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.

When and How to Evaluate Vitamin D Status? A Viewpoint from the Belgian Bone Club.

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.

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.

Navigating the Health Care Landscape for an Ageing Population: An International Survey of Strategies and Priorities.

OBJECTIVES: The global increase in the older population, which is expected to reach 1.5 billion by 2050, poses significant challenges for publicly funded health care systems. Life expectancy, although positive, is leading to an increase in chronic diseases requiring complex and costly health and social solutions. This study explores key strategies to address these challenges. DESIGN: Qualitative interviews followed by a survey. SETTING AND PARTICIPANTS: The study involved experts, students, artificial intelligence, and participants at a congress. METHODS: We first interviewed 5 experts from different countries representing health care management and psychology from Belgium, health economics from Canada, sociology from France, and geriatrics from Switzerland. In addition, a focus group session with medical students in physical therapy and queries to ChatGPT increased the range of perspectives. A synthesis of all opinions or insights was used to formulate concrete strategies. These strategies were incorporated into an online survey that was distributed to 215 participants of the Geriatric and Gerontologic Congress in Montreal, Canada, in September 2023. RESULTS: All 20 potential solutions were duly acknowledged, with particular attention paid to the following 5 priorities: the urgent need to integrate geriatric training into the education of future health professionals, the promotion of home-based care models, the establishment of comprehensive and integrated care systems, the strengthening of primary care services, and the emphasis on primary prevention strategies. CONCLUSION AND IMPLICATIONS: This study highlights key priorities for addressing the health needs of the older population. By emphasizing education, home-based care, and integrated services and strengthening primary care and prevention, health systems can respond effectively to the challenges of an ageing population. Although these needs may not be entirely unmet, they indicate areas where existing services are insufficient in providing adequate coverage and support to ensure tailored and sustainable health care solutions for older people.

The Impact of Nursing Home Culture Change: An Integrative Review.

OBJECTIVES: The Nursing Home Culture Change (NHCC) movement promotes a person- and relationship-centered approach and a small-scale, homelike model for NHs. The present study aimed to integrate the most recent empirical findings regarding the impact of NHCC on resident, staff, family, and organizational outcomes. DESIGN: Integrative review. SETTING AND PARTICIPANTS: Not applicable. METHODS: OVID MEDLINE, PsycINFO, Embase, and CINAHL databases were searched for quantitative or mixed studies published in English between 2018 and 2022 and examining the effect of NHCC on resident, staff, family, and/or organizational outcomes. A narrative and tabular synthesis of the results is provided. RESULTS: A total of 1687 references were identified. Following duplicate removal, title and abstract screening, and full-text screening, 75 studies were retained for synthesis and suggest a positive impact of NHCC on resident (eg, quality of life and neuropsychiatric function), staff (eg, job satisfaction and stress), family (eg, satisfaction and depressive symptoms), and organizational (eg, NH attractiveness and occupancy rate) outcomes. CONCLUSIONS AND IMPLICATIONS: NHCC shows promising results in all studied outcome categories. Future research should further investigate obstacles to NHCC implementation, conduct cost-benefit analyses supported by appropriate statistical tests, and define ways to improve NH staff education as well as NH policies and regulations to better support NHCC initiatives.

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).

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.

[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.

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.

The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example.

Osteoarthritis (OA) is a degenerative joint disease with a substantial global burden, causing chronic pain and reduced quality of life. Managing OA efficiently while maximizing healthcare resources is crucial. Health economics and health technology assessment (HTA) are central tools providing a framework to evaluate the clinical, economic, and ethical aspects of healthcare technologies and interventions. This article presents some insights into the role of health economics and the HTA process in OA management. It also illustrates an example of cost-effectiveness analysis in a specific healthcare context, on the basis of a recent clinical trial involving hyaluronic acid treatment for knee OA. While HTA offers valuable insights, it faces challenges like data availability and resource constraints. Integrating health economics into decision-making can enhance patient care and allocate resources effectively in OA and other healthcare domains.

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.

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.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

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.

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.

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.

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.

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.