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Background Malnutrition is a serious concern in older populations. Simple screening approaches are needed to identify signs of early nutritional risk in older people, to allow intervention before overt malnutrition develops, along with the poorer health outcomes associated with it, such as sarcopaenia and frailty. The main aim of this study was to compare nutrition risk scores, calculated from the DETERMINE Checklist (‘Determine Your Nutritional Health’, also known as the Nutrition Screening Initiative Checklist), with physical function variables in a group of community-dwelling older adults. Another aim was to assess the prevalence of nutrition risk using the DETERMINE and the MUST (Malnutrition Universal Screening Tool). Methods Participants of the Hertfordshire Cohort Study (HCS) were recruited and visited at home by a trained researcher. Self-reported physical function was assessed using the SF-36 PF (Short Form-36 Physical Function) scale. The Short Physical Performance Battery (SPPB) was performed, which included the assessment of gait speed, chair rise time and standing balance. Handgrip strength was measured using a Jamar dynamometer. Frailty was assessed according to the presence of at least three of the following Fried frailty criteria: unintentional weight loss, weakness, self-reported exhaustion, slow gait speed and low physical activity. Nutrition risk scores were calculated from the DETERMINE checklist (range 0–21). Nutritional risk was also assessed using the MUST. Analyses were adjusted for sex, age, age left education and number of comorbidities. Results In the study, 176 participants (94 men and 82 women), median age 83.3 (IQR 81.5–85.7) years, were assessed. Almost half (47%) scored either ‘moderate’ (score 3–5) or ‘high’ (score ≥ 6) nutritional risk (9% were at high risk), using the DETERMINE checklist, whereas 8% were at risk using the MUST. Higher nutrition risk scores, calculated from DETERMINE, were associated with poorer self-reported physical function (difference in SF-36 PF score: − 0.36, 95% CI (− 0.60, − 0.12) SD per unit increase in nutrition risk score, P = 0.004) and higher odds of being frail (odds ratio Fried frailty: 2.23, 95% CI (1.15, 4.33), P = 0.017). There were no significant associations between DETERMINE nutrition risk scores and the other variables examined. Conclusion Cross-sectional associations between higher nutrition risk scores, assessed from the DETERMINE checklist, and poorer self-reported physical function and greater likelihood of frailty suggest that this screening tool may have utility for screening older populations. Prospective studies are required to explore the ability of the tool to predict poor physical function and frailty, though these data suggest it has potential for early, simple detection of nutritional problems in community-living older adults.

Background Social relationships play a fundamental role in individuals’ lives and health, and social isolation is prevalent among older people. Chronic non-communicable diseases (NCDs) and frailty are also common in older adults. Aims To examine the association between number of NCDs and social isolation in a cohort of community-dwelling older adults in the UK, and to consider whether any potential association is mediated by frailty. Methods NCDs were self-reported by 176 older community-dwelling UK adults via questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale. Frailty was assessed by the Fried phenotype of physical frailty. Results The median (IQR) age of participants in this study was 83.1 (81.5–85.5) years for men and 83.8 (81.5–85.9) years for women. The proportion of socially isolated individuals was 19% in men and 20% in women. More women (18%) than men (13%) were identified as frail. The number of NCDs was associated with higher odds of being isolated in women (unadjusted odds ratio per additional NCD: 1.65, 95% CI 1.08, 2.52, p = 0.021), but not in men, and the association remained robust to adjustment, even when accounting for frailty (OR 1.85, 95% CI 1.06, 3.22, p = 0.031). Discussion Number of self-reported NCDs was associated with higher odds of social isolation in women but not in men, and the association remained after considering frailty status. Conclusions Our observations may be considered by healthcare professionals caring for community-dwelling older adults with multiple NCDs, where enquiring about social isolation as part of a comprehensive assessment may be important.

Background Older adults have been especially vulnerable to adverse effects from the COVID-19 pandemic including higher mortality and more severe disease complications. At the same time, social isolation, malnutrition and physical inactivity are serious concerns among older adults. The pandemic and associated restrictions may serve to exacerbate these issues, presenting increased risks to physical and mental health. The aims of this qualitative study were: i) to explore how community-living older people in the UK experienced the first wave of the COVID-19 pandemic, specifically how it impacted their well-being and associated health behaviours; ii) to explore how older people’s experiences and behaviours changed over time throughout the first wave. Methods Qualitative data were collected by conducting serial telephone interviews, with an interval of approximately three months. Participants were from the Hertfordshire Cohort Study, all aged over 80 years. Discussions were audio-recorded, information related to the COVID-19 pandemic was transcribed verbatim and transcripts analysed thematically. Interviews were conducted from March to October 2020. Results Data for twelve participants (7 men and 5 women) from a total of 35 interviews were used, comprising two or three timepoints per participant. Analysis identified five overarching themes: 1) shopping strategies and food accessibility, 2) limitations on activities and going out, 3) disruption to healthcare, 4) social and psychological repercussions, and 5) coping strategies. Findings highlight challenges associated with accessing shops, healthcare, and usual activities due to pandemic-related restrictions. Longitudinal findings showed that for some, the ongoing pandemic and related restrictions appeared to aggravate mental health issues (low mood, anxiety) over time, as well as greater feelings of isolation or loneliness, reduced activity and functional limitations; this was despite some relaxation of restrictions later on. Coping strategies used by participants included finding ways to keep busy and to do physical activity safely, maintaining social contact remotely, and having an optimistic or positive outlook, a ‘do what you can’ attitude. Conclusions Interventions are likely to be needed in the wake of the COVID-19 pandemic to support health behaviours, such as increasing physical activity, social engagement and improving mental health among community-living older adults.

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

Understanding how the epigenome deteriorates with age and subsequently impacts on biological function may bring unique insights to ageing-related disease mechanisms. As a central cellular apparatus, tRNAs are fundamental to the information flow from DNA to proteins. Whilst only being transcribed from ~46kb ( < 0.002%) of the human genome, their transcripts are the second most abundant in the cell. Furthermore, it is now increasingly recognised that tRNAs and their fragments also have complex regulatory functions. In both their core translational and additional regulatory roles, tRNAs are intimately involved in the control of metabolic processes known to affect ageing. Experimentally DNA methylation can alter tRNA expression, but little is known about the genomic DNA methylation state of tRNAs. Here, we find that the human genomic tRNA loci (610 tRNA genes termed the tRNAome) are enriched for ageing-related DNA hypermethylation. We initially identified DNA hypermethylation of 44 and 21 specific tRNA genes, at study-wide (p < 4.34 × 10 − 9 ) and genome-wide ( p < 4.34 × 10 − 9 ) significance, respectively, in 4,350 MeDIP-seq peripheral blood DNA methylomes (16 - 82 years). This starkly contrasted with 0 hypomethylated at both these significance levels. Further analysing the 21 genome-wide results, we found 3 of these tRNAs to be independent of major changes in cell-type composition (tRNA-iMet-CAT-1-4, tRNA-Ser-AGA-2-6, tRNA-Ile-AAT-4-1). We also excluded the ageing-related changes being due to the inherent CpG density of the tRNAome by permutation analysis (1,000x, Empirical p-value < 1 × 10 − 3 ). We additionally explored 79 tRNA loci in an independent cohort using Fluidigm deep targeted bisulfite-sequencing of pooled DNA (n=190) across a range of 4 timepoints (aged ~4, ~28, ~63, ~78 years). This revealed these ageing changes to be specific to particular isodecoder copies of these tRNA (tRNAs coding for the same amino acid but with sequence body differences) and included replication of 2 of the 3 genome-wide tRNAs. Additionally, this isodecoder-specificity may indicate the potential for regulatory fragment changes with age. In this study we provide the first comprehensive evaluation at the genomic DNA methylation state of the human tRNAome, revealing a discreet and strongly directional hypermethylation with advancing age.

BackgroundPhysical activity, nutrition and other lifestyle factors play important roles in maintaining musculoskeletal health. The coronavirus disease (COVID-19) originated in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020, and led to widespread behaviour change. The aim of this study was to use two existing cohorts, the Hertfordshire Cohort Study (HCS) and Health and Employment After Fifty Study (HEAF), to understand how wave one of the COVID-19 pandemic impacted lifestyle factors associated with musculoskeletal health in the UK.Methods125 eligible participants, 65 males and 60 females (drawn from the HCS study, median (IQR) age 84.3 (82.4-86.6) years, all Caucasian, and community dwelling) were contacted by telephone and asked to complete a questionnaire administered by a trained researcher. Data collection occurred over the period July 2020 to February 2021. 2469 participants, 1086 men and 1383 women (drawn from the HEAF study, median age 65.7 (62.0-69.3) years, mostly Caucasian and community dwelling) completed an online questionnaire in March 2021.ResultsIn HCS, 47% respondents reported being less physically active than before the pandemic (and only 5% more so), 27% said they consumed less alcohol compared to pre-pandemic times (and only 3% more so), and 18% reported eating less than before, although quality of diet was generally unchanged over this timeframe surveyed. In HEAF, 44% participants said they were less active than before the pandemic, while 17% reported being more active. The majority of participants reported no changes in alcohol consumption and diet; however, 19% said they drank more than before (32% of which was above recommended levels), 16% said their diet was less healthy, and 19% reported eating more than before.ConclusionWe have reported the experience of the first wave of the COVID-19 pandemic among participants of two Caucasian community dwelling UK cohorts, highlighting the impact of the pandemic on lifestyle factors associated with musculoskeletal health. Changed physical activity levels were reported in a high proportion of respondents in both studies; an investigation of reversibility of these changes is required.

Purpose of review The field of osteoporosis research has been active for the past 20 years and has allowed significant advancement in the management of osteoporosis. This review will give an overview of the latest data from international cohorts that relate to current and recent osteoporosis research. Recent findings The clinical diagnosis of osteoporosis relies heavily on bone mineral density (BMD) measured at femoral neck or spine and although BMD has excellent predictive value for future fractures, fracture risk assessment has evolved over the years, resulting in the birth of fracture prediction tools. Fracture risk factors not currently featured in these tools are being considered for inclusion, including imminent risk fracture following a sentinel fracture, number of falls, and previous vertebral fractures. Data from groups with comorbidities such as chronic obstructive pulmonary disease are helping us understand how to best manage patients with multiple comorbidities. Finally, the prevalence of vertebral fracture in the older general population and other selected populations has been explored, alongside the global burden of osteoporosis and its consequences. Summary Our understanding of osteoporosis continues to expand, but knowledge gaps remain.

Musculoskeletal disorders are common among older people. Preventive strategies require understanding of age-related changes in strength, function and body composition, including how they interrelate. We have described, and examined associations between, 9-year changes in these parameters among 2917 Health, Aging and Body Composition Study participants (aged 70–79 years). Appendicular lean mass (ALM), whole body fat mass and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. For each characteristic annualised percentage changes were calculated; measures of conditional change (independent of baseline) were derived and their interrelationships were examined using Pearson correlations; proportion of variance at 9-year follow-up explained by baseline level was estimated; and mean trajectories in relation to age were estimated using linear mixed models. Analyses were stratified by sex. Median [lower quartile, upper quartile] annual percentage declines were grip strength (1.5 [0.0, 2.9]), gait speed (2.0 [0.6, 3.7]), ALM (0.7 [0.1, 1.4]), fat mass (0.4 [− 1.1, 1.9]) and hip BMD (0.5 [0.0, 1.1]). Declines were linear for ALM and accelerated over time for other characteristics. Most conditional change measures were positively correlated, most strongly between ALM, fat mass and hip BMD (r > 0.28). Proportion of variation at follow-up explained by baseline was lower for grip strength and gait speed (39–52%) than other characteristics (69–86%). Strength and function declined more rapidly, and were less correlated between baseline and follow-up, than measures of body composition. Therefore, broader intervention strategies to prevent loss of strength and function in later life are required as those targeting body composition alone may be insufficient. Electronic supplementary material The online version of this article (10.1007/s00223-020-00679-2) contains supplementary material, which is available to authorized users.

Background Multimorbidity has been shown in several studies to relate to impaired physical function in later life. Aims To examine if self-report of multimorbidity predicts impaired physical functioning, as assessed by formal physical function testing, in community-dwelling older adults. Methods Non-communicable diseases (NCDs) were self-reported by 443 older community-dwelling UK adults via questionnaire, asking the question: ‘Have you been told by a doctor that you have any of the following conditions?’ Assessments of walking speed, chair stands and balance allowed us to create a composite score (0–12) on which impaired physical functioning was defined as ≤ 9. Results The mean age of participants was 75.5 ± 2.5 years for men and 75.8 ± 2.6 for women. The proportion of individuals with impaired physical functioning was 71.2% in women and 56.9% in men. Having four or more NCDs was associated with an increased risk of poor physical function in men and women (p p p Discussion and conclusion Self-report of 4 or more NCDs was associated with an increased risk of poor physical function, an outcome which has previously been associated with adverse clinical sequelae. This observation may inform development of a simple screening tool to look for poor physical function in older adults.

Objective To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults. Methods Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: Results The analysis included 15 700 patients. Ninety-five percent were Conclusion TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.

Background Lower birth rates and increasing longevity have resulted in ageing populations in European countries. These demographic changes place challenges on pension provision as numbers of those who are economically inactive and retired increase relative to those in paid work. Therefore, governments need workers to postpone retirement and work to older ages. Whilst health and wealth are important in retirement decision-making, considerably less is known about the effects of workplace factors. The aim of this study was to explore the views of recent UK retirees about the role that work-related factors played in their decision to retire. Methods This qualitative study was nested within the Health and Employment After Fifty (HEAF) cohort. People who had retired 3-6 years previously (not for health reasons) were purposively sampled to obtain the views of men and women from a range of socio-economic backgrounds and jobs. Semi-structured interviews were carried out by telephone using a pre-defined topic guide. Interviews were audio-recorded, transcribed and analysed thematically. Results Seventeen interviews were conducted. Thematic analysis showed that retirement decisions were complex and multi-factorial but that work-related factors contributed to decision-making in two main ways. First, some work factors pushed participants towards retirement. These were perceptions that: workplace change had affected the way they were valued or increased pressure on them; work demands, including commuting, had intruded excessively on personal time, effects that were exacerbated by modern technology; work was draining, isolating or under-appreciated; and /or that work was causing physical strain or discomfort relative to their perception of their capacity. In contrast, work factors could also cause participants to pull back towards work, particularly: autonomy; supportive work colleagues; a sense of being appreciated; and perceived job flexibility. Conclusions Recent retirees explained that their decision to retire was multi-factorial but work-related factors contributed importantly. Potentially, employers could: review workers’ perceptions about their work; their capacity in relation to job demands; increase flexibility; and facilitate a supportive work community to encourage longer working lives.

Purpose: the age-related loss of skeletal muscle mass and strength is associated with adverse health outcomes. However, to date, peripheral quantitative computed tomography (pQCT)-derived muscle density has been little studied. We used a well characterised cohort of older adults to identify lifestyle and anthropometric determinants of pQCT-derived muscle density measured 11 years later, and to report relationships between pQCT-derived muscle density with history of falls and prevalent fractures. Methods: a lifestyle questionnaire was administered to 197 men and 178 women, aged 59–70 at baseline. After a median of 11.5 (IQR 10.9, 12.3) years, pQCT (Stratec XCT2000) of the radius and tibia was performed to measure forearm muscle density (FMD) and calf muscle density (CMD). Presence of falls and fractures since the age of 45 were determined through participant recall; vertebral fractures were also ascertained through vertebral fracture assessment using iDXA. Total hip BMD (TH aBMD) was assessed using DXA. Baseline characteristics in relation to muscle density at follow-up were examined using linear regression; associations between muscle density and prior falls and fractures were investigated using logistic regression. All analyses were adjusted for sex and age. Results: mean (SD) age at muscle density measurement was 76.3 (2.6) years. Mean (SD) FMD was 79.9 (3.1) and 77.2 (3.2) among males and females, respectively; CMD was 80.7 (2.6) and 78.5 (2.6) among males and females, respectively. Significant sex-differences in muscle density were observed at each site (p < 0.001). Female sex, lower weight, and lower body mass index were associated (p < 0.05) with both lower FMD and CMD. Additional correlates of lower CMD included older age and shorter stature. Lifestyle measures were not associated with muscle density in this cohort. Lower FMD was related to increased risk of previous fracture (odds ratio (95 % CI) per SD lower FMD: 1.42 (1.07, 1.89), p = 0.015) but not after adjustment for TH aBMD (p > 0.08). No significant relationships were seen between muscle density and falls. Conclusion: female sex, older age, and lower BMI were associated with subsequent lower muscle density in older community-dwelling adults. Lower FMD was related to increased risk of previous fracture. Changes in muscle density over time might precede adverse outcomes such as falls and fractures and may be a long-term predictor of frailty. It could be also suggested that muscle density could be a more clinically meaningful surrogate of functional decline and disability than muscle size or mass, but more studies are needed to support this notion.

Ethnic differences in bone mineral density (BMD) and fracture risk are well-described; the aim of this study was to investigate whether central adiposity or inflammatory status contribute to these ethnic differences in BMD in later life. The Southall and Brent Revisited study (SABRE) is a UK-based tri-ethnic cohort of men and women of European, South Asian or African Caribbean origin. At the most recent SABRE follow-up (2014–2018), in addition to measures of cardiometabolic phenotype, participants had dual-energy X-ray absorptiometry (DXA) bone and body composition scans. Multiple linear regression was used to determine whether markers of body composition, central adiposity or inflammatory status contributed to ethnic differences in BMD. In men and women, age- and height-adjusted BMD at all sites was higher in African Caribbeans compared to Europeans (femoral neck: standardised β (95% confidence interval): men: 1.00SD (0.75, 1.25); women: 0.77SD (0.56, 0.99)). South Asian men had higher BMD than European men at the hip (femoral neck: 0.34SD (95%CI: 0.15, 0.54)). Although adjustment for body mass index (BMI) or lean mass index (LMI) at the lumbar spine reduced the size of the difference in BMD between African Caribbean and European men (age and height adjusted difference: 0.35SD (0.08, 0.62); age and BMI adjusted difference: 0.25SD (−0.02, 0.51)), in both men and women ethnic differences remained after adjustment for measures of central adiposity (estimated visceral adipose tissue mass (VAT mass) and android to gynoid ratio) and inflammation (interleukin-6 (logIL-6) and C-reactive protein (logCRP)). Furthermore, in women, we observed ethnic differences in the relationship between BMI (overall interaction: p = 0.04), LMI (p = 0.04) or VAT mass (p = 0.009) and standardised lumbar spine BMD. In this tri-ethnic cohort, ethnic differences in BMD at the femoral neck, total hip or lumbar spine were not explained by BMI, central adiposity or inflammatory status. Given ethnic differences in fracture incidence, it is important to further investigate why ethnic differences in BMD exist., Highlights • Ethnic differences in BMD in a UK tri-ethnic cohort of men and women exist. • In women associations between adiposity and spine BMD differed across ethnic groups. • Ethnic differences in BMD were not explained by BMI, adiposity or inflammation.

AIM: To investigate the associations between indices of bone health in childhood and corresponding parental measures.METHODS: The Southampton Women's Survey characterised 12,583 non-pregnant women aged 20-34 years; 3158 subsequently had singleton live births. In a subset, dual-energy X-ray absorptiometry (DXA) measurements of bone area (BA), bone mineral content (BMC) and areal bone mineral density (aBMD) lumbar spine and total hip were obtained in the parent/offspring (aged 8-9 years) trios. Another subset of children (aged 6-7 years), and their parents, had peripheral quantitative computed tomography (pQCT; 4% and 38% tibia) measures. Using multivariable linear regression we examined relationships between mother/father and offspring, adjusting for parental age, habitual walking speed and education; offspring age and sex; and the corresponding bone measure in the other parent (β-coefficients (95%CI) unit/unit for each bone measure).RESULTS: Data were available for 260 trios with DXA and 99 with pQCT. There were positive associations for BA, BMC and aBMD between either parent and offspring. Mother-child associations were of greater magnitude than father-child; for example, mother-child aBMD (β = 0.26 g·cm -2/g·cm -2 (0.21,0.32)) and father-child aBMD (β = 0.16 g·cm -2/g·cm -2 (0.11,0.21)), P-difference in β = 0.007. In the subset with pQCT there was a positive association for mother-offspring 4% tibial total area (β = 0.33 mm 2/mm 2 (0.17,0.48)), but little evidence of a father-offspring association (β = -0.06 mm 2/mm 2 (-0.17,0.06)). In contrast offspring 38% cortical density was more strongly associated with this measure in fathers (β = 0.48 mg·cm -3/mg·cm -3 (0.15,0.82)) than mothers (β = 0.27 mg·cm -3/mg·cm -3 (-0.03,0.56)). In general mother-father differences were attenuated by adjustment for height. CONCLUSIONS: Whilst offspring bone measures are independently associated with those of either parent, the magnitude of the association is often greater for maternal than paternal relationships. These findings are consistent with an in utero influence on offspring growth but might also reflect genetic and/or epigenetic parent of origin effects.SUMMARY: In an established parent-offspring cohort, associations between parent and offspring bone indices were generally greater in magnitude for mother-offspring than father-offspring relationships.

Background Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. Methods 115 males and 99 females (aged 72–81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011–2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011–2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. Results Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). Conclusion Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

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

Background The health benefits of physical activity (PA) participation in later life are widely recognised. Understanding factors that can influence the participation of community-dwelling older adults in PA is crucial in an ageing society. This will be paramount in aiding the design of future interventions to effectively promote PA in this population. The main aim of this qualitative study was to explore influences on PA among community-dwelling older people, and the secondary aim was to explore gender differences. Methods Qualitative data were collected in 2014 by conducting focus group discussions using a semi-structured discussion guide with older people resident in Hertfordshire, UK. Discussions were audio-recorded, transcribed verbatim and transcripts analysed thematically. Results Ninety-two participants were recruited to the study (47% women; 74–83 years) and a total of 11 focus groups were conducted. Findings indicated six themes that appeared to affect older adults’ participation in PA: past life experiences; significant life events; getting older; PA environment; psychological/personal factors; and social capital. Overall, the findings emphasised the role of modifiable factors, namely psychological factors (such as self-efficacy, motivation, outcome expectancy) and social factors (such as social support and social engagement). These factors exerted their own influence on physical activity participation, but also appeared to mediate the effect of other largely non-modifiable background and ageing-related factors on participants’ engagement with PA in later life. Conclusion In view of these findings, intervention designers could usefully work with behavioural scientists for insight as to how to enhance psychological and social factors in older adults. Our data suggest that interventions that aim to build self-efficacy, motivation and social networks have the potential to indirectly promote PA participation in older adults. This would be best achieved by developing physical activity interventions through working with participants in an empowering and engaging way.

Despite substantial advances in delineation of the epidemiology, pathophysiology, risk assessment and treatment of osteoporosis over the last three decades, a substantial proportion of men and women at high risk of fracture remain untreated - the so-called "treatment gap". This review summarises the important patient-, physician- and policyrelated causes of this treatment gap, before discussing in greater detail: (a) the evidence base for the efficacy of bisphosphonates in osteoporosis; (b) recent evidence relating to the adverse effects of this widely used therapeutic class, most notably atypical femoral fracture and osteonecrosis of the jaw; (c) available strategies to improve both secondary and primary prevention pathways for the management of this disorder.

Purpose Social isolation has been associated with both physical and psychological adverse outcomes and is prevalent in older adults. We investigated the impact of social isolation on bone mineral density (BMD) and physical capability in community-dwelling older adults. Methods Data were collected in 2011 and 2017 from the Hertfordshire Cohort Study. In 2011, we assessed social isolation using the six-item Lubben Social Network Scale (LSNS-6) and the Maastricht Social Participation Profile (MSSP) and depressive and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Physical capability was assessed by performing tests of gait speed, chair stands, timed up and go and balance at both time points. BMD was assessed using dual X-ray absorptiometry (DXA) at both time points. Results Data were available from 369 participants in 2011 and 184 in 2017. Forty percent of men and 42.4% of women were socially isolated. Isolated participants had higher odds of depressive disorder (OR 3.01, 95% CI 1.27–7.11, p p Conclusions Social isolation was associated with higher odds of having depressive symptoms and predicted the development of poor physical capability 6 years later. Further longitudinal studies that include loneliness as a covariate are warranted.

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

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70–79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2–3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10–14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p

BackgroundFrailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease.AimsWe investigated, in the UK Biobank, whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19.Methods502,640 participants aged 40–69 years at baseline (54–79 years at COVID-19 testing) were recruited across UK during 2006–10. A modified assessment of frailty using Fried’s classification was generated from baseline data. COVID-19 test results (England) were available for 16/03/2020–01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, after adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups.Results4510 participants were tested for COVID-19 (positive = 1326, negative = 3184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR = 1.4 [95%CI = 1.1, 1.8]), report slow walking speed (OR = 1.3 [1.1, 1.6]), report two or more falls in the past year (OR = 1.3 [1.0, 1.5]) and be multimorbid (≥ 4 comorbidity groupings vs 0–1: OR = 1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. However, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants.Discussion and conclusionsFrailty and multimorbidity do not appear to aid risk stratification, in terms of positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

The purpose of this study is to examine correlates of self-perceived fracture risk (SPR) and relationships between SPR and subsequent bone density and microarchitecture in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. 3912 women completed baseline questionnaires detailing medical history and SPR; 492 underwent HRpQCT scans of the radius and tibia and DXA scans of total body, hip, femoral neck and lumbar spine a median of 7.5 years later. Correlates of SPR were examined and a cluster analysis of potential predictors of SPR performed. SPR in relation to HRpQCT and aBMD parameters was examined using linear regression with and without adjustment for anthropometric, demographic and lifestyle covariates. Mean (SD) baseline age was 69.0 (9.0) years; 56.6% reported a similar SPR; 28.6% lower SPR; 14.9% higher SPR compared to women of similar age. In mutually-adjusted analysis, higher SPR was associated (p

Background Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance. Methods The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment. Results Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p Conclusions We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator.

Summary: Using data from the Hertfordshire cohort study, this study examined the effect of breastfeeding and bottle feeding on adult lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD). The type of infant milk feeding was significantly associated with lumbar spine BMD in males. Introduction: Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD. Methods: Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score. Results: Infant milk feeding was significantly associated with lumbar spine BMD (b = − 0.028; 95% CI, − 0.055; − 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females. Conclusions: Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females.

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

Among 365 Hertfordshire Cohort Study participants (aged 59–71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1β, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p

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.

The epidemiology and pathogenesis of fractures in postmenopausal women has previously been investigated in the Global Longitudinal study of Osteoporosis in Women (GLOW). To date, however, relationships between bone imaging outcomes and fracture have not been studied in this cohort. We examined relationships between high-resolution peripheral quantitative computed tomography (HRpQCT) parameters and fracture in the UK arm of GLOW, performing a cluster analysis to assess if our findings were similar to observations reported from older participants of the Hertfordshire Cohort Study (HCS), and extended the analysis to include tibial measurements. We recorded fracture events and performed HRpQCT of the distal radius and tibia and dual-energy X-ray absorptiometry (DXA) of the hip in 321 women, mean age 70.6 (SD 5.4) years, identifying four clusters at each site. We saw differing relationships at the radius and tibia. Two radial clusters (3 and 4) had a significantly lower hip areal bone mineral density (p < 0.001) compared to Cluster 1; only individuals in Cluster 4 had a significantly higher risk of fracture (p = 0.005). At the tibia, clusters 1, 3 and 4 had lower hip areal bone mineral density (p < 0.001) compared to Cluster 2; individuals in Cluster 3 had a significantly higher risk of fracture (p = 0.009). In GLOW our findings at the radius were very similar to those previously reported in the HCS, suggesting that combining variables derived from HRpQCT may give useful information regarding fracture risk in populations where this modality is available. Further data relating to tibial HRpQCT-phenotype and fractures are provided in this paper, and would benefit from validation in other studies. Differences observed may reflect age differences in the two cohorts.

Objective: to investigate the barriers that prevent or delay people seeking a sexually transmitted infection (STI) test.Methods: qualitative in-depth interviews were conducted with 24 university students, who are a group prone to behaviours putting them at risk of STIs, to understand the factors that had prevented or delayed them from going for an STI test in the past. Resulting data were thematically analysed employing a qualitative content analysis method, and a final set of themes identified.Results: there were three main types of barrier to STI testing. These were: personal (underestimating risk, perceiving STIs as not serious, fear of invasive procedure, self-consciousness in genital examination and being too busy); structural (financial cost of test and clinician attributes and attitude); and social (concern of being stigmatised).Conclusions and implications for public health: these data will help health providers and policy-makers provide services that minimise barriers and develop effective strategies for improving STI testing rates. The results of this study suggest a holistic approach to encouraging testing is required, which includes addressing personal beliefs, working with healthcare providers to minimise structural barriers and developing initiatives to change social views about STIs.

Sleep duration may be associated with risk of osteoporosis, with suggestions that too little or indeed too much sleep may be detrimental to bone health. In this study, we considered whether perceived sleep quality is also associated with bone health in older adults. We explored this association in a cohort of 443 older community-dwelling UK adults. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); poor sleep quality was defined as > 5 on this score system. Bone density, shape and microarchitecture were assessed using dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HRpQCT). Thirty-seven percent of men and 43% of women had a PSQI score greater than 5, indicative of poor perceived sleep. We found that quality of sleep was associated with altered bone microarchitecture. In men, poor sleep quality was associated with lower radial trabecular (4% slice, p p = 0.02) bone mineral density, as well as decreased tibial cortical density (p p p p p p p p

We investigated the relationship between lower limb osteoarthritis (OA) and muscle strength and power (assessed by jumping mechanography) in UK community-dwelling older adults. We recruited 249 older adults (144 males, 105 females). OA was assessed clinically at the knee according to ACR criteria and radiographically, at the knee and hip, using Kellgren and Lawrence grading. Two-footed jumping tests were performed using a Leonardo Mechanography Ground Reaction Force Platform to assess maximum muscle force, power and Esslinger Fitness Index. Linear regression was used to assess the relationship between OA and jumping outcomes. Results are presented as β (95% confidence interval). The mean age of participants was 75.2 years (SD 2.6). Males had a significantly higher maximum relative power during lift off (mean 25.7 W/kg vs. 19.9 W/kg) and maximum total force during lift off (mean 21.0 N/kg vs. 19.1 N/kg) than females. In adjusted models, we found significant associations in males between clinical knee OA and maximum relative power [− 6.00 (CI − 9.10, − 2.94)] and Esslinger Fitness Index [− 19.3 (− 29.0, − 9.7)]. In females, radiographic knee OA was associated with total maximum power [− 2.0 (− 3.9, − 0.1)] and Esslinger Fitness Index [− 8.2 (− 15.9, − 0.4)]. No significant associations were observed for maximum total force. We observed significant negative associations between maximum relative power and Esslinger Fitness Index and clinical knee OA in males and radiographic knee OA in females. We have used novel methodology to demonstrate relationships between muscle function and OA in older adults.

Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of the antenatal and early-life environment affect predisposition to diabetes in later life., This mendelian randomization study examines the association of birth weight with type 2 diabetes and glycemic traits., Importance Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures Type 2 diabetes and glycemic traits. Results This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10−5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

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.

Background: Previous intergenerational (parent to child) and transgenerational (grandparent to grandchild) studies have shown there is a link between parental and offspring birthweight. Objectives: The aim was to explore the association between the early-life weight gain of an individual and the adult height of their children and grandchildren. Methods: Study participants across three generations of the Hertfordshire Cohort Study (HCS) were included in this study. Health visitors recorded the birthweight (kg) and weight at 1 year (kg) of the original (F0 generation) HCS participants when they were born in Hertfordshire between 1931 and 1939. A conditional infant weight gain score for F0 participants was calculated using birthweight and weight at 1 year, and self-reported height (cm) of their children (F1 generation) and their grandchildren (F2 generation) was obtained from postal questionnaires. Due to the lack of clustering within family lines, linear regression analysis was used to compare intergenerational relationships. Results: Data were available from 139 F0, 148 F1, and 198 F2 participants. A positive association was found between parental birthweight (F0) and offspring adult height; on average, a 1 kg increase in F0 birthweight was associated with a 2.04 cm increase in F1 adult height (beta 2.04, 95% confidence interval [CI] −0.03, 4.10). A positive association was found between F0 conditional weight gain during the first year of life and offspring (beta 1.53, 95% CI 0.45, 2.62) and grandchild height (beta 1.06, 95% CI 0.03, 2.10). Positive associations were also found between F0 weight at 1 year and offspring (beta 1.83, 95% CI 0.79, 2.87) and grandchild height (beta 0.91, 95% CI −0.10, 1.91). Conclusion: This study demonstrates an association between grandparental weight gain in early life and the heights of their children and grandchildren. The results of these analyses highlight the importance of early-life weight gain on the adult stature of subsequent offspring.

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.

The co-existence of impaired bone health (osteopenia/osteoporosis), reduced muscle mass and strength (sarcopenia), and increased adiposity (obesity) in middle-aged and older people has been identified in recent studies, leading to a proposal for the existence of "osteosarcopenic obesity" as a distinct entity. Evidence for the pathophysiological overlap of these conditions is mounting, although a causal relationship is yet to be established. Each component condition occurs frequently with increasing age, and with shared risk factors in many instances, thus, an overlap of these three conditions is not surprising. However, whether the concurrent existence of sarcopenia, osteoporosis and obesity leads to an increased risk of adverse musculoskeletal outcomes and mortality above and beyond the risks associated with the sum of the component parts remains to be proven and is a question of research interest. In this article, we review evidence for the existence of osteosarcopenic obesity including the current operational definition of osteosarcopenic obesity, prevalence, pathophysiology, outcomes and exploratory approaches to the management of components. We conclude that, there is insufficient evidence to support a discrete clinical entity of osteosarcopenic obesity at this time. To expand knowledge and understanding in this area, there is a need for consensus on a definition of osteosarcopenic obesity which will allow for identification, further epidemiological studies and comparisons between studies. Additionally, studies should assess whether the clinical outcomes associated with osteosarcopenic obesity are worse than the mere addition of those linked with its components. This will help to determine whether defining a person as having this triad will eventually result in a more effective treatment than addressing each of the three conditions separately.

Background: Radiofrequency Echographic Multi Spectrometry (REMS) is a non-ionizing technology for the densitometric assessment of osteoporosis. It has already been validated in Italian women with respect to the current clinical reference technology, Dual-energy X-ray Absorptiometry (DXA). Purpose: Aim of the current study was to assess the diagnostic accuracy of REMS technology with respect to DXA in a wider European clinical context. Methods: A total of 4307 female Caucasian patients aged between 30 and 90 years underwent DXA and REMS scans at femoral neck and/or lumbar spine (the site depending on the medical prescription). The acquired data underwent a rigorous quality check in order to exclude the erroneous DXA and REMS reports. The diagnostic agreement between the two technologies was assessed, also stratifying for patients' age groups. The ability to recognise previously fractured patients was also investigated. Results: Overall, 4245 lumbar spine scans and 4271 femoral neck scans were performed. The ability to discriminate patients with and without osteoporosis by femoral neck investigation resulted in sensitivity and specificity of 90.4% and 95.5%, respectively. For lumbar spine scans, a sensitivity of 90.9% and a specificity of 95.1% were obtained. The areas under the curve (AUCs) of the Receiver Operating Characteristic (ROC) curve evaluating the ability to discriminate groups of patients with previous osteoporotic fracture using DXA and REMS T-score values were 0.631 and 0.683 (p < 0.0001), respectively, for femoral neck scans, whereas 0.603 and 0.640 (p = 0.0002), respectively, for lumbar spine scans. Conclusion: The diagnostic effectiveness of REMS technology at reference anatomical sites for the assessment of osteoporosis has been confirmed in a large series of female patients, spanning from younger and pre-menopausal to elderly women up to 90 years, in a multicenter European clinical context.

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVD). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, setting and participants: A pooled analysis of individual-participant-data from the Emerging Risk Factors Collaboration (ERFC; 162,036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and UK Biobank (UKB; 401,219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposure: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Centre for Epidemiological Studies Depression scale (CES-D; range 0-60; ≥16 indicates possible depressive disorder). UKB recorded the Patient Health Questionnaire-2 (PHQ-2; range 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal/nonfatal coronary heart disease (CHD), stroke and CVD (composite of CHD and stroke). Hazard ratios (HRs) per 1-SD higher log-CES-D or PHQ-2 adjusted for age, sex, smoking and diabetes were reported. Results: Among 162,036 participants from the ERFC, 73% were female, mean (SD) age at baseline was 63 (9) years, and 5,078 CHD and 3,932 stroke events were recorded (median follow-up, 9.5-years). Associations with CHD, stroke and CVD were log-linear. HRs (95%CI) per 1SD higher depression score for CHD, stroke and CVD respectively were 1.07 (1.03-1.11), 1.05 (1.01-1.10), and 1.06 (1.04-1.08). This reflects, 36 versus 29 CHD events, 28 versus 25 stroke events, and 63 versus 54 CVD events per 1000 individuals over 10 years in the highest versus lowest quintile of CES-D (geometric mean CES-D score, 19 versus 1). Among 401,219 participants from the UKB, 55% were female, mean baseline age was 56 (8) years, and 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1-years). HRs per 1SD higher depression score for CHD, stroke and CVD respectively were 1.11 (1.08-1.14), 1.10 (1.06-1.14) and 1.10 (1.08-1.13). This reflects, 21 versus 14 CHD events, 15 versus 10 stroke events, and 36 versus 25 CVD events per 1000 individuals over 10 years in those with PHQ2 ≥4 versus 0. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563,255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels below the threshold indicative of a depressive disorder. However, the magnitude of associations was modest., Lisa Pennells, Stephen Kaptoge and Sarah Spackman are funded by a British Heart Foundation Programme Grant (RG/18/13/33946). Steven Bell was funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Tom Bolton is funded by the National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Angela Wood is supported by a BHF-Turing Cardiovascular Data Science Award and by the EC-Innovative Medicines Initiative (BigData@Heart). John Danesh holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award.* *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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.

To determine feasibility of TNF inhibitor (TNFi) dose reduction for severe AS and PsA patients.A retrospective study in a real-world setting. Criteria for dose reduction of TNFi included BASDAI4 for ⩾6 months in AS; or DAS28-ESR ⩽ 3.2 for ⩾6 months in PsA. TNFi dose was reduced by one-third. Patients who flared (BASDAI4 in AS or DAS28-ESR3.2 in PsA) were re-escalated to standard treatment dose.Twenty-six per cent (33/125) of AS and 18% (15/83) of PsA patients fulfilled criteria and underwent TNFi dose reduction. Fifty-eight per cent (19/33) of AS and 60% (9/15) of PsA patients maintained TNFi dose reduction for mean (s.d) of 1.0 (0.8) years. Reinstating standard dose of TNFi recaptured low disease activity in all patients who failed dose reduction within 24 weeks, with no statistically significant difference in mean BASDAI compared with those maintaining TNFi dose reduction in AS at 24 weeks [mean (s.d) BASDAI 2.4 (1.1) vs 1.9 (1.5), respectively (P = 0.229)]; however in PsA, those who failed dose reduction had higher disease activity compared with patients maintained on TNFi dose reduction at 24 weeks [mean (s.d) DAS28-ESR 2.7 (0.6) vs 1.3 (0.5), respectively (P ⩽ 0.001)]. In PsA, a lower DAS28-ESR prior to dose reduction of TNFi was associated with more successful dose reduction.In a real-world setting, 60% of individuals with severe AS and PsA who achieve low disease activity can successfully reduce the dose of TNFi therapy by a third for a mean of 1 year.

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.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.

ObjectiveTo perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low MethodsA retrospective study of 1090 women aged ?40 and ?90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed.ResultsWhen analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4–7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4–20.2]; and among the 164 defined as high risk, 15.9% [10.6–24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group.ConclusionsOur findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.

Sarcopenia and muscle weakness are responsible for considerable health care expenditure but little is known about these costs in the UK. To address this, we estimated the excess economic burden for individuals with muscle weakness regarding the provision of health and social care among 442 men and women (aged 71–80 years) who participated in the Hertfordshire Cohort Study (UK). Muscle weakness, characterised by low grip strength, was defined according to the Foundation for the National Institutes of Health criteria (men

Untreated sexually transmitted infections (STIs) can lead to serious health complications and may be transmitted to uninfected individuals. Therefore, the early detection and subsequent management of STIs is crucial to control efforts. Time to presentation for STI symptoms and risk of transmission in this period has not been assessed in New Zealand to date.All new clients presenting to an urban sexual health clinic (SHC) were invited to complete a questionnaire, which included demographic information, sexual health history, and details about the clinic visit.Of 331 people approached, 243 (73.4%) agreed to complete the questionnaire. Four incomplete questionnaires were excluded, leaving 239 participants (47.3% female and 52.7% male, 43.8% under the age of 25). The most common reason for seeking healthcare was experiencing symptoms (39.4%) and 41.7% of people with symptoms waited more than seven days to seek healthcare. Around a third (30.6%) of people with symptoms had sex after they first thought they may need to seek healthcare. Infrequent condom use was reported more often by people who had sex with existing partners (84.6%) than by people who had sex with new partners (10.0%).This is the first study to quantify healthcare-seeking behaviour for STI in New Zealand. Delayed healthcare-seeking (defined as waiting more than seven days) was common and almost a third of people reported engaging in sex while symptomatic. Enabling prompt healthcare-seeking is crucial to minimise transmission risk. Structural barriers such as the financial cost of STI tests must be removed and education around symptom recognition and healthcare system navigation should be provided.

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.

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts.