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Background Osteoarthritis is the most prevalent type of arthritis. Many approaches exist for characterising radiographic knee OA, including machine learning (ML). Aims To examine Kellgren and Lawrence (K&L) scores from ML and expert observation, minimum joint space and osteophyte in relation to pain and function. Methods Participants from the Hertfordshire Cohort Study, comprising individuals born in Hertfordshire from 1931 to 1939, were analysed. Radiographs were assessed by clinicians and ML (convolutional neural networks) for K&L scoring. Medial minimum joint space and osteophyte area were ascertained using the knee OA computer-aided diagnosis (KOACAD) program. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was administered. Receiver operating characteristic analysis was implemented for minimum joint space, osteophyte, and observer- and ML-derived K&L scores in relation to pain (WOMAC pain score > 0) and impaired function (WOMAC function score > 0). Results 359 participants (aged 71–80) were analysed. Among both sexes, discriminative capacity regarding pain and function was fairly high for observer-derived K&L scores [area under curve (AUC): 0.65 (95% CI 0.57, 0.72) to 0.70 (0.63, 0.77)]; results were similar among women for ML-derived K&L scores. Discriminative capacity was moderate among men for minimum joint space in relation to pain [0.60 (0.51, 0.67)] and function [0.62 (0.54, 0.69)]. AUC Discussion Observer-derived K&L scores had higher discriminative capacity regarding pain and function compared to minimum joint space and osteophyte. Among women, discriminative capacity was similar for observer- and ML-derived K&L scores. Conclusion ML as an adjunct to expert observation for K&L scoring may be beneficial due to the efficiency and objectivity of ML.

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.

Sarcopenia and osteoporosis are associated with morbidity and mortality. The development and progression of these two interrelated conditions are related to genetic and lifestyle factors, including nutrition and physical activity. Restrictions placed on individuals due to the COVID-19 pandemic and infection have led to widespread lifestyle modifications, with data suggesting a negative impact on physical activity levels. There is an urgent need to understand the effect of the pandemic on musculoskeletal health in older adults, at a time when COVID-19 infection and restrictions remain a barrier to research studies. We tested the feasibility of recruiting local community-dwelling older people to establish a new cohort investigating musculoskeletal health—the Southampton Longitudinal Study of Ageing (SaLSA). We invited 1993 community-dwelling older adults registered at the Living Well GP partnership in Southampton, UK, to participate in a study. Questionnaires were completed by participants on health, lifestyle, medication use, comorbidities, physical activity, nutrition, sarcopenia, osteoporosis, and quality of life. Permission was sought for future contact. Descriptive statistics were used on the initial pilot of 175 returned questionnaire data. The median age of participants was 80.4 years in both sexes, 81.3 years (77.9–84) in females, and 81.1 years in males (77.3–83.6). The majority (N = 168/171, 98%) of participants were of white Caucasian background; 36/53 (68%) female participants and 38/119 (32%) male participants lived alone. Over 80% (295/353) consented to be contacted for future studies. Recruitment of participants from a primary care practice into a research study was feasible. The next steps are to perform detailed musculoskeletal phenotyping through physical performance measures, grip strength dynamometry, DXA scanning, high-resolution peripheral quantitative computed tomography (HRpQCT), thigh ultrasound, and muscle biopsy, in a subset of participants. Our vision for SaLSA is to build a platform for discovery science and mechanistic studies, with the goal of improving the health care of older people.

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.

Women make up a growing proportion of the workforce and therefore many women experience menopause while in paid employment. We explored the prevalence of menopausal symptoms, the relationship between symptoms and coping with work and the risk factors associated with struggling at work during the menopause. The Health and Employment After Fifty (HEAF) community-based cohort of people aged 50–64 years was incepted 2013–2014 to study health and work. In 2019, female participants were asked to complete a questionnaire about their menopausal symptoms, and effect of those symptoms on their ability to cope at work. 409 women were eligible for inclusion. The commonest symptoms were vasomotor (91.7%); trouble sleeping (68.2%); psychological (63.6%) and urinary (49.1%). The prevalence of reporting symptoms was similar no matter which type of occupation women were performing at the time. Around one-third of women reported moderate/severe difficulties coping at work because of menopausal symptoms. Risk factors for difficulties coping at work included: financial deprivation, poorer self-rated health, depression, and adverse psychosocial occupational factors but not physical demands. More awareness is needed amongst employers in all sectors but women with financial difficulties and those with jobs in which they feel insecure, unappreciated, or dissatisfied are at greatest risk.

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

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/., Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

Introduction: Osteoporotic fracture is a major public health burden worldwide, causing significant mortality and morbidity. Studies that have reported bone health in areas of high endemic fluorosis have commonly reported adverse skeletal, as well as dental effects. Vanuatu, sited in the Pacific, and never previously studied with regard to bone health, has six continuous degassing volcanoes on separate islands, resulting in a natural experiment for an ecological study of relationships between naturally occurring fluoride exposure and fracture incidence in paediatric populations. Methods: This ecological study recruited 1026 lifetime residents of the rural Vanuatu islands. A short questionnaire was administered detailing gender, age, and residential history. Participants were asked if they had broken a bone and, if so, were asked to mark its location on a questionnaire manikin. Dental fluorosis was assessed using Dean’s index. Community drinking-water samples were sampled for fluoride concentration. Results: The measured water fluoride concentration and recorded dental fluorosis displayed expected gradients from Aneityum (low) to Ambrym (high) (p &lt, 0.001). The age of participants studied varied from 7.8 (SD 1.2) in Aneityum to 10.6 (3.7) in Lamap/Uliveo. The highest self-reported fracture rates were recorded in the area with medium fluoride levels (Lamap/Uliveo), where 14.9% of boys and 15.6% of girls sampled reported a fracture. In Ambrym, where the mean age of participants was similar, corresponding fracture rates were 4.5% and 2.6%. (p value for differences all &lt, 0.05). Conclusions: Reports of fractures were common in children living in Vanuatu, but demonstrably higher in Lamap, the region with medium fluoride concentrations, rather than Ambrym which had very high rates of naturally occurring fluoride levels. Longer term studies that report validated fracture after peak bone mass acquisition are required.

Large variations in fluoride concentrations exist in natural waters, many of which are the source of community drinking-water supplies. Determining fluoride concentrations in community drinking waters can be challenging in developing Pacific countries such as Vanuatu that have limited laboratory capacity. Knowledge of naturally elevated fluoride concentrations that cause irreversible, adverse health outcomes may allow communities the opportunity to treat and manage their drinking-water supplies. Community drinking-water samples (n = 69), sourced from groundwaters, roof catchment rainwaters, surface waters and springs, were sampled on Tanna Island, Vanuatu between 2017 and 2020. In an 18 km2 area of Western Tanna, a set of 30 groundwater-based drinking-water samples had a median fluoride concentration of 3.3 mg/L, with 20 samples >1.5 mg/L and seven samples >4.0 mg/L. These concentrations increase the risk of dental and skeletal fluorosis, respectively. Repeat resampling at five sites showed little variation over the sampling period. Rainwater-fed drinking-water supplies were lower overall and highly variable in fluoride concentrations (

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.

BackgroundTraditional analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) images results in a multitude of cortical and trabecular parameters which would be potentially cumbersome to interpret for clinicians compared to user-friendly tools utilising clinical parameters. A computer vision approach (by which the entire scan is ‘read’ by a computer algorithm) to ascertain fracture risk, would be far simpler. We therefore investigated whether a computer vision and machine learning technique could improve upon selected clinical parameters in assessing fracture risk.MethodsParticipants of the Hertfordshire Cohort Study (HCS) attended research visits at which height and weight were measured; fracture history was determined via self-report and vertebral fracture assessment. Bone microarchitecture was assessed via HR-pQCT scans of the non-dominant distal tibia (Scanco XtremeCT), and bone mineral density measurement and lateral vertebral assessment were performed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Images were cropped, pre-processed and texture analysis was performed using a three-dimensional local binary pattern method. These image data, together with age, sex, height, weight, BMI, dietary calcium and femoral neck BMD, were used in a random-forest classification algorithm. Receiver operating characteristic (ROC) analysis was used to compare fracture risk identification methods.ResultsOverall, 180 males and 165 females were included in this study with a mean age of approximately 76 years and 97 (28 %) participants had sustained a previous fracture. Using clinical risk factors alone resulted in an area under the curve (AUC) of 0.70 (95 % CI: 0.56–0.84), which improved to 0.71 (0.57–0.85) with the addition of DXA-measured BMD. The addition of HR-pQCT image data to the machine learning classifier with clinical risk factors and DXA-measured BMD as inputs led to an improved AUC of 0.90 (0.83–0.96) with a sensitivity of 0.83 and specificity of 0.74.ConclusionThese results suggest that using a three-dimensional computer vision method to HR-pQCT scanning may enhance the identification of those at risk of fracture beyond that afforded by clinical risk factors and DXA-measured BMD. This approach has the potential to make the information offered by HR-pQCT more accessible (and therefore) applicable to healthcare professionals in the clinic if the technology becomes more widely available.

Objective: Childhood and adolescence are critical periods of bone development. Sporting activity is thought to impact peak bone mass acquisition, but most studies have used dual-energy X-ray absorptiometry (DXA) to assess bone health and reported associations between bone mass and elite sporting activity. The objective of this study was instead to assess the relationship between recreational sporting activity (RSA) and another bone assessment, calcaneal quantitative ultrasound (cQUS), in adolescents and young adults.Methods: We related recreational sporting activity, assessed through a lifestyle questionnaire, to heel ultrasound bone parameters in a cohort of New Zealand students aged 16-35 years. Complete datasets with data on all relevant confounders (body mass index (BMI), pubertal timing, smoking status, and alcohol consumption) were available for 452 participants. cQUS was performed using a Lunar Achilles EX II machine to obtain bone parameters, broadband ultrasound attenuation (BUA), and speed of sound (SOS); stiffness index (SI) was derived from these measures. All descriptive statistics and statistical analyses were carried out using SPSS Statistics for Macintosh, Version 23.0 (IBM Corp., Armonk, NY, USA). Results are presented as p-values and 95% CI.Results: Reported lifetime sport participation declined after an individual's mid-teens. Bone cQUS parameters (SI and BUA and T-score) were all positively associated with BMI, and current physical activity (SI, SOS, BUA, T-score, and Z-score) with SI and SOS measures most strongly associated with current high impact and past recreational sporting activity (all p

Biomineralization is the process by which organisms produce mineralized tissues. This crucial process makes possible the rigidity and flexibility that the skeleton needs for ambulation and protection of vital organs, and the hardness that teeth require to tear and grind food. The skeleton also serves as a source of mineral in times of short supply, and the intestines absorb and the kidneys reclaim or excrete minerals as needed. This Review focuses on physiological and pathological aspects of the hormonal regulation of biomineralization. We discuss the roles of calcium and inorganic phosphate, dietary intake of minerals and the delicate balance between activators and inhibitors of mineralization. We also highlight the importance of tight regulation of serum concentrations of calcium and phosphate, and the major regulators of biomineralization: parathyroid hormone (PTH), the vitamin D system, vitamin K, fibroblast growth factor 23 (FGF23) and phosphatase enzymes. Finally, we summarize how developmental stresses in the fetus and neonate, and in the mother during pregnancy and lactation, invoke alternative hormonal regulatory pathways to control mineral delivery, skeletal metabolism and biomineralization.

Introduction Frailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease. We therefore investigated whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19 in the UK Biobank. Method 502,640 participants aged 40–69 years at baseline (54–79 years at COVID-19 testing) were recruited across UK 2006–10. A modified assessment of frailty using Fried’s classification was generated from baseline data. COVID-19 test results (England) were available 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, adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups. Results 4,510 participants were tested for COVID-19 (positive = 1,326, negative = 3,184). 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. Furthermore, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants. Conclusions Frailty and multimorbidity do not appear to aid risk stratification, in terms of a 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.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-021-01817-y.

Summary: Low body mass index (BMI) is an established risk factor for fractures in postmenopausal women but the interaction of obesity with bone microarchitecture is not fully understood. In this study, obesity was associated with more favourable bone microarchitecture parameters but not after parameters were normalised for body weight. Introduction: To examine bone microarchitecture in relation to fat mass and examine both areal bone mineral density (aBMD) and microarchitecture in relation to BMI categories in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. Methods: Four hundred and ninety-one women completed questionnaires detailing medical history; underwent anthropometric assessment; high-resolution peripheral quantitative computed tomography (HRpQCT) scans of the radius and tibia and DXA scans of whole body, proximal femur and lumbar spine. Fat mass index (FMI) residuals (independent of lean mass index) were derived. Linear regression was used to examine HRpQCT and DXA aBMD parameters according to BMI category (unadjusted) and HRpQCT parameters in relation to FMI residuals (with and without adjustment for anthropometric, demographic and lifestyle covariates). Results: Mean (SD) age was 70.9 (5.4) years; 35.0% were overweight, 14.5% class 1 obese and 7.7% class 2/3 obese. There were significant increasing trends according to BMI category in aBMD of whole body, hip, femoral neck and lumbar spine (p ≤ 0.001); cortical area (p < 0.001), thickness (p < 0.001) and volumetric density (p < 0.03), and trabecular number (p < 0.001), volumetric density (p < 0.04) and separation (p < 0.001 for decreasing trend) at the radius and tibia. When normalised for body weight, all HRpQCT and DXA aBMD parameters decreased as BMI increased (p < 0.001). FMI residuals were associated with bone size and trabecular architecture at the radius and tibia, and tibial cortical microarchitecture. Conclusion: Significant trends in HRpQCT parameters suggested favourable bone microarchitecture at the radius and tibia with increasing BMI but these were not proportionate to increased weight.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital., SCOPUS: re.j, info:eu-repo/semantics/published

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

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.

IntroductionSeveral studies have reported the importance of vitamin D status to musculoskeletal health in populations of older adults. Here we report relationships between circulating serum 25(OH)D and musculoskeletal health in a community cohort of UK adults in midlife and investigate whether environmental (dietary intake, use of supplements) and/or genetic factors (4 SNPs previously related to vitamin D status) play more significant roles in determining vitamin D status in this population.MethodsParticipants were recruited from the Hertfordshire Cohort Study, an established longitudinal cohort study of community dwelling adults and were seen at baseline and follow up 9–12 years later. Lumbar spine and total femur BMD were measured at baseline using a Hologic QDR 4500 instrument. Osteoarthritis (OA) was defined by radiographs of the knees graded according to Kellgren & Lawrence at both time points. Serum 25(OH)D concentrations were measured using a DiaSorin Liaison chemiluminescent assay. Genotyping of 4 SNPs previously associated with 25(OH)D values were assessed: (rs12785878 (DHCR7), rs10741657 (CYP2R1) and rs6013897 (CYP24A1)) and a fourth SNP (rs4588), described as “a near-perfect proxy (i.e. substitute) for rs2282679 on the GC gene”.Results820 subjects (397 men, 423 women) participated at baseline, and 339 of these 820 subjects (164 men; 175 women) participated in a follow up study of OA progression. The median (IQR) age of participants at baseline was 64.0 (61.8–66.5) and 65.5 (63.3–67.6) for men and women respectively. Median circulating levels of 25(OH)D were 44.6 (35.0–63.0) nmol/L and 41.3 (29.8–53.5) nmol/L in men and women respectively. Circulating 25(OH)D was strongly associated with season of blood testing (p ConclusionCirculating 25(OH)D levels were generally lower than is recommended in community dwelling adults in midlife, with marked seasonal variation observed, but relationships with reported vitamin D supplementation were weaker. Circulating 25(OH)D was directly associated with hip BMD in men but relationships with BMD in women and radiographic OA were not seen in this sample.

Background The COVID-19 pandemic has led to dramatic changes in people’s lives globally. Older adults have been especially vulnerable to adverse effects from the 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 aim of this qualitative study was to explore how community-living older people in the UK experienced the first wave of the COVID-19 pandemic and how it impacted their health and well-being, and associated behaviours. 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 Twelve participants were included in the study (7 men and 5 women). Data from a total of 35 qualitative interviews were used, comprising two or three timepoints per participant. Preliminary 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. Initial findings highlight challenges associated with accessing shops, healthcare, and usual activities due to restrictions. Findings emphasize the issue of loneliness and isolation for some of the participants, especially those living alone, as well as fear of the virus, with restrictions leading to a loss of purpose for some, along with related effects on mental health (e.g. worry, anxiety). For some, these issues appeared to link to a reprioritisation of their behaviours (for example, exercise and diet were deprioritised). Coping strategies used by participants included finding ways to keep busy and to do physical activity safely, maintaining social contact online or by telephone, and having an optimistic or positive outlook, a ‘do what you can’ attitude. Conclusion Analysis is ongoing and will further aim to explore how older people’s experiences and behaviours might have changed over the duration of the pandemic. The findings from this study could improve understanding of how community-living older adults could be supported to be more resilient in the face of a variety of changing circumstances that might impact their health and well-being.

Background Covid-19, a coronavirus that originated in China in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020. The aim of this study was to usean existing cohort of community-dwelling older adults, the Hertfordshire Cohort Study (HCS), to understand how wave one of the Covid-19 pandemic impacted UK older adults, a group particularly vulnerable to severe disease. Methods 71 eligible participants, 39 males and 32 females (drawn from the HCS study, mean age 83.6 (2.5) 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 of July to October 2020. Results Over a third (37.1%) of respondents lived alone. Of the remainder, 86.4% lived with a spouse while the remaining 13.6% lived with family. Of concern, 19.7% of participants had felt they needed to go out despite not wanting to; 47.1% had heard of the NHS Volunteer Responders programme, although only 3 (4.2%) had made use of this or other support services. Almost a third (31%) of participants reported they had access to a smartphone, while 62% reported having unlimited internet access, usually using a tablet or computer. Over two thirds (69.0%) of participants rated their understanding of Covid-19 itself as good. Perhaps unsurprisingly, a large majority (88.7%) of participants said their life was different compared to before Covid-19; 80.3% had less social contact and more than half (52%) of respondents reported being less physically active than before the pandemic (and only 4% more so). However, levels of sleep, alcohol consumption and diet were reportedly generally unchanged over the timeframe surveyed. Conclusion We have reported the experience of the first wave of the Covid-19 pandemic among participants of an older Caucasian community-dwelling UK cohort, highlighting the need to consider this group when developing public health interventions to support health and wellbeing, including those employing smartphone technology. Further larger studies in groups of wider socioeconomic status and more diverse racial background are indicated.