[Show abstract][Hide abstract] ABSTRACT: Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) with anti-inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. It has also recently been shown to have protective effects against subchondral bone remodelling. Following the end of the revision procedure by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) constituted a panel of 11 experts to better define the real place of diacerein in the armamentarium for treating OA. Based on a literature review of clinical trials and meta-analyses, the ESCEO confirms that the efficacy of diacerein is similar to that of non-steroidal anti-inflammatory drugs (NSAIDs) after the first month of treatment, and superior to that of paracetamol. Additionally, diacerein has shown a prolonged effect on symptoms of several months once treatment was stopped. The use of diacerein is associated with common gastrointestinal disorders such as soft stools and diarrhoea, common mild skin reactions, and, uncommonly, hepatobiliary disorders. However, NSAIDs and paracetamol are known to cause potentially severe hepatic, gastrointestinal, renal, cutaneous and cardiovascular reactions. Therefore, the ESCEO concludes that the benefit-risk balance of diacerein remains positive in the symptomatic treatment of hip and knee osteoarthritis. Furthermore, similarly to other SYSADOAs, the ESCEO positions diacerein as a first-line pharmacological background treatment of osteoarthritis, particularly for patients in whom NSAIDs or paracetamol are contraindicated.
[Show abstract][Hide abstract] ABSTRACT: Purpose
This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate.
This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized.
The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr
eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects.
Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation.
Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.
No preview · Article · Jan 2016 · Aging - Clinical and Experimental Research
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities.
A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication.
A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia.
The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk.
No preview · Article · Dec 2015 · Aging - Clinical and Experimental Research
[Show abstract][Hide abstract] ABSTRACT: The publication outcomes of the abstracts presented during the ECCEO-IOF 2011 reflect a high research productivity, support the robustness of the selection process conducted by the Scientific Advisory Committee and suggest that IOF-ESCEO WCO is successful in its mission to promote and disseminate research.
The European (now World) Congress on Osteoporosis, Osteoarthritis and Musculo-Skeletal Diseases (IOF-ESCEO WCO, formerly ECCEO-IOF) is the largest worldwide event fully dedicated to the clinical, epidemiological, translational and economic aspects of bone, joint and muscle diseases. The role of the Scientific Advisory Committee is to select abstracts for oral communication or poster presentation based on a short summary of the research. The aim of the present survey was to determine the publication rate in international peer reviewed journals of abstracts accepted at the IOF-ESCEO WCO 2011 Meeting (formerly ECCEO-IOF11), the relationship, if any, between the presentation format of the abstract and its subsequent full publication and the impact factor of the journal in which research was published.
Of 619 abstracts accepted at the 2011 ECCEO-IOF11 annual meeting, 45 were accepted for oral communication and 574 accepted for poster presentation. In the subsequent 3 years (2011-2014), 191 abstracts were published as a full-length manuscript (30.9 %). The publication rate was significantly higher for oral communications (75.6 %) than for poster presentations (27.4 %; p < 0.0001). Publications derived from oral communications were published in journals with a higher impact factor (8.3 ± 10.1) than those arising from poster presentations (4.0 ± 2.3; p < 0.0001), but there was no difference in the time to publication (OC 16.3 [IQR 8.4-23.3] months vs PP 11.3 [IQR 5.3-21.4]; p = 0.14).
These results indicate a high research productivity and an appropriate selection of oral communication by the Scientific Advisory Committee of ESCEO-IOF.
Full-text · Article · Dec 2015 · Archives of Osteoporosis
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
Patients with anorexia nervosa (AN) have low serum IGF-I levels that may contribute to a lower bone mineral mass. We investigated the effects of a fermented, protein-fortified, dairy product on serum IGF-I levels in patients with AN during an in-hospital refeeding program.
In this multicenter, randomized, double-blind, placebo-controlled, clinical trial conducted at 3 university hospitals and 3 private clinics in France and Switzerland, 62 women recently admitted with confirmed AN and with a baseline low serum IGF-I level were randomized to 2 daily isocaloric fresh cheese pots containing either 15 g/150 g or 3 g/150 g (controls) of protein for 4 weeks. The primary outcome was the change in IGF-I levels.
In the primary intention-to-treat analysis, mean serum IGF-I levels increased during the intervention phase from 22.9 ± 1.5 to 28.6 ± 1.3 nmol/L (means ± SEM) (+20.2%) in the intervention group and from 20.2 ± 1.2 to 25.7 ± 1.5 nmol/L (+16.8%) in controls. In a preplanned analysis of covariance with repeated measures, the between-group difference was close to statistical significance (P = 0.071). In a post-hoc mixed-regression model analysis, the difference was statistically significant (4.9 nmol/l increase; P = 0.003), as was the change of the ratio IGF-I/IGF-BP3 (P=0.004). There was no between-group difference in biochemical markers of bone turnover (osteocalcin, P1NP, CTX) or in serum parathyroid hormone level. Serum calcium levels slightly increased during the intervention phase in the higher protein group (P = 0.02). IGF-BP2 decreased significantly more in the intervention group during the follow up period at week 4 after supplements cessation (P = 0.019).
Intake of a fermented, protein-fortified, isocaloric dairy product during 4 weeks may slightly increase serum IGF-I levels in women with AN, without significant changes in bone turnover markers.
Clinical trial registration number:
No preview · Article · Nov 2015 · Clinical nutrition (Edinburgh, Scotland)
[Show abstract][Hide abstract] ABSTRACT: Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.
No preview · Article · Oct 2015 · Calcified Tissue International
[Show abstract][Hide abstract] ABSTRACT: Background: the impact of sarcopenia on quality of life is currently assessed by generic tools. However, these tools may not detect subtle effects of this specific condition on quality of life.
Objective: the aim of this study was to develop a sarcopenia-specific quality of life questionnaire (SarQoL, Sarcopenia Quality of Life) designed for community-dwelling elderly subjects aged 65 years and older.
Settings: participants were recruited in an outpatient clinic in Liège, Belgium.
Subjects: sarcopenic subjects aged 65 years or older.
Methods: the study was articulated in the following four stages: (i) Item generation—based on literature review, sarcopenic subjects' opinion, experts' opinion, focus groups; (ii) Item reduction—based on sarcopenic subjects' and experts' preferences; (iii) Questionnaire generation—developed during an expert meeting; (iv) Pretest of the questionnaire—based on sarcopenic subjects' opinion.
Results: the final version of the questionnaire consists of 55 items translated into 22 questions rated on a 4-point Likert scale. These items are organised into seven domains of dysfunction: Physical and mental health, Locomotion, Body composition, Functionality, Activities of daily living, Leisure activities and Fears. In view of the pretest, the SarQoL is easy to complete, independently, in ∼10 min.
Conclusions: the first version of the SarQoL, a specific quality of life questionnaire for sarcopenic subjects, has been developed and has been shown to be comprehensible by the target population. Investigations are now required to test the psychometric properties (internal consistency, test–retest reliability, divergent and convergent validity, discriminant validity, floor and ceiling effects) of this questionnaire.
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates.
[Show abstract][Hide abstract] ABSTRACT: Objectives A history of prior fracture is one of the strongest predictors of a future fragility fracture. In FREEDOM, denosumab significantly reduced the risk of new vertebral, nonvertebral, and hip fractures. We carried out a post hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture. Methods 7808 women aged 60-90 years with a bone mineral density T-score of less than -2.5 but not less than -4.0 at either the lumbar spine or total hip were randomized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months. The anti-fracture efficacy of denosumab was analysed by prior fracture status, to assess secondary fragility fracture, and by subject age, prior fracture site and history of prior osteoporosis medication use. Results A prior fragility fracture was reported for 45% of the overall study population. Compared with placebo, denosumab significantly reduced the risk of a secondary fragility fracture by 39% (incidence, 17.3% versus 10.5%; p<0.0001). Similar results were observed regardless of age or prior fracture site. In the overall population, denosumab significantly reduced the risk of a fragility fracture by 40% (13.3% versus 8.0%; p<0.0001), with similar results observed regardless of history of prior osteoporotic medication use. Conclusions Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined, including those with prior fragility fractures. Identifying and treating high-risk individuals could help close the current care gap in secondary fracture prevention.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Abstract Despite the near concurrent publication by influential scientific organizations, there are important differences in interpretation of the evidence base and the conclusions derived from the recent Osteoarthritis Research Society International (OARSI) guidelines for the management of knee osteoarthritis, the American College of Rheumatology (ACR) (concerning also hip and hand osteoarthritis) and the algorithm recommendations by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This is particularly evident for the drug class of Symptomatic Slow-Acting Drugs in OsteoArthritis. In this paper, we highlight these differences and try to understand where they derive from, proposing an evidence-based interpretation.
Full-text · Article · Mar 2015 · Current Medical Research and Opinion
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.
[Show abstract][Hide abstract] ABSTRACT: It has been over 60 years since Huxley first described the essential force transmitting properties of voluntary striated skeletal muscle . At no time since then has the importance of skeletal muscle integrity been more pronounced. Although skeletal muscle comprises 40-50 % of total body mass, this tissue has been relatively understudied compared to brain, liver, cardiac, bone, and other tissues. Despite the fact that skeletal muscle is necessary for locomotion, oxygen consumption, whole-body energy metabolism, and substrate turnover and storage, a relative lack of attention has been paid to this tissue that is essential for many daily functions and activities .Robust skeletal muscle mass is essential for maintaining whole-body homeostasis and health . With advancing age, there is a loss of skeletal muscle mass and function that contributes to declines in physical functioning, increased disability, and mortality . It is with this background that we decided to devote this iss ...
Preview · Article · Feb 2015 · Calcified Tissue International
[Show abstract][Hide abstract] ABSTRACT: In humans, body magnesium content amounts to 25 g, with 66 % located in the bone, 33 % within cells, and only 1 % in the extracellular fluid (ECF), including blood [1–5] (see also Chap. 7). In the bone, magnesium as the divalent cation is adsorbed on the hydroxyapatite crystal and is in equilibrium with magnesium in the ECF. It is the most abundant intracellular cation together with potassium, reaching a concentration of approximately 0.5 mmol/l, which is thus close to that of magnesium in the ECF. Free cytosolic magnesium accounts for 5–10 % of total cellular magnesium. It binds to various organelles, 60 % of which is within mitochondria, where it is involved in phosphate transport, ATP synthesis, and utilization. ATP is synthesized by a magnesium-dependent oxidative phosphorylation process. Magnesium is a cofactor and regulator of a large series of enzymatic reactions, particularly those utilizing magnesium-ATP (glycolysis, oxidative phosphorylation), but also of DNA transcription and protein synthesis [1, 6]. In serum, 30 % of magnesium is protein bound. Circulating magnesium, which is between 0.7 and 1.0 mmol/l, is determined by bidirectional fluxes taking place at the levels of the intestine, kidney, and bone. Ionic magnesium interacts with the calcium-sensing receptor (CaSR) on parathyroid cells, and also on renal tubular cells, with a potency lower than calcium .
[Show abstract][Hide abstract] ABSTRACT: In the development and maintenance of bone structures resistant to usual mechanical stresses, adequate nutrition plays an important part. In addition to calcium associated with an adequate supply of vitamin D, dietary protein represents a key nutrient for bone health and thereby for the prevention of osteoporosis. During growth, protein under nutrition from infancy to childhood and adolescence results in reduced bone mass and strength, thereby increasing the risk of fragility fracture in later life. On the contrary, high protein intake, particularly when associated with physical activity, favors healthy development and peak bone mass acquisition, thereby enabling individuals to reach their genetic potential. There is a positive interaction between dietary protein, calcium-phosphate economy, and bone metabolism. This interaction appears to be mediated by the anabolic bone trophic factor IGF-I, the hepatic production of which is stimulated by amino acids supplied by dietary proteins. Amino acids such as arginine can exert a direct positive effect on the IGF-I production by bone forming cells. In young adulthood energy deficit, as observed in anorexia nervosa, can be associated with insufficient protein supply, low circulating IGF-I, bone loss and increased risk of fragility fracture. With aging, the reduction in the protein intake is associated in both genders with a decrease in the serum level of IGF-I, lower femoral neck aBMD, and poor physical performance. Protein under nutrition is often present in patients experiencing hip fracture. Furthermore, clinical outcome after hip fracture can be significantly improved by normalizing protein intake, which is associated with a rise in the serum IGF-I level. Thus, dietary protein contributes to bone health from early childhood to old age. An adequate intake of proteins should be recommended in the prevention and treatment of postmenopausal and age-dependent osteoporosis.
[Show abstract][Hide abstract] ABSTRACT: Sarcopenia, operationally defined as the loss of muscle mass and muscle function, is a major health condition associated with ageing, and contributes to many components of public health at both the patient and the societal levels. Currently, no consensual definition of sarcopenia exists and therefore it is still a challenge to establish the actual prevalence of sarcopenia or to establish the direct and indirect impacts of sarcopenia on public health. Anyway, this geriatric syndrome represents a huge potential public health issue because of its multiple clinical and societal consequences. Moreover, all these aspects have an impact on healthcare costs both for the patient and the society. Therefore, the implementation of effective and broadly applicable preventive and therapeutic interventions has become a medical and societal challenge for the growing number of older persons affected by sarcopenia and its disabling complications.
Full-text · Article · Dec 2014 · Archives of Public Health
[Show abstract][Hide abstract] ABSTRACT: 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 applicable in Europe and internationally. The knee was used as the model OA joint.
ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, clinical scientists). Existing guidelines were reviewed, all interventions listed and recent evidence retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a one-day meeting and shaped to the treatment algorithm. Fine tuning occurred by electronic communication and three consultation rounds until consensus.
Basic principles consist of the need of 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) and 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.
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.
Full-text · Article · Dec 2014 · Seminars in Arthritis and Rheumatism
[Show abstract][Hide abstract] ABSTRACT: Among the adverse events of glucocorticoid treatment are bone loss and fractures. Despite available, effective preventive measures, many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated for bone health and fracture risk. Populations with, or at risk of, glucocorticoid-induced osteoporosis (GIOP) to target for these measures are defined on the basis of dose and duration of glucocorticoid therapy and bone mineral density. That patients with GIOP should be treated as early as possible is generally agreed upon; however, diversity remains in intervention thresholds and management guidelines. The FRAX(®) algorithm provides a 10-year probability of fracture that can be adjusted according to glucocorticoid dose. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. Available anti-osteoporotic therapies such as anti-resorptives including bisphosphonates and the bone anabolic agent teriparatide are effective for the management of GIOP. Prevention with calcium and vitamin D supplementation is less effective than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be stopped at the time of glucocorticoid cessation, unless the patient remains at increased risk of fracture.
No preview · Article · Nov 2014 · Nature Reviews Rheumatology