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

Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

There is increasing emphasis on patient-centred research to support the development, approval and reimbursement of health interventions that best meet patients' needs. However, there is currently little guidance on how meaningful patient engagement may be achieved. An expert working group, representing a wide range of stakeholders and disciplines, was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the World Health Organization (WHO). Through a structured, collaborative process the group generated practical guidance to facilitate optimal patient engagement in clinical development and regulatory decisions. Patient engagement is a relational process. The principles outlined in this report were based on lessons learned through applied experience and on an extensive dialogue among the expert participants. This practice guidance forms a starting point from which tailoring of the approach to suit different chronic diseases may be undertaken.

Despite immunisation being one of the greatest medical success stories of the twentieth century, there is a growing lack of confidence in some vaccines. Improving communication about the direct benefits of vaccination as well as its benefits beyond preventing infectious diseases may help regain this lost confidence. A conference was organised at the Fondation Merieux in France to discuss what benefits could be communicated and how innovative digital initiatives can used for communication. During this meeting, a wide range of indirect benefits of vaccination were discussed. For example, influenza vaccination can reduce hospitalisations and deaths in older persons with diabetes by 45% and 38%, respectively, but the link between influenza and complications from underlying chronic non-communicable diseases such as diabetes is frequently underestimated. Vaccination can reduce antimicrobial resistance (AMR), which is growing, by reducing the incidence of infectious disease (though direct and indirect or herd protection), by reducing the number of circulating AMR strains, and by reducing the need for antimicrobial use. Disease morbidity and treatment costs in the elderly population are likely to rise substantially, with the ageing global population. Healthy ageing and life-course vaccination approaches can reduce the burden of vaccine-preventable diseases, such as seasonal influenza and pneumococcal diseases, which place a significant burden on individuals and society, while improving quality of life. Novel disease surveillance systems based on information from Internet search engines, mobile phone apps, social media, cloud-based electronic health records, and crowd-sourced systems, contribute to improved awareness of disease burden. Examples of the role of new techniques and tools to process data generated by multiple sources, such as artificial intelligence, to support vaccination programmes, such as influenza and dengue, were discussed. The conference participants agreed that continual efforts are needed from all stakeholders to ensure effective, transparent communication of the full benefits and risks of vaccination.

Gasparik, Andrea Ildiko/0000-0002-1848-2410; Gasparik, Andrea Ildiko/0000-0002-1848-2410; Cooper, Cyrus/0000-0003-3510-0709; Vrijens, Bernard/0000-0002-9090-1253; Abrahamsen, Bo/0000-0002-2730-6080; Dennison, Elaine/0000-0002-3048-4961 WOS:000501843100001 PubMed ID: 31388696 A Summary 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. European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) The meeting was funded by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

The recommended intake of vitamin D-fortified dairy products can substantially decrease the burden of osteoporotic fractures and seems an economically beneficial strategy in the general French population aged over 60 years.This study aims to assess the public health and economic impact of vitamin D-fortified dairy products in the general French population aged over 60 years.We estimated the lifetime health impacts expressed in number of fractures prevented, life years gained, and quality-adjusted life years (QALY) gained of the recommended intake of dairy products in the general French population over 60 years for 1 year (2015). A validated microsimulation model was used to simulate three age cohorts for both women and men (60-69, 70-79, and > 80 years). The incremental cost per QALY gained of vitamin D-fortified dairy products compared to the absence of appropriate intake was estimated in different populations, assuming the cost of two dairy products per day in base case.The total lifetime number of fractures decreased by 64,932 for the recommended intake of dairy products in the general population over 60 years, of which 46,472 and 18,460 occurred in women and men, respectively. In particular, 15,087 and 4413 hip fractures could be prevented in women and men. Vitamin D-fortified dairy products also resulted in 32,569 QALYs and 29,169 life years gained. The cost per QALY gained of appropriate dairy intake was estimated at a,notsign58,244 and fall below a threshold of a,notsign30,000 per QALY gained in women over 70 years and in men over 80 years.Vitamin D-fortified dairy products have the potential to substantially reduce the burden of osteoporotic fractures in France and seem an economically beneficial strategy, especially in the general population aged above 70 years.

Vaccines are available against human papillomavirus (HPV), the causal agent of cervical and other cancers. Efficacy data from the HPV-16/18 AS04-adjuvanted vaccine clinical trial program were reviewed. Six randomized, controlled phase II/III trials evaluating cervical endpoints enrolled women from diverse populations and geographical locations. The program analyzed extensively the cohorts most relevant from a public health perspective: the total vaccinated cohort (TVC), approximating a general population including those with existing or previous HPV infection, and TVC-naïve, approximating a population of young women before sexual debut. Results show that the vaccine reduces HPV-16/18 infection and associated cervical endpoints in women regardless of age, location, or sexual experience. It provides cross-protection against some non-vaccine oncogenic HPV types and types causing genital warts, and may be effective against vulvar, oral, and anal HPV infection. Early epidemiology data following its introduction suggest a decline in the prevalence of vaccine and some non-vaccine HPV types.

BACKGROUND: Sarcopenia is increasingly recognized as a correlate of ageing and is associated with increased likelihood of adverse outcomes including falls, fractures, frailty and mortality. Several tools have been recommended to assess muscle mass, muscle strength and physical performance in clinical trials. Whilst these tools have proven to be accurate and reliable in investigational settings, many are not easily applied to daily practice. METHODS: This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were afterwards organized for the whole group to make amendments and discuss further recommendations. RESULTS: This paper proposes some user-friendly and inexpensive methods that can be used to assess sarcopenia in real-life settings. Healthcare providers, particularly in primary care, should consider an assessment of sarcopenia in individuals at increased risk; suggested tools for assessing risk include the Red Flag Method, the SARC-F questionnaire, the SMI method or different prediction equations. Management of sarcopenia should primarily be patient centered and involve the combination of both resistance and endurance based activity programmes with or without dietary interventions. Development of a number of pharmacological interventions is also in progress. CONCLUSIONS: Assessment of sarcopenia in individuals with risk factors, symptoms and/or conditions exposing them to the risk of disability will become particularly important in the near future. ispartof: BMC Geriatrics vol:16 issue:1 pages:170-179 ispartof: location:England status: published

Background: Symptomatic slow-acting drugs (SYSADOA) have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA). Methods: The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations. Results: Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed. Conclusion: In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

A Summary Titrated supplementations with vitamin D-fortified yogurt, based on spontaneous calcium and vitamin D intakes, can be cost-effective in postmenopausal women with or without increased risk of osteoporotic fractures.Introduction The objective of this study is to assess the cost-effectiveness of the vitamin D-fortified yogurt given to women with and without an increased risk of osteoporotic fracture.Methods A validated cost-effectiveness microsimulation Markov model of osteoporosis management was used. Three personalized supplementation scenarios to reflect the Ca/Vit D needs taking into account the well-known variations in dietary habits and a possible pharmacological supplementation in Ca/Vit D, given above or in combination with anti-osteoporosis medications: one yogurt per day, i.e., 400 mg of Ca + 200 IU of Vit D (scenario 1 U), two yogurts per day, i.e., 800 mg of Ca + 400 IU of Vit D (scenario 2 U), or three yogurts per day, i.e., 1,200 mg of Ca + 600 IU of Vit D (scenario 3 U). Results One yogurt is cost-effective in the general population above the age of 70 years and in all age groups in women with low bone mineral density (BMD) or prevalent vertebral fracture (PVF). The daily intake of two yogurts is cost-effective above 80 years in the general population and above 70 years in the two groups of women at increased risk of fractures. However, an intake of three yogurts per day is only cost-effective above 80 years old in the general population, as well as in women with low BMD or PVF.Conclusions Our study is the first economic analysis supporting the cost-effectiveness of dairy products, fortified with vitamin D, in the armamentarium against osteoporotic fractures.

Summary: The incidence of hip fracture, death and the estimated incidence of major osteoporotic fracture in France were used to determine the lifetime and 10-year probability of fracture and incorporated into a probability model ( FRAX® ) calibrated to the French population. Introduction: Fracture probabilities in the French population have not been determined. Our aim was to determine the incidence of hip fracture in France and the estimated 10-year probabilities of hip and major osteoporotic fractures. Methods: The study population included adults over 50 years living in France in 2004. Incident hip fracture cases were identified from the French PMSI database. Incidence of the other major osteoporotic fractures was imputed from the relationship between hip fracture incidence and other major fracture in Sweden. These data were used to calculate population-based fracture probabilities according to age and BMD using cutoff values for femoral neck T-scores from the NHANES III data in Caucasian women. The probability model ( FRAX® ) calibrated to the French population was used to compute individual fracture probabilities according to specific clinical risk factors. Results: We identified 15,434 men and 51,469 women with an incident hip fracture. The remaining lifetime probability of hip fracture at 50 years was approximately 10 and 30% respectively. With a femoral neck T-score of −2 SD, one in two women and one in five men would sustain a major osteoporotic fracture in their lifetime. The 10-year probability of other major osteoporotic fractures increased with declining T-score and increasing age. Low body mass index and other clinical risk factors had an independent effect on fracture probability whether or not BMD was included in the FRAX® model. Conclusion: This analysis provides detailed estimation on the risk of fracture in the French population and may help to define therapeutic guidelines.

Background: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. Methods: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. Findings: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. Conclusion: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.

The first reports of osteonecrosis of the jaw in patients taking bisphosphonates to reduce excessive bone resorption were published in 2003. Subsequent reports raised concern and resulted in manufacturers writing letters of caution to physicians and dentists. Recommendations were issued by the US FDA, and the European Agency for the Evaluation of Medicinal Products requested that pharmaceutical companies update their product information and package leaflets. The European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the Foundation for Research on Osteoporosis and other Bone Diseases Working Group Meeting was convened on 14 December 2006 in Geneva, Switzerland, to review the available data and published guidelines on this rare but serious condition. The purpose of the meeting was to assess the impact of osteonecrosis of the jaw on the management of osteoporosis. The discussion focused on the current definition of osteonecrosis of the jaw, its epidemiology and pathophysiology, as well as identifying potential risk factors. Agreement was also reached on best practice in terms of diagnosis and management.

Background Dietary sources of calcium and vitamin D are recommended as a first-line strategy in prevention of osteoporosis-related fractures but their public health and economic impact has never been studied. Methods We designed a population-based model to forecast the potential health outcomes and medical effectiveness of the daily administration of dairy supplements containing 800 IU of vitamin D and 1 g of calcium in cohorts of subjects, from both genders, aged 50, 60, 70 and 80 years. Annual costs of dairy products were tested at €150, €250 and €350. Results In total, the daily intake of vitamin-D rich dairy products reduces by 30,376 and 16,105 events the number of osteoporotic fractures in women and men respectively and permits to gain 6605 and 6144 life-years, in women and men respectively. This intervention is cost-effective from 70 years on in the general population and from 60 years on in patients at increased risk of osteoporotic fractures. Conclusion The recommendation to use dairy products as the preferred source of calcium and vitamin D in aging males and females is supported by public health and health economic analyses. Electronic supplementary material The online version of this article (doi:10.1186/s13690-015-0099-3) contains supplementary material, which is available to authorized users.

Introduction The primary complaint of patients with hand osteoarthritis (OA) is frequently the inelegant appearance of their hands. Only one study has been conducted to assess the magnitude of and identify the determinants of aesthetic discomfort in hand OA. Methods The LIège Hand Osteoarthritis Cohort is a prospective cohort of 203 patients diagnosed with hand OA. At baseline, these patients rated their aesthetic discomfort on a 100-mm visual analogue scale (VAS) and used a Likert scale (range 0–7) to quantify the magnitude of their aesthetic damage. Results The median value of the aesthetic discomfort VAS was 35.0 [interquartile range (Q1–Q3) 6.0–59.0]. The median damage was rated 3.0 (Q1–Q3 1.0–4.0), corresponding to a moderate level. Both were significantly (p 10 years (p = 0.001), and presence of erosive joints (p

Radiological severity and impact of hand osteoarthritis on functional disability, health-related quality of life, and psychological status. (DOC 38 kb)

Characteristics of patients reporting high (HAD) or low (LAD) (aesthetic discomfort). (DOC 55 kb)

Results in women and men. (PDF 212 kb)

It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly elderly population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. In the European Union, in 2000, the number of osteoporotic fractures was estimated at 3.79 million. A baseline fracture is a very strong predictor of further fractures with 20% of patients experiencing a second fracture within the first year. The costs to health care services are already considerable and, on current trends, are predicted to double by 2050. The direct costs of osteoporotic fractures to the health services in the European Union in the year 2000 were estimated at 32 billion Euros. Guidelines for the diagnosis and treatment of osteoporosis are available in many countries; however, implementation is generally poor despite the availability of treatments with proven efficacy. Programs to increase awareness of osteoporosis and its outcomes are necessary for healthcare specialists and the general public. Earlier diagnosis and intervention prior to the first fracture are highly desirable.

Objective: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. Methods: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months. Results: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004). Conclusions: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.

Osteoporosis is a common, increasingly prevalent condition worldwide. Osteoporotic fractures are associated with substantial morbidity, mortality, and health service resource use. Current daily oral and weekly bisphosphonates are highly effective in managing osteoporosis but patients often fail to take their medication correctly and/or stop treatment prematurely. This poor adherence limits the benefits of bisphosphonates in routine clinical practice and adds to health service costs. More convenient bisphosphonate regimens, with a lower dosing frequency, would be predicted to improve adherence and optimize therapeutic benefits. Once-monthly oral and intermittent intravenous injection regimens now in late-stage clinical development for ibandronate show considerable potential to deliver these benefits.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 36 - N° 6 - p. 615-617

This paper provides recommendations for fair and unbiased relationship between academic scientists and the pharmaceutical industry. INTRODUCTION: Real or perceived problems in the relationship between academics and the industry have been the subject of much recent debate. It has been suggested that academic clinicians should sever all links with the industry-a view that is rarely challenged. METHODS: Academic experts and members of the pharmaceutical industry were invited to an expert consensus meeting to debate this topic. This meeting was organized by the Group for the Respect of Ethics and Excellence in Science. Conflict of interest, competing interest, right and duties of academic scientist, authorship, and staff and student education were discussed. RESULTS: Guidelines for a transparent, ethical, strong, and successful partnership between the academic scientist and the pharmaceutical industry have been provided. CONCLUSIONS: The Group support interactions between the industry and clinicians provided that it is transparent and ethical.

Bisphosphonates are the current mainstay of the management of osteoporosis worldwide. Oral daily and weekly formulations have been linked to poor adherence, yielding a decrease in antifracture efficacy, in real-life settings. Development of new bisphosphonates, with increased antiosteoclastic potency and affinity for bone matrix allowed intravenous administration and intervals between dosingsto be higher than weekly. Ibandronate and zoledronic acid have been investigated in established osteoporosis. Quarterly injections of ibandronate (3 mg) have been shown to be at least as effective in increasing bone mineral density and reducing bone turnover markers as the oral ibandronate regimen, which has proven antifracture efficacy. A once-yearly infusion of zoledronic acid (5 mg) during a 3-year period significantly reduced the risk of vertebral, hip and other fractures. Intravenous administration of bisphosphonates can now be considered as an important component of the management of postmenopausal osteoporosis.

Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care.

The role of calcium and vitamin D supplementation in the treatment of osteoporosis has been extensively studied. The aim of this paper was to reach, where possible, consensus views on five key questions relating to calcium and vitamin D supplementation in the management of osteoporosis. Whereas global strategies that target supplementation to the general population could not be justified in terms of efficacy and health economics, there is a clearer rationale for supplementing patients who are at increased risk of osteoporosis and those who have developed osteoporosis, including those already taking other treatments for osteoporosis. The combination of vitamin D with calcium may be beneficial in terms of efficacy and, perhaps, for optimising adherence.

Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis.Several medications have been unequivocally shown to decrease fracture rates in clinical trials. However, in real life settings, long-term persistence and compliance to anti-osteoporosis medication is poor, hence decreasing the clinical benefits for patients.An extensive search of Medline from 1985 to 2006 retrieved all trials including the keywords osteoporosis, compliance, persistence or adherence followed by a critical appraisal of the data obtained through a consensus expert meeting.The impact of non-adherence on the clinical development of interventions is reviewed, so that clinicians, regulatory agencies and reimbursement agencies might be better informed of the problem, in order to stimulate the necessary research to document adherence.Adherence to therapy is a major problem in the treatment of osteoporosis. Both patients and medication factors are involved. Adherence studies are an important aspect of outcomes studies, but study methodologies are not well developed at the moment and should be improved. Performing adherence studies will be stimulated when registration authorities accept the result of these studies and include the relevant information in Sect. 5.1 of the summary of product characteristics. Reimbursement authorities might also consider such studies as important information for decisions on reimbursement.

Background Dissatisfaction with hand appearance is frequently the presenting complaint of patients with hand osteoarthritis (HOA), yet no tool exists for its measurement and few studies have examined aesthetic discomfort. Objectives The aims of this study were to measure the extent and to explore the associations of aesthetic concerns in HOA. Methods 172 patients with HOA were assessed with tender joint and node count, global and pain scores, Functional Index for Hand Osteoarthritis, Short Form-12, Hospital Anxiety and Depression Scale and posterior–anterior hand radiographs. Patients scored the aesthetic impact of the disease on a Visual Analogue Scale of 0–100 mm and were classifi ed into low, intermediate and high aesthetic concern (HAC) based on this score. Results Of 172 patients (155 women), the majority (92%) had nodes and 46% had erosive disease. The mean aesthetic score was 44.8 mm (SD 35.9), and 59 (34.3%) patients scored their aesthetic discomfort ≥66 mm. Factors associated with HAC were female gender, a high number of tender joints and nodes, high global and pain scores, high radiological damage scores, the presence of erosions and high depression and anxiety levels. The multivariate analysis identifi ed two independent factors associated with HAC: patient’s global assessment (p=0.0005) and radiographic erosions (p=0.03). Conclusions Aesthetic discomfort is a major concern for a signifi cant number of patients with HOA, particularly women, those with a high burden of HOA disease and those with erosive osteoarthritis, and is also associated with depression, anxiety and poor health-related quality of life.

Background Whereas hand osteoarthritis (OA) is a frequent disease, which may lead to considerable pain and physical limitations, limited research has been performed, compared to lower limbs OA. Objectives To better understand the impact of hand osteoarthritis on quality of life and health resources utilization of interdigital osteoarthritis. Methods We decided to prospectively follow a cohort of 203 individuals, diagnosed with hand OA during consultations held at a tertiary care facility specialized in bone and cartilage metabolism and called the Liege Hand Osteoarthritis Cohort (LIHOC). Results As expected, the vast majority of patients (90.1%) were of female gender with 46.8% having a family history of hand OA. The median age of the population was 69.1 years (Q1 61.9-Q3 75.6). Body Mass Index (kg/m2) median was 25.6 (22.9-28.9). Hand OA was associated with other joint involvement in 87.1% of the cases {mainly spine (70.8%) and knee (69.0%)}. On a Visual Analog Scale reflecting pain in hand joints, graded from 0 to 100, the median score was 50.0 (29.0-59.0), with a median number of painful joints at pressure of 5.0 (2.0-10.0). The median number of swollen joints and of joint with bony deformations was respectively 2.0 (1.0-4.0) and 10.0 (6.0-15.0). The total normalized Auscan score (0-300) median value was 129.0 (71.1-182.5) while the median Functional Index for Hand Osteoarthritis (FIHOA) score (0-30) was 5.0 (2.0-11.0). Radiologic assessment of hand OA showed a Verbruggen total score (0-218) median value of 31.6 (20.9-48.2) whereas the Kellgren-Lawrence total score (0-128) median value was 54.0 (40.0-66.0). Conclusions The LIHOC will be followed for a total duration of 5 years, with the objective to better understand the determinants of clinical and radiologic progression as well as the impact of hand OA on quality of life and health resources utilization. Disclosure of Interest None declared

Background Whereas hand osteoarthritis (OA) is a frequent disease, which may lead to considerable pain and physical limitations, limited research has been performed, compared to lower limbs OA. The primary complaint of patients is frequently related to the disgracious appearance of their hand joints. However, few studies have been conducted to identify the magnitude and the determinants of aesthetic discomfort in hand OA. Objectives The LIege Hand Osteoarthritis Cohort (LIHOC) is a prospective cohort of 203 patients diagnosed with hand OA which are prospectively followed to better understand the impact of hand OA on quality of life and health resources utilization. Methods At baseline, these patients were asked to rate their aesthetic discomfort related to hand OA on a 100 mm Visual Analog Scale and also use a seven-point Likert scale (0-7), commonly used in forensic medicine, to quantify the magnitude of their aesthetic damage. Results The median value of the aesthetic discomfort VAS was 35.0 (Q1: 6.0-Q3: 59.0). Correlation analyses were performed between these scorings and clinical hand parameters. The median damage was rated at 3.0 (1.0-4.0), corresponding to a “moderate” level. Aesthetic discomfort (VAS) and the magnitude of the aesthetic damage (Likert) were significantly (p Conclusions Aesthetic discomfort and aesthetic damage are significant complaints in patients presenting with hand OA. The major determinants of their impact are gender, duration of hand OA, number of erosive joints and the Australian Canadian Osteoarthritis Hand Index. Disclosure of Interest None declared

UNLABELLED Currently available medications, such as bisphosphonates, selective estrogen receptor modulators, and teriparatides, have shown their ability to reduce vertebral and/or nonvertebral fractures. Questions remain regarding their long-term innocuousness and several studies showed that adhering to currently marketed anti-osteoporotic medications remain sub-optimal. There is, therefore, an urgent need for the development of new effective, safe, and user-friendly medications to optimize the treatment of postmenopausal osteoporosis. The current review was designed to assess, through an extensive literature search, the antifracture efficacy of strontium ranelate on the axial and appendicular skeleton. Two multinational Phase 3 clinical trials have shown its efficacy and safety in the treatment of postmenopausal osteoporosis. In the Spinal Osteoporosis Therapeutic Intervention trial, strontium ranelate (2 g/day) treatment reduced the relative risk of a new vertebral fracture by 41% after 3 years compared with placebo. Data from the Treatment of Peripheral Osteoporosis study showed a 16% reduction in the relative risk of nonvertebral fracture in all patients and a 36% reduction in hip fracture in high-risk patients. Strontium rane-late reduces the risk of all fragility fractures and is well tolerated, which makes it a new first-line alternative in the treatment of postmenopausal osteoporosis. LEVEL OF EVIDENCE Therapeutic study, Level II (lesser quality randomized controlled trial [eg, < 80% followup, no blinding, or improper randomization]). See the Guidelines for Authors for a complete description of the levels of evidence.

Summary Objective Our goal was to identify the magnitude of gastro-protective drugs (GPDs) co-prescription and the profile of patients who received GPD co-prescription, during nonsteroidal anti-inflammatory drugs (NSAIDs) treatment in a "real life setting" of primary care practice. Methods A pragmatic prospective 6-month survey of 2197 new takers of nonselective NSAIDs, selected and followed by general practitioners (GPs) on the bias of their usual standards of care. Results Forty-seven percent of our survey population used at least one GPD during the 6-month follow-up. No difference was identified between piroxicam, diclofenac, ibuprofen, meloxicam and nimesulid for the GPD co-prescription. Besides the presence of gastro-intestinal (GI) symptoms, previous use of GPD, previous occurrence of GI disorders and increase in age are the most prominent predictive factors of GPD use during NSAID treatment. When adjusted for other risk factors, co-prescription of GPD was significantly increased in patients aged 55 years and above (odds ratio (OR): 1.29, 95% confidence interval (CI): 1.01–1.64) with no further increase in the co-prescription in older subjects. Conclusion Patients above 55 years with previous history of GI symptoms or GPD use are more likely to benefit from cytoprotective medications.

To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes.A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up.All QoL dimensions were significantly (p0.01) decreased in patients with OA compared with controls. Significant improvement (p0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA.OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs.

Summary Objective To investigate, over 1-year, the relationship between X-ray and magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis (OA). Methods Sixty-two osteoarthritic patients (46 women) were followed for 1 year. At baseline and after 1 year, volume and thickness of cartilage of the medial tibia, the lateral tibia and the femur were assessed by MRI. A global score from the multi-feature whole-organ MRI scoring system (WORMS) was calculated for each patient at baseline and after 1 year. This score combined individual scores for articular cartilage, osteophytes, bone marrow abnormality, subchondral cysts and bone attrition in 14 locations. It also incorporated scores for the medial and lateral menisci, anterior and posterior cruciate ligaments, medial and lateral collateral ligaments and synovial distension. Lateral and medial femoro-tibial joint space width (JSW) measurements, performed by digital image analysis, were assessed from fixed-flexion, postero-anterior knee radiographs. Results One-year changes in medial femoro-tibial JSW reach 6.7 (20.5) % and changes in medial cartilage volume and thickness reach 0.4 (16.7) % and 2.1 (11.3) %, respectively. Medial femoro-tibial joint space narrowing (JSN) after 1 year, assessed by radiography, was significantly correlated with a loss of medial tibial cartilage volume ( r =0.25, P =0.046) and medial tibial cartilage thickness ( r =0.28, P =0.025), over the same period. We found also a significant correlation between the progression of the WORMS and radiographic medial JSN over 1 year ( r =−0.35, P =0.006). All these results remained statistically significant after adjusting for age, sex and body mass index. Conclusion This study shows a moderate but significant association between changes in JSW and changes in cartilage volume or thickness in knee joint of osteoarthritic patients.