they had difficulties with mobility, self-care, usual activities and movement around their house. Hip and knee radiographs were graded for overall Kellgren and Lawrence score (positive definition defined as a 2 or above). Clinical OA was defined using American College of Rheumatology criteria. Results: in men, a clinical diagnosis of hip or knee OA were both associated with reported difficulties in mobility, ability to self-care and performing usual-activities (hip OA: OR 17.6, 95% CI 2.07, 149, p = 0.009; OR 12.5, 95% CI 2.51, 62.3, p = 0.002; OR 4.92, 95% CI 1.06, 22.8, p = 0.042 respectively. Knee OA: OR 8.18, 95% CI 3.32, 20.2, p

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI.

Older adults with lower limb osteoarthritis (LLOA) are highly dependent on their physical and social environment for being physically active. Longitudinal data from 2286 older adults (M age = 73.8 years; 50.3% female) in six European countries were analyzed using cross-lagged Structural Equation Modeling (SEM) and multi-group SEM. In cross-sectional analyses, neighborhood resources were associated with physical activity (r = 0.26;p

Background Adolescent knee pain is a common complaint which may be due to patellar dislocation, meniscal tear, Osgood-Schlatter’s disease or patellofemoral maltracking. We studied the association of such pain with knee osteoarthritis (OA) 50 years later using a retrospective cohort design. Methods This study was based in the Hertfordshire Cohort Study, a cohort of men and women born in 1931 - 9. Participants completed a questionnaire detailing recall of adolescent knee pain, self-reported OA, demographics, lifestyle and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Clinical OA was defined based on the American College of Rheumatology (ACR) criteria and assessed at a clinical visit where knee radiographs were also taken and graded according to the methods of Kellgren and Lawrence. Results Completed data were available for 135 men and 139 women. The mean age was 78.8 (SD 2.6) years and the mean (SD) BMI was 26.3 (4.0). Two percent of men (n = 3) and 5% of women (n = 7) reported adolescent knee pain, of which 2 men and 3 women sought medical advice for their knee pain. 1 man and 2 women reported that their pain had been constant since teenage years while 2 men and 4 women reported that it was intermittent in nature. A report of adolescent knee pain was associated with an increased risk of clinical (odds ratio (OR) 5.45, p-value 0.015, 95% confidence interval (CI) 1.39 - 21.36); radiological (OR 2.33, p-value 0.228, 95% CI 0.60 - 9.24) and self-report (OR 2.71, p-value 0.134, 95% CI 0.74 - 10.0) of knee OA in later life. After adjustments for age, sex and BMI, adolescent knee pain was associated with an increased risk of clinical (OR 4.80, p-value 0.047, 95% CI 1.02 - 22.53); radiological (OR 1.85, p-value 0.404, 95% CI 0.44 - 7.78); self-report (OR 3.23, p-value 0.10, 95% CI 0.80 - 12.94) although relationships were only significant for clinical knee OA. Conclusion Recalled adolescent knee pain was associated with a clinical diagnosis of knee OA in later life. The lack of association with self-report of OA suggests that this is not simply a consequence of recall bias and exploration in other data sets is now indicated. Disclosures M.A. Clynes: None. F. Laskou: None. M.H. Edwards: None. C. Cooper: None. A. Taylor: None. M. Stokes: None. E.M. Dennison: None.

There are few longitudinal data on change in bone structure and muscle mass, strength and function in later life. We report these, and consider bone–muscle interrelationships in older men and women. We studied 188 men and 166 women from the Hertfordshire Cohort Study, who underwent peripheral quantitative computed tomography (pQCT) of the radius and tibia in 2004–2005 and then again in 2011–2012. Grip strength and gait speed were also assessed at both timepoints. Percentage change per year was calculated for grip strength, gait speed, muscle cross-sectional area (mCSA), fat cross-sectional area (fCSA) and diaphyseal bone parameters [total area (Tt.Ar), cortical area (Ct.Ar), cortical density (cBMD) and trabecular density (tBMD)]. The mean (SD) age of men and women at baseline was 68.9 (2.5) and 69.2 (2.6) years, respectively. Rates of muscle area and strength loss did not differ by sex. Tt.Ar increased with age and faster in men [mean (SD) 1.78 (1.64) %/year] than women [mean (SD) 1.03 (1.69) %/year] in the radius (p

Pain is a key symptom of osteoarthritis (OA) and has been linked to poor mental health. Pain fluctuates over time within individuals, but a paucity of studies have considered day-to-day fluctuations of joint pain in relation to affective symptoms in older persons with OA. This study investigated the relationship of pain severity as well as within-person pain variability with anxiety and depression symptoms in 832 older adults with OA who participated in the European Project on OSteoArthritis (EPOSA): a 6-country cohort study. Affective symptoms were examined with the Hospital Anxiety and Depression Scale, pain severity was assessed with the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand Osteoarthritis Index, and intraindividual pain variability was measured using pain calendars assessed at baseline, 6, and 12 to 18 months. Age-stratified multiple linear regression analyses adjusted for relevant confounders showed that more pain was associated with more affective symptoms in older-old participants (74.1–85 years). Moreover, older-old participants experienced fewer symptoms of anxiety (ratio = .85, 95% confidence interval [CI], .77–.94), depression (ratio = .90, 95% CI, .82–.98), and total affective symptoms (ratio = .87, 95% CI, .79–.94) if their pain fluctuated more. No such association was evident in younger-old participants (65–74.0 years). These findings imply that stable pain levels are more detrimental to mental health than fluctuating pain levels in older persons. Perspective This study showed that more severe and stable joint pain levels were associated with anxiety and depressive symptoms in older persons with OA. These findings emphasize the importance of measuring pain in OA at multiple time points, because joint pain fluctuations may be an indicator for the presence of affective symptoms.

Background Exposure to higher magnitude vertical impacts is thought to benefit bone health. The correlates of this high-impact physical activity (PA) in later life are unknown.Methods Participants were from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Associations of demographic, behavioural, physiological and psychological factors with vertical acceleration peaks ≥1.5 g (i.e. high-impact PA) from 7-day hip-worn accelerometer recordings were examined using linear regression.Results A total of 1187 participants (mean age = 72.7 years, 66.6% females) were included. Age, sex, education, active transport, self-reported higher impact PA, walking speed and self-rated health were independently associated with high-impact PA whereas BMI and sleep quality showed borderline independent associations. For example, differences in log-high-impact counts were 0.50 (P < 0.001) for men versus women and −0.56 (P < 0.001) for worst versus best self-rated health. Our final model explained 23% of between-participant variance in high impacts. Other correlates were not associated with high-impact activity after adjustment.Conclusions Besides age and sex, several factors were associated with higher impact PA in later life. Our findings help identify characteristics of older people that might benefit from interventions designed to promote osteogenic PA.

Objective: To determine whether there is an association between osteoarthritis (OA) and incident social isolation using data from the European Project on OSteoArthritis (EPOSA) study.Design: Prospective, observational study with 12 to 18 months of follow-up.Setting: Community dwelling.Participants: Older people living in six European countries.Measurements: Social isolation was assessed using the Lubben Social Network Scale and the Maastricht Social Participation Profile. Clinical OA of the hip, knee, and hand was assessed according to American College of Rheumatology criteria. Demographic characteristics, including age, sex, multijoint pain, and medical comorbidities, were assessed.Results: Of the 1967 individuals with complete baseline and follow-up data, 382 (19%) were socially isolated and 1585 were nonsocially isolated at baseline; of these individuals, 222 (13.9%) experienced social isolation during follow-up. Using logistic regression analyses, after adjustment for age, sex, and country, four factors were significantly associated with incident social isolation: clinical OA, cognitive impairment, depression, and worse walking time. Compared to those without OA at any site or with only hand OA, clinical OA of the hip and/or knee, combined or not with hand OA, led to a 1.47 times increased risk of social isolation (95% confidence interval = 1.03-2.09).Conclusion: Clinical OA, present in one or two sites of the hip and knee, or in two or three sites of the hip, knee, and hand, increased the risk of social isolation, adjusting for cognitive impairment and depression and worse walking times. Clinicians should be aware that individuals with OA may be at greater risk of social isolation.

Osteoarthritis (OA) can negatively impact levels of physical activity (PA), although current clinical advice promotes the benefits of staying active in preventing joint degeneration. In this study, we examine how knee OA, assessed by self-report, clinical assessment and radiographic assessment, impacts upon objectively measured PA 2 years later. The study population is comprised of 114 subjects from the Hertfordshire Cohort Study (HCS). The presence of OA at the knee was determined from self-report, and clinical and radiological examination, defined according to American College of Rheumatology (ACR) criteria and Kellgren and Lawrence grading system. Two years later, Gulf Coast Data Concepts (GCDC) tri-axial accelerometers were used to measure day-to-day levels of PA. Vertical acceleration peaks over 7 days, expressed in g units, were categorised into low (0.5 ≤ g

High-resolution peripheral quantitative computed tomography (HRpQCT) is increasingly used for exploring associations between bone microarchitectural and finite element analysis (FEA) parameters and fracture. We hypothesised that combining bone microarchitectural parameters, geometry, BMD and FEA estimates of bone strength from HRpQCT may improve discrimination of fragility fractures. The analysis sample comprised of 359 participants (aged 72–81 years) from the Hertfordshire Cohort Study. Fracture history was determined by self-report and vertebral fracture assessment. Participants underwent HRpQCT scans of the distal radius and DXA scans of the proximal femur and lateral spine. Poisson regression with robust variance estimation was used to derive relative risks for the relationship between individual bone microarchitectural and FEA parameters and previous fracture. Cluster analysis of these parameters was then performed to identify phenotypes associated with fracture prevalence. Receiver operating characteristic analysis suggested that bone microarchitectural parameters improved fracture discrimination compared to aBMD alone, whereas further inclusion of FEA parameters resulted in minimal improvements. Cluster analysis (k-means) identified four clusters. The first had lower Young modulus, cortical thickness, cortical volumetric density and Von Mises stresses compared to the wider sample; fracture rates were only significantly greater among women (relative risk [95%CI] compared to lowest risk cluster: 2.55 [1.28, 5.07], p = 0.008). The second cluster in women had greater trabecular separation, lower trabecular volumetric density and lower trabecular load with an increase in fracture rate compared to lowest risk cluster (1.93 [0.98, 3.78], p = 0.057). These findings may help inform intervention strategies for the prevention and management of osteoporosis. Electronic supplementary material The online version of this article (10.1007/s00223-019-00564-7) contains supplementary material, which is available to authorized users.

Resume Objectifs Les etudes epidemiologiques et fondamentales suggerent que les desordres lipidiques puissent etre impliques dans la physiopathologie de la gonarthrose. Les diverses etudes ayant evalue l’effet des statines ont montre des resultats contradictoires. Nous avons etudie l’effet des statines sur la progression radiologique chez des patients atteints d’une gonarthrose symptomatique confirmee sur les radiographies. Methodes 336 patients issus du groupe placebo de l’essai SEKOIA ont complete les 3 ans de suivi et ont ete inclus dans cette analyse post-hoc. La prise de statines etait evaluee lors de la visite d’inclusion. La mesure de l’interligne articulaire femorotibiale minimale etait effectuee sur des radiographies standards selon une methode automatisee a l’inclusion puis de facon annuelle. La progression radiologique etait definie comme un pincement ≥ 0,5 mm sur 3 ans. Resultats 71 patients etaient sous statines (21,1 %). Comparativement aux sujets non traites, ils avaient un BMI superieur (31,1 ± 5,3 vs. 29,3 ± 5,2 kg/m2, p = 0,008) et un plus grand nombre de facteurs metaboliques (≥ 3 facteurs : 43,7 % vs. 7,2 % ; pet 30 kg/m2) et des maladies cardiovasculaires [risque relatif 1,49 (IC95 % 1,10–2,02), pet = 0,010]. Conclusion Chez les patients ayant une gonarthrose symptomatique, l’utilisation de statines etait associee a une plus grande progression radiologique independamment des facteurs confondants (obesite, diabete de type 2, hypertension, duree de la maladie, intensite des symptomes et severite radiologique).

Background: This study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA). Methods: Data from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65–85 years). At baseline and 12–18 months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12–18 months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6 months follow-up and 12–18 months follow-up. Results: Of all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio = 0.95, 95% CI = 0.90–0. 99), but not in men (Ratio = 0.99, 95% CI = 0.85–1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio = 0.94, 95% CI = 0.89–0.99), but not in men (Ratio = 1.00, 95% CI = 0.87–1.11). Greater pain variability over 12–18 months was associated with more PA at follow-up in men (Ratio = 1.18, 95% CI = 1.01–1.38), but not in women (Ratio = 0.94, 95% CI = 0.86–1.03). Conclusions: Greater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research., The Indicators for Monitoring COPD and Asthma - Activity and Function in the Elderly in Ulm study (IMCA - ActiFE) was supported by the European Union [No.: 2005121] and the Ministry of Science, Baden-Württemberg. The Italian cohort study is part of the National Research Council Project on Aging (PNR). The Longitudinal Aging Study Amsterdam (LASA) is financially supported by the Dutch Ministry of Health, Welfare and Sports, Directorate of Long-term Care. The Penagrande study was partially supported by the National Fund for Health Research (Fondo de Investigaciones en Salud) of Spain [project numbers FIS PI 05/1898; FIS RETICEF RD06/0013/1013 and FIS PS09/02143]. The Swedish Twin Registry is supported in part by the Swedish Ministry of Higher Education. The Hertfordshire Cohort Study is funded by the Medical Research Council of Great Britain, Arthritis Research UK, the British Heart Foundation and the International Osteoporosis Foundation. The funding sources had no role in the study design, the collection, analysis and interpretation of the data, in the writing of the report and in the decision to submit the article for publication.

Objective To examine the role of comorbidity and pain in the associations of hand osteoarthritis (OA) with self-reported and performance-based physical function in a general population of elderly persons. Methods We studied data from 2,942 participants ages 65–85 years in the European Project on OSteoArthritis, a collaborative observational study of 6 European cohorts (from Germany, Italy, The Netherlands, Spain, Sweden, and the UK). Outcome measures included self-reported physical function of the hands measured by the AUStralian/CANadian Osteoarthritis Hand Index (AUSCAN) for hand OA physical function subscale and performance-based grip strength measured using a strain gauge dynamometer. Results Comorbidity was not a confounder in the association of hand OA with self-reported and performance-based functional limitations, while the role of pain as a mediator was confirmed. Anxiety, depression, stroke, and osteoporosis were associated with AUSCAN scores reflecting more impairment. Depression and osteoporosis were associated with less grip strength. Conclusion Although comorbidity was decidedly and independently associated with hand functional limitation, it had no effect on the relationship of hand OA with physical function. Hand OA was found to be associated with both self-reported and performance-based physical function impairment; the association was found to be partially mediated by pain, which reduced its impact.

This study aimed to examine the associations of perceptions of neighbourhood cohesion and neighbourhood problems and objectively measured neighbourhood deprivation with the use of neighbourhood resources by older adults with and without lower limb osteoarthritis (LLOA), and to assess whether these relationships are stronger in older persons with LLOA than in those without the condition. Data from the Hertfordshire Cohort Study were used. American College of Rheumatology classification criteria were used to diagnose clinical LLOA (knee and/or hip osteoarthritis). Use of neighbourhood resources was assessed using the Home and Community Environment instrument. Participants were asked about their perceptions of neighbourhood cohesion and neighbourhood problems. Objective neighbourhood deprivation was assessed using the Index of Multiple Deprivation score based on 2010 census data. Of the 401 participants (71-80 years), 74 (18.5 %) had LLOA. The neighbourhood measures were not significantly associated with use of resources in the full sample. A trend for a negative association between use of public transport and perceived neighbourhood problems was observed in participants with LLOA (OR = 0.77, 99 % CI = 0.53-1.12), whereas a trend for a positive association between perceived neighbourhood problems and use of public transport was found in participants without LLOA (OR = 1.18, 99 % CI = 1.00-1.39). The perception of more neighbourhood problems seems only to hinder older adults with LLOA to make use of public transport. Older adults with LLOA may be less able to deal with neighbourhood problems and more challenging environments than those without the condition.

PurposeOsteoarthritis (OA) has been shown to be associated with decreased physical function, which may impact upon a person’s self-rated health (SRH). Only a few studies have examined the association between OA and SRH in the general population, but to date none have used a clinical definition of OA. The objectives are: (1) To examine the cross-sectional association between clinical OA and fair-to-poor SRH in the general population; (2) To examine whether this association differs between countries; (3) To examine whether physical function is a mediator in the association between clinical OA and SRH.MethodsBaseline data of the European Project on OSteoArthritis (EPOSA) were used, which includes pre-harmonized data from six European cohort studies (n = 2709). Clinical OA was defined according to the American College of Rheumatology criteria. SRH was assessed using one question: How is your health in general? Physical function was assessed using the Western Ontario and McMaster Universities OA Index and Australian/Canadian OA Hand Index.ResultsThe prevalence of fair-to-poor SRH ranged from 19.8 % in the United Kingdom to 63.5 % in Italy. Although country differences in the strength of the associations were observed, clinical OA of the hip, knee and hand were significantly associated with fair-to-poor SRH in five out of six European countries. In most countries and at most sites, the association between clinical OA and fair-to-poor SRH was partly or fully mediated by physical function.ConclusionsClinical OA at different sites was related to fair-to-poor SRH in the general population. Most associations were (partly) mediated by physical functioning, indicating that deteriorating physical function in patients with OA should be a point of attention in patient care.

Objective To investigate patterns of physical activity in older adults with knee osteoarthritis (OA) compared to older adults without knee OA across 6 European countries. We expect country-specific differences in the physical activity levels between persons with knee OA compared to persons without knee OA. A varying degree of physical activity levels across countries would express a facilitating or impeding influence of the social, environmental, and other contextual factors on a physically active lifestyle. Methods Baseline cross-sectional data from the European Project on Osteoarthritis were analyzed. In total, 2,551 participants from 6 European countries (Germany, Italy, The Netherlands, Spain, Sweden, and the UK) were included. Results Participants with knee OA were less likely to follow physical activity recommendations and had poorer overall physical activity profiles than those without knee OA (mean 62.9 versus 81.5 minutes/day, respectively; P = 0.015). The magnitude of this difference varied across countries. Detailed analysis showed that low physical activity levels in persons with knee OA could be attributed to less everyday walking time (odds ratio 1.31, 95% confidence interval 1.07–1.62). Conclusion This study highlighted the fact that having knee OA is associated with a varying degree of physical activity patterns in different countries. This national variation implies that low levels of physical activity among persons with knee OA cannot be explained exclusively by individual or disease-specific factors, but that social, environmental, and other contextual factors should also be taken into account.

Objective.Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW).Methods.A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2–3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries). Minimal tibiofemoral joint space and KL grade on plain radiograph of the knee were assessed at baseline and at yearly followup up to 3 years. In a subset, serial knee MRI examinations were performed. Individuals with a bone marrow lesion (BML) ≥ grade 2 at the tibiofemoral joint at baseline were classified as BML-positive. Relationships between change in JSW and risk factors were assessed using linear regression.Results.The mean age of study participants was 62.8 (SD 7.5) years and 73% were female; 38.6% had BML. Mean baseline JSW was 3.65 mm. This reduced by 0.18 (0.30) mm/year in men and 0.13 (0.23) mm/year in women. Those with BML had a significantly higher rate of annualized change in JSW; this relationship remained robust after adjustment for age, sex, and baseline KL grade [β = −0.10 (95% CI −0.18, −0.02) mm/yr]. Age, sex, baseline KL grade, and other MRI findings did not influence the rate of change in JSW.Conclusion.The rate of change in JSW was similar in men and women. BML on knee MRI predicted the rate of radiographic change in JSW. This relationship was independent of age, sex, and baseline KL grade.

Objective Epidemiological and experimental studies have suggested that lipid disorders might be involved in the pathophysiology of knee osteoarthritis (OA). Studies assessing the effect of statins on knee OA progression have shown conflicting results. We investigated the impact of statin use on radiological progression in patients with radiological and symptomatic knee OA. Methods In total, 336 patients from the placebo arm of SEKOIA trial completed the 3-year follow-up and were included in this post-hoc analysis. Statin use was recorded at baseline interview. Minimal medial tibiofemoral joint space was measured on plain radiographs by an automated method at baseline and then annually. Radiologic progression was defined as joint space narrowing ≥ 0.5 mm over 3 years. Results Overall, 71 patients were statin users (21.1%). They had a higher BMI (31.1 ± 5.3 vs. 29.3 ± 5.2 kg/m2, P = 0.008), a higher sum of metabolic factors (≥ 3 factors: 43.7% vs 7.2%; P for trend < 0.001) and a higher rate of radiological progression (49.3% vs. 32.1%, P = 0.007) as compared to statin non-users. The significant association between radiological progression and statin use was independent of age, gender, WOMAC global score, disease duration, baseline joint space width, hypertension, type 2 diabetes, obesity (BMI > 30 kg/m2) and cardiovascular diseases [relative risk 1.49 (95% CI: 1.10–2.02), P = 0.010]. Conclusion Among patients with knee OA, statin use was associated with radiological worsening over 3 years, regardless of other potential confounding factors (obesity, type 2 diabetes, hypertension, disease duration, symptom intensity and radiological severity).

There are few data describing associations between dietary patterns and bone microarchitecture. This study investigated the relationship between diet quality and HRpQCT and pQCT measures in older adults. Data were available for 184 men and 166 women. Dietary data were collected at baseline (1998–2003) using an administered food frequency questionnaire. A ‘prudent’ diet score (PDS) was identified using principal component analysis and used as an indicator of dietary quality. HRpQCT and pQCT images were acquired at follow-up in 2012, from the non-dominant distal radius and tibia using Scanco XtremeCT and Stratec XCT2000 instrument scanners, respectively. The mean (SD) PDS was − 0.24 (1.23) for men and 0.62 (1.14) for women. In women, a significant positive relationship was found between baseline dietary pattern and total and trabecular area at both the radius and the tibia, measured by HRpQCT. Similar trends were observed with pQCT parameters. Positive associations were observed for tibia total area (38% slice). At the radius, significant positive associations were found for total area (4% slice) and polar strength strain index (33% slice). All relationships remained robust to adjustment. For men, although patterns were similar, there were no significant associations for HRpQCT outcomes. Significant associations were observed for baseline PDS and polar strength strain and total area (66% slice) at the radius, measured by pQCT. Our data suggest that diets high in fruit, vegetables, oily fish and whole grain cereals in early old age are associated with greater bone size but not volumetric bone density or microarchitecture in later life in women. Electronic supplementary material The online version of this article (10.1007/s00223-018-0445-x) contains supplementary material, which is available to authorized users.

© 2018 Oxford University Press. All rights reserved. Background: High impact physical activity (PA) is thought to improve skeletal health, but its relation to other health outcomes are unclear. We investigated associations between PA impact magnitude and body mass index (BMI) in older adults. Methods: Data were taken from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), Hertfordshire Cohort Study, and MRC National Survey of Health and Development. Vertical acceleration peaks from 7-day hip-worn accelerometer recordings were used to classify PA as low (0.5 < g < 1.0g), medium (1 < g < 1.5g), or higher (=1.5g) impact. Cohort-specific associations of low, medium, and higher impact PA with BMI were examined using linear regressions and estimates combined using random-effects meta-analysis. Results: A total of 1182 participants (mean age = 72.7 years, 68% female) were included. Low, medium, and higher impact PA were inversely related to BMI in initial models. After adjustment for confounders and other impacts, low, but not medium or higher, impacts were inversely related to BMI (-0.31, p < .001: overall combined standard deviation change in BMI per doubling in the number of low impacts). In adjusted analyses of body composition measured by dual-energy X-ray absorptiometry in COSHIBA, low, but not medium or higher, impacts were inversely related to total body fat mass (-0.19, p < .001) and android:gynoid fat mass ratio (-0.16, p = .01), whereas high impact PA was weakly and positively associated with lean mass (0.05, p = .06). Conclusions: Greater exposure to PA producing low magnitude vertical impacts was associated with lower BMI and fat mass at older age. Low impact PA may help reduce obesity risk in older adults.

This study investigated the association between mild cognitive impairment (MCI) and physical function and bone health in older adults. MCI was associated with poor physical performance but not bone mineral density or bone microarchitecture. Purpose: Cross-sectional study to investigate the association between mild cognitive impairment (MCI) and physical performance, and bone health, in a community-dwelling cohort of older adults. Methods: Cognitive function of 222 men and 221 women (mean age 75.5 and 75.8 years in men and women, respectively) was assessed by the Strawbridge questionnaire and Mini Mental State Exam (MMSE). Participants underwent dual-energy x-ray absorptiometry (DXA), peripheral-quantitative computed tomography (pQCT) and high-resolution peripheral-quantitative computed tomography (HR-pQCT) scans to assess their bone density, strength and microarchitecture. Their physical function was assessed and a physical performance (PP) score was recorded. Results: 11.8% of women and 8.1% of men in the study were cognitive impaired on the MMSE (scoreConclusion: MCI in older adults was associated with poor physical performance, but not bone density, shape or microarchitecture.

Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18-80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.

Background:Significant correlation has been previously demonstrated between radiographic and clinical diagnoses of knee osteoarthritis (OA); however, the specific findings on clinical examination that relate best to a radiographic diagnosis have not been fully elicited.Aims:We aimed to explore the relationship between clinical symptoms and physical findings with radiographic diagnoses of tibiofemoral and patellofemoral OA.Methods:This study was based on 409 individuals from the Hertfordshire Cohort Study, born between 1931 and 1939. Antero-posterior and lateral radiographs were taken of both knees. The presence of tibiofemoral and patellofemoral OA was defined according to the Kellgren and Lawrence score. Clinical symptoms, assessed using WOMAC, and physical findings were ascertained by examination. Relationships were assessed using multilevel univariate logistic regression.Results:In the 775 knees studied, the prevalence of physical findings was crepitus (25%), tibiofemoral tenderness (15%), bony swelling (12%), and pain on flexion (10%). Thirty-one percent (n = 238) knees demonstrated tibiofemoral OA, 28% (n = 220) showed patellofemoral OA, and 16% demonstrated OA in both locations. A global clinical symptom score was associated with increased risk of tibiofemoral OA (OR 12.5, 95% CI 5.4–29.0) and patellofemoral OA (OR 5.1, 95% CI 2.3–13.1). On clinical examination, the presence of crepitus, tibiofemoral tenderness, bony swelling, and pain on flexion was associated with increased risk of tibiofemoral OA; however, only tenderness was found to be associated with patellofemoral OA.Conclusion:Global clinical symptom score was associated with radiographic tibiofemoral and patellofemoral OA. However, individual clinical signs were more strongly associated with tibiofemoral than patellofemoral OA.

Summary Purpose Recent studies have suggested that metabolic factors (obesity, diabetes, hypertension and dyslipidemia) and their clustering in metabolic syndrome (MetS) might be involved in the pathophysiology of knee osteoarthritis (OA). We investigated their impact on radiographic progression by an annualised measure of the joint space narrowing (JSN) of the medial tibiofemoral compartment. Methods 559 patients older than 50 years with symptomatic knee OA were recruited for the placebo arm of the SEKOIA trial. The presence of diabetes, hypertension and dyslipidemia was determined at baseline interview. Body mass index (BMI) was calculated, obesity was considered >30 kg/m 2 . MetS was defined by the sum of metabolic factors ≥3. Minimal medial tibiofemoral joint space on plain radiographs was measured by an automated method at baseline and then annually for up to 3 years. Results The mean age of patients was 62.8 [62.2–63.4] years; 392 were women. A total of 43.8% was obese, 6.6% had type 2 diabetes, 45.1% hypertension, 27.6% dyslipidemia and 13.6% MetS. Mean annualised JSN was greater for patients with type 2 diabetes than without diabetes (0.26 [−0.35 to −0.17] vs 0.14 [−0.16 to −0.12] mm; P = 0.001). This association remained significant after adjustment for sex, age, BMI, hypertension and dyslipidemia ( P = 0.018). In subgroup analysis, type 2 diabetes was a significant predictor of JSN in males but not females. The other metabolic factors and MetS were not associated with annualised JSN. Conclusion Type 2 diabetes was a predictor of joint space reduction in men with established knee OA. No relationships were found between MetS or other metabolic factors and radiographic progression.

In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate geometric, volumetric and microstructural parameters at the distal radius and at the distal tibia in participants with ischaemic heart disease. We found that, compared with participants without ischaemic heart disease, they had substantially lower cortical volumetric bone mineral density (BMD) at the distal radius.HR-pQCT captures novel aspects of bone geometry and volumetric bone mineral density (vBMD) and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique in patients with ischemic heart disease (IHD) are lacking.Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from HR-pQCT of distal radius and distal tibia in 350 participants (184 men and 166 women) aged 71.5-80.5 years with or without IHD (e.g. heart attack, angina or heart failure; n = 75 and n = 275, respectively).Analyses for all participants (men and women together) revealed that cortical vBMD (Ct.vBMD) was lower (p 0.001) and cortical thickness (Ct.th) was not different (p = 0.519), whereas cortical porosity (Ct.Po) was higher (p = 0.016) in participants with IHD at the distal radius. Moreover, trabecular microarchitectural parameters were not significantly different in patients with IHD (p 0.05 for all). Adjustment for a priori confounders (age, gender, body mass index, smoking status, alcohol consumption, high blood pressure and diabetes mellitus) did not materially affect the relationship described for Ct.vBMD (p = 0.002), but differences in Ct.Po were attenuated. Analyses in men alone revealed that only Ct.vBMD was lower at the distal radius in participants with IHD with and without adjustment for a priori confounders (p = 0.0002 and p = 0.004, respectively), whereas no statistical differences were found in women, although patterns of differences were similar in both sexes. Moreover, no association was found between IHD and bone parameters at the distal tibia either in men or women.We have demonstrated that IHD is associated with lower Ct.vBMD of the distal radius.

Osteoporosis is a common condition which mainly affects older individuals and is more common in women than in men. Rates vary significantly across the world with higher rates in Northern Europe, North America, and Australasia. There are also differences by country and sometimes on a more local level. This review describes the variation and explores how secular trends in fracture rates have changes over recent years and may alter in the future. Although overall rates tend to be increasing, due largely to an ageing population, age-specific rates appear to be declining in some areas. This has considerable importance for the socioeconomic burden of the disease in years to come. Osteoporotic fractures are associated with significant morbidity and in some cases mortality. Consequently, they often require hospital treatment and may lead to long-term institutional care. This leads not only to effects on the individual’s quality of life but also to major health care and social costs.

High impact physical activity (PA) is thought to benefit bone. We examined associations of lifetime walking and weight bearing exercise with accelerometer-measured high impact and overall PA in later life. Data were from 848 participants (66.2% female, mean age = 72.4 years) from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Acceleration peaks from seven-day hip-worn accelerometer recordings were used to derive counts of high impact and overall PA. Walking and weight bearing exercise up to age 18, between 18–29, 30–49 and since age 50 were recalled using questionnaires. Responses in each age category were dichotomised and cumulative scores derived. Linear regression was used for analysis. Greater lifetime walking was related to higher overall, but not high impact PA, whereas greater lifetime weight bearing exercise was related to higher overall and high impact PA. For example, fully-adjusted differences in log-overall and log-high impact PA respectively for highest versus lowest lifetime scores were: walking [0.224 (0.087, 0.362) and 0.239 (− 0.058, 0.536)], and weight bearing exercise [0.754 (0.432, 1.076) and 0.587 (0.270, 0.904)]. For both walking and weight bearing exercise, associations were strongest in the ‘since age 50’ category. Those reporting the most walking and weight bearing exercise since age 50 had highest overall and high impact PA, e.g. fully-adjusted difference in log-high impact PA versus least walking and weight bearing exercise = 0.588 (0.226, 0.951). Promoting walking and weight bearing exercise from midlife may help increase potentially osteogenic PA levels in later life., Highlights • Exposure to higher impact PA in old age is thought to improve skeletal health. • It is unclear how walking and exercise history relate to high impact PA in old age. • More frequent weight bearing exercise was more strongly related to high impact PA. • Associations were strongest for highest levels of walking and weight bearing exercise. • Performing both activity types from midlife might promote osteogenic PA at old age.

Priming of naive CD8+ and CD4+ T cells by dendritic cells (DCs) requires effective antigen presentation on both MHC class I and II molecules. We have developed a novel technology to use recombinant overlapping peptides (ROP) that stimulate both CD8+ and CD4+ T cell immune responses. The single chain protein of a ROP is made up of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, a protease found in the endosomes of DCs. We designed synthetic genes encoding ROPs derived from ovalbumin (OVA), tuberculosis protein (CFP10-ESAT6), human papilloma virus (HPV) protein (E7) and survivin, a protein commonly over-expressed in tumour cells. An epitope from ROP-OVA was cross-presented and detected by a CD8+ T cell receptor-like antibody (TCR like Ab). Human DCs pulsed with ROP-survivin activated CD8+ T cells. CD4-low PBMCs from HIV and TB co-infected patients recognized ROP-CFP10-ESAT6 compared to a soluble form of the antigen. Immunization of mice with ROP-survivin or ROP-HPV-E7 generated specific cellular immune responses and protected mice from inoculation with melanoma B16 cells expressing survivin or HPV-E7 proteins. Together these data provide evidence to support ROP as a central component of a new platform for therapeutic vaccines and diagnostics.

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius. Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters. The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n = 83) vs. 17.3 % (n = 28), p

BACKGROUND: poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies. OBJECTIVE: to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries. METHODS: a total of 2,942 men and women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0-12); low PP was defined as a score of ≤9. RESULTS: the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain. CONCLUSION: lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites.

Background:Older adults with osteoarthritis (OA) often report that their disease symptoms are exacerbated by weather conditions. This study examines the association between outdoor physical activity (PA) and weather conditions in older adults from 6 European countries and assesses whether outdoor PA and weather conditions are more strongly associated in older persons with OA than in those without the condition.Methods:The American College of Rheumatology classification criteria were used to diagnose OA. Outdoor PA was assessed using the LASA Physical Activity Questionnaire. Data on weather parameters were obtained from weather stations.Results:Of the 2439 participants (65–85 years), 29.6% had OA in knee, hand and/or hip. Participants with OA spent fewer minutes in PA than participants without OA (Median = 42.9, IQR = 20.0 to 83.1 versus Median = 51.4, IQR = 23.6 to 98.6; P < .01). In the full sample, temperature (B = 1.52; P < .001) and relative humidity (B = –0.77; P < .001) were associated with PA. Temperature was more strongly associated with PA in participants without OA (B = 1.98; P < .001) than in those with the condition (B = 0.48; P = .47).Conclusions:Weather conditions are associated with outdoor PA in older adults in the general population. Outdoor PA and weather conditions were more strongly associated in older adults without OA than in their counterparts with OA.

Kidney stones are common, with a multifactorial etiology involving dietary, environmental, and genetic factors. In addition, patients with nephrolithiasis are at greater risk of hypertension, diabetes mellitus, metabolic syndrome, and osteoporosis, although the basis for this is not fully understood. All of these renal stone-associated conditions have also been linked with adverse early-life events, including low-birth weight, and it has been suggested that this developmental effect is due to excess exposure to maternal glucocorticoids in utero. This is proposed to result in long-term increased hypothalamic-pituitary-axis activation; there are mechanisms through which this effect could also promote urinary lithogenic potential. We therefore hypothesize that the association between renal stone disease and hypertension, diabetes mellitus, metabolic syndrome, and osteoporosis may be related by a common pathway of programming in early life, which, if validated, would implicate the developmental origins hypothesis in the etiology of nephrolithiasis.

Sarcopenia is associated with a greater fracture risk. This relationship was originally thought to be explained by an increased risk of falls in sarcopenic individuals. However, in addition, there is growing evidence of a functional muscle-bone unit in which bone health may be directly influenced by muscle function. Because a definition of sarcopenia encompasses muscle size, strength, and physical performance, we investigated relationships for each of these with bone size, bone density, and bone strength to interrogate these hypotheses further in participants from the Hertfordshire Cohort Study. A total of 313 men and 318 women underwent baseline assessment of health and detailed anthropometric measurements. Muscle strength was measured by grip strength, and physical performance was determined by gait speed. Peripheral quantitative computed tomography (pQCT) examination of the calf and forearm was performed to assess muscle cross-sectional area (mCSA) at the 66% level and bone structure (radius 4% and 66% levels; tibia 4% and 38% levels). Muscle size was positively associated with bone size (distal radius total bone area ??=?17.5 mm2/SD [12.0, 22.9]) and strength (strength strain index (??=?23.3 mm3/SD [18.2, 28.4]) amongst women (p?0.001). These associations were also seen in men and were maintained after adjustment for age, height, weight-adjusted-for-height, limb-length-adjusted-for-height, social class, smoking status, alcohol consumption, calcium intake, physical activity, diabetes mellitus, and in women, years since menopause and estrogen replacement therapy. Although grip strength showed similar associations with bone size and strength in both sexes, these were substantially attenuated after similar adjustment. Consistent relationships between gait speed and bone structure were not seen. We conclude that although muscle size and grip strength are associated with bone size and strength, relationships between gait speed and bone structure and strength were not apparent in this cohort, supporting a role for the muscle-bone unit

Introduction: sarcopenia is associated with adverse health outcomes. The aim of this study was to describe the prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus definition.Methods:we applied the EWGSOP definition to 103 community-dwelling men participating in the Hertfordshire Sarcopenia Study (HSS) using both the lowest third of dual-energy X-ray absorptiometry (DXA) lean mass (LM) and the lowest third of skin-fold-based fat-free mass (FFM) as markers of low muscle mass. We also used the FFM approach among 765 male and 1,022 female participants in the Hertfordshire Cohort Study (HCS). Body size, physical performance and self-reported health were compared in participants with and without sarcopenia.Results: the prevalence of sarcopenia in HSS men (mean age 73 years) was 6.8% and 7.8% when using the lowest third of DXA LM and FFM, respectively. DXA LM and FFM were highly correlated (0.91, P < 0.001). The prevalence of sarcopenia among the HCS men and women (mean age 67 years) was 4.6% and 7.9%, respectively. HSS and HCS participants with sarcopenia were shorter, weighed less and had worse physical performance. HCS men and women with sarcopenia had poorer self-reported general health and physical functioning scores.Conclusions: this is one of the first studies to describe the prevalence of sarcopenia in UK community-dwelling older people. The EWGSOP consensus definition was of practical use for sarcopenia case finding. The next step is to use this consensus definition in other ageing cohorts and among older people in a range of health-care settings.