Appraisal of quality and analysis of the similarities and differences between osteoarthritis Clinical Practice Guideline recommendations: A systematic review.

OBJECTIVE: Clinical Practice Guidelines (CPGs) aim to support management of hip and knee osteoarthritis (OA), but recommendations are often conflicting and implementation is poor, contributing to evidence-to-practice gaps. This systematic review investigated the contextual and methodological factors contributing to conflicting recommendations for hip and knee OA. METHOD: Our systematic review appraised CPGs for managing hip and knee OA in adults ≥18 years (PROSPERO CRD42021276635). We used AGREE-II and AGREE-REX to assess quality and extracted data on treatment gaps, conflicts, biases, and consensus. Heterogeneity of recommendations was determined using Weighted Fleiss Kappa (K). The relationship between (K) and AGREE-II/AGREE-REX scores was explored. RESULTS: We identified 25 CPGs across eight countries and four international organisations. The ACR, EULAR, NICE, OARSI and RACGP guidelines scored highest for overall AGREE-II quality (83%). The highest overall AGREE-REX scores were for BMJ Arthroscopy (80%), RACGP (78%) and NICE (76%). CPGs with the least agreement for pharmacological recommendations were ESCEO and NICE (-0.14), ACR (-0.08), and RACGP (-0.01). The highest agreements were between RACGP and NICE (0.53), RACGP and ACR (0.61), and NICE and ACR (0.91). Decreased internal validity determined by low-quality AGREE scores(<60%) in editorial independence were associated with less agreement for pharmacological recommendations. CONCLUSION: There were associations between guideline quality and agreement scores. Future guideline development should be informed by robust evidence, editorial independence and methodological rigour to ensure a harmonisation of recommendations. End-users of CPGs must recognise the contextual factors associated with the development of OA CPGs and balance these factors with available evidence.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Mapping the Lequesne Functional Index Into the EQ-5D-5L Utility Index in Patients With Knee Osteoarthritis.

OBJECTIVE: This study aimed to map the Lequesne index onto the EuroQol 5 Dimension (EQ-5D-5L) utility index for patients with knee osteoarthritis. METHODS: Baseline data from a previous randomized controlled trial were used; 461 patients were involved in the mapping development, and 230 in the validation phase. Various modeling techniques, including generalized linear models, tobit, and beta regression, were used. Factors such as age, sex, and body mass index were considered as covariates. Model selection was based on criteria such as Akaike and Bayesian information criteria, adjusted R2, mean absolute error, and root mean squared error. Validation involved assessing the preselected models using mean absolute error, root mean squared error, and intraclass correlation coefficient. This study follows the Mapping Onto Preference-Based Measures Reporting Standards statement. RESULTS: Five models were developed, with 2 incorporating age, sex, with or without body mass index along with the Lequesne index showing the best fit across regressions. Validation results were similar for the 3 regressions, with beta regression models exhibiting wider ranges closer to the validation data set. Intraclass correlation coefficient values were better for beta regression models. Both models tended to overpredict for lower EQ-5D-5L values and underpredict for better health status. CONCLUSION: These mapping functions, the first of their kind, effectively translate the Lequesne index to EQ-5D-5L values in patients with knee osteoarthritis. They demonstrate satisfactory fit and precision, providing valuable tools for clinicians and researchers, particularly in situations where generic preference-based health-related quality of life instruments are inaccessible for utility derivation in cost-effectiveness studies.

Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population.

OBJECTIVES: To evaluate some confounding factors that influence the concentrations of S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1) in older individuals. Indeed, recent guidelines have proposed the combined use of S100B and the "GFAP-UCH-L1" mTBI test to rule out mild traumatic brain injuries (mTBI). As older adults are the most at risk of mTBI, it is particularly important to understand the confounding factors of those mTBI rule-out biomarkers in aging population. METHODS: The protein S100B and the "GFAP and UCH-L1" mTBI test were measured using Liaison XL (Diasorin) and Alinity I (Abbott), respectively, in 330 and 341 individuals with non-suspected mTBI from the SarcoPhAge cohort. RESULTS: S100B, GFAP and UCH-L1 were all significantly correlated with renal function whereas alcohol consumption, Geriatric Depression Score (GDS), smoking habits and anticoagulant intake were not associated with any of these three biomarkers. Body mass index (BMI) and age were associated with GFAP and UCH-L1 expression while sex and mini-mental state examination (MMSE) were only associated with GFAP. According to the manufacturer's cut-offs for mTBI rule-out, only 5.5 % of participants were positive for S100B whereas 66.9 % were positive for the "GFAP-UCH-L1" mTBI test. All positive "GFAP-UCH-L1" mTBI tests were GFAP+/UCH-L1-. Among individuals with cystatin C>1.55 mg/L, 25 % were positive for S100B while 90 % were positive for the mTBI test. CONCLUSIONS: Our data show that confounding factors have different impacts on the positivity rate of the "GFAP-UCH-L1" mTBI test compared to S100B.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Does health literacy mediate the relationship between socioeconomic status and health related outcomes in the Belgian adult population?

BACKGROUND: Health literacy (HL) has been put forward as a potential mediator through which socioeconomic status (SES) affects health. This study explores whether HL mediates the relation between SES and a selection of health or health-related outcomes. METHODS: Data from the participants of the Belgian health interview survey 2018 aged 18 years or older were individually linked with data from the Belgian compulsory health insurance (n = 8080). HL was assessed with the HLS-EU-Q6. Mediation analyses were performed with health behaviour (physical activity, diet, alcohol and tobacco consumption), health status (perceived health status, mental health status), use of medicine (purchase of antibiotics), and use of preventive care (preventive dental care, influenza vaccination, breast cancer screening) as dependent outcome variables, educational attainment and income as independent variables of interest, age and sex as potential confounders and HL as mediating variable. RESULTS: The study showed that unhealthy behaviours (except alcohol consumption), poorer health status, higher use of medicine and lower use of preventive care (except flu vaccination) were associated with low SES (i.e., low education and low income) and with insufficient HL. HL partially mediated the relationship between education and health behaviour, perceived health status and mental health status, accounting for 3.8-16.0% of the total effect. HL also constituted a pathway by which income influences health behaviour, perceived health status, mental health status and preventive dental care, with the mediation effects accounting for 2.1-10.8% of the total effect. CONCLUSIONS: Although the influence of HL in the pathway is limited, our findings suggest that strategies for improving various health-related outcomes among low SES groups should include initiatives to enhance HL in these population groups. Further research is needed to confirm our results and to better explore the mediating effects of HL.

Towards a core outcome set (COS) for intrinsic capacity (IC) intervention studies in adults in midlife and beyond: a scoping review to identify frequently used outcomes and measurement tools.

This scoping review was conducted to identify the outcomes and measurement tools used in IC intervention studies, as first step towards the development of a core outcome set (COS) for IC trials. PRISMA-ScR and COS-STAD were followed. The review considered randomized controlled trials targeting IC published in Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, until June 2023. Of 699 references, 534 studies were screened once duplicates were removed, 15 were assessed for eligibility, and 7 (4 articles and 3 protocols) met eligibility criteria. Twenty-eight outcomes were identified (19 related to IC and its domains and 9 unrelated). The most reported primary outcome was the change in IC levels postintervention (5 over 7 studies) and the most reported outcomes (either as primary and/or secondary) were the changes in physical performance and in depressive symptoms (6 over 7 studies). Fifty-five tools used to construct the domains' z-scores and/or assess the effect of interventions were identified (47 related to IC and its domains and 8 unrelated). The most reported tool was an IC Z-score, calculated by 4 domains' z-scores: locomotor, vitality, cognitive, and psychological (5 over 7 studies). The tools differed among studies (10 locomotor related, 6 vitality related, 16 cognitive related, 8 psychological related, 6 sensorial related, 8 unrelated tools). The vast heterogeneity (28 outcomes and 55 tools within 7 studies) highlighted the need of a COS. These outcomes and tools will be presented to experts in a future step, to select the ones that should be taken into consideration in IC trials.

Association of circulating hsa-miRNAs with sarcopenia: the SarcoPhAge study.

OBJECTIVE: To identify a microRNA signature associated to sarcopenia in community-dwelling older adults form the SarcoPhAge cohort. METHODS: In a screening phase by next generation sequencing (NGS), we compared the hsa-miRome expression of 18 subjects with sarcopenia (79.6 ± 6.8 years, 9 men) and 19 healthy subjects without sarcopenia (77.1 ± 6 years, 9 men) at baseline. Thereafter, we have selected eight candidate hsa-miRNAs according to the NGS results and after a critical assessment of previous literature. In a validation phase and by real-time qPCR, we then analyzed the expression levels of these 8 hsa-miRNAs at baseline selecting 92 healthy subjects (74.2 ± 10 years) and 92 subjects with sarcopenia (75.3 ± 6.8 years). For both steps, the groups were matched for age and sex. RESULTS: In the validation phase, serum has-miRNA-133a-3p and has-miRNA-200a-3p were significantly decreased in the group with sarcopenia vs controls [RQ: relative quantification; median (interquartile range)]: -0.16 (-1.26/+0.90) vs +0.34 (-0.73/+1.33) (p < 0.01) and -0.26 (-1.07/+0.68) vs +0.27 (-0.55/+1.10) (p < 0.01) respectively. Has-miRNA-744-5p was decreased and has-miRNA-151a-3p was increased in the group with sarcopenia vs controls, but this barely reached significance: +0.16 (-1.34/+0.79) vs +0.44 (-0.31/+1.00) (p = 0.050) and +0.35 (-0.22/+0.90) vs +0.03 (-0.68/+0.75) (p = 0.054). CONCLUSION: In subjects with sarcopenia, serum hsa-miRNA-133a-3p and hsa-miRNA-200a-3p expression were downregulated, consistent with their potential targets inhibiting muscle cells proliferation and differentiation.

Radiofrequency echographic multi spectrometry (REMS) in the diagnosis and management of osteoporosis: state of the art.

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Recommendations for the optimal use of bone forming agents in osteoporosis.

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.

Comparing remote and face-to-face assessments of physical performance in older adults: A reliability study.

INTRODUCTION: Older people often experience a decline in their physical performance. Tests have been approved to evaluate this performance in person. Yet, the constraints associated with in-person assessments (e.g. lack of medical facilities, pandemic lockdown, and contagion risk) are making us contemplate setting up assessments remotely. OBJECTIVES: To determine whether remote physical performance measurements of older adults are reliable and valid compared to face-to-face measurements. METHODS: Forty-five subjects aged 65 and over completed the normal/fast speed test (NWT/FWT), the unipodal balance test (UBT), the normal/fast timed up and go test (NTUG/FTUG), the 5 and 10 rep sit to stand test (5STS and 10STS), the 30 sec chair stand (30CS), the 2 minute step test (2MST) and the flexibility before standing (SAD) once face-to-face and twice remotely, by two different observers. The intraclass correlation coefficients (ICC), the standard errors of measurement (SEM%) and minimum detectable changes (MDC%) were calculated for both intra- and inter-observer conditions, to assess the relative and the absolute reliability. An ICC value exceeding 0.90 indicates a very high reliability, while an ICC between 0.70 and 0.89 signifies a high reliability. In clinical practice, a SEM % of less than 10% is considered acceptable. A smaller MDC % indicates a measurement that is more sensitive to detecting changes. RESULTS: Intra-observer relative reliability was very high (ICC>0.9) for the UBT, NWT, NTUG, FTUG, 5STS, 10STS, 30CS and the SAD; and high (ICC>0.7) for the 2MST and FWS. SEM% values ranged from 0% to 24.03% and MDC from 0% to 9.93%. Inter-observer relative reliability was considered very high (ICC>0.9) for all tests. SEM% values ranged from 0% to 17.68% and MDC from 0% to 7.32%. CONCLUSION: Our findings demonstrate that remote assessments exhibited consistently high to very high levels of intra- and inter-observer relative reliability when compared to face-to-face assessments. Additionally, certain remote evaluations showed acceptable absolute reliability, making them viable alternatives for healthcare professionals when in-person assessments are not feasible in clinical practice.

[Preventing falls in older adults]. / Prévention des chutes chez les personnes âgées.

Preventing falls in older adults requires a comprehensive approach that distinguishes between accidental falls and falls related to underlying medical problems, such as syncope. For unintentional falls, prevention follows a three-stage model. The primary level focuses on encouraging regular physical activity, assessing, and reducing footwear and environmental risks, managing comorbidities, and promoting healthy lifestyles. The secondary level aims to identify and manage all risk factors, including in-depth medical assessment and education of older people and their careers. Finally, the tertiary level aims to minimise the consequences of falls through post-fall care, regular medical monitoring and the introduction of mobility aids or monitoring technologies. Educating older people about the risks, adopting safe behaviours, promoting physical activity, and creating safe environments go beyond these levels. This holistic approach anticipates, identifies, and mitigates risks, promotes safe and active ageing, and aims to achieve overall well-being, reduce adverse outcomes, and promote optimal quality of life throughout the ageing process.

La prévention des chutes chez les personnes âgées exige une approche complète, distinguant les chutes accidentelles des chutes liées à des problèmes médicaux sous-jacents, comme la syncope. Pour les chutes accidentelles, la prévention adopte un modèle en trois niveaux. Le niveau primaire favorise l'encouragement à l'exercice physique régulier, l'évaluation et la réduction des risques liés au chaussage ou à l'environnement, l'équilibration de comorbidités et la promotion d'un mode de vie sain. Le niveau secondaire cible l'identification et la prise en charge de l'ensemble des facteurs de risque, impliquant une évaluation médicale approfondie et une éducation du sujet âgé et de ses aidants proches. Enfin, le niveau tertiaire vise à minimiser les conséquences des chutes par des soins post-chute, un suivi médical régulier, et l'introduction d'aides à la mobilité ou de technologies de surveillance. L'éducation des personnes âgées sur les risques, l'adoption de comportements sécuritaires, la promotion de l'activité physique, et la création d'environnements sûrs transcendent ces niveaux. Cette approche holistique anticipe, identifie, et atténue les risques, favorisant un vieillissement actif et sécurisé, et visant le bien-être global, la réduction des conséquences néfastes des chutes et la promotion d'une qualité de vie optimale au cours du vieillissement.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Measures of attributes of locomotor capacity in older people: a systematic literature review following the COSMIN methodology.

BACKGROUND: Locomotor capacity (LC) is an important domain of intrinsic capacity and key determinant of functional ability and well-being in older age. The United Nations Decade of Healthy Ageing (2021-2030) calls for strengthening data and research on healthy ageing, including the measurement of older persons' LC. To advance the measurement and monitoring of LC, there is pressing need to identify valid and reliable measures. OBJECTIVE: To identify all the available tools that were validated for measurement of LC or of its specific attributes in older people and to assess the methodological quality of the studies and measurement properties of the tools. DESIGN: Systematic review. SETTING: Anywhere (Community-dwelling; long-term care facility; etc.). SUBJECTS: Older people. METHODS: We used highly sensitive search strategies to search the following databases: Medline, Embase, Scopus, CINAHL and PsycINFO. The study was conducted following the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology for systematic review of outcome measurement instruments. RESULTS: A total of 125 studies were included, which assessed tools for balance (n = 84), muscle power (n = 12), muscle strength (n = 32, including four studies about tools for balance and muscle power) and endurance (n = 1). No studies on tools for muscle function, joint function, or locomotor capacity overall, were retrieved. We identified 69 clinician-report or objective assessment tools for balance, 30 for muscle strength, 12 for muscle power and 1 endurance assessment tool. The GRADE assessment of quality of evidence showed that only a few tools have high quality evidence for both sufficient validity and reliability: The Balance Evaluation Systems Test (BESTest), the Mini-Balance Evaluation Systems Test (Mini-BESTest), the Berg Balance Scale (BBS) and the Timed Up and Go (TUG) test. CONCLUSIONS: A few tools with high quality evidence for sufficient validity and reliability are currently available for balance assessment in older people that may be recommended for use in clinical and research settings. Further validation studies are required for muscle strength, muscle power and endurance assessment tools.

Assessment of risk factors associated with long-term mortality in nursing homes: result from the SENIOR cohort.

BACKGROUND: Previous studies on risk factors for death in nursing homes have focused on short-term observation and limited number risk factors. AIMS: This study aims to identify factors predictive of 8-year survival in nursing homes. METHODS: The study used the baseline measurements from the SENIOR cohort collected in 2013-2014. Data included clinical assessments (i.e., body composition, nutritional status, physical performance, level of dependence and cognition, frailty phenotype) as well as demographic information, number of medications and medical history. Mortality data were collected annually for 8 years. Univariate analyses were initially performed to assess potential predictive factors, followed by a Cox regression model using stepwise selection. RESULTS: Of the 662 participants enrolled in the cohort, 58 (8.8%) were not further assessed due to the withdrawal of 2 nursing homes and 71 (10.7%) had no mortality data available (i.e., relocation, refusal to continue the study). Among the 533 patients included, 111 (20.8%) were still alive in 2022. Median survival time was 4 years (1.93-6.94). Multivariate regression showed that younger age (HR = 1.04 (1.03-1.06)), higher body mass index (HR = 0.96 (0.94-0.98)), higher score on the Mini-Mental State-Examination (HR = 0.97 (0.94-0.99)) and higher score on the Short Physical Performance Battery (HR = 0.93 (0.90-0.97)) were protective factors against mortality. CONCLUSIONS: This study highlights that certain modifiable factors related to physical or mental health contribute to increased survival in nursing homes. Because of its ability to improve physical performance and partly cognitive function, promoting physical activity in nursing homes appears to be a public health priority.

Neurofilament-light chains (NF-L), a biomarker of neuronal damage, is increased in patients with severe sarcopenia: results of the SarcoPhAge study.

BACKGROUND: As clinical tests, such as gait speed, require nervous system integrity to be performed properly, sarcopenia shares features with neurological diseases. Neurofilament light chains (NF-L) are now used as a blood-biomarker of neuronal damage, and its expression might be altered in sarcopenia. We aimed to assess NF-L concentrations in a large cohort of older individuals screened for sarcopenia. METHODS: The SarcoPhAge cohort is a Belgian cohort of 534 community-dwelling older adults with an ongoing 10-year follow-up. Sarcopenia diagnosis was established at inclusion according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was evaluated with a hydraulic hand dynamometer, appendicular lean mass by Dual-Energy X-ray Absorptiometry (DXA) and physical performance by the Short Physical Performance Battery (SPPB). NF-L was measured on all available sera collected at the time of inclusion (n = 409) using SiMoA technology (Quanterix°). RESULTS: In the multivariate model, NF-L was associated with performance tests such as gait speed (p < 0.0001) and SPPB scores (p = 0.0004). An association was also observed with muscle strength (p = 0.0123) and lean mass (p = 0.0279). In the logistic regression model, NF-L was an independent predictor of severe sarcopenia (p = 0.0338; OR = 20.0; 95% CI 1.39-287.7) with satisfactory diagnostic accuracy (AUC: 0.828) and subjects with an SPPB score ≤ 8 had higher odds of having increased NF-L (p < 0.0001; OR = 23.9; 95% CI 5.5-104). CONCLUSIONS: These data highlight the potential for using NF-L to investigate the pathophysiology of sarcopenia severity and the neurological features associated with performance tests. However, these results need to be confirmed with other cohorts in different settings.