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Objectives: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. Setting and Participants: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. Measurements: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). Results: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) — all based on muscle mass and muscle strength — showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. Conclusion: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health. [ABSTRACT FROM AUTHOR]

Summary: Using a discrete choice experiment, we aimed to assess patients' preferences with regard to adopting lifestyle behaviours to prevent osteoporotic fractures. Overall, the 1042 patients recruited from seven European countries were favourable to some lifestyle behaviours (i.e., engaging in moderate physical activity, taking calcium and vitamin D supplements, reducing their alcohol consumption and ensuring a normal body weight). Introduction: Alongside medical therapy, healthy lifestyle habits are recommended for preventing osteoporotic fractures. In this study, we aimed to assess patients' preferences with regard to adopting lifestyle changes to prevent osteoporotic fractures. Methods: A discrete choice experiment was conducted in seven European countries. Patients with or at risk of osteoporosis were asked to indicate to what extent they would be motivated to adhere to 16 lifestyle packages that differed in various levels of 6 attributes. The attributes and levels proposed were physical activity (levels: not included, moderate or high), calcium and vitamin D status (levels: not included, taking supplements, improving nutrition and assuring a minimal exposure to sunlight daily), smoking (levels: not included, quit smoking), alcohol (levels: not included, moderate consumption), weight reduction (levels: not included, ensure a healthy body weight) and fall prevention (levels: not included, receiving general advice or following a 1-day fall prevention program). A conditional logit model was used to estimate a patient's relative preferences for the various attributes across all participants and per country. Results: In total, 1042 patients completed the questionnaire. Overall, patients were favourable to lifestyle behaviours for preventing osteoporotic fractures. However, among the lifestyle behaviours proposed, patients were consensually not prone to engage in a high level of physical activity. In addition, in Ireland, Belgium, the Netherlands and Switzerland, patients were also not inclined to participate in a 1-day fall prevention program and Belgian, Swiss and Dutch patients were not prone to adhere to a well-balanced nutritional program. Nevertheless, we observed globally that patients felt positively about reducing their alcohol consumption, engaging in moderate physical activity, taking calcium and vitamin D supplements and ensuring a normal body weight, all measures aimed at preventing fractures. Conclusions: In a patient-centred approach, fracture prevention should take these considerations and preferences into account. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis.Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting.Methods: Systematic reviews were updated.Results: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment.Conclusions: A platform is provided on which specific guidelines can be developed for national use. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis represents a significant and increasing healthcare burden in Europe, but most patients at increased risk of fracture do not receive medication, resulting in a large treatment gap. Identification of patients who are at particularly high risk will help clinicians target appropriate treatment more precisely and cost-effectively, and should be the focus of future research. Introduction: The purpose of the study was to review data on the identification and treatment of patients with osteoporosis at increased risk of fracture. Methods: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review current data on the epidemiology and burden of osteoporosis and the patterns of medical management throughout Europe. Results: In Europe in 2010, the cost of managing osteoporosis was estimated at €37 billion and notably the costs of treatment and long-term care of patients with fractures were considerably higher than the costs for pharmacological prevention. Despite the availability of effective treatments, the uptake of osteoporosis therapy is low and declining, in particular for secondary fracture prevention where the risk of a subsequent fracture following a first fracture is high. Consequently, there is a significant treatment gap between those who would benefit from treatment and those who receive it, which urgently needs to be addressed so that the burden of disease can be reduced. Conclusions: Implementation of global fracture prevention strategies is a critical need. Future research should focus on identifying specific risk factors for imminent fractures, periods of high fracture risk, patients who are at increased risk of fracture and therapies that are most suited to such high-risk patients and optimal implementation strategies in primary, secondary and tertiary care. [ABSTRACT FROM AUTHOR]

A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. Osteoporos Int, 10.1007/s00198-018-4704-5, 2018). This manuscript updates the previous guideline document, published in 2013 (Kanis et al. Osteoporos Int 24:23-57, 2013) and is written from a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document (Fig. 1). [ABSTRACT FROM AUTHOR]

Summary: Despite the proven predictive ability of bone mineral density, Fracture Risk Assessment Tool (FRAX®), bone turnover markers, and fracture for osteoporotic fracture, their use as targets for treatment of osteoporosis is limited. Introduction: Treat-to-target is a strategy applied in several fields of medicine and has recently become an area of interest in the management of osteoporosis. Its role in this setting remains controversial. This article was prepared following a European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group meeting convened under the auspices of the International Osteoporosis Foundation (IOF) to discuss the feasibility of applying such a strategy in osteoporosis in Europe. Methods: Potential targets range from the absence of an incident fracture to fixed levels of bone mineral density (BMD), a desired FRAX® score, a specified level of bone turnover markers or indeed changes in any one or a combination of these parameters. Results: Despite the proven predictive ability of all of these variables for fracture (particularly BMD and FRAX), their use as targets remains limited due to low sensitivity, the influence of confounders and current lack of evidence that targets can be consistently reached. Conclusion: ESCEO considers that it is not currently feasible to apply a treat-to-target strategy in osteoporosis, though it did identify a need to continue to improve the targeting of treatment to those at higher risk (target-to-treat strategy) and a number of issues for the research agenda. These include international consensus on intervention thresholds and definition of treatment failure, further exploration of the relationship between fracture and BMD, and FRAX and treatment efficacy and investigation of the potential of short-term targets to improve adherence. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2008. This manuscript updates these in a European setting. Methods: Systematic literature reviews. Results: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk, general and pharmacological management of osteoporosis, monitoring of treatment, assessment of fracture risk, case finding strategies, investigation of patients and health economics of treatment. Conclusions: A platform is provided on which specific guidelines can be developed for national use. [ABSTRACT FROM AUTHOR]

Summary: Health claims for food products in Europe are permitted if the nutrient has been shown to have a beneficial nutritional or physiological effect. This paper defines health claims related to bone health and provides guidelines for the design and the methodology of clinical studies to support claims. Introduction: Regulation (EC) no. 1924/2006 on nutrition and health claims targeting food products was introduced in Europe stating that health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. The objective of this paper is to define health claims related to bone health and to provide guidelines for the design and the methodology of clinical studies which need to be adopted to assert such health claims. Methods: Literature review followed by a consensus discussion during two 1-day meetings organized by the Group for the Respect of Ethics and Excellence in Science (GREES). Results: The GREES identified six acceptable health claims related to bone health based on the potential of food products to show an effect on either the bioavailability of calcium or osteoclast regulatory proteins or bone turnover markers or bone mineral density or bone structure or fracture incidence. The GREES considers that well-designed human randomized controlled trial on a relevant outcome is the best design to assess health claims. The substantiation of health claim could also be supported by animal studies showing either an improvement in bone strength with the food product or showing the relationship between changes induced by the food product on a surrogate marker and changes in bone strength. Conclusion: The consensus reached is that the level of health claim may differ according to the surrogate endpoint used and on additional animal studies provided to support the claim. [ABSTRACT FROM AUTHOR]

Summary: Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women. Introduction: Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods: Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results: In the intention-to-treat population ( n = 83, age: 64 ± 8 years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) ( P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance ( P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan ( P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort ( P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated. Conclusions: Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method. [ABSTRACT FROM AUTHOR]

Summary: Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit. Introduction: A number of economic models have been developed to evaluate osteoporosis therapies and support decisions regarding efficient allocation of health care resources. Adherence to treatment is seldom incorporated in these models, which may reduce their validity for decision-making since adherence is poor in real-world clinical practice. Methods: An ad hoc working group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review key issues concerning the incorporation of partial adherence in health economic models. Results: Observational data have shown that poor adherence is associated with an increase in the risk for fragility fracture. Health economic modelling indicates that full adherence is associated with more quality-adjusted life years gained than partial adherence, as well as higher treatment costs and lower fracture-related costs. Although adherence appears as an important driver of cost-effectiveness, the effect is dependent on a range of other variables, such as offset time, fraction of benefit, fracture risk, fracture efficacy, fracture-related costs, and drug cost, some of which are poorly defined. Current models used to evaluate cost-effectiveness in osteoporosis may oversimplify the contributions of compliance and persistence. Conclusion: Partial adherence has a significant impact on cost-effectiveness. Further research is required to optimise thresholds of compliance and persistence, the impact of gap length, offset times, and fraction of benefit. [ABSTRACT FROM AUTHOR]

Summary: This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. Introduction: A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. Methods: A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. Results: Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these 'atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. Conclusions: Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fractures. [ABSTRACT FROM AUTHOR]

The original version of this article, published on 15 October 2018, unfortunately, contained a mistake. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting" published in the perodical.

Objective: Although aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults., Design: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial., Setting and Participants: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status., Methods: The numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids., Results: Among the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007)., Conclusions and Implications: Our findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults., Competing Interests: Disclosure As part of the DO-HEALTH independent and investigator-initiated clinical trial, H.A.B.-F. reports, as the principal investigator of the DO-HEALTH trial, grants from the European Commission, the University of Zurich, Nestec, Pfizer Consumer Healthcare, and Streuli Pharma, and nonfinancial support from DSM Nutritional Products and Roche Diagnostics. Further, H.A.B.-F. reports speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics, and independent and investigator-initiated grants from Pfizer and from Vifor, outside of the submitted work. E.J.O. was also funded by DO-HEALTH. J.A.K. is a director of Osteoporosis Research Ltd. that maintains FRAX. M.D.B. reports speaking engagements for Roche Pharma (Schweiz) AG and consulting roles for Hoffmann-La Roche Ltd., Roche Pharma (Schweiz) AG, and ZEISS meditec (Deutschland). He is a lead user for Oertli (Schweiz) and holds patents and equity in Ophthorobotics AG. His contracted research includes work with Roche Pharma (Schweiz) AG, Novertis Pharma Schweiz AG, Chengdu Kanghong, and Bayer (Schweiz) AG. He has also received grant support from the W.H. Spross Stiftung zur Förderung der Augenheilkunde and the Stiftung für wissenschaftliche Forschung am Stadtspital Zürich. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hand osteoarthritis is the most common joint condition and is associated with significant morbidity. It is of paramount importance that patients are thoroughly assessed and examined when complaining of hand stiffness, pain, deformity or disability and that the patient's concerns and expectations are addressed by the healthcare professional. In 2019 the American College of Rheumatology and Arthritis Foundation (ACR/AF) produced guidelines which included recommendations for the treatment of hand osteoarthritis. An ESCEO expert working group (including patients) was convened and composed this paper with the aim to assess whether these guidelines were appropriate for the treatment of hand osteoarthritis therapy in Europe and whether they met with the ESCEO patient-centered approach. Indeed, patients are the key stakeholders in healthcare and eliciting the patient's preference is vital in the context of an individual consultation but also for informing research and policy-making. The patients involved in this working group emphasised the often-neglected area of aesthetic changes in hand osteoarthritis, importance of developing pharmacological therapies which can alleviate pain and disability and the need of the freedom to choose which approach (out of pharmacological, surgical or non-pharmacological) they wished to pursue. Following robust appraisal, it was recommended that the ACR/AF guidelines were suitable for a European context (as described within the body of the manuscript) and it was emphasised that patient preferences are key to the success of individual consultations, future research and future policy-making., (© 2022. Crown.)

Objective: To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities., Design: Cross-sectional study of baseline data from DO-HEALTH., Setting and Participants: DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline., Primary Outcome Measures: Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy., Results: 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy., Conclusion: Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy., Trial Registration Number: NCT01745263., Competing Interests: Competing interests: As part of the DO-HEALTH independent and investigator initiated clinical trial, HB-F reports as the PI of the DO-HEALTH trial, grants from European Commission, from University of Zurich, from NESTEC, from PFIZER Consumer Healthcare, from Streuli Pharma, plus nonfinancial support from DSM Nutritional Products and non-financial support from Roche Diagnostics. Further, HB-F reports speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics, and independent and investigator-initiated grants from Pfizer and from Vifor, outside the submitted work. BV reports personal fees from BIOGEN, CERECIN, ROCHE, MSD, outside the submitted work. RR reports personal fees from Abiogen, Danone, Echolight, EMF, Mithra, ObsEva, Pfizer Consumer Health, Theramex, outside the submitted work. JEO reports grants from Zurich University, during the conduct of the study. CdGRCM received funding from the National Council for Scientific and Technological Development (CNPq), with process Nos. 164700/2015-3, from the São Paulo Research Foundation (FAPESP), with process No. 2016/13700-9, and Coordination for the Improvement of Higher Education Personnel/PhD Sandwich Programs Abroad (PDSE), with process No. 88881.132169/2016-01. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the preferences of patients with osteoarthritis for treatment., Methods: A discrete-choice experiment was conducted among adult OA patients who were presented with 12 choice sets of two treatment options and asked in each to select the treatment they would prefer. Based on literature reviews, expert consultation, patient survey and expert meeting, treatment options were characterized by seven attributes: improvement in pain, improvement in walking, ability to manage domestic activities, ability to manage social activities, improvement in overall energy and well-being, risk of moderate/severe side effects and impact on disease progression. Random parameters logit model was used to estimate patients' preferences and a latent class model was conducted to explore preferences classes., Results: 253 OA patients from seven European countries were included (74% women; mean age 71.3 years). For all seven treatment attributes, significant differences were observed between levels. Given the range of levels of each attribute, the most important treatment attribute in this group was impact on disease progression (29.5%) followed by walking improvement (17.1%) and pain improvement (16.3%). The latent class model identified two preference classes. In the first class (probability of 56%), patients valued impact of disease progression the most (39%). In the second class, walking improvement and improvement in overall energy and well-being were the most important (23%)., Conclusion: This study suggests that all seven treatment attributes were important for OA patients. Overall, given the range of levels, the most important outcomes were impact on disease progression and improvement in pain and walking., Competing Interests: Declaration of Competing Interest Professor Bruyère reports grants from Biophytis, IBSA, MEDA, Servier, SMB, Theramex, outside the submitted work. Professor Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. Professor Conaghan has received consulting fees or done speakers bureaus for AbbVie, EMD Serono, Flexion Therapeutics, Galapagos, Novartis, Pfizer, Samumed and Stryker. Professor Dennison has received consulting fees from UCB and Pfizer. Dr. Herrero-Beaumont reports grants from Novartis, grants from Sandoz, grants from Pfizer, grants from Amgen, grants from Mylan, grants from Servier, outside the submitted work; In addition, Dr. Herrero-Beaumont has a patent Patent for the use of 6-shogaol on osteoporosis treatment. Spanish patent issued, and a patent Patent on the use of osteostatin in osteoarthritis treatment issued. Professor Reginster reports grants and personal fees from IBSA-GENEVRIER, grants and personal fees from MYLAN, grants and personal fees from RADIUS HEALTH, personal fees from PIERRE FABRE, grants from CNIEL, personal fees from DAIRY RESEARCH COUNCIL, outside the submitted work. Professor Thomas reports personal fees from Abbvie, grants and personal fees from Amgen, personal fees from Arrow, personal fees from Biogen, personal fees from BMS, grants and personal fees from Chugai, personal fees from Expanscience, personal fees from Gilead, personal fees from Grunenthal, grants and personal fees from HAC-Pharma, personal fees from LCA, personal fees from Lilly, personal fees from Medac, grants and personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Sanofi, personal fees from Theramex, personal fees from Thuasne, personal fees from TEVA, grants and personal fees from UCB, grants from Bone therapeutics, personal fees from Nordic, outside the submitted work. Professor Rizzoli reports personal fees from Amgen, CNiEL, Danone, Mylan, Nestle, Radius health, Sandoz, TEVA/Theramex, outside the submitted work. The other authors have no conflict of interest relevant to the content of this study., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally., Methods: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed., Results: An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses., Conclusions: The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions., Introduction: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication., Methods: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken., Results: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it., Conclusion: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. in Osteoporos Int https://doi.org/10.1007/s00198-018-4704-5 , 2018). This manuscript updates the previous guidelines document, published in 2013 (Kanis et al. in Osteoporos Int 24:23-57, 2013) and is written in a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document.

Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis., Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting., Methods: Systematic reviews were updated., Results: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment., Conclusions: A platform is provided on which specific guidelines can be developed for national use.

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA)., Design: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process., Results: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing)., Conclusions: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Several compounds are produced along the complex pathways of vitamin D3 metabolism, and synthetic analogs have been generated to improve kinetics and/or vitamin D receptor activation. These metabolites display different chemical properties with respect to the parental or native vitamin D3, i.e., cholecalciferol, which has been, so far, the supplement most employed in the treatment of vitamin D inadequacy. Hydrophilic properties of vitamin D3 derivatives facilitate their intestinal absorption and their manageability in the case of intoxication because of the shorter half-life. Calcidiol is a more hydrophilic compound than parental vitamin D3. Active vitamin D analogs, capable of binding the vitamin D receptor evoking vitamin D-related biological effects, are mandatorily employed in hypoparathyroidism and kidney failure with impaired 1α-hydroxylation. They have been shown to increase BMD, supposedly ameliorating calcium absorption and/or directly affecting bone cells, although their use in these conditions is jeopardized by the development of hypercalciuria and mild hypercalcemia. Further studies are needed to assess their overall safety and effectiveness in the long-term and new intermittent regimens, especially when combined with the most effective antifracture agents.

Background: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach., Objectives: To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions., Methods: Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards., Results: Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided., Conclusions: The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the standardisation and comparability of studies that evaluate therapeutic strategies of OA in terms of costs and effectiveness., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint., Methods: ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shaped to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus., Results: Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight, and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for re-alignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) or pharmacological. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (e.g., prescription glucosamine sulfate and/or chondroitin sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intra-articular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before surgery are represented by weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult-to-manage alternative when surgery is contraindicated., Conclusions: The proposed treatment algorithm may represent a new framework for the development of future guidelines for the management of OA, more easily accessible to physicians., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe., Introduction: The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis., Methods: The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap)., Results: There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe., Conclusions: The scorecard will enable healthcare professionals and policy makers to assess their country's general approach to the disease and provide indicators to inform future provision of healthcare.

Unlabelled: Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis., Introduction: The European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting., Methods: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case finding strategies; investigation of patients; health economics of treatment., Results and Conclusions: A platform is provided on which specific guidelines can be developed for national use.

Osteoporosis increases fracture risk, especially in metaphyseal bone. Fractures seriously impair function and quality of life and incur large direct and indirect costs. Although the prevention of fractures is certainly the option, a fast and uneventful healing process is optimal when fractures do occur. Many new therapeutic strategies have been developed to accelerate fracture-healing or to diminish the complication rate during the course of fracture-healing. However, widely accepted guidelines are needed to demonstrate the positive or negative interactions of bioactive substances, drugs, and other agents that are being used to promote fracture-healing. For each study design, the primary study goal should be indicated. Outcome variables should include both objective and subjective parameters. The guidelines should be harmonized between European and American regulatory authorities to ensure comparability of results of studies and to foster global harmonization of regulatory requirements.